Acute hepatitis in pregnancy – the truth is more than skin deep

Nneka Ufere

Case

A 28-year-old woman presents with progressive right upper quadrant pain, fever, and non-productive cough. She is 32 weeks pregnant. On admission she is febrile to 39°C and her physical examination is notable for right upper quadrant tenderness as well as a gravid uterus. She has no scleral icterus. Her lungs are clear. She has no visible oral or genital lesions or skin rashes on examination. She is not encephalopathic. She only takes folic acid and denies taking any other medications. She does not drink alcohol or use illicit drugs. She has not had any recent travel. Her labs on admission are WBC 2.8, Hct 30, Plts 85, ALT 9678, AST 8756, ALP 150, Tbili 1.4, INR 1.8. A Tylenol level is undetectable. Hepatitis A, B, and C testing are negative. A pelvic ultrasound shows a viable fetus. A doppler ultrasound of the liver is normal.

What is the next best step in management?

Correct Answer:

IV acyclovir

Herpes Simplex Virus (HSV) Hepatitis – Clinical Presentation

Back to the case

In our clinical case above, our patient presented with an anicteric severe hepatitis which would make acute hepatitis E less likely (typically presents with jaundice). The presentation with fever and upper respiratory infection symptoms makes pregnancy-related conditions such as acute fatty liver of pregnancy or HELLP syndrome less likely. Complicated gallstone disease is common in pregnancy and should be considered given her RUQ pain and fever, however her severe hepatitis, leukopenia, and thrombocytopenia makes this diagnosis unlikely. Given her clinical presentation, HSV hepatitis should be strongly suspected and empiric acyclovir should be started while awaiting additional diagnostics.

Two great reviews of acute hepatitis in pregnancy can be seen in the 2015 ACG Clinical Guideline: Liver Disease and Pregnancy and the 2020 AASLD Practice Guidance: Reproductive Health and Liver Disease (see Figure 1). 

An approach to abnormal liver enzymes in pregnancy is also reviewed in a recent Liver Fellow Network post.

Figure 1: Evaluation of abnormal liver tests pregnancy

Taken from: Sarkar, M., et al., Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology, 2020. Epub ahead of print.

HSV Hepatitis – Diagnostics  

Figure 2: HSV hepatitis on liver biopsy

Taken from: WebPathology – Visual Survey of Surgical Pathology, Herpes Simplex Virus Hepatitis.

Back to the case

In our clinical case above, our patient was started on empiric acyclovir and underwent a transjugular liver biopsy to rule out other potential etiologies of acute hepatitis. An example of HSV hepatitis on liver biopsy pathology above shows evidence of hemorrhagic and coagulative necrosis with multinucleated hepatocytes with ground-glass appearance suggestive of viral inclusions. 

HSV Hepatitis – Treatment

  • High dose IV acyclovir should be started once HSV hepatitis is suspected.
  • Acyclovir has been shown to be safe and well-tolerated in pregnancy and during lactation.
  • Early acyclovir treatment is associated with improved outcomes in HSV hepatitis including improved mortality and reduced need for liver transplantation
  • The duration of anti-viral therapy is unclear but should be guided by clinical factors such as improvement in liver enzyme tests, negative serum PCR, and improvement in symptoms
  • Acyclovir-resistance should be considered in patients who are not improving on acyclovir therapy, and use of additional agents such as foscarnet should be considered under the guidance of infectious disease consultation

Take Home Points:

  • Keep a high index of suspicion for HSV hepatitis – while a rare cause of acute liver failure, it has high mortality and is most often diagnosed post-mortem
  • Common features of HSV hepatitis on presentation include fever, upper respiratory infection symptoms, an anicteric hepatitis with high ALT/AST, leukopenia, and thrombocytopenia
  • The characteristic mucocutaneous lesions associated with HSV are present in less than half of cases of HSV hepatitis
  • The diagnosis of HSV hepatitis should be with HSV PCR or liver biopsy as HSV serologies have limited sensitivity/specificity in diagnosing acute hepatitis
  • Despite its high mortality, HSV hepatitis is one of the few treatable causes of acute liver failure and early/empiric initiation of acyclovir treatment significantly lowers the risk of death or need for liver transplantation

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