Hepatic Abscesses: Where Hepatology meets Infectious Disease

Parita Patel

Case

A 63-year-old female presents to the ER with right upper quadrant pain and jaundice. History is notable for a hepatic abscess thought to be secondary to acute cholecystitis three months ago at an outside hospital. At that time, AST was 300 U/L, ALT 200 U/L, alkaline phosphatase 113 U/L, and total bilirubin of 3.5 mg/dL. Hospital course was complicated by Escherichia coli bacteremia. The hepatic abscess was ultimately drained and culture results were positive for Klebsiella pneumoniae and Escherichia coli. The patient was discharged on antibiotics and told to follow up with surgeons for a cholecystectomy. The patient now re-presents with pain and jaundice. On exam, the patient is febrile to 38.9°C, BP 120/60, heart rate 96 bpm. Labs are now significant for conjugated hyperbilirubinemia of 8.8 mg/dL, alkaline phosphatase of 1844 U/L, AST 418 U/L, and ALT 215 U/L. No leukocytosis or eosinophilia is present. An ultrasound in the ER reveals signs of chronic cholecystitis and a large fluid collection in the right lobe of the liver.

What do you do next?

Correct Answer:

Obtain additional imaging and blood cultures

Although the clinical picture fits with a diagnosis of a hepatic abscess, the etiology still remains unclear. Given that the patient is not critically ill with septic shock at this time, empiric antibiotic therapy was withheld until drainage could be arranged within the next few hours and further culture data could be obtained. Given the significant elevation of alkaline phosphatase and bilirubin, there was concern for a possible obstructive cause and further imaging with a MRI/MRCP was obtained. A surgical consult was deemed too premature as the etiology of hepatic abscess remained unanswered, and further characterization of the abscess needed to be made. While E. Histolytica serology can be considered, further workup of a possible pyogenic liver abscess was thought to be more appropriate given the patient’s history.

Understanding the etiology of a hepatic abscess

First, try to identify the cause of the hepatic abscess. This will help elucidate what additional work up is needed aside from just starting antibiotics. While it’s important to treat the issue at hand, it is not enough to stop there. You need to ask, “WHY?”

A review by Mavilia et al provides a good framework about different etiologies of hepatic abscesses: infectious, malignant, and iatrogenic causes.

Figure 1 - Categorization of hepatic abscesses

Taken from: Mavilia M, Molina M, Wu G. The Evolving Nature of Hepatic Abscess: A Review. J Clin Transl Hepatol. 2016

Infectious abscess:

A pyogenic liver abscess most commonly develops via contiguous spread from surrounding infected tissues (i.e. biliary infection via direct spread), spread via portal circulation (i.e. leakage of intra-abdominal bowel contents with spread to portal circulation), or from arterial hematogenous seeding (i.e. bacteremia).

Figure 2 - Routes of infection

Taken from: Mavilia M, Molina M, Wu G. The Evolving Nature of Hepatic Abscess: A Review. J Clin Transl Hepatol. 2016

Malignant abscess:

A malignant abscess can be seen in the setting of  secondary infection of a primary liver tumor (i.e. HCC developing in an area of central necrosis that can then become infected with bacteria, HCC causing biliary obstruction), secondary infection of liver metastases, or superinfection of spontaneous necrosis.

Iatrogenic abscess:

Several procedures have been associated with an increased risk of hepatic abscess formation. TACE/RFA can induce necrosis of tumor and surrounding liver tissue, which may then serve as a nidus for infection.  Surgical procedures can potentially cause ischemic necrosis, biliary strictures, or hematomas in the liver which can all predispose to possible hepatic abscess formation.  In addition, biliary procedures can allow for ascending infection leading to development of hepatic abscesses. 

Diagnosis:

After thinking through the etiology and risk factors for possible hepatic abscess, diagnosis is generally achieved via imaging. Typically, ultrasound and/or CT are used for identification of a liver abscess, with CT as a more sensitive modality. 

CT or ultrasound guided drainage should be attempted to confirm the diagnosis and to identify the responsible pathogen(s). 

Back to the case

Blood cultures were obtained at time of presentation. MRI/MRCP showed a common bile duct stricture with intrahepatic biliary ductal dilation and a 5 x 3 cm abscess within the right dome of the liver. Another smaller lesion was also noted in hepatic segment 4A.

She underwent drain placement of the larger abscess as well as an ERCP for further evaluation of the biliary dilation. This revealed an indeterminate biliary stricture in the middle third of the common bile duct, which was brushed for cytology and FISH. Cholangioscopy was performed. Direct biopsies of the stricture and a common bile duct stent was successfully placed. The patient was started on empiric antibiotics until further culture data resulted. 

