Tag Archives: gastrointestinal

EM@3AM – Acute Cholecystitis

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 41-year-old obese female presents for evaluation of severe right upper quadrant pain and nausea without emesis. The patient reports post-prandial pain of one months duration, acutely worsening prior to presentation following the consumption of a bacon cheeseburger. ROS is negative for sick contacts, foreign travel, and changes in bowel habits. The patient denies a surgical history.

Triage VS: T101.6°F Oral, HR 134, BP 147/99, RR 24, SpO2 98% on room air

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?

Answer: Acute Cholecystitis1-4

  • Risk Factors: oral contraceptives or estrogen replacement therapy (alters cholesterol and bile salt metabolism leading to gallstone formation and gallbladder hypomotility1), diseases of the terminal ileum (e.g. Crohns; secondary to poor bile salt reabsorption), cirrhosis (decreased bile acid secretion), hemolytic diseases (pigmented gallstones), pregnancy, obesity, TPN
  • Presentation: RUQ or epigastric pain, postprandial pain, nausea +/- emesis, +Murphy’s sign (+LR: 2.8; 95% CI, 0.8-8.62), +/- fever
  • Evaluation:
    • US (Sensitivity 95%, Specificity 98%3): sonographic Murphy’s, pericholecystic fluid, gallstones/biliary sludge, gallbladder wall thickening > 3mm.
    • CBC, LFTs
      • CBC: often demonstrates leukocytosis
      • LFTs: transaminitis; allows for evaluation of choledocolithiasis
  • Treatment:
    • Antimicrobials:
      • Mildly ill: ciprofloxacin 400 mg IV + metronidazole 500 mg IV
      • Critically ill: vancomycin 20 mg/kg (up to 2 g) IV + piperacillin/tazobactam 4.5 g IV
    • Fluid Resuscitation
    • Pain control
    • Anti-emetic PRN
    • Surgical Consultation – cholecystectomy
  • Pearls:
    • Diabetes is a risk factor for emphysematous cholecystitis:3 initiate antibiotic therapy directed against Gram-negative rods and anaerobes, and consult surgery.
    • Include acalculous cholecystitis in your differential diagnosis of the critically ill: RUQ pain, epigastric pain, and nausea are absent upon initial evaluation in up to 75% of these patients.1



  1. Welch J, Chike V, Bowens N, Arnell T, Ferri F. Acute Cholecystitis. First Consult. 2011. Elsevier, Philadelphia, PA.
  2. Trowbridge R, Rutkowski N, Shojania K. Does this patient have acute cholecystitis? JAMA. 2003; 289(1): 80-86.
  3. Glasgow R, Mulvihill S. Treatment of Gallstone Disease. In: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Philadelphia: Saunders Elsevier, 2016:1134-1151.e5.
  4. Senturk S, Miroglu T, Cilici A, Gumua H, Tekin R, et al. Diameters of the common bile duct in adults and postcholecystectomy patients: a study with 64-slice CT. Eur J Radiol. 2012; 81(1): 39-42.

The Sick Bowel Obstruction Patient

Authors: Nicholas Mancuso, MD (EM Resident Physician, University of Kentucky) and Michael Sweeney, MD (Assistant Professor, University of Kentucky, Dept. of Emergency Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


A 68-year-old female presents to the ED with abdominal pain, bloating, and nausea which she states began this morning upon wakening about 3 hours prior to arrival.  She appears moderately uncomfortable and pale.  She is urgently brought to an acute care room and evaluated by the resident physician.  Her initial vital signs reveal tachycardia of 120 beats/minute, blood pressure of 103/52, oxygen saturation of 90% room air, respiratory rate of 24 breaths/minute, and an oral temperature of 99.0° F.  Prior medical history includes hypertension and hypercholesterolemia, and she has a surgical history of two caesarean sections, bilateral tubal ligation, and open cholecystectomy.

She says it is worse “right in the middle,” and she “feels like vomiting but hasn’t yet”.  She does report belching several times with a “foul smell”.  Her daughter and granddaughter are sick with a stomach virus, and she thinks she has the same.  Her last bowel movement was the evening prior and was formed.

She is rolling on the bed. She is tender over her upper quadrants diffusely with guarding but no rebound. Her exam otherwise is unremarkable.  Analgesic and anti-emetic medicine is administered, as well as a bolus of intravenous fluid.  Labs results reveal a leukocytosis of 15, lactate of 5.3, and normal lipase and CMP.  Urinalysis is unremarkable.  KUB for her 7/10 pain shows slightly dilated small bowel concerning for “possible obstruction, please base on history”.   CT with IV and PO contrast is obtained which shows complete obstruction with transition point in the RUQ consistent with a small bowel obstruction (SBO), trace contrast distal to this point, and mild free fluid around the dilated bowel.


Bowel obstructions are a relatively common presentation in Emergency Departments (EDs) across the country and are most often due to mechanical obstruction.  The majority (~75%) of bowel obstructions occur in the small bowel (1), with the remainder afflicting the large bowel (LBO).

Bowel obstructions may present along a spectrum and can pose a diagnostic challenge, with early or low grade obstruction manifesting with non-specific symptoms and a non-focal exam in a relatively well appearing patient.   Others are more obvious with classic symptoms of abdominal distention, feculent belching or emesis, significant pain, and decreased to no bowel movements/flatus.  Presentation will also vary depending on the location of the obstruction (proximal versus distal).

Recognition of risk factors can aid in the timely workup and diagnosis of an ill patient with bowel obstruction.  It is well known that previous abdominal surgeries are a risk factor due to development of adhesions, which complicate up to 90-93% intra-abdominal surgeries (2,3).  75% of small bowel obstructions are caused by adhesions in adults in one review (4). In another meta-analysis that looked at 196 studies, those with a known cause of SBO had adhesions as the etiology in 56% (5). Other common causes include a history or current abdominal or groin hernia, prior radiation treatment, neoplasm, inflammation, abscess, or ingested foreign body.

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Notably, those with a previous obstruction due to any cause have higher rates of re-obstruction and tend to have them occur sooner (6, 7).

A common misconception among some is that ongoing passage of stools is inconsistent with small bowel obstruction.  However, flatus and feces may pass for 12 to 24 hours after obstruction as the distal bowel decompresses.

Large bowel obstruction typically occurs in older patients. The most common cause is a colorectal malignancy in up to 60%.  Other etiologies include volvulus, hernia with incarceration, repetitive diverticular disease, and less frequently, ischemia, adhesions, or intussusception (8).


According to Eastern Association for the Surgery of Trauma (EAST) guidelines, Level III Evidence recommends obtaining plain abdominal films in a patient with a concern for a bowel obstruction (9).  CT can delay surgical management and may be unnecessary in the unstable patient with plain film evidence of bowel obstruction.  On plain film, signs of bowel obstruction include dilated loops of bowel (>3 cm), air-fluid levels, and paucity of gas in the distal bowel. However, many providers will go straight to CT, which is often the required test for diagnosis.

Per EAST guidelines, if plain films are inconclusive (and the patient is stable enough), CT with IV and oral contrast is indicated (Level I), which will reliably identify the degree and location of obstruction, and often the cause. In 2015 the American College of Radiology (ACR) Appropriateness criteria actually recommended against PO contrast as it increased time to CT, patient discomfort, and symptoms, and it was not found to increase accuracy (10). IV contrast helps to distinguish ischemia. A study did find up to 70% of institutions still use PO contrast, and this is highly institution and surgeon specific.   Findings include a “transition point” between distended and decompressed bowel, bowel wall and mesenteric edema, and transudative fluid or ascites. These findings do not require PO contrast (10).

A meta-analysis in 2013 pooled data from 5 large studies and demonstrated x-ray to have a sensitivity of 75% and specificity of 66%.  CT with IV and PO had a sensitivity of 87% and specificity of 81%.  Modern scanners demonstrate sensitivity as high as 96% to 100% (11). CT without PO contrast demonstrates similar statistics with modern scanning technology (10,11).

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Finally, ultrasound can assist at the bedside. In one prospective study with 123 patients, a sensitivity of 95% and specificity of 82% were reported (12), with a second study demonstrating sensitivity and specificity of  91% and 84%, respectively (13). This can be learned reportedly in a 10-15 minute session, with different diagnosis requirements all focusing on non-compressible bowel next to compressible segments. A high-frequency probe is most commonly used to evaluate for bowel greater than 2.5 cm in diameter next to compressible bowel, while edema of bowel wall and free fluid are secondary signs (14). Please see this post for more information on US in bowel obstruction: http://www.emdocs.net/ultrasound-small-bowel-obstruction/.

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From: http://www.em.emory.edu/ultrasound/ImageWeek/Abdominal/small_bowel_obstruction1.html.

An important subset of bowel obstruction which can be missed on exam and imaging studies is a closed loop obstruction.  This is a true emergency and occurs when the bowel is obstructed in two places, creating a “closed loop” with no anterograde or retrograde flow possible.  Closed loop obstructions have higher complication rates for ischemia and perforation, and for a septic presentation.  Many are diagnosed in the OR.  Signs to look for on CT are a distended, fluid-filled bowel loop in C or U shape, the “whirl sign” (abdomen bowel rotated around its mesentery resembling a whirlpool), the “beak sign” (tapering bowel loops at the point of obstruction), or two adjacent collapsed loops of bowel at the site of obstruction (15).

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For LBOs, radiographs can be an appropriate starting point, though again CT displays better sensitivity and specificity. Two classic findings are useful for distinguishing sigmoid versus cecal volvulus. The sigmoid colon is mobile on the mesentery, and the classic “coffee-bean” sign is seen on x-ray in sigmoid volvulus, which is more common in elderly (16,17). Cecal volvulus is typically seen in younger patients (20-60 years old), who present with a dilated loop in the mid abdomen pointing to the epigastrium or left upper quadrant (16,17).

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Early surgical intervention is the most important step in the management of the unstable patient with bowel obstruction.  With high grade obstructions, bowel wall ischemia can lead to perforation and pneumoperitoneum.  If leukocytosis, fever, peritonitis, metabolic acidosis, or a high lactic acidosis are present, exploratory laparotomy is Level 1 recommendation according to EAST guidelines.

Serum lactate is a sensitive marker of bowel ischemia or severe volume depletion.  In addition to routine labwork such as CBC and CMP, pre-operative labs such as type and screen and coagulation studies should be added to the unstable patient.  Confirmation of code status and goals of care in selected patients with significant comorbidities and increase peri-operative mortality is advised.

