Reappraisal of the importance of mutations in the NS5A-PKR-binding domain of hepatitis C-1b virus in the era of optimally individualized therapy.

Past studies have reported that mutations in the protein kinase R-binding domain (PKRBD) sequences of hepatitis C virus (HCV) NS5A proteins are correlated with response to fixed-duration interferon (IFN)-based therapy in patients infected with HCV-1b. In this study, we investigated whether the substitutions in PKRBD, including the IFN sensitivity-determining region (ISDR) and 26 additional downstream amino acids from ISDR, will have effects upon patients infected with chronic HCV-1b in the era of individualized therapy with peginterferon and ribavirin. Thirty-seven patients were treated with optimally tailored therapy guided by baseline viral load combined with rapid and early virological responses while 23 patients were treated without guidance and/or assigned suboptimal treatment duration. The amino acid sequences of the PKRBD were determined by PCR and sequencing. The overall sustained virological response (SVR) rate of patients who received optimally individualized therapy was 78.4%, which was better than the SVR rate of patients who received suboptimal therapy (47.8%, P = 0.015). Multivariate analysis showed that optimally individualized therapy (P = 0.019) and 80/80/80 adherence (P = 0.006) were independent favourable predictors of SVR in the entire cohort. Further sub-analysis of the predictive factors of SVR in patients treated with optimally individualized therapy showed that mutations in the 26-amino acid downstream from the ISDR (P = 0.024) were the only independent predictor of SVR. We concluded that mutations in 26-amino acid downstream portion from the ISDR remained a prognosticator of SVR in the era of optimally tailored therapy.

[Long-term surveillance after basic elimination of bancroftian filariasis].

The longitudinal and cross-sectional systemic surveillance have been conducted for 9-11 consecutive years in six counties (cities) of Guangxi Zhuang Autonomous Region after basic elimination of bancroftian filariasis. The two different control regimens had been used with DEC selective treatment followed by mass treatment of all persons and selective treatment followed by taking DEC medicated salt. During the former 6 years, residual microfilaremia cases could still be detected; whereas during the latter 5 years, no microfilaremia cases could be detected at all. The natural infection of vector mosquitoes showed negative. The positive rate of antibody in the populations was reduced to 1.4-5.5% detected by IFAT, reaching to the level of local non-endemic areas. The result indicated that the transmission of filariasis in these areas has been blocked. The authors suggested that a period of 10 years might be appropriate for surveillance after basic elimination of bancroftian filariasis.

Performance of risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B) score in classifying treatment eligibility under 2012 Asian Pacific Association for the Study of the Liver (APASL) guideline for chronic hepatitis B patients.

BACKGROUND: REACH-B [Risk Estimation for Hepatocellular Carcinoma (HCC) in Chronic Hepatitis B] scoring system was developed to predict the risk of HCC in noncirrhotic chronic hepatitis B (CHB) patients. AIM: To evaluate the discriminatory performance of REACH-B scoring system in classifying anti-viral treatment eligibility of CHB patients according to the 2012 Asian Pacific Association for the Study of the Liver (APASL) treatment guideline. METHODS: A total of 904 noncirrhotic CHB were enrolled. Patients' age, gender, liver biochemistry, HBeAg status and HBV DNA levels were recorded. RESULTS: The minimum REACH-B risk score for patients to be eligible for anti-viral treatment was 7 for HBeAg-positive and 6 for HBeAg-negative patients. Among them, increasing REACH-B score was not significantly associated with eligibility for treatment [adjusted odds ratio (OR): 1.210, 95% confidence interval (CI): 0.979-1.494, P = 0.078] in HBeAg-positive patients, as shown by logistic regression analysis after adjusting for gender. In HBeAg-negative patients, REACH-B score significantly predicted the treatment eligibility (adjusted OR: 1.783, 95% CI: 1.607-1.979, P < 0.001). Discriminatory ability of REACH-B score to classify eligibility was poor for HBeAg-positive patients ≥40 years [area under receiver operating characteristic (AUC): 0.664, 95% CI: 0.533-0.795], but good/excellent for HBeAg-positive patients <40 years (AUC: 0.903; 95% CI: 0.841-0.964), HBeAg-negative patients ≥45 years (AUC: 0.883; 95% CI: 0.848-0.917) and HBeAg-negative patients <45 years (AUC: 0.907; 95% CI: 0.874-0.940). CONCLUSION: The discriminatory performance of the REACH-B scoring system in classifying anti-viral treatment eligibility based on the 2012 APASL guideline was good/excellent, except for ≥40 years old HBeAg-positive patients.