Hepatic Abscess: Pearls for Emergency Medicine Clinicians

Authors: Suresh K. Pavuluri, MD, MPH (EM Resident, The Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai); Benjamin Laraway, MD (EM Resident, The Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai); and Kaushal Shah, MD (Vice Chair of Education, New York Presbyterian Hospital, Weill Cornell Medical College) // Edited by Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case

A 56-year-old Taiwanese male with a past medical history of type II diabetes on metformin, hypertension, and hyperlipidemia presents to the ED with right upper quadrant (RUQ) pain for the past two days. He complains of fever, chills, and nausea, but no vomiting. He has no past surgical history. Currently, he denies any vomiting, diarrhea, dysuria, or hematuria. He’s a social drinker, but has never smoked.

Vitals: T 38.8 C, HR 103, BP 110/80, RR 20, SpO2 96% RA, and POC glucose 154

Physical exam reveals a middle-aged male who appears uncomfortable, with localized tenderness to the RUQ. Exam is otherwise normal.

Point-of-care ultrasound of the RUQ reveals the following:

Figure 1: sonographic finding of the RUQ shows anechoic regions separated by a hyperechoic border¹.  From Fernandez, L. Figure 3, Hepatic Amebic Abscess. Sonoworld. https://sonoworld.com/CaseDetails/Hepatic_Amebic_Abscess.aspx?ModuleCategoryId=643

Based on the patient’s presentation, history of diabetes, immigration from an endemic region, and your POCUS, you place hepatic abscess high on your differential. Given that the patient meets SIRS criteria, you decide to immediately draw labs, blood cultures, start fluids, and order antibiotics. After these interventions, you send out consults to Surgery and Interventional Radiology.

History & Risk Factors

In the ED, RUQ pain has almost become pathognomonic for biliary pathology. Unlike the more common biliary processes, hepatic abscess can be an insidious cause of a patient’s presentation. Among all intraabdominal abscesses, hepatic abscesses account for merely 13%². Despite their low prevalence of 2.3 cases per 100,000 in North America³, liver abscesses are associated with a 10-40% mortality rate⁴; therefore, it is imperative to diagnose and to treat the condition promptly. Though different pathophysiological mechanisms underlie their formation, certain patient risk factors should alert a clinician to consider hepatic abscess.

The average age of presentation for pyogenic hepatic abscess is >57 years⁶, with males affected at twice the rate as females⁷. Immunocompromised patients such as diabetics, cirrhotics, patients undergoing chemotherapy, patients who have received transplants, patients on immunosuppression therapy, or patients with immunological deficiencies are at a higher risk for developing hepatic abscesses^6-9. In addition, patients with recent abdominal surgery; penetrating wounds to the abdomen; or recent traveled to or emigrated from certain parts of Asia (e.g., India, Taiwan), Africa, Central or South America are also at an increased risk for hepatic abscesses^10,11.

Pathophysiology

To better conceptualize the pathophysiology of hepatic abscesses, hepatic abscesses can be classified into infectious, iatrogenic, or malignancy-associated¹². Infectious liver abscesses can form via direct spread of infection from adjacent abdominal pathologies^13-15, via hematogenous seeding from systemic or intra-abdominal infections, or by spread of infection through the portal venous system from intra-abdominal infections such as diverticulitis or appendicitis. Amongst the different pathophysiological mechanisms, the most common way of forming hepatic abscesses is through direct spread from the biliary tree¹², resulting in pyogenic infection. Gallstone disease, strictures, or malignancy can lead to obstruction, bacterial proliferation through the biliary tract (a cause of ascending cholangitis), and eventual hepatic abscess formation¹².

Most infectious causes of hepatic abscesses involve a mixed group of microorganisms. Escherichia coli, Klebsiella pneumoniae, Bacteroides, enterococci, anaerobic streptococci, or microaerophilic streptococci are typically the most common organisms^13,16. The three most common causative organisms of hepatic abscesses via hematogenous spread are Staphylococci, hemolytic streptococci, and Streptococcus milleri¹⁶.

