Epidemiology of viral hepatitis in Somalia: Systematic review and meta-analysis study.

AIM: To provide a clear understanding of viral hepatitis epidemiology and their clinical burdens in Somalia. METHODS: A systematic review and meta-analysis was conducted as Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search of published studies on viral hepatitis was performed from 1977-2016 in PubMed, Google Scholar, Science Direct, World Health Organization African Index Medicus and the Africa Journals Online databases, as well as on the Ministry of Health website. We also captured unpublished articles that were not available on online systems. RESULTS: Twenty-nine studies from Somalia and Somali immigrants (United Kingdom, United States, Italy, Libya) with a combined sample size for each type of viral hepatitis [hepatitis A virus (HAV): 1564, hepatitis B virus (HBV): 8756, hepatitis C virus (HCV): 6257, hepatitis D virus (HDV): 375 and hepatitis E virus (HEV): 278] were analyzed. The overall pooled prevalence rate of HAV was 90.2% (95%CI: 77.8% to 96%). The HAV prevalence among different age groups was as follows: < 1 year old, 61.54% (95%CI: 40.14% to 79.24%); 1-10 years old, 91.91% (95%CI: 87.76% to 94.73%); 11-19 years old, 96.31% (95%CI: 92.84% to 98.14%); 20-39 years old, 91.3% (95%CI: 83.07% to 95.73%); and > 40 years old, 86.96% (95%CI: 75.68% to 93.47%). The overall pooled prevalence of HBV was 18.9% (95%CI: 14% to 29%). The overall pooled prevalence among subgroups of HBV was 20.5% (95%CI: 5.1% to 55.4%) in pregnant women; 5.7% (95%CI: 2.7% to 11.5%) in children; 39.2% (95%CI: 33.4% to 45.4%) in patients with chronic liver disease, including hepatocellular carcinoma (HCC); 7.7% (95%CI: 4.2% to 13.6%), 12.4% (95%CI: 6.3% to 23.0%) and 11.8% (95%CI: 5.3% to 24.5%) in age groups < 20 years old, 20-39 years old and > 40 years old, respectively. The HBV prevalence among risk groups was 20% (95%CI: 7.19% to 44.64%) in female prostitutes, 21.28% (95%CI: 7.15% to 48.69%) in hospitalized adults, 5.56% (95%CI: 0.99% to 25.62%) in hospitalized children, 60% (95%CI: 31.66% to 82.92%) in patients with acute hepatitis, 33.55% (95%CI: 14.44% to 60.16%) in patients with ancylostomiasis, 12.34% (95%CI: 7.24% to 20.26%) in patients with leprosy and 20.19% (95%CI: 11.28% to 33.49%) in schistosomiasis patients. The overall pooled prevalence of HCV was estimated as 4.84% (95%CI: 3.02% to 7.67%). The prevalence rates among blood donors, risk groups, children and patients chronic liver disease (including HCC) was 0.87% (95%CI: 0.33% to 2.30%), 2.43% (95%CI: 1.21% to 4.8%), 1.37% (95%CI: 0.76% to 2.46%) and 29.82% (95%CI: 15.84% to 48.98%), respectively. The prevalence among genotypes of HCV was 21.9% (95%CI: 15.36% to 30.23%) in genotype 1, 0.87% (95%CI: 0.12% to 5.9%) in genotype 2, 25.21% (95%CI: 18.23% to 33.77%) in genotype 3, 46.24% (95%CI: 37.48% to 55.25%) in genotype 4, 2.52% (95%CI: 0.82% to 7.53%) in genotype 5, and 1.19% (95%CI: 0.07% to 16.38%) in genotype 6. The overall pooled prevalence of HDV was 28.99% (95%CI: 16.38% to 45.96%). The HDV prevalence rate among patients with chronic liver disease, including HCC, was 43.77% (95%CI: 35.09% to 52.84%). The overall pooled prevalence of HEV was 46.86% (95%CI: 5.31% to 93.28%). CONCLUSION: Our study demonstrates a high prevalence of all forms of viral hepatitis in Somalia and it also indicates that chronic HBV was the commonest cause of chronic liver disease. This highlights needs for urgent public health interventions and strategic policy directions to controlling the burden of the disease.

Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV).

OBJECTIVE: An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. PATIENTS AND METHODS: In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. RESULTS: At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. CONCLUSION: In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.

Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia.

AIM: To evaluate addition of boceprevir to peginterferon/ribavirin (PR) in Russian patients with chronic hepatitis C virus (HCV). METHODS: Treatment-naive (TN) and treatment-experienced (TE) patients (who had failed prior treatment with PR for ≥ 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebo-controlled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. TN patients randomized to triple therapy received boceprevir (800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8 (TW8) HCV RNA levels. TE patients received boceprevir plus PR for 32 wk and then further therapy according to TW8 HCV RNA levels. Treatment was discontinued for TN patients with detectable HCV RNA at TW24 and TE patients with detectable HCV RNA at TW12 because of futility. The primary efficacy end point was sustained virologic response (SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy. RESULTS: SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2% (95%CI: 16.4-41.5; P < 0.0001). Rates of SVR were higher in the boceprevir arm in both TN and TE patient groups (TN 78.4% vs 56.3%; TE 69.4% vs 30.0%). Within TE patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type (null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both TN (86%) and TE (71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone (47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia (< 10 g/dL) and those without anemia (71.2% vs 77.4%). CONCLUSION: Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.

Alcohol dehydrogenase ADH2-1 and ADH2-2 allelic isoforms in the Russian population correlate with type of alcoholic disease.

The frequency ADH2-2 allele in the Moscow urban population and a correlation between the ADH2-2 allele, alcoholic dependence without cirrhosis, symptomatic alcoholic cirrhosis and status on hepatitis B and C infection have been studied. One hundred and twenty-three inhabitants of Moscow (50 healthy donors, 36 patients with alcoholic cirrhosis (subdivided into infected and uninfected by HBV and/or HCV) and 37 patients with alcoholic dependence) of a similar age/sex and drinking pattern have been analysed. The frequency of 41% for ADH2-2 allele is characteristic for an urban Moscow population. This value is intermediate between that found for Asian peoples and for Central and Western Europe. There is a negative correlation between the ADH2-2 allele and alcohol misuse (both alcoholic dependence and alcoholic cirrhosis). This correlation is expressed more in alcoholic dependence. In spite of the possession of the ADH2-2 allele (or genotype ADH2-1/2), alcohol misuse increases the risk of cirrhosis. At the same time, positive status for active hepatitis B, C or combined infection B + C (replication markers HBV-DNA or HCV-RNA) increases the risk for symptomatic alcoholic cirrhosis in alcohol abusing patients, independently of ADH2 genotype.

Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C.

HCV infects approximately 2-3% of the global population and is a leading cause of end-stage liver disease and hepatocellular carcinoma. Treatment of HCV infection with Peg-IFN in combination with ribavirin can eradicate HCV infection in 40-90% of patients; however, a major barrier to treatment uptake and delivery is the association of this therapy with frequent and, at times, serious adverse effects. Recognition and effective management of these adverse effects are critical components of the successful treatment of chronic HCV infection. In clinical trials, approximately 10-15% of patients discontinue Peg-IFN and ribavirin therapy due to adverse effects; however, in clinical practice, the rate of treatment discontinuation has been reported to be substantially higher. The off-target effect of Peg-IFN and ribavirin impacts most, if not all, organ systems; the most common adverse effects are hematologic, dermatologic, neurologic, immunologic, gastrointestinal, pulmonary, cardiovascular, and ocular. Regional and global variability exists in the nature of these adverse effects and the strategies employed to ameliorate their impact. This article provides a comprehensive literature review that systematically describes the adverse effects of Peg-IFN-α and ribavirin on various organ systems and, more importantly, recommends consensus approaches to managing those effects.