Patient With Nonalcoholic Steatohepatitis Posttransplant Develops Acute Hepatitis B Virus Causing Graft Failure

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Abbreviations

ALF

acute liver failure

Alk Phos

alkaline phosphatase

ALT

alanine aminotransferase

AST

aspartate aminotransferase

HBIG

hepatitis B immune globulin

HBsAb

hepatitis B surface antibody

HBV

hepatitis B virus

INR

international normalized ratio

NA

nucleoside analogue

NASH

nonalcoholic steatohepatitis

Key Points

• Early identification and management of acute liver failure (ALF) and acute hepatitis B infection is paramount to patient survival.

• Close partnership with primary care providers in patients posttransplant is important to ensure optimal education of new hepatitis B virus (HBV) diagnosis.

• Serial hepatitis B surface antibody (HBsAb) titers are recommended both before and every 6 to 12 months posttransplant to ensure immunity.

Nonalcoholic steatohepatitis (NASH) is a common reason for liver transplantation in the United States. This review examines a case whereby a patient with NASH received a liver transplant and then experienced development of acute hepatitis B, causing graft failure.

Case Study

A 53‐year‐old woman received a liver transplant for decompensated cirrhosis caused by NASH. She recovered well and received standard postoperative care with routine clinic visits per usual transplant center protocol. Approximately 11 months after her transplant, she became acutely ill with symptoms of nausea, vomiting, and right upper quadrant pain. Her liver enzymes were strikingly elevated (see Figs. 1 and 2), and additional testing was performed including viral hepatitis panel, radiological imaging, EGD, and liver biopsy. Liver biopsy results showed moderate acute cellular rejection (treated with high‐dose intravenous steroids) and severe steatosis with lobular hepatitis, as well as presence of diffuse, predominantly cytoplasmic staining and focal nuclear staining with the hepatitis B core antigen; however, they were negative for the hepatitis B surface antigen. Notably, pretransplant testing showed core antibody (Ab)‐negative/HBsAb‐negative; at time of HBV diagnosis, testing showed core Ab‐positive/HBsAb‐negative/HBV DNA: >170,000,000 IU/mL. Acute hepatitis B was treated with tenofovir. Due to persistent evidence of graft failure (elevated liver function tests combined with coagulopathy and hepatic encephalopathy), she underwent urgent evaluation for retransplantation, resulting in listing for a second liver transplant. She experienced acute renal failure requiring continuous renal replacement therapy, and her condition deteriorated to needing intensive care unit stay; she received her second transplant 10 days later.

Figure 1.

Laboratory data overview, part 1.

Figure 2.

Laboratory data overview, part 2.

Acute Hepatitis B and Liver Failure

Acute hepatitis B can progress to ALF in 1% to 4% of cases.1 In particular, ALF caused by HBV infection in an immunosuppressant state can be fatal.2 In one retrospective study, Karvellas et al.2 noted that patients with HBV‐associated ALF receiving immunosuppression had a significantly higher mortality than those who did not receive immunosuppression. They recommend that this population of patients be screened for HBV infection and be treated accordingly when infection is present.2 In the case of our earlier patient, she was extremely immunosuppressed having just received a liver transplant a few months before, thus increasing her mortality risk.

ALF is a rare but fatal complication of severe liver injury.3, 4 The incidence in developed countries is less than 10 cases per million people per year.4 ALF can be caused by a variety of reasons, including viral hepatitis, toxins, or drugs, among several others. The diagnosis of ALF is made by meeting these three criteria: (1) absence of a history of liver disease, (2) rapid hepatocellular dysfunction (i.e., international normalized ratio [INR] >1.5), and (3) any degree of encephalopathy.3, 4 Clinically, the patient appears jaundiced, confused, with the presence of coagulopathy (elevated INR). Symptoms can progress rapidly, causing cerebral edema, seizures, bleeding, renal failure, sepsis with shock, and multiorgan failure.3 Liver transplant is the only known definitive treatment for ALF, with survival at 1 year ranging from 50% to 75%.3 One study by Xiong et al.1 identified peak prothrombin time activity less than 20% (low) and grade III‐IV hepatic encephalopathy as independent predictors requiring LT or high risk for mortality.1

Treatment for HBV‐Related ALF

Prior to the 1990s, active hepatitis B infection was a contraindication to liver transplantation. This changed in recent years with the medical advances of antiviral treatment (nucleoside analogues [NAs]) and the development of hepatitis B immune globulin (HBIG).5 Currently, use of a combination of NAs with HBIG is considered the most effective way to prevent reinfection of HBV after transplant.6 Shalimar and Acharya7 note that for the patient with hepatitis B–related ALF, antivirals (i.e., entecavir or tenofovir) are recommended.7 In the case study mentioned earlier, once active HBV infection was known, she was prescribed renally adjusted tenofovir for HBV treatment and was given HBIG at the time of her second transplant.

One aspect that was important to discuss with the patient was the risk for transmission of HBV to others. We partnered closely with her primary care team to provide counseling to the patient regarding her new HBV diagnosis, as well as education on prevention of HBV transmission to others (see Fig. 3).8

Figure 3.

Recommendations for infected persons regarding prevention of transmission of HBV to others. Reproduced from Hepatology.8 Copyright 2018, American Association for the Study of Liver Diseases.

Hepatitis B and the Transplant Process

At the time of liver transplant evaluation, practice guidelines recommend the risk for infection be thoroughly investigated.9 Viral hepatitis serology is reviewed and, if needed, vaccinations are given to prevent future infection, given the posttransplant immunosuppressed state. HBV vaccination given to immunocompetent patients will usually provide lifelong immunity. In patients who are immunosuppressed, protection from infection is very important for graft and patient survival.10 AASLD Practice Guidelines11 state that after transplantation, HBV antibody levels should be measured annually and if immunity is low, boosters should be considered. If vaccinations are required after transplant or in a immunocompromised state, administration should be delayed until prednisone doses are less than 10 mg daily.12 Studies have shown that immune response to vaccination in the posttransplant setting is not optimal.13, 14 Danzinger‐Isakov and Kumar14 recommend, to ensure ongoing immunity, serial HBsAb titers be evaluated both before transplant and every 6 to 12 months posttransplant.14