entecavir and Acidosis--Lactic

The aim of this study is to evaluate the clinical implications of lactate concentrations in patients with hepatitis B with or without cirrhosis during treatment with nucleos(t)ide analogues.. One hundred and seven consecutive patients with chronic hepatitis B and median age 57 (24-85) years were prospectively included. Lactate concentrations were measured at baseline and at 12, 24, 36, 48, and 60 months following the baseline measurements. Eight (n=8, 7.5%) patients received lamivudine, 38 (n=38, 35.5%) patients received tenofovir, 34 (n=34, 31.8%) patients received entecavir, and 27 (n=27, 25.2%) patients received combined therapy.. None of the patients developed lactic acidosis during follow-up [median: 58 (6-155) months]. Overall, no trends of the lactic acid evolution were observed over time; however, there was a nonsignificant increasing trend in patients with cirrhosis up to 24 months of treatment. This increasing trend was significant in female patients with cirrhosis (P=0.016). The age of the patients, the presence of cirrhosis, and hepatocellular carcinoma were strongly associated with the survival of all patients. In the group of cirrhotic patients, the only independent prognostic factor that was associated with patients' survival was the Child-Pugh class.. None of the patients developed lactic acidosis. There is an indication of an increasing trend of lactic acid levels up to 24 months of therapy in female cirrhotic patients.

Topics: Acidosis, Lactic; Adenine; Adult; Aged; Aged, 80 and over; Antiviral Agents; Biomarkers; Drug Therapy, Combination; Female; Guanine; Hepatitis B, Chronic; Humans; Lactic Acid; Lamivudine; Liver Cirrhosis; Male; Middle Aged; Organophosphonates; Prospective Studies; Risk Factors; Sex Factors; Tenofovir; Time Factors; Treatment Outcome; Up-Regulation; Young Adult

Topics: Acidosis, Lactic; Aged; Antiviral Agents; End Stage Liver Disease; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Middle Aged; Multiple Organ Failure; Retrospective Studies; Severity of Illness Index

Entecavir is a potent nucleoside inhibitor of the hepatitis B virus (HBV) polymerase with a high antiviral efficacy and a high genetic barrier to viral resistance. After approval in 2006, knowledge on the side effect profile in patients with advanced liver disease and impaired liver function is still limited. Here, we report on 16 patients with liver cirrhosis and chronic hepatitis B who were treated with entecavir. Five of these patients developed lactic acidosis during entecavir treatment. All patients who developed lactic acidosis had highly impaired liver function (Model for End-Stage Liver Disease [MELD] score >or= 20). Lactic acidosis (lactate 26-200 mg/dL, pH 7.02-7.40, base excess -5 mmol/L to -18 mmol/L) occurred between 4 and 240 days after treatment initiation with entecavir. Lactic acidosis was lethal in one patient but resolved in the other cases after termination/interruption of entecavir treatment. No increased lactate serum concentrations were observed during treatment with entecavir in the other 11 patients with chronic hepatitis B and liver cirrhosis who all had MELD scores below 18. The MELD score correlated with the development of lactic acidosis (P < 0.005) as well as its single parameters bilirubin, international normalized ratio, and creatinine. In contrast, Child-Pugh Score did not correlate with the development of lactic acidosis. Our data indicate that entecavir should be applied cautiously in patients with impaired liver function.

Topics: Acidosis, Lactic; Adult; Aged; Aged, 80 and over; Antiviral Agents; Female; Guanine; Hepatitis B, Chronic; Humans; Liver Failure; Male; Middle Aged