High sustained virologic response in genotypes 3 and 6 with generic NS5A inhibitor and sofosbuvir regimens in chronic HCV in myanmar.

Exclusive HCV therapy clinical trials with genotype 6 patients in high prevalence areas have been sparse. We analysed the safety and efficacy of two generic, pangenotypic NS5A/NS5B combination oral DAA regimens, primarily in genotypes 3 and 6, in a real-world setting: (a) daclatasvir/sofosbuvir (DCV/SOF) ± ribavirin (RBV) and (b) Velpatasvir/sofosbuvir (VEL/SOF ± RBV). Between December 2015 and November 2017, data from 522 patients were analysed, 311 of whom were treated with DCV/SOF ± RBV for 12/24 weeks (genotype 3: n = 193, genotype 6: n = 89) and 211 were treated with VEL/SOF ± RBV for 12/24 weeks (genotype 3: n = 83, genotype 6: n = 77). Overall SVR rates were high for both DCV/SOF ± RBV (96.1%, n = 299/311) and VEL/SOF ± RBV (95.3%, n = 201/211), and there was a good adverse event profile. Treatment naïve status and inclusion of RBV (in advanced fibrosis/cirrhosis) were significant independent predictors of achieving SVR12, while type of DAA regimen was not predictive. In this large cohort of genotypes 3 (n = 276) and 6 (n = 166; n = 127 unique subtype of 6c-l), high SVR rates of 94.9% (n = 262/276) and 95.2% (n = 158/166), respectively, were noted. In conclusion, generic and pangenotypic DCV/SOF and VEL/SOF ± RBV regimens were highly effective and safe, in genotypes 3 and 6 chronic HCV in Myanmar. These efficacious pangenotypic regimens suggest that baseline genotype testing can be eliminated moving forward. While RBV may still be needed for those with advanced fibrosis/cirrhosis, in a global elimination strategy it would not be practical even if it does compromise SVR in a minority with difficult to treat characteristics.

Hepatitis C virus therapy with peg-interferon and ribavirin in Myanmar: A resource-constrained country.

AIM: To investigate peg-interferon (peg-IFN) and ribavirin (RBV) therapy in Myanmar and to predict sustained virologic response (SVR). METHODS: This single-center, open-label, study was conducted in Myanmar between 2009 and 2014. A total of 288 patients infected with HCV genotypes 1, 2, 3 and 6 were treated with peg-IFN alpha-2a (180 µg/wk) or alpha-2b (50 to 100 µg as a weight-based dose) and RBV as a weight-based dose (15 mg/kg/d). Treatment duration was 48 wk for genotypes 1 and 6, 24 wk for genotype 2, and 24 or 48 wk for genotype 3 based on rapid virologic response (RVR). Those co-infected with hepatitis B received 48 wk of therapy. RESULTS: Overall, SVR was achieved for 82% of patients and the therapy was well tolerated. All patients achieved SVR at equivalent rates regardless of HCV genotype (P = 0.314). Low fibrosis scores (P < 0.001), high baseline albumin levels (P = 0.028) and low baseline viral loads (P = 0.029) all independently predicted SVR. On the other hand, IL-28B TT and CC genotypes were not found to significantly predict SVR (P = 0.634; P = 0.618). Among those who completed treatment, the occurrence of RVR showed a > 96% positive predictive value for achieving SVR. Treatment duration did not significantly impact the likelihood of achieving SVR for patients infected with genotype 3 HCV (P = 0.371). The most common adverse events were fatigue (71%) and poor appetite (60%). Among patients with genotype 3 HCV, more patients in the 48-wk treatment group required erythropoietin than in the 24-wk treatment group (61.1% vs 49.2%). CONCLUSION: SVR rates were high with peg-IFN and RBV therapy in Myanmar. Fibrosis scores, baseline albumin, HCV RNA levels and RVR independently predicted SVR.

Full-length sequence of hepatitis B virus belonging to genotype H identified in a Japanese patient with chronic hepatitis.

We have isolated and cloned the full-length nucleotide sequence of the hepatitis B virus (HBV) genome (denoted HBV-IM806-2) recovered from a Japanese patient with chronic hepatitis. This patient had a history of travel to Bangkok, Thailand, and then suffered the onset of acute hepatitis B 3 months after his return to Japan. The HBV-IM806-2 isolate was composed of 3,215 nucleotides and showed the highest similarity to genotype H of HBV. Interestingly, 24 amino acid residues specific for genotype H were identified throughout the full genome sequence. Furthermore, phylogenetic analysis based on the full genome sequence confirmed that IM806-2 belonged to genotype H and was more closely related to the prototype of the Los Angeles strain than to the Nicaragua strain.

Evaluation of tumor markers for the detection of hepatocellular carcinoma in Yangon General Hospital, Myanmar.

Levels of alpha-fetoprotein (AFP), its glycoforms AFP-L3 and AFP-P4, and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) were determined in sera obtained from patients in Yangon General Hospital (20 with hepatocellular carcinoma (HCC), 29 with chronic liver diseases, including 3 with chronic hepatitis and 26 with cirrhosis of the liver, and 9 with other hepatobiliary diseases). Forty-five percent of the patients with HCC had serum AFP levels above 10,000 ng/ml, indicating that nearly half of the HCC patients were at an advanced stage of the disease. Thus, the AFP sensitivity was as high as 70% with 100% specificity for a cutoff level of 200 ng/ml. The sensitivity of AFP-L3 was 75% and a specificity 90% for a cutoff level of 15%. AFP-P4 showed a higher sensitivity of 80% and a similar specificity of 86% for a cutoff level of 12%. Combined evaluation of AFP-L3 and/or AFP-P4 increased the sensitivity to 90% with the same specificity of 86%, indicating that AFP-L3 and AFP-P4 are useful as adjuncts for diagnosis of HCC in the present population. PIVKA-II had a high sensitivity of 90%, although the specificity was lower than 45%, probably due to the low cutoff level, as some cholestatic patients were included in the control group.