HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death

Abstract

Background & Aims: Acute liver failure (ALF) due to hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune suppressive therapy, compared to patients with HBV-associated ALF without immunosuppression (controls). Methods: We performed a retrospective multi-center study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, model for end-stage liver disease (MELD) score, and King’s College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival 21 days in HBV-associated ALF (the primary outcome). Results: Among patients with HBV-associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (controls, 82%). Significantly greater proportions of patients with Hepatitis B-associated ALF after immunosuppression were non-white, and had anemia or thrombocytopenic than controls (P<.02 for all). The serologic profile of HBV infection, severity of liver failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P>.17 for all). Significantly smaller proportions of patients with ALF after immunosuppression than controls survived for 21 days (42.9% vs 62.5% of controls; P=.0096). Factors associated with 21 day transplant-free survival (c-statistic = 0.866) were increased MELD score (odds ratio, 0.894 per increment), requirement for mechanical ventilation (odds ratio, 0.111), and immunosuppressive therapy (odds ratio, 0.274). Conclusion: Within a cohort study of HBV-associated ALF patients, 18% had received immunosuppressive therapy. Significantly smaller proportions of HBV-associated ALF patients after immunosuppression survive beyond 21 days than patients with HBV-associated ALF who did not receive immunosuppression. Patients undergoing chemotherapy should be screened for HBV infection and given appropriate anti-viral therapies to reduce preventable mortality.

Significant lung injury and its prognostic significance in acute liver failure: A cohort analysis

“…Clinical data including organ support requirements (invasive mechanical ventilation, vasopressors and renal replacement therapy) and medical therapies (use of mannitol, hypertonic saline, barbiturates, hypothermia, sedatives, blood products and antibiotics) were recorded during the first 7 days post‐study enrolment or until discharge, death or transplant if before 7 days. Data retrieved on outcomes at 21 days post‐study enrolment included LT, TFS and overall survival …”

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

“…Acute hepatitis B can progress to ALF in 1% to 4% of cases . In particular, ALF caused by HBV infection in an immunosuppressant state can be fatal . In one retrospective study, Karvellas et al noted that patients with HBV‐associated ALF receiving immunosuppression had a significantly higher mortality than those who did not receive immunosuppression.…”

“…In particular, ALF caused by HBV infection in an immunosuppressant state can be fatal . In one retrospective study, Karvellas et al 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 .…”

“…In one retrospective study, Karvellas et al 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 . 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.…”

Human genomics of acute liver failure due to hepatitis B virus infection: An exome sequencing study in liver transplant recipients

“…There is high inter‐individual variability in the clinical presentation of HBV infection, which ranges from self‐limited to fulminant acute disease and from mild chronic hepatitis to liver cirrhosis and hepatocellular carcinoma . Differences in viral or environmental factors only explain a fraction of this variability . Previous studies have identified some human genetic factors that play a modulating role in the clinical course `of HBV infection .…”