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

Abstract

SUMMARY BackgroundFactors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined.

Long‐term therapy with adefovir dipivoxil in hepatitis B e antigen‐negative patients developing resistance to lamivudine

“…The fact that a trend towards higher baseline HBV-DNA levels was observed in patients under combination therapy could not feeble our results, because high HBV-DNA prior treatment is associated with higher risk of druginduced mutations. 16 In conclusion, our results clearly demonstrate that in HBeAg-negative CHB patients with LAM resistance, adding ADV to continuing LAM therapy maximizes anti-viral efficacy because of prevention of viral resistance. Baseline high viraemia levels and suboptimal response to ADV are associated with an increased risk of subsequent ADV resistance.…”

“…Previous retrospective analysis of patients with CHB receiving LAM or ADV have shown similar results indicating that high levels of viral replication may reduce the magnitude of HBV-DNA suppression and thus facilitate the emergence of drug resistance. 10,16 Therefore, an early initiation of additional therapy in patients at high risk of drug resistance could prevent resistance and may be a promising future therapeutic strategy. Studies evaluating the treatment of patients who have developed resistance to ADV are lacking.…”

“…15 HBV genotypes and LAM-resistant mutations were presented in 27 and 34 patients, respectively, from a previous published study. 16 ADV-associated mutations were determined with a line probe assay for YMDD mutants (INNO-LiPA; Innogenetics NV, Gent, Belgium). The histological lesions were evaluated according to Ishak classification system.…”

Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: A systematic review

“…Studies were considered to be of high quality for this review if they fulfilled three of the following five criteria: (a) provided definitions for HCC diagnosis, (b) described HCC screening at baseline, (c) described HCC surveillance during therapy, (d) provided HCC data separately in patients with and without cirrhosis, and (e) provided HCC data in relation to virological response. According to these criteria, 14 studies were characterized to be of high [19][20][21][22][24][25][26][27]29,32,[35][36][37][38] and 7 to be of low quality [18,23,28,30,31,33,34]. Ten studies were considered as large [18,20,22,26,29,32,33,[36][37][38] and 11 as small [19,21,[23][24][25]27,28,30,31,34,35] if the total number of patients was more than 100 or less than 100, respectively.…”

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

“…Patients with normal ALT given ''lamivudine pulse'' therapy resulted in ALT elevation and enhanced overall sustained HBeAg and HBV DNA loss [23]. Other predictors have been reported including female gender, negative HBV DNA level by month 6 of therapy [6], younger age [18], high histological necroinflammatory grade [24], reduction in intrahepatic cccDNA and serum HBsAg level after lamivudine therapy with or without peginterferon [25,26], and genotype D compared to A [27]. There was no difference in treatment response between patients with genotypes B and C [28].…”