Effect of prolonged administration of pegylated interferon/ribavirin therapy in genotypes 2a and 2b: propensity score-matched analysis.

BACKGROUND AND AIM: Chronic hepatitis C genotype 2 patients show high susceptibility to pegylated interferon plus ribavirin therapy (PEG/RBV). However, the differences in response to therapy between genotypes 2a and 2b, and the efficacy of prolonged therapy for refractory patients have not been evaluated. We investigated the differences in response to PEG/RBV between each genotype and examined the efficacy of prolonged therapy. METHODS: A total of 343 chronic hepatitis patients infected with hepatitis C virus (HCV) genotype 2 (2a: n = 195; 2b: n = 148) were enrolled in this study. All patients received PEG/RBV for 24 (24 week group, n = 242) or more weeks (prolonged group, n = 101). We analyzed the differences in virological response between genotypes 2a and 2b. Clinical and virological factors of patients in the 24-week group and the prolonged treatment group were matched using propensity score analysis, and the efficacy of prolonged therapy established by comparing time of serum HCV disappearance for each genotype. RESULTS: Virological response tended to be higher for genotype 2a compared with genotype 2b; however, there was no significant difference in sustained virological response rates between genotypes (2a: 78.3%; 2b: 70.2%; P = 0.19). After propensity score matching, the adjusted P-value for sustained virological response rate was significantly different for genotype 2b patients with undetectable HCV-RNA between weeks 5 and 8, and for genotype 2a patients with detectable HCV-RNA at week 8. CONCLUSION: Prolonged therapy with PEG/RBV may be effective when serum HCV-RNA is detectable at week 4 and week 8 for genotype 2b and 2a patients, respectively.

Predictors for microinvasion of small hepatocellular carcinoma ≤ 2 cm.

BACKGROUND: Hepatocellular carcinoma (HCC) ≤ 2 cm in diameter is considered to have a low potential for malignancy. METHODS: A retrospective review was undertaken of 149 patients with primary solitary HCC ≤ 2 cm who underwent initial hepatic resection between 1994 and 2010. The independent predictors of the microinvasion (MI) such as portal venous, hepatic vein, or bile duct infiltration and/or intrahepatic metastasis were identified by multivariate analysis. Prognosis of patients with HCC ≤ 2 cm accompanied by MI was compared to that of patients with HCC ≤ 2 cm without MI. RESULTS: Forty-three patients with HCC ≤ 2 cm had MI in patients (28.9%). Three independent predictors of the MI were revealed: invasive gross type (simple nodular type with extranodular growth or confluent multinodular type), des-γ-carboxy prothrombin (DCP) >100 mAU/ml, and poorly differentiated. Disease-free survival rates of patients with HCC ≤ 2 cm with MI (3 year 44%) were significantly worse than those for HCC ≤ 2 cm without MI (3 year 72%). This disadvantage of disease-free survival rate of patients with HCC ≤ 2 cm with MI could be dissolved by hepatic resection with a wide tumor margin of ≥ 5 mm (P = 0.04). CONCLUSIONS: Even in cases of HCC ≤ 2 cm, patients who are suspected of having invasive gross type tumors in preoperative imaging diagnosis or who have a high DCP level (>100 mAU/ml) are at risk for MI. Therefore, in such patients, hepatic resection with a wide tumor margin should be recommended.

Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study.

BACKGROUND: In Japan, daclatasvir (DCV) and asunaprevir (ASV) therapy was the first IFN-free treatment to be approved, and thousands of patients have since been successfully treated, with an SVR rate of around 90%. The converse, however, is that around 10% of patients fail to achieve viral eradication and must be retreated using a different approach. This study is to evaluate treatment efficacy of ledipasvir/sofosbuvir and ribavirin in patients who failed to respond to DCV and ASV therapy. METHODS: Thirty patients were treated with 12 weeks of ledipasvir/sofosbuvir and ribavirin. We evaluated the rate of sustained virological response 12 weeks after the end of treatment (SVR12) and examined the incidence of adverse events during ledipasvir/sofosbuvir and ribavirin treatment. NS5A and NS5B resistance-associated variants (RAVs) in treatment failure cases were examined. RESULTS: The overall SVR12 rate was 86.7% (26/30). Large decreases in mean log10 HCV RNA levels were observed in patients without cirrhosis, and the SVR12 rate for these patients was 100% (12/12). In cases of cirrhosis, SVR12 rate was 72.2% (13/18). The common factors in treatment failure cases were the presence of liver cirrhosis and both NS5A L31M/I and Y93H RAVs. The frequency of RAVs did not change before and after treatment among patients who relapsed. CONCLUSION: Ledipasvir/sofosbuvir with ribavirin is an effective retreatment option for patients with chronic hepatitis C who failed to respond to prior daclatasvir and asunaprevir therapy.