What infections cause cholestatic hepatitis?

Infections That Cause Cholestatic Hepatitis

The primary infectious causes of cholestatic hepatitis are viral hepatitis A (HAV), hepatitis B (HBV), cytomegalovirus (CMV), and sepsis/endotoxemia, with HAV being the most common viral etiology causing cholestatic patterns in 10-15% of cases. 1

Viral Hepatitis

Hepatitis A Virus (HAV)

• HAV is the most well-documented viral cause of cholestatic hepatitis, occurring in approximately 10-15% of patients with hepatitis A infection 1
• The cholestatic variant presents with prolonged jaundice and elevated alkaline phosphatase, with clinical, laboratory, and pathologic findings consistent with cholestatic hepatitis 1
• Cholestatic HAV can cause severe pruritus and hyperbilirubinemia that may remain elevated (>150 μmol/L) for more than a month, with mean hospital stays of approximately 49 days 2
• The condition typically resolves spontaneously, though a short course of rapidly tapered corticosteroids can reduce symptoms and hasten resolution 1
• Rare cases may present with hemolytic anemia and renal failure, requiring corticosteroids and plasma exchange 3

Hepatitis B Virus (HBV)

• HBV can cause fibrosing cholestatic hepatitis (FCH), a severe cholestatic form that occurs primarily as allograft reinfection after liver transplantation or as severe reactivation in immunosuppressed patients 4
• FCH is characterized by rapid progression and, without treatment, is universally fatal within months of diagnosis 4
• Antiviral therapy with lamivudine (or modern nucleos(t)ide analogues) can dramatically alter the natural history and improve outcomes 4

Cytomegalovirus (CMV)

• CMV can cause acute cholestatic hepatitis even in immunocompetent patients, though it is more common in immunocompromised individuals 5
• Severe cases may require treatment with ganciclovir, which can lead to immediate response and total resolution of symptoms 5
• CMV-related cholestasis should be considered in the differential diagnosis, particularly in transplant recipients and HIV-infected patients 1

Bacterial Infections

Sepsis and Endotoxemia

• Sepsis-induced cholestasis is a recognized cause of intrahepatic cholestatic hepatitis 1
• This typically presents in critically ill patients with systemic infection and endotoxemia 1
• The mechanism involves inflammatory cytokines and endotoxins disrupting hepatocellular bile transport 1

Infectious Cholangitis

• Infectious cholangitis related to AIDS and other forms of immunosuppression can cause secondary sclerosing cholangitis with cholestatic features 1
• This represents a cholangiocellular rather than hepatocellular form of cholestasis 1

Diagnostic Approach

Initial Evaluation

• Obtain thorough history including fever (especially with rigors), which is suggestive of cholangitis but may rarely occur with viral hepatitis 1
• Perform abdominal ultrasound as the first step to exclude extrahepatic obstruction 1, 6
• Test for acute viral hepatitis markers: anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, and consider CMV IgM in appropriate clinical contexts 2, 3, 5

Key Laboratory Patterns

• Cholestatic hepatitis shows elevated alkaline phosphatase and bilirubin with variable aminotransferase elevation 1
• In HAV cholestatic variant, transaminases may still be markedly elevated (mean >2000 U/L in some series) despite the cholestatic pattern 2
• Prolonged elevation of bilirubin (>150 μmol/L for >1 month) suggests cholestatic HAV 2

Management Considerations

Treatment Principles

• Most viral cholestatic hepatitis resolves spontaneously with supportive care 1
• For HAV with severe cholestasis and pruritus, consider short-course corticosteroids 1
• For HBV-related FCH, immediate antiviral therapy is essential and life-saving 4
• For CMV in severe cases, ganciclovir therapy should be considered even in immunocompetent patients 5
• Manage pruritus with cholestyramine as first-line, rifampicin as second-line 6, 7

Important Caveats

• Always exclude extrahepatic obstruction first before attributing cholestasis to infectious causes 1, 6
• Consider genetic variants in hepatocanalicular transporters (ABCB11, ABCB4) that may predispose to more severe cholestatic reactions to viral infections 8
• Rule out drug-induced liver injury, as medications taken within 6 weeks of presentation may be responsible 1
• In immunosuppressed patients (transplant recipients, HIV-infected), maintain high suspicion for opportunistic infections causing cholestasis 1