Lamivudine monotherapy in HBeAg‐negative chronic hepatitis B: prediction of response‐breakthrough and long‐term clinical outcome

• Published in: Alimentary pharmacology & therapeutics Vol. 23; no. 6; pp. 787 - 795
• Main Authors: MANOLAKOPOULOS, S., BETHANIS, S., ELEFSINIOTIS, J., KARATAPANIS, S., TRIANTOS, C., SOURVINOS, G., TOULOUMI, G., ECONOMOU, M., VLACHOGIANNAKOS, J., SPANDIDOS, D., AVGERINOS, A., TZOURMAKLIOTIS, D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 15.03.2006; Blackwell
• Subjects: Adolescent; Adult; Aged; Antiviral Agents - therapeutic use; Biological and medical sciences; Digestive system; DNA, Viral - analysis; Drug Resistance, Viral; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis B e Antigens - immunology; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - virology; Human viral diseases; Humans; Infectious diseases; Lamivudine - therapeutic use; Liver - immunology; Liver - pathology; Long-Term Care; Male; Medical sciences; Middle Aged; Mutation; Pharmacology. Drug treatments; Proportional Hazards Models; Retrospective Studies; Treatment Outcome; Viral diseases; Viral hepatitis; Antiretroviral agent; RNA-directed DNA polymerase; Prognosis; Enzyme; Transferases; Prediction; Enzyme inhibitor; Hepatic disease; Lamivudine; Long term; Infection; Viral hepatitis B; Nucleotidyltransferases; Dideoxynucleoside; Reverse transcriptase inhibitor; Viral disease; Nucleoside analog; Digestive diseases; Antiviral; Predictive factor; Pyrimidine nucleoside; Monotherapy
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2006.02806.x

Summary Background Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg‐negative chronic hepatitis B have not been well defined. Aim To determine pre‐treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg‐negative chronic hepatitis B receiving long‐term lamivudine. Methods Seventy‐nine patients, with chronic HBeAg‐negative hepatitis B, who received lamivudine for a median of 31 months were included in the study. Results Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre‐treatment serum hepatitis B virus DNA concentrations of more than 106 copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated. Conclusions In HBeAg‐negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 106 copies/mL is a strong predictor for breakthrough because of drug‐resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre‐existing cirrhosis.