Bowel obstruction, especially proximal SBO, can present with significant vomiting and fluid losses.  IV fluid resuscitation is indicated in those with abnormal vitals or signs of shock.  Some surgeons favor early surgical management, as fluid resuscitation carries the risk of significant bowel edema, which can complicate operative intervention.

Early administration of antibiotics after blood and urine cultures are obtained is indicated in unstable or febrile patient.  Regimens include Piperacillin/Tazobactam (3.375 grams IV q 6hr) or the combination of Cefepime (2 grams IV q8 hr) and Metronidazole (500 mg IV q8hr).

Nasogastric tube placement and low intermittent suction can help decompress the bowel proximal to the obstruction and relieve bowel wall ischemia due to high intraluminal pressures.   In actively vomiting patients, this may also reduce the incidence of aspiration.

For a partial or chronic SBO, or a hemodynamically stable complete obstruction, NG placement, NPO status, appropriate analgesics and anti-emetics, and IV fluid are indicated.  Non-operative management is often successful for up to 3-5 days (Level III).  Call a surgical service for admission.

LBOs from volvulus are treated typically with a rectal tube or flexible sigmoidoscopy for sigmoid volvulus, with admission for observation given high rate of recurrence.  (17,18). However, cecal volvulus more commonly requires surgical management (17,18). Patients often need fluid resuscitation. For perforation or cases due to malignancy, surgery is needed.

In terms of morbidity and mortality, numbers vary greatly by institution and surgeon. In one retrospective study from 1991 to 2002 using the VA database, the 30 day mortality for SBOs was 7.7%, with an odds of death reported higher in sicker patients and older patients (over 80) (19,20). In another, all postop mortality were due to patients 75 and older, long term affected by ASA class III disease, number of “obstructed structures”, and number of surgical complications such as intestinal injury (21).


-For the unstable patient with bowel obstruction early surgical consultation and laparotomy are crucial.  Manage ABCs, administer resuscitative IV fluids, and place a nasogastric tube to decrease chance of aspiration and for pain control.  Abdominal upright x-ray is not as sensitive as CT; if x-ray unremarkable and clinical concern still exists, obtain CT. CT first may be warranted.

– Ultrasound is a viable newer alternative that appears to take place between X-ray and CT in sensitivity and specificity, is faster, but will be difficult to convince surgeons for now.

If peritonitic or septic, cover with antibiotics (institution-specific, not a lot of evidence).

Be wary of nonspecific findings in early presentations of bowel obstruction.  Labwork directed to detect signs of ischemia (lactate, blood gas).  Ongoing passage of stools or flatus does not rule out an obstruction.

Closed loop obstruction represents both a diagnostic challenge and a complication with high morbidity and mortality.  These patients may present with very little distention but can be very ill.  Look for C or U signs, whirl sign, or beak sign on CT.

– For LBOs, most common cause is by far malignancy (~60%).  Sigmoid volvulus shows up as the “coffee-bean” sign, more common in elderly and nursing home patients.  Cecal volvulus points to the left upper quadrant and is typically seen in a younger patient (20-60 years old).

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References / Further Reading

  1. DrożdżW, Budzyński P. Change in mechanical bowel obstruction demographic and etiological patterns during the past century: observations from one health care institution.  Arch Surg. 2012 Feb;147(2):175-80.
  2. Parker MC, Ellis H, Moran BJ, Thompson JN, Wilson MS, Menzies D, et al. Postoperative adhesions: ten–year follow–up of 12,584 patients undergoing lower abdominal surgery.Dis Colon Rectum. 2001 Jun;44(6):822–829. discussion 9–30.
  3. Menzies D, Ellis H. Intestinal obstruction from adhesions––how big is the problem? Ann R Coll Surg Engl. 1990 Jan;72(1):60–63.
  4. Bizer LS, Liebling RW, Delany HM, Gliedman ML. Small bowel obstruction: the role of nonoperative treatment in simple intestinal obstruction and predictive criteria for strangulation obstruction. 1981 Apr;89(4):407–413
  5. Ten Broek, Richard P G et al. “Burden of Adhesions in Abdominal and Pelvic Surgery: Systematic Review and Met-Analysis.”The BMJ 347 (2013): f5588. PMC. Web. 16 Jan. 2017.
  6. Miller G, Boman J, Shrier I, Gordon PH. Natural history of patients with adhesive small bowel obstruction. Br J Surg. 2000 Sep;87(9):1240-7. PMID 10971435
  7. Barkan H, Webster S, Ozeran S. Factors predicting the recurrence of adhesive small-bowel obstruction. Am J Surg. 1995 Oct;170(4):361-5 PMID 7573729
  8. Kahi CJ, Rex DK. Bowel obstruction and pseudo-obstruction Gastroenterol Clin North Am. 2003 Dec;32(4):1229-47
  9. Maglinte DD, Reyes BL, Harmon BH, et al. Reliability and role of plain film radiography and CT in the diagnosis of small-bowel obstruction. AJR Am J Roentgenol. 1996;167:1451–1455
  10. Katz DS, Baker ME, Rosen MP, Lalani T, Carucci LR, Cash BD, Kim DH, Piorkowski RJ, Small WC, Smith MP, Yaghmai V, Yee J, Expert Panel on Gastrointestinal Imaging. ACR Appropriateness Criteria® suspected small-bowel obstruction. [online publication]. Reston (VA): American College of Radiology (ACR); 2013.
  11. Mark R. Taylor, MD, and Nadim Lalani, MD, FRCPC. Adult Small Bowel Obstruction EVIDENCE-BASED DIAGNOSTICS, SAEM publication. 2013
  12. Schmutz, G.R. et al. Small bowel obstruction: role and contribution of sonography. Eur Radiol 7, 1054-1058
  13. Jang, Timothy B. Schindler, Danielle. Kaji, Amy H. Bedside ultrasonography for the detection of small bowel obstruction in the emergency department. Emerg Med J 2011 28:676-678
  14. Dawson, Matthew. Mallin, Mike. Introduction to Bedside Ultrasound: Volumes 1 and 2. Chapter 29: Small Bowel Obstruction
  15. Balthazar EJ, Birnbaum BA, Megibow AJ, Gordon RB, Whelan CA, Hulnick DH. Closed-loop and strangulating intestinal obstruction: CT signs. Radiology. 1992 Dec;185(3):769-75.
  16. Brant WE, Helms CA. Fundamentals of Diagnostic Radiology. Lippincott Williams & Wilkins. (2007) ISBN:0781761352.
  17. Salati U, Mcneill G, Torreggiani WC. The coffee bean sign in sigmoid volvulus. Radiology. 2011;258 (2): 651-2
  18. Swenson BR, Kwaan MR, Burkart NE, Wang Y, Madoff RD, Rothenberger DA, Melton GB. Colonic volvulus: presentation and management in metropolitan Minnesota, United States. Dis Colon Rectum. 2012 Apr;55(4):444-9.
  19. Jose J. Diaz, Jr., MD, Faran Bokhari, MD, Nathan T. Mowery, MD, Jose A. Acosta, MD, Ernest F. J. Block, MD, William J. Bromberg, MD, Bryan R. Collier, DO, Daniel C. Cullinane, MD, Kevin M. Dwyer, MD, Margaret M. Griffen, MD, John C. Mayberry, MD, and Rebecca Jerome, MLIS, MPH. Guidelines for Management of Small Bowel Obstruction. J Trauma. 2008;64:1651–1664
  20. Margenthaler JA, Longo WE, Virgo KS, Johnson FE, Grossmann EM, Schifftner TL, Henderson WG, Khuri SF. Risk factors for adverse outcomes following surgery for small bowel obstruction Ann Surg. 2006 Apr;243(4):456-64.
  21. Duron JJ, du Montcel ST, Berger A, Muscari F, Hennet H, Veyrieres M, Hay JM; French Federation for Surgical Research. Prevalence and risk factors of mortality and morbidity after operation for adhesive postoperative small bowel obstruction. Am J Surg. 2008 Jun;195(6):726-34. doi: 10.1016/j.amjsurg.2

Cholangitis: Pearls & Pitfalls

Author: Rachel Ely, DO, MHA, EMT-P (EM Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


A 61-year-old male presents to your ED with one week of epigastric pain and vomiting.  He tells you that he had a cholecystectomy earlier this year, and his current pain is very similar to what prompted his gallbladder removal.  He also says that his girlfriend mentioned that his eyes seemed “yellow”, and he complains of whole-body pruritis.   He has vomited multiple times at home, and he is having difficulty answering your questions because of persistent nausea.  His vitals on presentation are BP 171/99, HR 70, RR 16, oral temp 98.5, SpO2 99%.  On exam, you notice obvious scleral and sublingual icterus, as well as generalized jaundice of the skin.  His abdomen is mildly distended, with tenderness in the right upper quadrant without guarding or rebound tenderness. What should you be considering? What are the keys to evaluation and management?


