The sustained virologic response of nonresponder hepatitis C virus patients with retreatment.

BACKGROUND: Pegylated interferon and ribavirin combination therapy remain the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the large number of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegylated interferon based therapy is not much reported. OBJECTIVES: The aim of this retrospective study was to focus on the efficacy of pegylated interferon alpha and ribavirin in retreated chronic hepatitis C patients. PATIENTS AND METHODS: All patients were treated with pegylated interferon alpha either 2a (180 µg) or 2b (1.5µg/kg) subcutaneously once weekly for a 48-week period, plus ribavirin 1000-1200 mg/day. The patient who had a negative HCV RNA at the end of 48 weeks were followed up for 24 weeks, and the patients who relapsed in the post-treatment follow-up period of 24 weeks were treated again with pegylated interferon alpha; but if the first treatment was administered with pegylated interferon alpha 2a, the second was administered with pegylated interferon alpha 2b and if pegylated interferon alpha 2b, then the second with pegylated interferon alpha 2a. RESULTS: We evaluated the outcome of our patients with chronic HCV who achieved a viral response at the end of the therapy, but did not achieve sustained virologic response; 54% (38/70) of patients did achieve sustained virologic response, while 46% (32/70) of patients did not (eight patients did not achieve early virologic response, five patients were nonresponders at 24th week of the treatment, the remaining 19 patient had negative HCV at the end of the therapy but did not achieve sustained virologic response). We began from 19 patients to 8 patients, who had negative HCV RNA at the end of the treatment, but did not achieve sustained virologic response, interferon plus ribavirin therapy again. If the patient had interferon alpha 2a, we gave in the second tour alpha 2b; and if alpha 2b, then alpha 2a. The early virologic response of these nine patients were found to be 63% (5/8). These 5 patients who had rapid virologic response and early virologic response at the second therapy achieved sustained virologic response this time. CONCLUSIONS: These findings suggest that the standard 48-week treatment is insufficient and that an extended course of treatment may be necessary. Relapse is a poorly understood clinical outcome in the treatment of chronic HCV patients. Retreatment can give a chance to some patients specially who have early virologic response and negative HCV RNA at the end of the first therapy.

Frequency and mutation patterns of resistance in patients with chronic hepatitis B infection treated with nucleos(t)ide analogs in add-on and switch strategies.

BACKGROUND: Treatment for chronic hepatitis B (CHB) has improved over the last 10 years mainly due to the development of effective oral antiviral agents [nucleoside/nucleotide analogs (NUCs)]. OBJECTIVES: The aim of the present study is to identify the frequency and major patterns of resistance to the hepatitis B virus (HBV) in a Turkish population of CHB patients treated with NUCs using add-on and switch therapy strategies. PATIENTS AND METHODS: The investigation involved a total of 194 patients (88 were treated using add-on therapy, and 106 were treated using switch therapy). We analyzed the HBV polymerase gene by amplification and direct sequencing procedures. RESULTS: Primary drug-resistance mutations were detected in 84 patients (43%; 42 in add-on therapy, and 42 in switch therapy) taking lamivudine (LAM), 10 patients (5%; 6 in add-on therapy, and 4 in switch therapy) taking entecavir (ETV), and 16 patients (8%; 8 in add-on therapy, and 8 in switch therapy) taking adefovir (ADV). The most common LAM and ETV resistance mutations were rtM204I/V, rtL180M and rtT184A/I/S, respectively, while rtA181T/V and rtN236T substitutions were the most frequently observed ADV resistance mutations. CONCLUSIONS: Patients with CHB who developed NUC resistance were managed using 2 different rescue strategies. The frequency and mutation pattern of resistance were similar in patients treated with add-on and switch strategies. These findings may be helpful in the management of rescue strategies in LAM-resistant patients.

Genotype A2/adw2 Strain of Hepatitis B Virus in Turkey.

