Faculty Development Case of the Month: April 2024

Monthly Case from the Department of Medicine 
Trust but Verify  

Submitted by:
Navila Sharif, MD
Resident Physician
Division of Hospital Medicine

Edited by:
Kari Esbensen, MD, PhD
Assistant Professor
Division of Hospital Medicine

Mary Ann Kirkconnell Hall, MPH
Senior Medical Writer
Division of Hospital Medicine

STORY AND CASE
A 77-year-old man with hypertension and type 2 diabetes presented with 5 days of worsening nausea, vomiting, non-bloody diarrhea, abdominal pain, and jaundice following a cruise to Mexico. He reported eating a sandwich prior to reboarding after a shore excursion and experiencing severe gastrointestinal symptoms within <1 hour. He was hospitalized locally, diagnosed with hepatitis A, and treated supportively. On his flight home, symptoms worsened, and he presented to the hospital directly from the airport.  

On arrival, he was afebrile but mildly tachycardic without hypotension. Initial labs were significant for total bilirubin 8.8, alkaline phosphatase 218, platelets 120, INR 1.35, and normal aspartate aminotransferase and alanine aminotransferase. Abdominal ultrasound was non-diagnostic. Viral studies were ordered. Due to concern for biliary obstruction, he underwent magnetic resonance cholangiopancreatography revealing acute gangrenous cholecystitis with early perforation, small pericholecystic and hepatic capsular collections, and splenomegaly. He emergently underwent laparoscopic cholecystectomy with purulence noted around the gallbladder, requiring surgical drain placement and antibiotic therapy.  

What’s the Diagnosis?
Acute hepatitis E infection. 

ANSWER AND EXPLANATION
Viral studies returned positive for hepatitis E virus (HEV) IgM. Autoimmune and remaining hepatitis workup (hepatitis A IgM and IgG) was negative.  The patient was discharged home after drain removal and, on follow-up calls, continued to do well several months later.  

DISCUSSION 
Hepatitis E is a leading cause of acute viral hepatitis worldwide, especially among travelers to endemic regions. Like other acute viral hepatitis, clinical features include rapid onset of fever, nausea, vomiting, jaundice, and elevated liver function tests. Interestingly, our patient presented with a cholestatic pattern of liver injury (R factor <2) with initially normal transaminases, supporting biliary obstruction rather than hepatocellular injury as the likely etiology of jaundice.  

The finding of gangrenous cholecystitis was unexpected given clinical presentation. Extrahepatic manifestations including hematologic, renal, and neurologic dysfunction have been linked to viral hepatitis. Though rare, acalculous cholecystitis has been associated with other forms of viral hepatitis and is suspected to result from direct ischemic injury versus vasculitis. However, gangrenous cholecystitis is previously unreported in association with HEV.  

HEV is generally self-limited with supportive treatment, although patients can present with acute liver failure, and chronic hepatitis E can be seen in immunocompromised patients. As HEV can be misdiagnosed as other forms of hepatitis, diagnosis requires a high index of suspicion, investigation into extrahepatic manifestations, and appropriate testing.  

 Take aways: 

• Suspect enterically transmitted viruses such as HEV in recent travelers to endemic regions. 
• HEV infection is generally self-limited, but possible extrahepatic manifestations should be investigated. 
• Avoid anchoring bias and premature closure: It is important to maintain complete differential diagnoses until prior (presumed) diagnoses are adequately verified (e.g., documented confirmatory test results), especially when the evolving clinical picture calls prior diagnoses into question. 

CITATIONS 
Hartl J, Wehmeyer MH, Pischke S. Acute hepatitis E: two sides of the same coin. Viruses. 2016; 8(11):299. doi: 10.3390/v8110299. 

Unal H, Korkmaz M, Kirbas I, Selcuk H, Yilmaz U. Acute acalculous cholecystitis associated with acute hepatitis B virus infection. Int J Infect Dis. 2009;13(5):e310-2. doi: 10.1016/j.ijid.2009.01.015.  

Wagner JJ, Patel I, Debesai M, St. Cyr N, Bernstein M. Abstratc S3294: Acute hepatitis e infection with false positive cross-reactivity to Epstein-Barr virus. Am J Gastroenterol. 2022;117(10S):e2095. doi: 10.14309/01.ajg.0000869816.55272.38  

Acknowledgements:
The author would like to thank the hospitalists involved in caring for this patient: Dr. Kari Esbensen, MD, PhD; Dr. David Minkoff, MD; and Dr. Kyle James, MD.