Cholangitis is a life-threatening infection of the biliary tract.  It was first described in 1877, and for many decades the mortality secondary to cholangitis approached 100%.1  Identification and treatment of cholangitis has significantly improved over the last century, however there is still progress to be made.  Challenges include not only early recognition of biliary infection, but also identification of those patients requiring emergent versus urgent biliary decompression.2  With these advances in identification and management, mortality has been cut to approximately 10%.1

For another great case and background on cholangitis, please see http://www.emdocs.net/cholangitis-deadly-cause-of-right-upper-quadrant-abdominal-pain/

General Physiology & Risk Factors

Cholangitis is a result of biliary obstruction and bacterial growth in the bile.1  Bacteria, primarily E. coli, Klebsiella species, and Enterococcus species, are thought to ascend from the duodenum into the common hepatopancreatic duct in the setting of ductal obstruction.3  Intraductal pressures increase as a result of obstruction, leading to a disruption of the tight junctions in the hepatic cellular architecture and serving as a route for bacteria to enter the bloodstream.1,4  Characteristics which predispose patients to the development of cholangitis include primarily bile duct stones and manipulation of the biliary tree such as ERCP or surgery.  Less common risk factors include orthotopic liver transplantation, primary sclerosing cholangitis, and AIDS-related cholangiopathy.1,4  Malignancy is a common cause of biliary obstruction; however, it is less likely to develop cholangitis primarily as a result of malignant obstruction rather than as a result of biliary manipulation to relieve a malignant obstruction.4  Patients with indwelling biliary stents, or who have recently had instrumentation of their biliary tree, are more likely to have infection with Enterococcus, Pseudomonas, MRSA, or VRE.5


Charcot’s triad of fever, right upper quadrant pain, and jaundice yields a 25% sensitivity for the detection of ascending cholangitis.6  Reynold’s pentad, which adds hypotension and altered mental status to the classic triad, is present in only of 5-7% of cases.4  The most common presenting signs and symptoms are fever, which is observed in about 90% of patients, and abdominal pain, seen in approximately 80% of patients. Cholangitis should be suspected in patients with fever, altered mental status, occult sepsis, or an otherwise unexplained elevated bilirubin, especially in the setting of biliary stones or recent biliary instrumentation. Because cholangitis is nearly uniformly fatal without appropriate treatment, it must remain high on the differential in adult patients with unexplained fever.7,8


While no specific laboratory study is in itself indicative of cholangitis, elevation of liver function tests can be suggestive.  Specifically, elevation of both GGT and alkaline phosphatase is approximately 90% sensitive for acute cholangitis.8  While elevations of white blood cell count, ESR, and CRP are non-specific, in the right clinical context this is highly suggestive of overwhelming systemic disease.9  Up to 70% of patients with cholangitis will have positive blood cultures, and while the IDSA does not recommend routine blood culture collection in mild community-acquired intra-abdominal infection, it should certainly be considered in those with severe disease or recent instrumentation.4,10

CT is the imaging study of choice to visualize the biliary system in suspected cholangitis. While ultrasound is often the preferred modality to visualize the biliary system, CT can better characterize complications such as hepatic abscess and can identify external sources of obstruction such as malignancy.4,7,11  CT carries an 87% sensitivity in actually identifying the etiology of biliary obstruction.12  Findings such as intra- and extrahepatic ductal dilation, duct wall thickening, liver enhancement, and the presence of gallstones can be suggestive of cholangitis.  The finding of papillitis, or inflammation at the ampulla of Vater, and the presence of an ampullary stone on CT can also be indicative of cholangitis.13

Diagnostic Criteria and Classification

Because elevated LFTs, leukocytosis, and imaging evidence of biliary dilation can be indicative of other disease processes (such as cholecystitis or choledocholithiasis), attempts have been made to develop a set of diagnostic criteria for cholangitis.  The Tokyo Guidelines are the best-known criteria and offer a sensitivity of 91.8% and specificity of 77.7% in derivation studies, though external validation studies have yet to be published.14,15  Three diagnostic categories are used to apply the tool: indicators of systemic inflammation, evidence of cholestasis, and imaging evidence.  One indicator of systemic inflammation plus either imaging evidence or cholestasis evidence should prompt strong suspicion of cholangitis. Criteria to indicate inflammation are fever or shaking chills, white blood cell count less than 4,000 or greater than 10,000, or C-reactive protein greater than 1.  Cholestasis can be indicated by total bilirubin greater than or equal to 2 mg/dL, or alkaline phosphatase, GGT, AST, or ALT above 1.5 times the upper limit of normal. Finally, imaging is considered confirmatory if biliary dilation or other evidence of a likely inciting etiology of obstruction and subsequent cholangitis, such as biliary stent, stricture, or malignancy.14 

Table 1 TG13 Diagnostic Criteria for Acute Cholangitis.14

Category Threshold
A. Systemic Inflammation
Fever or Shaking Chills Body Temperature >38°C
Laboratory evidence of inflammatory response WBC <4,000 or >10,000

CRP >1

B. Cholestasis
Jaundice T-Bili ³2 mg/dL
Abnormal LFT Alk Phos >1.5 x upper limit normal

GGT >1.5x upper limit normal

AST >1.5x upper limit normal

ALT >1.5x upper limit normal

C. Imaging
Biliary dilatation
Evidence of etiology on imaging
Diagnosis should be suspected if one item from A plus one item from B or C are present

Diagnosis is considered definite if one item from, A, B and C are present.


Early identification and appropriate management of cholangitis is imperative because of its impressive mortality risk if not aggressively treated.  Often, these patients present with evidence of sepsis and should be treated accordingly with fluid resuscitation and antibiotics.  However, ultimately the presence of biliary obstruction is the factor allowing cholangitis to occur, and this obstruction must be relieved.  While convention teaches that earlier biliary decompression is better, there have been some attempts to stratify the severity of disease in order to prioritize the urgency of decompression, as discussed below.

Antibiotic selection

As discussed, the most common organisms isolated in ascending cholangitis are E. coli, Klebsiella species, and Enterococcus species, but because these patients have often had recent biliary instrumentation and likely other nosocomial exposures, initial antibiotic therapy should remain broad.  The most current Infectious Diseases Society of America guidelines, published in 2009, recommends metronidazole plus either a carbapenem, piperacillin-tazobactam, ciprofloxacin or levofloxacin, or cefepime, with the addition of vancomycin in those with likely health-care associated biliary infection.16  However, the most recent Tokyo treatment guidelines, published in 2013, warn against the use of fluoroquinolones because of increasing regional E. coli resistance to these agents.10

The Tokyo Guidelines recommend a severity-based hierarchy of antibiotic selection.  Criteria for grading disease can be found in the table below.  Mild or Grade I disease might be managed with a cephalosporin or ertapenem, or a fluoroquinolone in regions where resistance patterns are favorable.  Grade II disease options include piperacillin/tazobactam, a third or fourth generation cephalosporin, or ertapenem.  Finally, antibiotic coverage for severe (Grade III) disease or health-care associated infections include piperacillin/tazobactam, third or fourth generation cephalosporin, imipenem/cilastatin or meropenem, aztreonam plus metronidazole, plus vancomycin in addition to any of these options.4,10

Table 2 TG13 Severity Criteria for Acute Cholangitis14

Grade III:  Severe

Dysfunction in at least one of following systems:

Cardiovascular Hypotension requiring dopamine ³5 mcg/kg/min, or any dose of norepinephrine
Respiratory PaO2/FiO2 ratio <300
Renal Oliguria, or serum creatinine >2.0 mg/dl
Hepatic INR > 1.5
Hematologic Platelet Count <100,000/mm3
Grade II: Moderate

Any two of the following

Abnormal WBC count >12,000/mm3 or <4,000/mm3
High Fever ³39°C
Advanced Age ³75 years
Hyperbilirubinemia Total bilirubin ³5 mg/dL
Hypoalbuminemia <70% lower limit normal
Grade I:  Mild
Does not meet criteria of Severe or Moderate at diagnosis.

Biliary Decompression

In certain cases of mild infection, patients may respond well to medical management alone.  However, this remains the exception rather than the rule, and identifying these patients remains a challenge that requires further study.  The 2007 and 2013 Tokyo Guidelines suggest that their disease stratification, discussed above, may aid in the decision of performing immediate or delayed biliary decompression, or whether decompression is necessary at all in cases of mild disease.6,10  The TG13 authors make no hard and fast recommendations about severity-based management, other than emphasizing that those with Grade III disease require near-immediate biliary decompression.10


In nearly all cases, patients with cholangitis will require admission, and many will require ICU care for continued resuscitation and vasopressor support in cases of septic shock. However, source control is important to changing the course of disease, and this will require relief of the biliary obstruction.  The most common option is bile duct stenting or stone removal via endoscopic retrograde cholangiopancreatography (ERCP).2  In cases in which this is not possible, such as in malignant obstruction or extremely unstable patients, percutaneous drainage of the gallbladder may be a better temporizing measure.17  Open surgical biliary decompression carries a higher morbidity and mortality than ERCP, but may be required in certain unique situations.4  In most cases the first consult should be to gastroenterology, as ERCP is the typical first step in decompression, however it is important to recognize that inpatient care is likely to be multidisciplinary, potentially including general surgery, gastroenterology, interventional radiology, and medical or surgical intensivists.

Case Conclusion

Your patient is not febrile, and the white blood cell count is 10.6.  Knowing this, you reflexively move cholangitis lower on your differential list. However, the direct bilirubin returns at 7.0, and an alkaline phosphatase of 894 supports an obstructive lesion.  The lab seems to be having difficulty analyzing the lipase because of the elevated bilirubin.   You start with an ultrasound to evaluate for retained or spontaneous common bile duct stone; however, this study is grossly normal with the exception of heterogeneity of the pancreatic head, thought to be incidental.  Seeking an explanation for the patient’s pain and obvious jaundice, you order a CT of the abdomen and pelvis, and you are surprised when you see this image:


 CT demonstrating choledocholithiasis and extra- and intra-hepatic ductal dilatation.  Case courtesy of Dr. Roberto Schubert, Radiopaedia.org, rID/ 16704.

Your radiologic skills don’t typically allow you to pick out the common bile duct on CT, and the inflammation you see here clues you in that this patient may actually be harboring infection on top of his biliary obstruction.  The lack of fever and leukocytosis initially threw you, but you soon realize that this patient meets the three diagnostic criteria for cholangitis per the Tokyo guidelines.  You start piperacillin/tazobactam and metronidazole, give a fluid bolus, and call gastroenterology for consult and internal medicine for admission.  When you follow up on the patient a few days later, you learn that the patient underwent ERCP with sphincterotomy, and stones and purulent fluid were drained from the common bile duct, confirming the diagnosis of cholangitis.  His cholangitis and concurrent pancreatitis quickly resolved, and he is discharged on hospital day five.

Pearls & Takeaways

  • Cholangitis can be subtle and only rarely presents with the classic triad of fever, jaundice, and right upper quadrant pain
  • While ultrasound can be useful, CT is often required to support the diagnosis and can often identify the source of obstruction
  • While early antibiotics are important, most patients require biliary decompression
  • Consult gastroenterology early, and the patient may require ICU-level care
  • The Tokyo Guidelines (TG13) may help support your working diagnosis in subtle cases, and can also help to stratify severity of disease. In the future, we may be able to use this severity stratification to guide urgency of biliary decompression.

References/Further Reading

1         Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K, Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007;14:15–26. doi:10.1007/s00534-006-1152-y.

2         Salek J, Livote E, Sideridis K, Bank S. Analysis of risk factors predictive of early mortality and urgent ERCP in acute cholangitis. J Clin Gastroenterol 2009;43:171–5. doi:10.1097/MCG.0b013e318157c62c.

