What are the likely etiologies and recommended management for a 15‑week pregnant woman presenting with three‑day fever, elevated transaminases and ultrasound findings of acute hepatitis after recent travel to India?

Acute Hepatitis in a 15-Week Pregnant Woman with Travel to India

Test immediately for hepatitis E virus (HEV), as this is the most likely and most dangerous diagnosis in a pregnant woman with acute hepatitis after travel to India, and initiate supportive care while monitoring closely for acute liver failure. 1

Most Likely Etiology: Hepatitis E Virus

HEV genotype 1 is the exclusive cause of acute hepatitis in India and carries uniquely severe risks in pregnancy, with maternal mortality rates of 16-56% and fetal mortality up to 50%. 1, 2, 3 The combination of fever, elevated transaminases, and recent travel to India in a pregnant woman makes HEV the primary diagnostic consideration. 1, 4

Why HEV is Most Dangerous in Pregnancy

• HEV genotype 1 has a unique ORF4-encoded protein that enhances viral replication specifically in pregnant women, particularly in the second and third trimesters. 2
• Acute liver failure occurs more frequently in pregnant women with HEV than with any other hepatitis virus, with risk increasing as pregnancy progresses. 1, 4
• Vertical transmission occurs in 36.9% of cases when maternal HEV RNA is detectable, with viral loads >13,266 copies/ml conferring highest risk. 1

Immediate Diagnostic Workup

Essential Serologic Testing

• HEV IgM and IgG antibodies plus HEV RNA by PCR must be obtained immediately, as these confirm acute infection. 1, 3, 5
• Hepatitis A IgM to exclude HAV, which also causes severe disease in pregnancy but has different management implications. 1, 6
• Hepatitis B surface antigen, core IgM, and surface antibody to assess for acute HBV. 1
• Anti-HCV antibody with reflex HCV RNA if positive. 1

Critical Additional Testing

• Complete blood count with platelets, PT/INR, fibrinogen, and ammonia to assess for impending acute liver failure. 1
• Serial liver enzymes and bilirubin every 24-48 hours to monitor for progression. 1
• Blood glucose monitoring, as hypoglycemia indicates severe hepatic dysfunction. 1

Alternative Diagnoses to Consider

Herpes Simplex Virus Hepatitis

HSV hepatitis must be considered and treated empirically with IV acyclovir if oral lesions are present or if transaminases are markedly elevated (>1000 IU/L), as this is rapidly fatal without treatment. 7, 4 The American Association for the Study of Liver Diseases states that oral lesions in a pregnant patient with markedly elevated liver enzymes are pathognomonic for disseminated HSV. 7

• Do not wait for confirmatory testing before starting acyclovir if HSV is suspected, as immediate treatment is life-saving. 7
• HSV hepatitis can occur in the second trimester and requires ICU-level monitoring. 7

Other Viral Causes

• Hepatitis A can cause severe disease in pregnancy but is less common than HEV in India. 6
• Acute HBV and HCV are less likely to cause fulminant hepatitis in pregnancy compared to HEV. 4, 6
• Varicella-zoster virus (VZV) testing is not routinely recommended in immunocompetent pregnant women. 1

Management Strategy

Supportive Care is Primary Treatment

There is no specific antiviral therapy for HEV; management is entirely supportive with close monitoring for acute liver failure. 1, 2, 3

• Admit to a facility with hepatology and high-risk obstetric capabilities, ideally with access to liver transplantation. 1, 7
• Monitor for hepatic encephalopathy with serial neurologic assessments. 1
• Maintain adequate nutrition and hydration; avoid hepatotoxic medications. 1

Prognostic Assessment

Calculate MELD score (using bilirubin, INR, and creatinine) rather than King's College Criteria, as MELD has superior sensitivity (77% vs 61%) for predicting need for transplantation. 1

• A MELD score ≥30.5 predicts need for liver transplantation. 1
• Serial MELD scores help track disease trajectory. 1

Obstetric Management

Multidisciplinary care involving hepatology, obstetrics, and maternal-fetal medicine is essential. 1

• Fetal monitoring is necessary given maternal illness severity. 7
• Preliminary data suggest early termination of pregnancy may improve maternal outcomes in patients with lower grades of encephalopathy, though this requires case-by-case discussion. 2
• Vaginal delivery should not be discouraged if HEV is confirmed and the patient is stable. 1

Liver Transplantation Considerations

Transplant evaluation should be initiated if the patient progresses to acute liver failure despite supportive care. 1, 7

• Pregnancy is not an absolute contraindication to liver transplantation. 1
• Maternal survival takes priority, as fetal survival depends on maternal stability. 1

Critical Pitfalls to Avoid

Do not assume this is drug-induced liver injury or pregnancy-specific liver disease (HELLP, acute fatty liver) without excluding viral hepatitis, as HEV is the most common cause of acute liver failure in pregnant women in endemic areas. 3, 5

Do not perform routine liver biopsy, as it carries significant bleeding risk in the setting of coagulopathy and rarely changes management. 1

Do not delay empiric acyclovir if HSV hepatitis is in the differential, particularly if oral lesions are present or transaminases exceed 1000 IU/L. 7

Prognosis

Maternal mortality with HEV in pregnancy ranges from 16-56%, with better outcomes when acute liver failure is recognized and managed aggressively. 2, 3 Fetal mortality approaches 50% in severe cases. 3 Early recognition, supportive care, and access to transplantation when needed are the key determinants of survival. 1, 2