Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Abstract

India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. ( J CLIN EXP HEPATOL 2016;6:119-145) T here have been revolutionary changes in the management of chronic hepatitis C (CH-C) over the last few years. Pegylated interferon alfa (Peg-IFNa) plus ribavirin (RBV) therapy, which till the recent past was the standard of care, has been eclipsed by the arrival of newer directly acting antiviral agents (DAAs). Not only do the DAAs have better efficacy, they are also associated with lower side effects, have better tolerability, a shorter duration of therapy, and have simpler administration.In the recent guidelines issued by the American Association for the study of Liver Diseases (AASLD), in collaboration with the Infectious Diseases Society of America 1 and the European Association for Study of the Liver z (EASL), 2 the role of Peg-IFNa/RBV therapy in the management of HCV has been relegated to second-line, backup status. These newer guidelines, however, cannot be implemented in India as many of the recommended drugs are yet to be marketed in India. Other considerations for the treatment of HCV in India are a predominance of

Sofosbuvir with NS5A inhibitors in hepatitis C virus infection with severe renal insufficiency

“…The recommended all‐oral DAA regimens for HCV infected patients with stage 4‐5 CKD are elbasvir/grazoprevir and glecaprevir/pibrentasvir which are not available in many countries. In countries where these drugs are not available, Peginterferon with ribavirin is recommended for these patients because of the presence of sofosbuvir in oral DAA approved regimens and concern over the accumulated sofosbuvir metabolite. There is limited data on the use of sofosbuvir in this group of patients (Tables and ) .…”

“…The recommended all‐oral regimens for stage 4‐5 CKD patients are currently not available in our country. Therefore, treatment option in these patients is confined to Pegylated interferon with or without ribavirin despite suboptimal tolerance and sustained virological response (SVR) rates …”

Systematic review and meta-analysis: real-world effectiveness of direct-acting antiviral therapies in chronic hepatitis C genotype 3 in Asia

“… 13 The current Indian National Association for Study of the Liver recommends (1) SOF+DCV for 12 weeks or SOF+weight-based RBV for 24 weeks for those unwilling/intolerant to DCV non-cirrhotic patients; (2) SOF+DCV+weight-based RBV for 24 weeks for patients with cirrhosis, and alternative SOF+weight-based RBV+Peg-IFN for 12 weeks for patients with compensated cirrhosis or SOF+RBV for up to 48 weeks for patients with decompensated cirrhosis. 10 In 2017, the Pakistan National Consensus Practice Guidelines of Hepatitis C offered the three following recommendations for GT3 patients: (1) SOF+DCV for 12 weeks or SOF+velpatasvir (VEL) for 12 weeks for both treatment-naïve and IFN/RBV treatment-experienced and (2) SOF+weight-based RBV+Peg-IFN for 12 weeks for IFN-eligible patient or SOF+weight-based RBV for 24 weeks for IFN-ineligible patient; and (3) SOF+DCV for 24 weeks or SOF+VEL for 12 weeks for either non-cirrhotic patients or patients with cirrhosis. 11…”

Daclatasvir and reduced‐dose sofosbuvir: An effective and pangenotypic treatment for hepatitis C in patients with estimated glomerular filtration rate <30 mL/min

“…The NS5B inhibitors have a higher barrier of resistance than the other two DAA classes . Hence, most of the recommended DAA‐based anti‐HCV treatment regimens have included an NS5B inhibitor, primarily sofosbuvir, in combination with one or two agents from the remaining classes. Sofosbuvir is metabolized in the human body into an inactive metabolite GS‐331007, with a predominantly renal excretion .…”

“…The treatment was planned for 12 weeks, except for those with clinical evidence of cirrhosis or concurrent use of immunosuppressive drugs. In these latter groups, treatment for 24 weeks was planned.…”