3         Van den Hazel SJ, Speelman P, Tytgat GNJ, Dankert J, Van Leeuwen DJ. Role of antibiotics in the treatment and prevention of acute and recurrent cholangitis. Clin Infect Dis 1994;19:279–86. doi:10.1093/clinids/19.2.279.

4         Attasaranya S, Fogel EL, Lehman GA. Choledocholithiasis, Ascending Cholangitis, and Gallstone Pancreatitis. Med Clin North Am 2008;92:925–60. doi:10.1016/j.mcna.2008.03.001.

5         Tanaka A, Takada T, Kawarada Y, Nimura Y, Yoshida M, Miura F, et al. Antimicrobial therapy for acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007;14:59–67. doi:10.1007/s00534-006-1157-6.

6         Kiriyama S, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Pitt HA, et al. New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines. J Hepatobiliary Pancreat Sci 2012;19:548–56. doi:10.1007/s00534-012-0537-3.

7         Block J, Lawrence LM FR. The Atlas of Emergency Radiology. In: Block J, Jordanov MI, Stack LB TR, editor. Atlas Emerg. Radiol., New York, NY: McGraw-Hill; 2013, p. Chapter 7.

8         Mosler P. Diagnosis and management of acute cholangitis. Curr Gastroenterol Rep 2011;13:166–72. doi:10.1007/s11894-010-0171-7.

9         Qin Y-S, Li Q-Y, Yang F-C, Zheng S-S. Risk factors and incidence of acute pyogenic cholangitis. Hepatobiliary Pancreat Dis Int 2012;11:650–4. doi:10.1016/S1499-3872(12)60240-9.

10       Gomi H, Solomkin JS, Takada T, Strasberg SM, Pitt HA, Yoshida M, et al. TG13 antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci 2013;20:60–70. doi:10.1007/s00534-012-0572-0.

11       Schubert R. Choledocholithiasis | Radiology Case | Radiopaedia.org n.d. http://radiopaedia.org/cases/choledocholithiasis-4.

12       Balthazar EJ, Birnbaum BA, Naidich M. Acute cholangitis: CT evaluation. J Comput Assist Tomogr n.d.;17:283–9.

13       Lee NK, Kim S, Lee JW, Kim CW, Kim GH, Kang DH, et al. Discrimination of suppurative cholangitis from nonsuppurative cholangitis with computed tomography (CT). Eur J Radiol 2009;69:528–35. doi:10.1016/j.ejrad.2007.11.031.

14       Kiriyama S, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Pitt HA, et al. TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci 2013;20:24–34. doi:10.1007/s00534-012-0561-3.

15       Yokoe M, Takada T, Mayumi T, Yoshida M, Hasegawa H, Norimizu S, et al. Accuracy of the Tokyo Guidelines for the diagnosis of acute cholangitis and cholecystitis taking into consideration the clinical practice pattern in Japan. J Hepatobiliary Pancreat Sci 2011;18:250–7. doi:10.1007/s00534-010-0338-5.

16       Solomkin, Joseph S.  et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010;50:133–64. doi:10.1086/649554.

17       Lee CC, Chang IJ, Lai YC, Chen SY, Chen SC. Epidemiology and prognostic determinants of patients with bacteremic cholecystitis or cholangitis. Am J Gastroenterol 2007;102:563–9. doi:10.1111/j.1572-0241.2007.01095.x.


Elevated Liver Enzymes: ED-focused Management Pearls & Pitfalls

Authors: Eric Sulava, MD (EM Resident at Naval Medical Center Portsmouth) and Samuel Bergin, MD (EM Resident at University Medical Center of Southern Nevada)  // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


An 18 year-old female presents at 6 am with nausea and non-bloody, non-bilious emesis. Her mother reports that the patient just went through a recent break up with her boyfriend.  The patient admits that last night she took some ‘painkillers’ at 11pm. She has vomited 3-4 times at home. Her mother identifies the pills as a previously unopened 30-count bottle of 500mg acetaminophen – 9 tablets remain.

Exam reveals vital signs: temperature 37.9C, pulse 103, respiratory rate 17, blood pressure 114/76, and weight 50kg. She is awake, alert, and quietly answering all questions appropriately. She appears disheveled and concerned, but with goal directed speech and appropriate demeanor.   HEENT, cardiac, and pulmonary exams do not reveal any abnormalities. Her abdominal exam is notable for minimal right upper quadrant tenderness, but is otherwise normal. She is now denying any current suicidal ideation.

What labs should be drawn in this case?  Would the liver function tests (LFTs) show abnormalities 7 hours following ingestion, and if so, in which pattern? Should activated charcoal or any other medications be given before or after acetaminophen levels are drawn?


In today’s medical system, marginal laboratory values can lead to expensive, unnecessary, and potentially harmful further diagnostic evaluations.  A 2012 retrospective, multi-center cohort study of patients presenting to the ED showed that laboratory testing has a direct effect on patients’ emergency department (ED) length of stay, with an average increase of 10 minutes for every five individual tests ordered (1). With routine incorporation of hepatic tests in blood chemical panels, it is crucial to have a detailed understanding of the pathophysiologic basis of liver function tests in order to establish appropriate clinical correlation and patient disposition.

Liver Biology: a little understanding goes a long way

The liver is a complex organ with multiple roles. Hepatocytes are organized into primary functioning units called the liver acinus, each of which is bordered by the ‘portal triad’ consisting of a branch of the hepatic artery, portal vein, and bile duct. This organization allows the liver to complete a wide array of tasks: glucose storage, glycogen breakdown, carbohydrate – fat – protein metabolism, bile synthesis, lipoprotein – plasma protein synthesis, detoxification, and waste product metabolism.  All of these interacting roles can be impacted during liver disease, with corresponding alteration in liver function tests.

An LFT panel typically includes aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), prothrombin time (PT), and albumin.  Clinically, LFT results are described in a ‘hepatocellular’ or ‘cholestatic’ arrangement based on the pattern of elevation.  Tables 1 and 2 display the different LFTs and causes of elevation.  Out of the most commonly ordered liver chemistry tests, true measurement of synthetic hepatic function is only assessed by prothrombin time (PT) and albumin. A hepatocellular pattern depicts a disproportionate elevation in the transaminases in comparison to ALP.  The inverse, a disproportionate elevation of ALP in comparison to the transaminases, represents a cholestatic pattern.  Serum bilirubin can be elevated in either pattern, and may indicate an extrahepatic disorder. Table 1 summarizes the commonly associated disorders that cause hepatocellular and cholestatic patterned abnormalities.

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Aminotransferases are used to monitor and detect the progression of hepatocellular injury.  Aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) are abundant hepatic enzymes crucial to citric acid cycle function.  ALT and AST are released from damaged hepatocytes after hepatocellular injury or death.  Both aminotransferases are highly concentrated in the liver, but ALT is generally considered to be more specific to liver damage; AST is amply expressed in the brain, skeletal muscle, kidney, and heart.  Aminotransferase levels vary based on age and sex, so institutional reference limits should be specifically defined (3).

Alkaline phosphatase is an enzyme that transports metabolites across cell membranes.  Liver and bone disease are the most common causes of pathological elevation, though other sites of origin include the intestines, kidney, and placenta (4).  Due to the high body tissue prevalence, non-pathologic processes, like pregnancy, can cause elevation in laboratory values.  During pregnancy, ALP begins to rise by the late first trimester and can reach twice normal values by term (5).  In the liver, ALP is present in the bile duct epithelial cells; thus, biliary stasis can increase the release of the enzyme (6).  Given the overlap in values with liver and bone disease, GGT can be used to differentiate the location of release. GGT is a glycoprotein located on the membranes of cells with high secretory or absorptive activities and is not abundant in bone.

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Initial evaluation

When evaluating a patient with abnormal liver biochemical tests, the initial focus will be identifying potential risk factors of liver disease. The past medical history should be focused on conditions with associated hepatobiliary disease as seen in Table 3 (2, 7-10).  The social and medication history should assess for potential hepatotoxins, including medications, drugs, and alcohol. Other rare methods of hepatotoxin exposure include recreational mushroom picking (Amanita phalloides) and occupational exposure to chemicals like vinyl chloride. The patient should be directly questioned on over the counter medications, herbal remedies, dietary supplements, and illicit drug use.  The type and route of illicit drug should be identified, noting that IV drug use is a risk factor for viral hepatitis.  Other risk factors for viral hepatitis include blood transfusion prior to 1992, travel to endemic hepatitis areas, and exposure to patients with jaundice (4).

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During the evaluation a standard head to toe examination should be completed, focusing on the abdomen.  In cases of chronic liver disease stigmata of cirrhosis can be seen: spider nevi, palmar erythema, gynecomastia, and caput medusae.  Other common features of alcoholic cirrhosis include Dupuytren’s contractures (persistent digit flexion), parotid gland enlargement, and testicular atrophy (11).  The abdominal exam characterizes the size and consistency of the liver. An enlarged tender liver could be due to acute viral hepatitis, while an enlarged, hard, nodular liver would represent a possible malignancy.  Further palpation would reveal right upper quadrant tenderness with associated Murphy’s sign, suggesting cholestatic disease.  The major physical exam findings of each syndrome will be explained in detail below.


Differential based on Magnitude of Transaminase Elevation

The National Health and Nutrition Examination Survey evaluated 6800 American patients and found elevated liver transaminase levels in up to 8.9% of the survey population (12).  With this high of a prevalence, an algorithmic approach can aid in evaluation. Both the magnitude and ratio of AST and ALT can aid in narrowing the spectrum of disease.  True “reference ranges” for these enzymes vary between establishments, and therefore will be addressed by magnitudes elevated above normal.  Overall magnitude of aminotransferase elevation can be used to guide an initial diagnosis by categorizing the disorder based off of mild (<5x), moderate (5-10x), or marked elevation (>10x).


Mild Transaminase Elevation
1. Non-Alcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease is the most common cause of mildly altered liver enzyme levels in the western world, with a point-prevalence of 23% among American adults (13). Of note, it is a diagnosis of exclusion. NAFLD is a continuum, ranging from benign steatosis to steatohepatitis and cirrhosis.  The fatty liver change occurs secondary to metabolic syndrome: obesity, diabetes mellitus, hypertension, and dyslipidemia (14).  NAFLD is found in a bimodal distribution of age – it is the most common liver abnormality of children ages 2-19 (15).  This patient demographic usually presents with vague complaints and has an incidental finding of transaminase elevations.  The transaminase levels rarely exceed 4x the upper limit of normal with an AST/ALT ratio of < 2. Other conditions should be ruled out with history, exam, and laboratory testing. Treatment of this disorder is going to be completed through outpatient follow up.  Lifestyle modification with weight loss, blood sugar control, and reduction of cholesterol is the mainstay of therapy.