Extraintestinal liver manifestations of amebiasis, caused by the protozoan Entamoeba histolytica, are also common. It is theorized that the protozoan ascends through the portal venous system to establish an infection in the liver¹⁷. Though the factors that result in invasive amebiasis are not fully understood, patients with compromised cell-mediated immunity are more susceptible to invasive amebiasis¹⁸.

Hepatic abscesses can be formed via secondary infection of a primary liver tumor or from liver metastases¹². Procedures such as transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) used in cases of inoperable hepatocellular carcinoma can also result in hepatic abscesses^19-23. TACE induces an area of necrosis within a tumor, which can serve as a nidus for an infection. Other procedures such as biliary stenting have also been shown to cause hepatic abscesses^24,25. In about 15% of hepatic abscesses, no identifiable cause is found⁴⁰.

Clinical Presentation

Patient presentation may vary based on the age of the patient and the underlying etiology of the hepatic abscess. With amebic liver abscesses, patients may have symptoms for days or weeks and may or may not appear chronically ill^42-45. Patients with multiple liver abscesses may have acute and more pronounced systematic symptoms compared to those with a single abscess⁴⁰. Moreover, elderly patients typically present with more occult symptoms than younger patients⁴⁰.

Most liver abscess patients typically present with fever (seen in 90%-92% patients) and/or abdominal symptoms such as RUQ pain, tenderness, or guarding (seen in ~50%-75% of patients)^13,14,25-27. Patients with amebic liver abscesses tend to present more with abdominal pain than those with bacterial liver abscesses⁵¹. Fevers tend to be waxing and waning in nature and may be accompanied with nocturnal sweating. About 50% of patients with liver abscesses may have hepatomegaly or jaundice,²⁷ with the latter more common in bacterial liver abscesses⁵¹. Moreover, some patients may experience constitutional symptoms of nausea, vomiting, fatigue, malaise, and anorexia or weight loss, whereas others may not even have any abdominal pain.

Because the symptoms of a liver abscess can be non-specific in nature, it is important to obtain detailed medical and surgical histories. Inevitably, having a high-index of suspicion while risk stratifying a patient based on their history and physical exam findings is critical for diagnosis.

Evaluation

Laboratory Studies

For hepatic abscesses, laboratory tests are neither specific nor diagnostic. As per routine management, blood cultures should be obtained in all patients in whom hepatic abscess is considered. Though they are positive in only half of the patients, they may help guide antibiotic therapy^13,28. Normocytic, normochromic anemia, leukocytosis, elevated erythrocyte sedimentation rate (ESR), and hyperbilirubinemia with or without jaundice may also be noted. Serum transaminases may be elevated, but to a lesser extent than serum alkaline phosphatase (seen in 90% of patients)^13,14,27. Though bacterial and amebic causes of hepatic abscesses may have similar findings, there are certain markers that point toward an amebic abscess. Lodhi, et al found that mean albumin level was lower in bacterial liver abscesses than in amebic ones⁵¹. Unlike most other parasitic infections, eosinophilia is characteristically absent in amebiasis, so it should not be used as a diagnostic marker to exclude amebic abscess⁴⁹. If a patient is at high-risk for amebiasis, stool cultures and/or serologic testing such as indirect hemagglutination (IHA) for Entamoeba histolytica may be diagnostic^46-48,50,51. IHA titers may remain positive several years after infection. In Lodhi, et al IHA titers of 1:32 were found in patients with pyogenic abscesses indicating prior amebiasis whereas titers of 1:256 pointed toward pyogenic abscesses.⁵¹

Imaging

For liver abscesses, ultrasound of the RUQ is typically the first diagnostic modality, given its convenience, lack of exposure to radiation, and cost-effectiveness in most EDs²⁹. However, CT scan of abdomen with IV contrast (preferably) confers greater sensitivity (85% vs. 95%) and can be utilized if ultrasound is non-diagnostic^30,31. An MRI may also be utilized in certain populations (i.e., pregnant patients), but its relative high cost and lack of access make it a less-utilized option³². Though there are different imaging modalities to diagnose hepatic abscesses, it is not possible to distinguish between the different types (i.e., bacterial vs amebic) on imaging alone³³. Having a high-index of suspicion, risk stratifying a patient based on history, and/or serological testing may help distinguish bacterial hepatic abscesses from amebic ones.

