Recent Trends in the Treatment of Hepatitis C Infection

HCV is a blood-borne RNA virus with six major genotypes. In India genotype 3 predominates, followed by genotype 1; genotype 4 is seen in some regions.

Acute hepatitis C is uncommon but chronic infection is prevalent in the elderly. Up to 85% are asymptomatic and at least half have normal transaminases, so it is missed unless actively sought.

The end point of treatment is sustained virological response at 12 weeks (SVR12), which equals cure. Cure reduces all-cause mortality, hepatic decompensation, hepatocellular carcinoma and the need for transplantation.

Fibrosis is now staged non-invasively — FIB-4, APRI and transient elastography (FibroScan) have largely replaced liver biopsy. The Older Modalities (of historical and viva importance)

Interferon-alfa, then pegylated interferon plus ribavirin gave SVR of only about 40–55% in genotype 1 and needed 24–48 weeks. It was particularly poorly tolerated in the elderly — flu-like symptoms, cytopenias, depression, thyroid and autoimmune disease, and ribavirin-induced haemolytic anaemia.

The first-generation protease inhibitors boceprevir and telaprevir (2011) added efficacy but also anaemia, rash and a heavy pill burden. Both interferon-based therapy and first-generation protease inhibitors are now obsolete.

Three DAA classes are combined: NS3/4A protease inhibitors ('-previr'), NS5A inhibitors ('-asvir'), and NS5B polymerase inhibitors ('-buvir'), of which sofosbuvir is the nucleotide backbone.

Pan-genotypic regimens are now standard, so routine genotyping is no longer required:

Sofosbuvir 400 mg + velpatasvir 100 mg, one tablet daily for 12 weeks — the most widely used pan-genotypic regimen.

Glecaprevir 300 mg + pibrentasvir 120 mg daily for 8 weeks in treatment-naive patients without cirrhosis or with compensated cirrhosis — the shortest course, and safe in severe renal impairment and dialysis.

Sofosbuvir 400 mg + daclatasvir 60 mg for 12 weeks — WHO-recommended, generic, inexpensive, and the workhorse regimen of India's national programme.

Simplified treatment algorithms allow treatment of all patients aged 12 and above with minimal baseline testing and minimal on-treatment monitoring; the SVR12 rate exceeds 95% across genotypes.

Compensated cirrhosis (Child–Pugh A): the same pan-genotypic regimens are used, usually for 12 weeks.

Decompensated cirrhosis (Child–Pugh B or C): protease inhibitors are contraindicated (glecaprevir, voxilaprevir) because of hepatotoxicity. Use sofosbuvir/velpatasvir with weight-based ribavirin for 12 weeks, or 24 weeks without ribavirin if ribavirin is not tolerated.

Retreatment after DAA failure: sofosbuvir/velpatasvir/voxilaprevir for 12 weeks is the salvage regimen, with SVR of 96–98%.

Renal disease: glecaprevir/pibrentasvir requires no dose adjustment at any level of renal function including dialysis; sofosbuvir-based regimens are now also considered safe at eGFR below 30.

DAAs are as effective and as well tolerated in older patients as in the young — age is not a reason to withhold treatment. The dominant issue is drug–drug interaction, not toxicity.

Key interactions: amiodarone with sofosbuvir causes severe symptomatic bradycardia and is contraindicated; proton pump inhibitors and antacids reduce absorption of velpatasvir and ledipasvir; statins (especially rosuvastatin and atorvastatin) need dose reduction; rifampicin, carbamazepine, phenytoin, phenobarbitone and St John's wort are contraindicated as enzyme inducers.

Screen for HBsAg before starting a DAA — HBV reactivation is a black-box warning and can be fulminant. Give prophylactic antiviral cover or monitor closely.

After cure, hepatocellular carcinoma surveillance must continue lifelong with six-monthly ultrasound in patients with cirrhosis or advanced (F3) fibrosis, because SVR reduces but does not abolish HCC risk. Varices screening also continues in cirrhotics.

The textbook cites the CDC birth-cohort recommendation (one-time anti-HCV testing for all adults born 1945–1965). This has since been widened to one-time testing of all adults at least once in a lifetime, plus periodic testing for those at ongoing risk.

There is no vaccine for hepatitis C, and cure does not confer immunity — reinfection is possible. Prevention rests on injection and blood safety, single-use needles, sterile dental and salon practice, and harm-reduction services.

India's National Viral Hepatitis Control Programme (NVHCP), launched in 2018 under the National Health Mission, provides free diagnosis and free treatment with generic pan-genotypic DAAs, targeting elimination as a public health threat by 2030.

AASLD–IDSA HCV Guidance (2023 update, and subsequent revisions): a simplified treatment algorithm for treatment-naive adults without cirrhosis or with compensated cirrhosis — no genotyping, minimal pre-treatment work-up and reduced monitoring.

Shortened salvage therapy: based on POLARIS-3, 8 weeks of sofosbuvir/velpatasvir/voxilaprevir gave the same SVR12 (96%) as 12 weeks of sofosbuvir/velpatasvir in treatment-naive genotype 3 patients with compensated cirrhosis — useful where resistance-associated substitution testing is unavailable.

Lancet 2025 factorial randomised non-inferiority trial: sofosbuvir–daclatasvir was non-inferior to sofosbuvir–velpatasvir. This is a major finding for low- and middle-income countries, as it validates the cheapest generic first-line combination.

Shortening therapy: the Indian RESOLVE multicentre randomised trial (ILBS-led) compared 8 versus 12 weeks of sofosbuvir/velpatasvir in treatment-naive non-cirrhotic adults; shorter courses reduce cost and improve completion rates in programme settings.

WHO Global Hepatitis Report 2024: viral hepatitis deaths are rising, and although curative therapy exists, diagnosis and treatment coverage remain low — only a minority of infected people worldwide have been diagnosed or treated. Hepatitis is now the second leading infectious cause of death globally.

Point-of-care HCV RNA testing (GeneXpert, molecular finger-stick platforms) enables same-visit 'test-and-treat', removing the loss to follow-up that has been the main programme bottleneck.

Reflex RNA testing from the same anti-HCV-positive sample is now recommended, replacing the two-visit model.

HCV-viraemic donor organs (kidney, liver, heart) are now transplanted into HCV-negative recipients with short-course DAA prophylaxis, expanding the donor pool — directly relevant to older transplant candidates.

Elderly-specific data: real-world cohorts and meta-analyses confirm SVR rates above 95% in patients over 65 and over 75, with no increase in serious adverse events; the barrier is drug–drug interaction and under-referral, not efficacy.

Cure improves extrahepatic outcomes — cohort data show reduced cardiovascular events, improved glycaemic control in type 2 diabetes, improved cognition and quality of life, and resolution of cryoglobulinaemic vasculitis and HCV-related lymphoproliferative disease.

Indian data: HCV prevalence is estimated at roughly 0.3–0.5% nationally with regional clustering (Punjab, north-east, Andhra Pradesh). Punjab's Mukh Mantri Punjab Hepatitis-C Relief Fund demonstrated large-scale public-sector cure and became a model for NVHCP scale-up.