 2. Drug Induced Liver Injury

Idiosyncratic drug-induced liver injury (DILI) covers a wide spectrum of disease and accounts for 13% of acute liver failure cases in the U.S. (16).  DILI is a broad term applied to any injury to the liver by a prescribed medication, over-the-counter medication, herb, or dietary supplement. The National Institutes of Health maintains a searchable database of over 1000 DILI associated substances (17).  A 2008 study on 300 DILI patients in the United States listed Amoxicillin/clavulanate (8%), Nitrofurantoin (4%), Isoniazid (4%), and Trimethoprim-sulfamethoxazole (4%) as the most common inducing agents, excluding acetaminophen (18).  Table 4 includes other commonly reported medications (19). Statins are frequently associated with elevated transaminase levels in new onset users; however, recent data shows that increases in transaminase levels have not been proven significantly different than those in patients taking placebo, and that elevated transaminase levels spontaneously resolve in up to 70% of persons taking statins, even with continued use (20,21).

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Diagnostically approaching a patient with DILI is difficult due to the vast array of possible sources and clinical presentation.  An algorithm developed by the Mayo Clinic is included below, as Table 5 (22). A list of all medications, herbals, and OTC substances should be obtained.  As step 2 shows, it is important to determine if DILI is the primary diagnosis or simply a correlating factor to disease.  Other common causes of liver dysfunction (viral hepatitis, alcohol related, EBV, NAFLD, and biliary obstruction) must be considered. Removal of the offending substance is the mainstay of treatment.  All non-essential medications should be removed, following a risk-benefit discussion with the patient.  Depending on severity, supportive care with 2-4 week follow up labs in the primary care setting is appropriate (22).  A small subset of DILI patients present with elevated levels of gamma-globulins, antinuclear, and/or anti-smooth muscle antibodies.  These patients are classified as having drug-induced autoimmune-like hepatitis (DI-AIH), which is responsive to prednisone therapy; this will likely be identified outside the ER setting (23).

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3. Alcohol Induced Liver Injury

The liver is the main site of alcohol metabolism and a major target organ of alcohol-induced injury. There are three basic forms of alcohol related liver disease: alcoholic fatty liver disease, alcoholic cirrhosis, and alcoholic hepatitis, discussed below. Of note, alcoholic hepatitis can cause moderate LFT elevation. Fatty liver disease and cirrhosis are chronic issues due to a long history of alcohol use.  The clinical manifestations of long-standing alcohol disease depend on its severity and chronicity.

Fatty liver disease is typically asymptomatic, while cirrhosis may have the classic findings of ascites, spider angiomata, gynecomastia, and palmar erythema. Diagnostic evaluation for patients with a strong history of chronic alcohol abuse will include CBC, LFT (serum transaminases, bilirubin, alkaline phosphatase, GGT, albumin), coagulation studies, and a complete chemistry panel.  If other risk taking behaviors are reported (e.g. unprotected sex and IV drug use) viral hepatitis panels would be appropriate. The characteristic biochemical results includes an AST/ALT ratio greater than 2, with elevated GGT.  The AST elevation is usually less than 8x the upper limit of normal, and the ALT elevation is typically less than 5x the upper limit of normal, categorizing chronic alcohol disease as mild to moderate transaminase elevation (2). Hematologic findings in patients with alcoholic liver disease may include thrombocytopenia with a macrocytic anemia.  Longstanding alcoholics are at risk for poor nutrition with electrolyte and vitamin abnormalities, including vitamin B12, B1 and folate deficiency.  The mainstay of treatment for chronic alcohol abuse will be the recommendation of abstinence from alcohol. Acute treatment in the ER will include vitamin, nutrient, and electrolyte repletion (24).  Due to the synergistically destructive effect of chronic alcohol disease and thiamine deficiency, these patients are at risk for Wernicke-Korsakoff Syndrome.  Supplementation with an IV bag of fluid containing thiamine, folic acid, and magnesium sulfate is recommended (25).  Depending on the history, these patients are at risk for acute alcohol withdrawal, which should be considered.


Moderate Transaminase Elevation

1. Alcoholic Hepatitis

A 2015 US study on over 550,000 hospitalizations demonstrated the rate of alcoholic hepatitis related hospitalizations has significantly increased over the last decade, accounting for significant morbidity, mortality, and financial burden (26).  Although the term ‘alcoholic hepatitis’ represents a spectrum of disease, ranging from asymptomatic steatohepatitis to acute hepatic encephalopathy, it is typically used to describe the acute onset of alcohol induced jaundice, anorexia, fever, and tender hepatomegaly.  Patients with AH are usually 40-50 years old, with risk factors including female gender, Hispanic ethnicity, drinking multiple types of alcohol, drinking alcohol between mealtimes, poor nutrition, and obesity (27, 28).  As with all alcohol related liver disease, the amount of alcohol consumption which places an individual at risk of developing alcoholic hepatitis is not known, but most patients with alcoholic hepatitis drink more than 100 g ⁄ day (29). Patients often stop drinking as they become ill, so it is common for patients to decrease their alcohol intake several weeks prior to presentation.  Due to the acute hepatic inflammation, physical exam will show hepatomegaly with right upper quadrant tenderness.  An audible hepatic bruit has been reported in a minority of patients.  AH can be an acute complication to chronic cirrhosis, and therefore patients may present with stigmata of chronic liver disease (28).

Patients with AH typically present with moderate elevations of AST/ALT (less than 300un/L), AST:ALT >2, elevated serum bilirubin, elevated GGT, moderate leukocytosis (neutrophils), and elevated INR (30). The above mentioned clinical and laboratory features are often adequate to secure the diagnosis of AH in a patient with a long history of heavy alcohol use, following appropriate rule out of mimicking disorders.  The differential diagnosis for AH is extensive, including DILI, acute viral hepatitis, ischemic hepatitis, NASH, and chronic liver disease.  Initial workup with an acute viral hepatitis panel, consisting of Anti-hepatitis A IgM, Hepatitis B surface antigen, anti-hepatitis B core IgM, and Anti-hepatitis C virus (HCV) antibodies is warranted, along with a transabdominal ultrasound (Doppler) to evaluate for viral hepatitis, biliary obstruction, and Budd Chiari syndrome. If the diagnosis is uncertain, then a liver biopsy can establish the diagnosis with greater certainty. Understandably, although generally recommended, a majority of these interventions are unrealistic in emergent care.  Supportive care will be the primary focus of an ED provider, with the above-mentioned diagnostics organized by an admitting team or outpatient provider.  Supportive care in acute episodes of AH includes alcohol abstinence, prevention and treatment of alcohol withdrawal, fluid management, nutritional support, infection surveillance, and PPI prophylaxis. Various calculators have been developed to determine disease severity and additional therapy. The Maddrey discriminant function score is a calculation using PT and serum bilirubin that estimates overall mortality risk. Patients with a score over 32 [DF= (4.6 x (PT – control PT)) + serum bilirubin] have high short-term mortality and may benefit from glucocorticoid therapy (31).  Typical course is prednisone 40mg for 28 days, followed by an appropriate taper.  Admitting teams may discuss Pentoxifylline, a TNF inhibitor, which has been suggested as replacement therapy for glucocorticoids.  This has overall weak supporting data and currently has little utility in the ED. Table 6, a table from a NEJM review of alcoholic hepatitis, shows the other therapy options for acute AH.  Most are not indicated due to risk for increased mortality or lack of overall benefit (30).

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 2. Biliary Tract Disease

The third National Health and Nutrition Examination Survey estimated that in the U.S., 6.3 million men and 14.2 million women had gallbladder disease, making it a very common primary complaint in the ER setting (32).  Gallstones can cause significant colicky pain, biliary obstruction, or ascending biliary infection depending on their size and location.  Risk factors for biliary disease include age over 40, female sex, number of pregnancies, obesity, family history, diabetes mellitus, cirrhosis, hemolysis, and medications (33).  Medications commonly involved in biliary sludging and biliary disorders include estrogen, oral contraceptives, octreotide, clofibrate, and ceftriaxone (34). Patients with uncomplicated gallstone disease typically present with right upper quadrant (RUQ) pain, which radiates to the scapula and worsens with eating.  A lodged stone can lead to biliary obstruction and cholangitis, presenting with Charcot’s triad of fever, jaundice, and RUQ pain.  If left untreated, cholangitis can cause sepsis and altered mental status, making up Reynold’s pentadAcute cholecystitis will show a moderate to severe increase of the transaminases depending on the severity of the disease.  As disease progresses to choledocholithiasis and cholangitis, patients will produce elevated serum total bilirubin, indirect bilirubin, ALP, GGT, and at times leukocytosis (4).  Confirmation of the diagnosis requires additional imagining.  RUQ ultrasound may reveal gallstones, thickened gallbladder wall, sonographic Murphy’s sign, or dilated common bile duct.  If the RUQ ultrasound is inconclusive, a hepatoiminodiacetic acid scan (HIDA) is indicated, but unfortunately often impractical for use in the ED setting. In this test technetium labeled HIDA is taken up by the hepatocytes and excreted into the bowel.  A normal study will have visualization of contrast in the gallbladder, common bile duct, and small intestine by 30-60 minutes.  Failure to do so identifies a blockage. Cholescintigraphy has a sensitivity and specificity for acute cholecystitis of approximately 90 to 97% and 71 to 90%, respectively (35).

ED management depends directly on the severity and type of biliary disease.  Patients with uncomplicated biliary colic can be discharged with surgical follow up for an elective cholecystectomy, following pain control with NSAIDs or opioids.  A commonly used NSAID is ketorolac, which is dosed at 30 – 60mg (IV/IM) depending on age and renal function. Symptomatic or complicated cholecystitis patients will likely require admission and should be placed NPO while receiving IV hydration, analgesia, and antiemetics.  A surgical consultation is appropriate depending on clinical status.  If choledocholithiasis is suspected, further diagnostics are needed.  The admitting team will organize an ERCP or MRCP depending on the patient’s clinical status and risk.  ERCP is both diagnostic and therapeutic, while MRCP is much less invasive. Due to serious complications of pancreatitis, bleeding, and perforation, ERCP is reserved for patients who are at high risk for having a common bile duct stone, particularly if there is evidence of cholangitis (36).  As mentioned above, sepsis is an immediate concern for acute cholangitis patients.  Hemodynamic stabilization and antibiotic treatment with a broad-spectrum agent should be initiated in the ED.  Although there is no consensus for a superior regimen for biliary sepsis, broad coverage for gram negative and anaerobic organisms is generally recommended.  Once admitted, antibiotic therapy can be modified to reflect blood culture results.  Consultations for ERCP biliary drainage should be placed as soon as possible if available. Percutaneous transhepatic cholangiography (PTC) can be considered when ERCP is unavailable, unsuccessful, or contraindicated (37).


