Who this is for: GPs and medical officers who want to screen, stage and treat uncomplicated chronic hepatitis C in the OPD, referring only cirrhotic and complicated patients.

Epidemiology in Pakistan

Pakistan carries the largest national burden of hepatitis C on earth: prevalence surveys suggest roughly 5 to 6 percent of adults are anti-HCV positive, on the order of 9 to 10 million people living with the virus. Genotype 3 dominates. The main drivers remain therapeutic injections with reused syringes, unscreened historical transfusions, barbers razors and dental procedures. WHO has set 2030 elimination targets, and Pakistan launched a national elimination programme; none of it works unless primary care finds and treats patients, because cheap DRAP-registered generic DAAs have made cure a primary-care task.

Who to screen and how

Screen: anyone with a history of transfusion or surgery, therapeutic injections, dialysis, tattooing or shaving at barbers, household contacts of patients, healthcare workers, people who inject drugs, pregnant women per local ANC protocols, raised ALT found incidentally, and realistically any adult who has never been tested, given national prevalence.

Stepwise, cheapest first:

  1. Anti-HCV antibody (rapid immunochromatographic test or ELISA): widely available, low cost. A positive antibody means exposure, not necessarily active infection.
  2. HCV RNA PCR (qualitative or quantitative) confirms viraemia. Roughly 25 percent of antibody-positive patients have cleared spontaneously and need no treatment. Do not start DAAs on antibody alone.
  3. Baseline before treatment: CBC, ALT, AST, bilirubin, albumin, creatinine, and for women of childbearing age a pregnancy test. HBsAg should be checked because HBV reactivation during DAA therapy is recognised.
  4. Stage fibrosis without a FibroScan using blood-based scores. APRI (AST-to-platelet ratio index) above 1.0, or FIB-4 above 3.25, suggests cirrhosis; APRI below 0.5 and FIB-4 below 1.45 make cirrhosis unlikely. WHO endorses APRI and FIB-4 precisely for settings where elastography is scarce. Where FibroScan is accessible (major cities), a reading of 12.5 kPa or more indicates cirrhosis.

Genotyping is no longer required with pan-genotypic regimens, per WHO 2018 and 2022 guidance; that removes a costly step.

Treatment in primary care

Pan-genotypic regimens recommended by WHO, AASLD-IDSA and EASL, all available as DRAP-registered generics at low cost:

  • Sofosbuvir 400 mg plus daclatasvir 60 mg once daily for 12 weeks in non-cirrhotic adults; extend to 24 weeks in compensated cirrhosis (per WHO simplified approach).
  • Sofosbuvir plus velpatasvir once daily for 12 weeks treats both non-cirrhotic and compensated cirrhotic patients and is the simpler choice where the fixed-dose combination is stocked.
  • WHO 2022 guidance extends DAA treatment down to children aged 3 years and above with weight-adjusted formulations; treat adolescents 12 and over with adult regimens, and refer younger children to paediatric services.

Practical points:

  • Check drug interactions: amiodarone is contraindicated with sofosbuvir; rifampicin, carbamazepine and phenytoin reduce DAA levels; proton pump inhibitors blunt velpatasvir absorption (give with food, cap PPI dose).
  • Sofosbuvir regimens need caution when eGFR is below 30; refer renal patients.
  • No routine ribavirin in the simplified pathway; it belongs to specialist-managed decompensated disease.
  • Adherence counselling matters more than monitoring; mid-treatment PCR is unnecessary in the simplified WHO algorithm.

Test of cure: HCV RNA PCR 12 weeks after completing therapy (SVR12). Undetectable RNA at SVR12 is cure, with real-world rates above 95 percent for genotype 3 with these regimens.

Counsel at the start of treatment, not the end: the drugs must be taken daily without gaps, alcohol should stop, household members should be screened, and the patient must understand that cure does not confer immunity. Address injection-safety habits directly, since the same clinic that treats the infection often administered the injections that transmitted it; committing to oral medication over injectable therapy in your own practice is part of elimination.

Red flags: who to refer instead of treating

  • Decompensated cirrhosis: ascites, jaundice, variceal bleed, encephalopathy, albumin below 3.5, bilirubin above 2, platelets below 100,000 with stigmata.
  • APRI above 2.0 or clinical cirrhosis: treat only alongside a plan for variceal screening and HCC surveillance, ideally with a gastroenterologist.
  • HBV co-infection, HIV co-infection, pregnancy (defer DAAs until after delivery), eGFR below 30, prior DAA failure, and children under 12.

Follow-up schedule

  • Week 4: adherence and side-effect review (fatigue and headache are typical, serious events rare).
  • Week 12: treatment completion.
  • Week 24 from start (SVR12): PCR for cure.
  • Cured non-cirrhotic patients with normal ALT can be discharged with prevention advice; cured cirrhotic patients still need six-monthly ultrasound with or without AFP for HCC surveillance for life.
  • Reinfection is possible; counsel on injection safety and screen again if risk continues.

Because DAA courses fail mostly through lost follow-up, the MyPatient EHR recall list for week 4, week 12 and SVR12 visits quietly does the elimination work. Hand patients the patient guide to share so families understand testing and cure.

Key points

  • Antibody screens, PCR confirms; never treat on anti-HCV alone.
  • APRI and FIB-4 replace FibroScan for staging in most OPDs.
  • Sofosbuvir-daclatasvir or sofosbuvir-velpatasvir for 12 weeks cures over 95 percent without genotyping.
  • Check HBsAg, pregnancy status and drug interactions before starting.
  • SVR12 PCR is the test of cure; cirrhotic patients need lifelong HCC surveillance even after cure.
  • Refer decompensated, co-infected, renal-impaired and paediatric patients.

References

  • Guidelines for the Care and Treatment of Persons Diagnosed with Chronic Hepatitis C Virus Infection. World Health Organization, 2018.
  • Updated Recommendations on Treatment of Adolescents and Children with Chronic HCV Infection. World Health Organization, 2022.
  • HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. AASLD and IDSA, 2023.
  • EASL Recommendations on Treatment of Hepatitis C: Final Update. European Association for the Study of the Liver, 2020.
  • National Hepatitis Strategic Framework for Pakistan. Ministry of National Health Services, 2017.

Clinical judgement and local protocols take precedence.