BACKGROUND AND AIMS: Previous studies have demonstrated the dominance of genotype D subtype ayw in patients with hepatitis B virus infection in Turkey. The aim of the present study is to report, for the first time, genotype A2 subtype adw2 of hepatitis B virus in a patient who is an inactive hepatitis B carrier in Turkey. MATERIALS AND METHODS: Hepatitis B virus DNA isolated from the serum sample was amplified by polymerase chain reaction. The polymerase gene segment of the hepatitis B virus was directly sequenced. A distance matrix/UPGMA comparison was used for phylogenetic analysis, and the genotype of the virus was identified accordingly. The subgenotype and subtype of hepatitis B virus were also detected. RESULTS: The genotyping of the patient revealed that the isolated hepatitis B virus was genotype A2/adw2. DISCUSSION: The subtype is inconsistent with the previous data from Turkey; specifically, the identification of the A2/adw2 subtype of the hepatitis B virus in an inactive carrier is the first such case in Turkey. This finding suggests that the transmission of another genotype besides genotype D subtype ayw of the hepatitis B virus is possible in Turkey.

[Entecavir resistance in entecavir naive lamivudine treated chronic hepatitis B patients]. / Lamivudin tedavisi uygulanmis ve entekavir naif kronik hepatit B'li hastalarda entekavir ilaç direnci.

Approved hepatitis B virus (HBV) therapies include interferon-alpha and nucleos(t)ide analogues. Lamivudine (LVD) is a nucleoside analogue and following long term LVD therapy, resistance emerges in a significant number of patients. Entecavir (ETV) is a novel deoxyguanosine analogue with potent activity against HBV in chronically infected patients. ETV is highly efficacious in treating nucleoside naive and LVD refractory patients. The aim of the present study was to determine the prevalence of ETV drug resistance in LVD treated/ETV naive (study group) and in untreated naive (control group) patients with chronic B hepatitis. DNA sequencing was applied to 80.-250. amino acid positions on HBV polymerase gene to investigate the ETV resistance and also HBV genotype and HBV polymerase gene overlapped S-gene segment mutations. Primary LVD and ETV drug resistance were detected in 37 (42.6%) and 4 (4.5%) of 87 patients, respectively in the study group. rtT184A, rtT1841 and rtT1845 mutations were found related to primary ETV resistance. In these patients also rtL180M and rtQ215S mutations were detected as compensatory mutations and YVDD and YIDD variants were observed at the 204. amino acid codon position. None of the patients in the control group had LVD or ETV resistance. Two of the patients in the study group had mutations at the positions sG145R and sC137G in the overlapped S-gene segment. However, mutations at the overlapped S-gene segment were not affected by the mutations associated with ETV resistance. All of the patients in the study and the control group were of HBV genotype D. The results obtained from this study may guide the treatment choices with ETV in chronic HBV patients treated with LVD and developed resistance to LVD.

Response to interferon-alpha in chronic hepatitis B patients with and without precore mutant strain and effects on HBsAg titers.

BACKGROUND: Chronic hepatitis B (CHB) affects 400 million people worldwide and is a major cause of morbidity and mortality. It is known that HBV DNA sequences were detected after the clearance of serum hepatitis B surface antigen (HBsAg) often in serum, liver and peripheral blood mononuclear cells. The objectives of our study were to evaluate the previous measurements of HBsAg titers versus. quantitative hepatitis B virus (HBV) DNA and ALT measurements in order to predict the nonresponse and response in interferon-alpha (IFN-alpha)-treated HBeAg-positive and HBeAg-negative chronic HBV patients. METHODS: We investigate whether the presence of precore mutant affects the response to IFN-alpha therapy and on the titer of HBsAg or not. Twenty-one HBeAg-positive (group 1), 38 HBeAg-negative (group 2), and 47 healthy inactive carriers (group 3) made up this study. Liver biopsy showed chronic hepatitis, there was no cirrhosis and none of the patients had IFN-alpha therapy before. RESULTS: The decrease in HBsAg titers was found as statistically not significant in groups 1 (p = 0.192) and 3 (p = 0.236) and statistically significant in group 2 (p = 0.0001) within a 6-month interval. CONCLUSION: HBsAg titer may be a factor to predict the primary responders and nonresponders specially in HBeAg-negative patients.