Severe Transaminase Elevation

  1. Acute Viral Hepatitis

Although the incidence of hepatitis A, hepatitis B, and hepatitis C have all been declining over the past two decades, their clinical relevance remains, and they continue to be reportable diseases (38). While few patients will require hospitalization and exact determination of viral hepatitis is unlikely in the ED, early initiation of diagnosis is important. On initial evaluation serological hepatitis panels, transaminases (10-100x increase, with ALT>AST), and bilirubin (5-25 mg/dL) should be evaluated.  The most common emergent interventions for patients with viral hepatitis will consist of fluid and electrolyte corrections due to diarrhea and vomiting. Some patients with altered mental status with reduction in hepatic synthetic function (INR above 1.5 or hypoglycemia) should be admitted and observed for possible fulminant hepatitis (39).

Hepatitis A (HAV), a fecal-oral RNA virus, has had a nationally routine childhood vaccine since 2005, with a corresponding decrease in incidence.  The primary risk factors are now men who have sex with men, intravenous drug users, and international travelers (38,40,41).  The symptoms of hepatitis A include a gradual development of fever, nausea, vomiting, diarrhea, abdominal pain, and occasional jaundice, following a 2-8 week incubation period.  Clinical research has shown that only 10%-30% of HAV patients develop these symptoms, making clinical suspicion heavily historically based (41). Since the maximal viremia and infectivity are prior to onset of symptoms, HAV is diagnosed with an antibody test, Anti-HAV IgM (42). Treatment is primarily symptomatic, though immune serum globulin can help in post-exposure prophylaxis. Hand washing and proper food preparation are the primary defenses (41). Hepatitis E is similar to Hepatitis A in the aspects of transmission, being fecal-oral, and symptomatology.  HEV, known for causing significant disease in pregnant women, lacks a widespread vaccine.  Its geographical distribution is primarily limited to Asia, Africa, and Russia. The diagnosis of (HEV) is made via serum / stool PCR, or by the detection of IgM antibodies to HEV.  Unfortunately there are no commercial tests for HEV licensed in the U.S., and CDC research labs must be contacted for testing (43).  Ribavirin and pegylated interferon are being investigated as potential treatments for chronic HEV (44,45).

Hepatitis B is a profoundly infectious enveloped DNA virus that has highest incidence, like Hepatitis A, among men who have sex with men and with intravenous drug abuse. Age strongly determines likelihood of chronic carrier state with it occurring in only 10% of adults compared to 90% of neonates (46). The symptoms include: malaise, fever, nausea, vomiting, occasional arthralgia, and resolving jaundice (47).  A notable difference is the absence of diarrhea in HBV.  Diagnosis is established using HB-surface antigen, HB-core IgM (acute), HB-core IgG (chronic), and HB-envelope antigen (corresponds to infectivity). While the infection may be occult, it can occasionally lead to fulminant hepatitis, hepatic failure, and encephalopathy; this is most common in the presence of an HBV and HDV co-infection. Fulminant hepatitis is recognized via altered mentation and spontaneous mucosal bleeding (48). Post-exposure prophylaxis for unvaccinated and vaccinated (dependent on titer) patients may include one time HBIG and HBV vaccine. Hepatitis D is only found in patients who are actively infected with HBV, with a worldwide incidence of approximately 5% of chronic HBV carriers. Presence of HDV is suggestive of a more sinister disease course (49).

Hepatitis C is most common among intravenous drug users, HIV-positive patients, those with greater than 20 sexual partners, and persons who received blood transfusions prior to 1992 (50). Like other viral hepatitis causes, acute HCV infections are typically asymptomatic. However, unlike Hepatitis A & B, progression to chronic hepatitis with HCV is very common and approaches 90% of patients (51). Diagnosis is partially performed by elimination of other causes and can be confirmed via HCV enzyme immunoassay, PCR or ELISA. Classically treatment may include interferon alfa-2b (with or without polyethylene glycol) and ribavirin (52). There are now newer and very effective medications, ledipasvir and sofosbuvir, with treatment protocols dependent on the genotype (53). Post-exposure prophylaxis is unclear at this time.

 2. Ischemic Injury

Severe transaminase elevations are due to global hepatocellular injury or necrosis, which can be caused by an acute hypoxic event. The liver’s complex vascular supply and high metabolic rate make it vulnerable to circulatory disturbances.  Ischemic hepatitis, also referred to as ‘shock liver’, refers to severe hepatic injury secondary to acute hypoperfusion.  This injury is not mediated by an inflammatory process, as the name hepatitis implies, but by hemodynamic instability.  This includes global circulatory compromise from extrahepatic sources, like acute ACS, CHF, sepsis, and trauma.  More focal causes of hepatic hypoperfusion include hepatic artery thrombosis, portal vein thrombosis, surgical ligation, or hepatic sickle cell crisis (54).  The hemodynamic instability is usually apparent clinically before evidence of liver injury appears.  Lab chemistries usually show a rapid rise in serum aminotransferases to >25X the upper limit of normal, followed by a dramatic increase in LDH.  The transaminase levels will peak within three days of the initiating event, and in the absence of continued clinical decline, will normalize by days 7-10 (55).  Managing ischemic hepatitis includes hemodynamic resuscitation, with close monitoring of end organ perfusion.  After acute stabilization of the patients in the ED, immediate transfer to ICU level care should occur.

3. Acetaminophen Toxicity

Acetaminophen, the most widely used analgesic-antipyretic in the United States, is the most common cause of drug induced hepatic failure (4).  The Annual Report of the American Association of Poison Control reported that in 2014 there were over 70,000 acetaminophen related overdoses, resulting in 107 deaths (56).  The medication’s potency is partially due to its rapid and complete uptake in the intestinal tract, causing peak concentrations 1.5-2 hours following administration.  When doses exceed the maximum daily recommendations of 80 mg/kg in children and 4 g in adults, acetaminophen begins to rapidly deplete hepatic glutathione stores via the overproduction of NAPQI by the cytochrome 450 pathway.  When hepatic glutathione stores are depleted, NAPQI begins to cause irreversible oxidative hepatocyte injury and hepatocellular centrilobular necrosis.  Patients who are chronic alcoholics have increased CYP2E1 activity, which further depletes glutathione levels, and puts them at increased risk for acetaminophen toxicity (57).  Other medications that cause a similar reaction include anticonvulsants, antituberculosis drugs (isoniazid – rifampin), and Bactrim.

Clinical manifestations of acetaminophen overdose are often mild and nonspecific, but due to the importance of a proper ingestion timeline, a four stage clinical course has been developed.  Stage 1 represents 0.5-24 hours after the overdose with nausea, vomiting, diaphoresis, pallor, and malaise.  Progression to stage 2, 24-72 hours after ingestion, includes rapid transaminase elevation with symptomatic hepatic injury of RUQ pain, hepatic enlargement, and abdominal tenderness. LFT abnormalities peak during stage 3, representing 72-96 hours, during which time the severe complications of hepatic encephalopathy, hyperammonemia, and bleeding diathesis can occur. Death can occur in this stage from a combination of multiorgan failure and lactic acidosis (58).  Stage 4 represents the recovery phase following the 96 hour timestamp.

For further evaluation a 4-hour post ingestion acetaminophen serum level should be drawn.  If the ingestion was more than four hours ago it should be drawn immediately.  If the time of ingestion is unknown, draw a lab immediately and then again in four hours for continued monitoring.  The time of ingestion and acetaminophen serum level will be used with the Rumack-Matthew nomogram to determine the severity of acetaminophen toxicity and the need for treatment with N-acetylcysteine (NAC).  NAC rapidly repletes glutathione stores, preventing toxic metabolite formation if given within 8 hours of ingestion.  NAC was found to be safe for administration up to 24 hours following ingestion, noting the treatment was only effective if given within the first 8 hours (59).  It can be given intravenously with a 20 hour protocol or orally with a 72 hour protocol.  The oral regimen is the treatment of choice, if not otherwise contraindicated.  FDA-approved dosage regimen for oral NAC starts with a loading dose of 140 mg/kg, followed by 17 doses, each at 70 mg/kg, given every 4 hours.  Other treatment includes gastrointestinal decontamination with 1g/kg of activated charcoal, if within four hours of ingestion (60).



LFT are commonly ordered laboratory tests with a variety of abnormalities in a vast array of disorders.  By understanding the biochemical basis of each test, it is possible to correlate laboratory findings to a patient’s clinical presentation.  By separating common hepatic disorders into subcategories based on the magnification of transaminase elevation, a more simplistic algorithm like approach can be taken to help narrow the spectrum of a differential diagnosis.  This can be used to help eliminate waste in costly and unnecessary follow up studies by maximizing the understanding of what an LFT result represents.

  • LFTs = ‘hepatocellular’ or ‘cholestatic’ arrangement based on the pattern of elevation.
    • Hepatocellular pattern = transaminases >  ALP
  • ALT is generally considered to be more specific to liver damage
  • Past medical history and social history are crucial insight to hepatic risk factors (table 3)
  • Magnitude of aminotransferase elevation => guide initial diagnosis: mild (<5x), moderate (5-10x), or marked elevation (>10x)
    • Mild = NAFLD, Drug Induced Liver Injury, Alcohol Induced Liver Injury
    • Moderate = Alcoholic Hepatitis, Biliary Tract Disease
    • Severe = Acute Viral Hepatitis, Ischemic Injury, Acetaminophen Toxicity
  • As always, supportive care is key in the ED!

