Treatment of fulminant acute Hepatitis B with nucles(t)id analogues is safe and does not lead to secondary chronification of Hepatitis B

Abstract

Acute hepatitis B virus (HBV) infection is still a major cause of acute liver failure (ALF), necessitating a high rate of emergency liver transplantation (LTx). Acute infection is followed by high viral replication rates leading to hepatocyte death and, ultimately, ALF. The objective of treating HBV-induced ALF thus is to eliminate, or significantly suppress, HBV replication and therefore reduce cell death and support regeneration. In this retrospective study, we want to evaluate the timing, the safety, and the long-term virological outcome of this approach. In this study, we included 32 patients (16 female and 16 males; median age 39.5 years) with ALF due to hepatitis B, who were transferred to the university hospital Essen, Germany between January 2009 and December 2013. Before treatment, transaminases were highly elevated, bilirubin was increased, and elevated international normalized ratio (INR) revealed impaired liver function. HBV-DNA and HBsAg were positive. All 32 patients received oral antiviral treatment (3 lamivudine, 21 entecavir, and 8 tenofovir) between 1 day and 4 months after diagnosis of acute hepatitis B. One patient died, 2 were transplanted, one died shortly after LTx the other patient survived after LTx. These 3 patients received treatment in a state of advanced liver failure, and 1 patient 4 months after initial diagnosis of hepatitis B. Twenty-nine patients survived without LTx. Five patients were discharged without further follow-up. All 24 remaining patients became HBV-DNA negative in median of 100 days. Twenty-two patients were followed further, and all patients lost their HBsAg in median of 108 days. Sixteen of the 22 patients experienced a seroconversion to anti-HBs in median of 137 days. Four patients who were followed for 1 more year after HBsAg did not develop anti-HBs. None of the patients developed chronic hepatitis B. Immediate treatment of HBV-induced ALF with nucleos(t)id-analogues (NUCs) appears save and prevents LTx and death, and there is no indication for increased chronicity.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…107,180 Although randomised controlled trials are lacking, several cohort studies indicate that the early antiviral therapy with highly potent NAs can prevent progression to acute liver failure and subsequently liver transplantation or mortality. 107,181 This effect, however, is not seen if antiviral therapy is initiated late in the course of severe acute hepatitis B in patients with already manifested acute liver failure and advanced hepatic encephalopathy. 182 Data supports the use of TDF, ETV or even LAM.…”

“…183 Large case series, however, support that TDF, ETV or LAM can be safely used in acute severe hepatitis B. 181,184 In principle, TAF should be also effective in this setting, but no data are currently available on the use of TAF in severe acute hepatitis B. The use of glucocorticoids in acute severe hepatitis B is supported by older studies, but these studies in most cases did not include current antiviral drugs.…”

“…185 The management of acute liver failure and the indication for liver transplantation are discussed in detail in separate EASL CPGs. 151,180 Early NA treatment does not increase the risk of chronicity 181,186 ; in fact, observational data from a multicentre cohort even indicated reduced rates of chronicity, if NA treatment was initiated within 8 weeks of acute hepatitis B presentation in genotype A infected individuals.…”

KASL clinical practice guidelines for management of chronic hepatitis B

“…There is insufficient evidence from randomized controlled trials for early antiviral therapy in hepatitis B infection. In one cohort study, on the other hand, early administration of a potent antiviral medication was associated with prevention of acute hepatic failure as well as lower rate of liver transplantation ultimately and improved survival [402,408].…”

Acute Liver Failure

“…Relevant studies support and encourage this principle in terms of safety as well as of efficacy. [80][81][82] Once BCS diagnosis is established, the timely initiation of anticoagulation in therapeutic doses and-when available -angioplasty can improve the patient's prognosis. 50 Finally, in mushroom-induced ALF, it is crucial to apply all dispensable measures, including prompt administration of silibinin (the major active constituent of silymarin), gastric lavage and activated charcoal, and enough diuresis on top of proper hydration.…”