Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population. The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates. Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 & 3. As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematological complications. Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, < 0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age <40 years. New therapeutic approaches are under study like interferon related systems, modified forms of ribavirin, internal ribosome entry site (HCV IRES) inhibitors, NS3 and NS5a inhibitors, novel immunomodulators and specifically targeted anti-viral therapy for hepatitis C compounds. More remedial therapies include caspase inhibitors, anti-fibrotic agents, antibody treatment and vaccines.

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Hepatitis C Treatment: current and future perspectives

To characterize hepatitis C virus (HCV) epidemiology in Pakistan and estimate the pooled mean HCV antibody prevalence in different risk populations, we systematically reviewed all available records of HCV incidence and/or prevalence from 1989 to 2016, as informed by the Cochrane Collaboration Handbook. This systematic review was reported following the PRISMA guidelines. Populations were classified into six categories based on the risk of exposure to HCV infection. Meta-analyses were performed using DerSimonian and Laird random-effects models with inverse variance weighting. The search identified one HCV incidence study and 341 prevalence measures/strata. Meta-analyses estimated the pooled mean HCV prevalence at 6.2% among the general population, 34.5% among high-risk clinical populations, 12.8% among populations at intermediate risk, 16.9% among special clinical populations, 55.9% among populations with liver-related conditions and 53.6% among people who inject drugs. Most reported risk factors in analytical epidemiologic studies related to healthcare procedures. Pakistan is enduring an HCV epidemic of historical proportions—one in every 20 Pakistanis is infected. HCV plays a major role in liver disease burden in this country, and HCV prevalence is high in all-risk populations. Most transmission appears to be driven by healthcare procedures. HCV treatment and prevention must become a national priority.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.180257

The epidemiology of hepatitis C virus in Pakistan: systematic review and meta-analyses

Objective To assess the effectiveness of treatment for hepatitis C virus (HCV) infection in low- and middle-income countries and identify factors associated with successful outcomes. Methods We performed a systematic review and meta-analysis of studies of HCV treatment programmes in low- and middle-income countries. The primary outcome was a sustained virological response (SVR). Factors associated with treatment outcomes were identified by random-effects meta-regression analysis. Findings The analysis involved data on 12 213 patients included in 93 studies from 17 countries. The overall SVR rate was 52% (95% confidence interval, CI: 48–56). For studies in which patients were predominantly infected with genotype 1 or 4 HCV, the pooled SVR rate was 49% (95% CI: 43–55). This was significantly lower than the rate of 59% (95% CI: 54–64) found in studies in which patients were predominantly infected with other genotypes (P = 0.012). Factors associated with successful outcomes included treatment with pegylated interferon and ribavirin, infection with an HCV genotype other than genotype 1 or 4 and the absence of liver damage or human immunodeficiency virus infection at baseline. No significant difference in the SVR rate was observed between weight-adjusted and fixed-dose ribavirin treatment. Overall, 17% (95% CI: 13–23) of adverse events resulted in treatment interruption or dose modification, but only 4% (95% CI: 3–5) resulted in treatment discontinuation. Conclusion The outcomes of treatment for HCV infection in low- and middle-income countries were similar to those reported in highincome countries.

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Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

The changing epidemiology pattern and frequency distribution of hepatitis C virus in Pakistan

Case definitions for acute hepatitis C virus infection: a systematic review.

Sustained virological response based on rapid virological response in genotype-3 chronic hepatitis C treated with standard interferon in the Pakistani population

Objective: To determine the frequency of acute HCV infection after needle stick injury and its treatment outcome. Methodology: Patients with HCV positive needle stick injury and reporting within 72 hours of incident were selected. Co-infections with HBV, HDV, HIV, hematological disorders and depression were excluded. Anti-HCV was done at presentation and those testing positive were excluded. HCV RNA was done after two weeks or anti-HCV after six weeks of incident. Those testing positive were kept under observation for 16 weeks for spontaneous resolution. After this period HCV RNA and Genotype were done and therapy with Peg-interferon was started. Rapid, early and sustained virological responses were checked. Results: Two hundred eight patients with HCV positive needle stick injury were selected, 10 (4.8%) developed acute HCV infection out of them one (10%) had spontaneous recovery during the observation period of 16 weeks. seven (77.8%) achieved rapid virological response and eight (88.9%) achieved sustained virological response. Conclusions: Acute HCV is an uncommon disease to diagnose; it has favorable response to therapy if initiated early after a strict surveillance of patients for 8-16 weeks.

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Frequency of acute hepatitis C after needle stick injury and its treatment outcome.

Objectives: To determine frequency of depression in chronic hepatitis C naive patients before interferon therapy using CES-D questionnaire. Methodology: Patients testing positive antibodies to HCV by EIA of more than 6 months duration and who have not taken interferon therapy previously were included after taking informed consent. Patients who had co-infections such as hepatitis B and D virus or human immunodeficiency virus, or patients with other coexisting chronic liver disease like primary biliary cirrhosis, chronic autoimmune hepatitis and Wilson disease were excluded from study. Urdu version of CES-D a self-reporting questionnaire in public domain was administered. A score of >10 was taken consistent with depression. Results: Ninety-six patients were included and 59.4% were depressed. These included 57.9% males and 42.1% females. Highest frequency was seen in under-graduates and positive correlation was seen with duration of hepatitis C infection. Conclusions: This study showed that 59.4% of patients with hepatitis C have depression before initiation of therapy and this should be evaluated and treated if necessary before starting interferon therapy.

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Sajjad Ali Memon

Papers

Sustained virological response based on rapid virological response in genotype-3 chronic hepatitis C treated with standard interferon in the Pakistani population

Frequency of acute hepatitis C after needle stick injury and its treatment outcome.

Frequency of depression in chronic Hepatitis C naïve patients