References/Further Reading

  1. Li L, Georgiou A, Vecellio E, Eigenstetter A, George Toouli MPH (2015). The effect of laboratory testing on emergency department length of stay: A multihospital longitudinal study applying a cross classified random-effect modeling approach. Academic of Emergency Medicine 22: 38-46.
  2. Giannini, E.G., Testa, R., Savarino, V. Liver enzyme alteration: a guide for clinicians. CMAJ.2005;172:367–379.
  3. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem 2000;46(12):2050-68.
  4. Fishman WH. Alkaline phosphatase isoenzymes: recent progress. Clin Biochem 1990;23(2):99-104
  5. Green RM, Flamm S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 2002;123(4):1367-84.
  6. Fishman WH, Bardawil WA, Habib HG, Anstiss CL, Green S. The placental isoenzymes of alkaline phosphatase in sera of normal pregnancy. Am J Clin Pathol 1972;57:65–74
  7. Moss DW. Physiochemical and pathophysiological factors in the release of membrane-bound alkaline phosphatase from cells. Clin Chim Acta 1997;257 (1):133-40.
  8. Gizard, E., A. C. Ford, J.-P. Bronowicki, and L. Peyrin-Biroulet. “Systematic Review: The Epidemiology of the Hepatobiliary Manifestations in Patients with Inflammatory Bowel Disease.” Alimentary Pharmacology & Therapeutics Aliment Pharmacol Ther 40.1 (2014): 3-15. Web.
  9. Younossi, Zobair. “Changes in the Prevalence of the Most Common Causes of Chronic Liver Diseases in the United States from 1988 to 2008.” SciVee (n.d.): n. pag. Web.
  10. Valdivieso, V. “Pregnancy and Cholelithiasis: Pathogenesis and Natural Course of Gallstones Diagnosed in Early Puerperium.” Hepatology 17.1 (1993): 1-4. Web.
  11. Ford, Ryan M., Wendy Book, and James R. Spivey. “Liver Disease Related to the Heart.” Transplantation Reviews29.1 (2015): 33-37. Web
  12. Rosen, Peter, John A. Marx, Robert S. Hockberger, Ron M. Walls, and James Adams. “Chapter 90: Disorders of the Liver and Biliary Tract. “Rosen’s Emergency Medicine: Concepts and Clinical Practice. 8th ed. Philadelphia, PA: Mosby Elsevier, 2006. 1186-204. Print.
  13. Ioannou GN, Boyko EJ, Lee SP. The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999-2002. Am J Gastroenterol. 2006;101(1):76-82.
  14. Harrison SA, Kadakia S, Lang KA, Schenker S. Nonalcoholic steatohepatitis: what we know in the new millennium. Am J Gastroenterol 2002;97(11):2714-24.
  15. Maheshwari A, Thuluvath PJ. Endocrine diseases and the liver. Clin Liver Dis. 2011;15:55–67.
  16. Pacifico L, Poggiogalle E, Cantisani V, Menichini G, Ricci P, Ferraro F, Chiesa C. Pediatric nonalcoholic fatty liver disease: a clinical and laboratory challenge. World J Hepatol. 2010;2(7):275–288.
  17. Lammert C, Einarsson S, Saha C, et al. Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: search for signals. Hepatology. 2008;47:2003–2007
  18. http://www.livertox.nih.gov/
  19. Chalasani N, Fontana RJ, Bonkovsky HL, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135(6):1924-1934, 1934.e1-4
  20. Navarro, Victor J., and John R. Senior. “Drug-Related Hepatotoxicity.” New England Journal of Medicine N Engl J Med7 (2006): 731-39. Web
  21. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97(8A):52C-60C.
  22. Bays H. Statin safety: an overview and assessment of the data—2005. Am J Cardiol. 2006;97(8A):6C-26C.
  23. Leise, Michael D., John J. Poterucha, and Jayant A. Talwalkar. “Drug-Induced Liver Injury.” Mayo Clinic Proceedings1 (2014): 95-106. Web.
  24. Czaja, Albert J. “Drug-Induced Autoimmune-Like Hepatitis.” Dig Dis Sci Digestive Diseases and Sciences4 (2011): 958-76. Web.
  25. Blendis, L. M. “Review Article: The Treatment of Alcoholic Liver Disease. “Alimentary Pharmacology & Therapeutics5 (2007): 541-48. Web. Flannery, A. H., and D. A. Adkins.
  26. “Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU.” Crit Care MedMarch (2015): n. pag. Web.
  27. Jinjuvadia, Raxitkumar, and Suthat Liangpunsakul. “Trends in Alcoholic Hepatitis-related Hospitalizations, Financial Burden, and Mortality in the United States.” Journal of Clinical Gastroenterology6 (July, 2015): 506-11. Web.
  28. Mandayam S, Jamal MM, Morgan TR. Epidemiology of alcoholic liver disease. Semin Liver Dis 2004; 24: 217–32
  29. Cohen, S. M., and J. Ahn. “Review Article: The Diagnosis and Management of Alcoholic Hepatitis.” Alimentary Pharmacology & Therapeutics1 (2009): 3-13. Web.
  30. Sohail, Umair, and Sanjaya K. Satapathy. “Diagnosis and Management of Alcoholic Hepatitis.” Clinics in Liver Disease4 (2012): 717-36. Web.
  31. Lucy, Michael, and Philippe Mathurin. “Alcoholic Hepatitis.” New England Journal of Medicine N Engl J Med15 (2009): 1512-513. Web.
  32. Maddrey WC, Boitnott JK, Bedine MS et al. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978; 75(2):193-199.
  33. Everhart, James E., Meena Khare, Michael Hill, and Kurt R. Maurer. “Prevalence and Ethnic Differences in Gallbladder Disease in the United States.” Gastroenterology3 (1999): 632-39. Web.
  34. Conte, Dario, Mirella Fraquelli, Fabio Fornari, Lucia Lodi, Paolo Bodini, and Luigi Buscarini. “Close Relation Between Cirrhosis and Gallstones.” Arch Intern Med Archives of Internal Medicine1 (1999): 49. Web.
  35. Shiffman, M. L., and F. B. Keith. “Pathogenesis of Ceftriaxone-associated Biliary Sludge. In Vitro Studies of Calcium-ceftriaxone Binding and Solubility.” 99.6 (1990): 1772. Web.
  36. Kiewiet, Jordy J. S., Marjolein M. N. Leeuwenburgh, Shandra Bipat, Patrick M. M. Bossuyt, Jaap Stoker, and Marja A. Boermeester. “A Systematic Review and Meta-Analysis of Diagnostic Performance of Imaging in Acute Cholecystitis.” Radiology3 (2012): 708-20. Web.
  37. Giljaca, Vanja, Kurinchi Selvan Gurusamy, Yemisi Takwoingi, David Higgie, Goran Poropat, Davor Štimac, and Brian R. Davidson. “Endoscopic Ultrasound versus Magnetic Resonance Cholangiopancreatography for Common Bile Duct Stones.” Cochrane Database of Systematic Reviews2 (2015)
  38. Bornman, Philippus C., Johan I. Van Beljon, and Jake Krige. “Management of Cholangitis.” Journal of Hepato-Biliary-Pancreatic Surgery6 (2003): 406-14. Web.
  39. Centers for Disease Control and Prevention (CDC): Surveillance for acute viral hepatitis—United States, 2007. MMWR Surveill SUMM 2009: 58: pp. 1-27
  40. Gotthardt, D., C. Riediger, K. H. Weiss, J. Encke, P. Schemmer, J. Schmidt, and P. Sauer. “Fulminant Hepatic Failure: Etiology and Indications for Liver Transplantation.” Nephrology Dialysis TransplantationSupplement 8 (2007): Viii5-iii8. Web.
  41. McNabb SJ, et al: Summary of notifiable disease—United States, 2005. MMWR Morb Mortal Wkly Rep 2007; 54: pp. 1
  42. Fiore AE, Wasley A, and Bell BP: Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006; 55: pp. 1
  43. “Positive Test Results for Acute Hepatitis A Virus Infection Among Persons With No Recent History of Acute Hepatitis–United States, 2002-2004.” JAMA: The Journal of the American Medical Association8 (2005): 894-96. Web
  44. Takahashi, M., S. Kusakai, H. Mizuo, K. Suzuki, K. Fujimura, K. Masuko, Y. Sugai, T. Aikawa, T. Nishizawa, and H. Okamoto. “Simultaneous Detection of Immunoglobulin A (IgA) and IgM Antibodies against Hepatitis E Virus (HEV) Is Highly Specific for Diagnosis of Acute HEV Infection.” Journal of Clinical Microbiology1 (2005): 49-56. Web.
  45. Kamar N, Izopet J, Tripon S, Bismuth M, Hillaire S, Dumortier J, Radenne S, Coilly A. “Ribavirin for chronic hepatitis E virus infection in transplant recipients” N Engl J Med.2014;370:1111–1120.
  46. Kamar, Nassim, Lionel Rostaing, Florence Abravanel, Cyril Garrouste, and Laure Esposito. “Pegylated Interferon‐α for Treating Chronic Hepatitis E Virus Infection after Liver Transplantation.” Clinical Infectious Diseases CLIN INFECT DIS5 (2010): n. pag. Web.
  47. Dienstag JL: Hepatitis B virus infection. N Engl J Med 2008; 359: pp. 1486-1500).
  48. Wasley A, Miller JT, and Finelli L: Surveillance for acute viral hepatitis—United States, 2005. MMWR Surveill Summ 2007; 56: pp.1
  49. Yurdaydin C, IDilman R, Bozkaya H, and Bozdayi AM: Natural history and treatment of chronic delta hepatitis. J Viral Hepat 2010; 17: pp. 749-756
  50. Romeo, Raffaella. “Hepatitis Delta Virus: Making the Point from Virus Isolation up to 2014.” WJH World Journal of Hepatology22 (2015): 2389. Web.
  51. Sears, Dawn M., Dan C. Cohen, Kimberly Ackerman, Jessica E. Ma, and Juhee Song. “Birth Cohort Screening for Chronic Hepatitis During Colonoscopy Appointments.” Am J Gastroenterol The American Journal of Gastroenterology6 (2013): 981-89. Web.
  52. Jaeckel E, et al: Treatment of acute hepatitis C with interferon alfa-2b. NEJM 2001; 345: pp. 1452-1457
  53. Swain, Mark G., Ming–Yang Lai, Mitchell L. Shiffman, W. Graham E. Cooksley, Stefan Zeuzem. “A Sustained Virologic Response Is Durable in Patients With Chronic Hepatitis C Treated With Peginterferon Alfa-2a and Ribavirin.” Gastroenterology5 (2010): 1593-601. Web.
  54. Chhatwal, Jagpreet, Fasiha Kanwal, Mark S. Roberts, and Michael A. Dunn. “Cost-Effectiveness and Budget Impact of Hepatitis C Virus Treatment With Sofosbuvir and Ledipasvir in the United States.” Annals of Internal Medicine Ann Intern Med6 (2015): 397. Web.
  55. Seeto, Reginald K., Ben Fenn, and Don C. Rockey. “Ischemic Hepatitis: Clinical Presentation and Pathogenesis.” The American Journal of Medicine2 (2000): 109-13. Web.
  56. Gitlin, N., and Km Serio. “Ischemic Hepatitis: Widening Horizons.” Am J Gastroenterol. 87.7.831 (1992):Web.
  57. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015 Dec. 53 (10):962-1147.
  58. Zimmerman, Hyman J., and Willis C. Maddrey. “Acetaminophen (paracetamol) Hepatotoxicity with Regular Intake of Alcohol: Analysis of Instances of Therapeutic Misadventure.” Hepatology3 (1995): 767-73. Web.
  59. Bessems, Jos G. M., and Nico P. E. Vermeulen. “Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches.” Critical Reviews in Toxicology1 (2001): 55-138. Web.
  60. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988 Dec 15. 319(24):1557-62.
  61. Brok, Jesper, Nick Buckley, and Christian Gluud. “Interventions for Paracetamol (acetaminophen) Overdose. “Cochrane Database of Systematic Reviews(2006): n. pag. Web