Types of bacteria seen with hepatic abscess:

Most pyogenic liver abscesses tend to be polymicrobial, with mixed enteric and anaerobic species as the most common pathogens.  Given the variability of causes and geographic differences, a microbiological diagnosis is essential in most cases. 

Table 1- Common pathogens in pyogenic liver abscess

Adapted from: Davis J, McDonald M. Pyogenic liver abscess. UpToDate. Sep 2020.

Infectious Disease Clinical Pearl

When obtaining an abscess specimen, the character of the aspirate should be evaluated. Purulent material is expected for pyogenic liver abscesses and if this is not seen, alternative diagnoses should be evaluated. The aspirate can also be sent for pathology and/or cytology to evaluate for malignancy. 

Of note, cultures should not be obtained from existing drains as they can be contaminated with other pathogens and may lead to inappropriate antibiotic therapy. 

When to think about amebic liver abscesses:

Entamoeba histolytica abscesses should be considered in patients who may not have risk factors for pyogenic abscess. Risk factors for pyogenic abscesses include recent surgery, abdominal infection, recent biliary procedure, or systemic infection with positive blood cultures. Epidemiologic risk factors for amebic abscesses include living in endemic areas including India, Mexico, Africa, Central and South America. 

On imaging, 70-80% of amebic abscesses are solitary subcapsular lesions.  Serology and antigen detection can also aid in the diagnosis as 90% of patients with amebic liver abscess develop antibodies by time of presentation. In cases where further diagnosis is needed, aspiration can be performed but is not necessary for diagnostic or therapeutic purposes. Aspiration can yield a brown fluid consisting of necrotic hepatocytes, often compared to ‘anchovy paste.’ Antigen testing and/or PCR on aspirated fluid can be helpful in solidifying the diagnosis, if needed. Most cases of amebic liver abscesses can be treated with metronidazole or tinidazole.

Table 2 - Characteristics of pyogenic vs amebic liver abscess

Taken from: Leder K, Weller P. Extraintestinal Entamoeba histolytica amebiasis. UpToDate. Sep 2020.

Entamoeba or Echinococcus?

Any mass occupying lesion can clinically be mistaken for an echinococcal cyst. Symptoms of echinococcus generally do not present until a cyst reaches 10 cm. If enlarged, cysts can cause hepatomegaly, RUQ pain, venous obstruction from mass effect, cholestasis or even portal hypertension. Hydatid cysts can generally be seen on ultrasound, but CT or MRI may be more helpful in establishing the number of cysts, presence of daughter cysts and presence of ruptured or calcified cysts. Management options include drug therapy with albendazole, surgery, or percutaneous management. 

Treatment 

Management should be determined with a multidisciplinary team as it can involve interventional treatment, specific pathogen testing and/ or even surgical treatment. Abscess size and consistency should be considered when choosing a strategy. Below is a proposed figure outlining treatment strategies of hepatic abscesses.

Figure 3- Hepatic abscess treatment algorithm

Taken from: Mavilia M, Molina M, Wu G. The Evolving Nature of Hepatic Abscess: A Review. J Clin Transl Hepatol. 2016

Infectious Disease Clinical Pearl

Antibiotic therapy should be tailored to findings on aspirate, when available. If gram stain and culture do not yield a bacterial pathogen, atypical organisms should be considered (See Table 3).

It is always helpful to save some aspirate fluid so that further testing can be obtained, if needed (i.e microscopy, culture for fungi and mycobacteria, PCR testing for Entamoeba histolytica, stains for parasites, etc).

Table 3- Uncommon causes of hepatic abscesses

Adapted from: Davis J, McDonald M. Pyogenic liver abscess. UpToDate. Sep 2020. and Leder K, Weller P. Liver flukes:fascioliasis. UpToDate. Sept 2020

Back to the case

Culture data revealed negative blood cultures, and polymicrobial abscess culture data. Biopsies from ERCP revealed invasive adenocarcinoma.

At an outpatient follow up visit, the patient was clinically doing well after completion of antibiotic therapy with resolution of fevers, jaundice and RUQ pain.

Repeat imaging was obtained at this time which showed improved biliary ductal dilation, and improvement in fluid collection adjacent to pigtail catheter. However, the smaller lesion in segment 4A was noted to be mildly larger when compared to previous.

CT was reviewed at tumor conference and determined to represent extrahepatic cholangiocarcinoma with liver metastasis. She was seen in oncology clinic with plans to initiate chemotherapy.

Take Home Points:

  • It isn't enough to just treat a hepatic abscess; you need to understand why an abscess developed
  • Hepatic abscesses can be further categorized as infectious, malignant or iatrogenic
  • If a patient lacks typical risk factors for a pyogenic liver abscess, E. Histolytica and Echinococcosis should also be considered in the differential
  • Management should be determined with a multidisciplinary team as treatment can include antibiotics, drainage by interventional radiologists, and may even require surgery

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