On ultrasound of the RUQ, abscesses can look hypoechoic or hyperechoic and may have septations or debris (see Figure 2).

Figure 2: A rounded lesion is seen on the left lobe of the liver with an anechoic center and a hazy, irregular border. This particular patient was diagnosed with amebiasis, but there is no definitive way distinguishing amebiasis vs. other causes of hepatic abscess¹.  From Fernandez, L. Figure 3, Hepatic Amebic Abscess. Sonoworld. https://sonoworld.com/CaseDetails/Hepatic_Amebic_Abscess.aspx?ModuleCategoryId=643

On contrast-enhanced CT scan, a “double target sign” where a low-attenuation fluid area is surrounded by high-attenuation inner ring and a low-attenuation outer ring can be seen^32,34,35. The inner ring contains the fluid-filled contents of the abscess, and the outer ring encompasses the parenchymal edema³². Sometimes a “cluster sign” where a hepatic abscess is surrounded by other small abscesses may also be seen (see Figure 3)^36-38. Once a pyogenic liver abscess is confirmed on imaging, prompt treatment with broad-spectrum antibiotics is needed, as well as consultation with IR and surgery.

Figure 3: hepatic abscess with a double target sign, where abscesses are separated by inner ring of fluid-filled content and an outer ring encompassing the parenchymal edema. Case courtesy of Dr Laughlin Dawes, Radiopaedia.org, rID: 35962 

Treatment

In the ED, patients with hepatic abscesses may present with a wide-range in acuity: some may be acutely septic, and others may have a more sub-acute presentation. Treatment is based on the size of the abscess, whether it has ruptured, underlying etiology, and whether the abscess is multi-loculated or uni-loculated. Generally, for all patients with hepatic abscesses, broad-spectrum antibiotic therapy should be initiated as soon as blood cultures are drawn³⁷.

For abscesses < 3 cm, antibiotic therapy alone may be sufficient³⁸. However, the gold standard treatment for hepatic abscesses is percutaneous drainage^37,38. For unilocular abscesses measuring > 3-5 cm, percutaneous drainage is the first treatment of choice. If the first attempt at percutaneous drainage fails to resolve the abscess, a second attempt is reasonable, but surgical resection is also an option³⁸. For multilocular abscesses measuring > 3-5 cm, surgical drainage or resection has been found to be the most effective treatment modality³⁸. For ruptured abscesses, surgical treatment is recommended^38,39.

As most hepatic abscesses are polymicrobial in nature, broad-spectrum coverage that includes gram-positive, gram-negative, and anaerobes should be initiated. Zosyn, metronidazole, and/or clindamycin is recommended^12,51. For highly-resistant organisms, carbapenems can be used as a monotherapy followed by fluoroquinolones for long-term parenteral therapy. Treatment duration is based on clinical picture, response to treatment, as well as serial US examination of the size of abscess(es). Typically, IV antibiotics are used for 1-3 weeks followed by PO antibiotics for 2-3 months until the resolution of the fever, leukocytosis, and documented evidence of resolution of abscesses via ultrasound¹². For amebic abscesses, 10-day antiprotozoal therapy alone may be sufficient^52-54. Typically, therapeutic aspiration is reserved for large abscesses, those that are non-responsive to pharmacological therapy, enlarging abscesses, or those at high-risk for rupture⁵⁵.

Take Home Points

1. Hepatic abscesses are associated with a high-mortality rate. Prompt recognition and resuscitation are paramount in successfully treating this disease entity.
2. CT with contrast is the diagnostic modality of choice, but abscesses may also be seen on ultrasound.
3. Broad-spectrum antibiotic coverage that includes gram-positives, gram-negatives, and anaerobes as well as anti-protozoal therapy for suspected amebic abscesses is important.
4. Ultimately, percutaneous drainage or surgical drainage may be needed along with IV antibiotics for 1-3 weeks and PO antibiotics for 1-2 months or until resolution of clinical symptoms such as fever and resolution of abscess(es) on repeat ultrasound.

References/Further Reading

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