Guidelines for Imaging: Abdominal Pain in the Pediatric and Gravid Populations

Author: Geoff Jara-Almonte, MD (PEM Fellow, New York Methodist Hospital) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

The computed tomography (CT) scan is a commonly utilized test for abdominal pain in the emergency department (ED).  CT is so ubiquitous in the evaluation of abdominal pain in the ED that it sometimes seems as though the scan is done prior to physician evaluation. But CT is not the best test for everyone as it involves a relatively large dose of ionizing radiation, which can cause harm to a developing fetus. CT is also theorized to be associated with an increased risk of cancer in children. Additionally, some specific pediatric complaints are better evaluated, at least initially, with other diagnostic studies.

Case 1: A 10 year-old previously healthy boy presents with 16 hours of abdominal pain that was initially periumbilical, but is now worse in the right lower quadrant (RLQ). His pain is also associated with nausea, vomiting and anorexia without any diarrhea.  He lies still in bed and tenses with any abdominal palpation.  He will jump up and down, but he seems to be in significant pain.

Appendicitis is a notoriously difficult-to-diagnose condition, particularly in children and pregnant patients. Missed appendicitis is the most common cause of lawsuits in cases with patients aged 6-17 years.[i]  Children, especially younger children, are more likely to present late in the course of the disease or with a perforated appendicitis.

In the case of the pediatric patient with suspected appendicitis in whom the diagnosis remains equivocal after physical exam and laboratory testing, imaging is indicated.  The American College of Radiology (ACR) recommends ultrasound of the abdomen as the most appropriate first test in evaluating appendicitis.[ii] The American College of Emergency Physicians (ACEP) recommends using ultrasound to rule-in appendicitis, and using CT of the abdomen and pelvis to exclude appendicitis.i

A positive ultrasound has a high positive likelihood ratio for the diagnosis of appendicitis.  However a negative ultrasound generally has inadequate sensitivity to rule out appendicitis, and equivocal studies or non-visualization of the appendix are common.  In the case of an equivocal ultrasound a CT is the recommended next step. Contrast is generally favored in CT for appendicitis, however, adequate studies in the pediatric population are lacking.i

Magnetic resonance imaging (MRI) has good sensitivity for appendicitis in children however it is not recommended as a routine study due to limitations including duration of study, need for sedation, and limited experience in most centers.ii

Case 1b: 26 year-old pregnant G1P0 at 14 weeks by last menstrual period (LMP) complains of lower abdominal pain, worse on the right side for the past two days.  She has had nausea and vomiting without diarrhea.  She has had no dysuria, fever, vaginal bleeding or discharge.

 The use of ionizing radiation in pregnant patients is particularly concerning because of the radiosensitivity of the developing fetus.  MRI and ultrasound are safe in pregnancy and are the favored means of abdominal imaging in pregnancy.  The ACR recommends abdominal ultrasound and/or MRI as the most appropriate tests in the pregnant patient with RLQ pain suspicious for appendicitis or acute non-localized abdominal pain and fever.ii, [iii]  ACEP’s guidelines on the evaluation of suspected appendicitis specifically exclude pregnant patients.i

The American College of Obstetrics and Gynecology (ACOG) guidelines for diagnostic imaging during pregnancy do not address specific clinical conditions or suggest any particular imaging algorithms.  ACOG recommends that when available and appropriate, ultrasound and MRI should be used preferentially. However, the society adds the following recommendation:

With few exceptions, radiation exposure through radiography, computed tomography scan, or nuclear medicine imaging techniques is at a dose much lower than the exposure associated with fetal harm. If these techniques are necessary in addition to ultra-sonography or magnetic resonance imaging or are more readily available for the diagnosis in question, they should not be withheld from a pregnant patient.[iv]

 Case 2: A 3 week-old female is brought in by her concerned parents after vomiting up “green stuff” twice this afternoon.  The patient is the product of a term pregnancy, born by normal vaginal delivery without complications. Up to this point, she has been breast feeding 15-20 minutes every two hours without any issues. 

Acute bilious vomiting in a child under a year of age should raise suspicion for malrotation with midgut volvulus.  Malrotation is a congenital condition of inappropriate fixation of the mesentery.  The bowel may rotate about the points of abnormal fixation leading to obstruction, ischemia, and necrosis of the bowel.

The presentation of midgut volvulus may include acute bilious vomiting, with or without abdominal pain. However, it may also demonstrate gradually progressive vomiting.  Abdominal tenderness and distention may or may not be present.  Plain radiographs may show a classic “double bubble sign” with gaseous distention of the stomach and duodenum and paucity of air elsewhere. However, plain films may also be show non-specific findings or be completely normal.

Some textbooks recommend a rapid abdominal x-ray as the initial study of choice for diagnosing midgut volvulus[v], however the ACR recommends an upper gastrointestinal (GI) series as the initial diagnostic study.[vi]  The GI series will show an abnormally positioned duodenum and an absent ligament of TreitzApproximately 25% of cases of malrotation are diagnosed in children over 1 year of age.  These may present with acute bilious vomiting or recurrent intermittent episodes of abdominal pain and vomiting.  CT of the abdomen and pelvis has demonstrated high sensitivity for malrotationvii but is not part of the ACR recommendations for criteria for children under 3 months; consensus guidelines are lacking for evaluation in children outside of this age group.

Case 3a: A 5 week-old infant is brought in for vomiting.  The parents report he has been vomiting after every feed for the past 5 days.  Initially, they thought he was spitting up, but now it has become projectile.  The emesis consists of milk and is non-bloody and non-bilious.  Immediately after vomiting, the patient is hungry again and tries to feed.

New onset non-bilious vomiting in the first several weeks of life should raise suspicion for hypertrophic pyloric stenosis.  This occurs more commonly in males and firstborn children. Both an upper GI series and/or abdominal ultrasound can show real-time transit through the pyloric channel.

The ACR recommends abdominal ultrasound as the most appropriate initial study for diagnosing pyloric stenosis. A thickened and elongated pylorus can be visualized on ultrasound, and real-time evaluation can demonstrate a failure to pass gastric contents.  The ACR allows that in some centers with less experience with pyloric ultrasound, or in atypical cases, upper GI series may be an appropriated first study.

Case 3b: An 11 month-old infant has had two uncharacteristic episodes of inconsolable screaming at home.  The first one lasted about 20 minutes and resolved spontaneously. After this first episode, she was fine, happy and playful. However, about 2 hours later, the patient had a second episode and thus, her parents brought her to the ED.  On the way to the ED, the crying resolved and she became once again, happy, curious, and playful.  She has had no fever, cough, vomiting, or diarrhea.  She did have a cold one week ago. 

 The history of intermittent colicky episodes of screaming are suspicious for the diagnosis of intussusception.  In the pre-verbal child, a history of abdominal pain cannot be elucidated, but parents may report drawing of the knees to the chest.  Bloody or “currant jelly” stools and vomiting are late findings as bowel ischemia and obstruction progress.  Parents may also note pallor and lethargy during these periods.  Children may have no symptoms between episodes.  The frequency and intensity of colicky episodes typically progresses.

Consensus guidelines for the best initial study in the diagnosis of intussusception are lacking.  Plain abdominal X-ray has poor sensitivity and specificity for the condition, though it is useful to rule out free air. Plain abdominal x-ray may also demonstrate a paucity of bowel gas in the RLQ or a target sign.  Abdominal ultrasound has very high (near 100%) sensitivity and specificity for intussusception.  Typically, ultrasound is the initial test of choice.  Air or contrast enema under fluoroscopic guidance can also be used to diagnose and reduce an intussusception, either as an initial study or following a diagnostic ultrasound.

References / Further Reading

[i] Howell, John M., et al. “Clinical policy: critical issues in the evaluation and management of emergency department patients with suspected appendicitis.” Annals of emergency medicine 55.1 (2010): 71-116.

[ii] American College of Radiology – ACR Appropriateness Criteria: Right Lower Quadrant Pain – Suspected Appendicitis; https://acsearch.acr.org/docs/69357/Narrative/

[iii] American College of Radiology – ACR Appropriateness Criteria: Acute (Nonlocalized) Abdominal Pain and Fever or Suspected Abdominal Abscess https://acsearch.acr.org/docs/69467/Narrative/

[iv] Guidelines for diagnostic imaging during pregnancy and lactation. Committee Opinion No. 656. American College of Obstetricians and Gynecologists. Obstet Gynecol 2016;127:e75–80.

[v] Fleisher, Gary R., and Stephen Ludwig, eds. Textbook of pediatric emergency medicine. Lippincott Williams & Wilkins, 2010.

[vi] American College of Radiology – ACR Appropriateness Criteria: Vomiting in Infants up to Three Months of Age; https://acsearch.acr.org/docs/69445/Narrative/

viiTackett JJ, Muise ED, Cowles RA. Malrotation: Current strategies navigating the radiologic diagnosis of a surgical emergency. World Journal of Radiology. 2014;6(9):730-736. doi:10.4329/wjr.v6.i9.730.