Hepatitis C in Pakistan: the one condition where we are ahead

Almost every clinical guide written for Pakistan ends with some version of the same sentence: the drug the international guideline assumes is not available here. Hepatitis C is the exception, and it is worth dwelling on.

Pakistan has the largest hepatitis C burden in the world — around 9.8 million people, a prevalence of 7.5%, and roughly 37,000 deaths a year from hepatitis B and C combined. And the generic drugs available here cure it about 98% of the time.

The numbers that reframe it

Pakistani real-world series report sustained virological response at 12 weeks of 98.5% for sofosbuvir plus daclatasvir in genotype 3, and around 94–95% across large cohorts on sofosbuvir/daclatasvir or sofosbuvir/velpatasvir. Those are cure rates matching any high-income health system, achieved with generics.

The contrast worth acting on: in one head-to-head series, sofosbuvir plus daclatasvir gave 98.5% against 75% for sofosbuvir plus ribavirin. If you still have patients on ribavirin-based regimens outside the specific indications for them, that 23-point gap is the argument for changing.

Genotype 3 country

Genotype 3 accounts for 72.73% of Pakistani infections, with subtype 3a alone at 60%. Genotype 1 is 9.75%. Much international guidance was written against a genotype 1 background, which is worth remembering when reading regimen tables from elsewhere.

One exception is easy to miss: in end-stage renal disease and post-renal-transplant patients, genotype 1 predominates rather than genotype 3.

You do not need a biopsy

The national consensus guideline — produced jointly by the Pakistan Society of Gastroenterology & GI Endoscopy, the Pakistan Society of Hepatology and the Society of Therapeutic Endoscopy Pakistan — states it plainly:

Liver biopsy is not required. For the purpose of this guidance, a patient is presumed to have cirrhosis if they have a FIB-4 score >3.25 or any of the following findings from a previously performed test.

Those other findings: FibroScan stiffness above 12.5 kPa, non-invasive serologic tests above their cut-offs, clinical evidence such as liver nodularity or splenomegaly on imaging or a platelet count below 150,000/mm³, or a prior biopsy showing cirrhosis.

And for the setting most Pakistani doctors actually work in, the guideline says this out loud:

In resource limited regions and in places where fibroscan is not available scores such as FIB-4, APRI or RFI can be used.

FIB-4 = (age × AST) ÷ (platelets × √ALT). Age in years, AST and ALT in U/L, platelets in ×10⁹/L. Four numbers you already have. Above 3.25, presume cirrhosis and calculate a Child-Pugh score — a CTP of 7 or more means decompensated, which changes both the regimen and where the patient should be treated.

The programme is designed for you, not for hepatologists

The Prime Minister's Programme for the Elimination of Hepatitis C aims to screen 50% of the over-12 population in phase one — about 82.5 million people — treat half of those infected by 2027, and meet WHO elimination targets by 2030, with the federal government funding half the cost.

The detail that matters clinically: national treatment guidance under the programme is deliberately simplified to fewer than two clinic visits during treatment, with care deliverable by non-specialists. That is not a compromise. Reaching 9.8 million people through liver units is arithmetically impossible, so the pathway was built to be delivered by medical officers.

Three interactions that matter more here than anywhere

Rifampicin. The guideline states sofosbuvir should not be given with known P-gp inducers — rifampicin, carbamazepine, phenobarbital, phenytoin. Pakistan has both the world's highest hepatitis C burden and one of the highest tuberculosis burdens, so this combination arrives in clinic regularly rather than theoretically. Rifampicin lowers sofosbuvir concentrations enough to risk an ineffective course: twelve weeks of treatment wasted, and resistance risked.

Proton pump inhibitors. Velpatasvir solubility falls as gastric pH rises, so for most patients on sofosbuvir/velpatasvir, PPIs should be avoided. PPIs are heavily prescribed here and available without prescription, so many patients are taking one without thinking of it as medication. If a PPI is genuinely necessary, give sofosbuvir/velpatasvir with food, four hours before the PPI, at no more than an omeprazole 20 mg equivalent.

Amiodarone. Sofosbuvir-based regimens are contraindicated because of the risk of life-threatening arrhythmias. If there is no pacemaker in situ, wait three months after stopping amiodarone before starting.

All three are reasons the guideline asks for a full drug history "including all prescribed medications, over-the-counter drugs, herbal and vitamin preparations." In a country where most drug classes are obtainable without a prescription, that instruction is doing real work.

What the guideline recommends but you cannot get

The document does something unusual and useful — it marks certain regimens "RECOMMENDED BUT NOT AVAILABLE IN PAKISTAN."

The main casualty is glecaprevir plus pibrentasvir, the 8-week course, listed for adolescents and in weight-banded doses for children aged 3–11, and named as preferred for genotype 1b in renal impairment. It is not obtainable here. The practical consequence: the 8-week option is off the table, and 12-week sofosbuvir-based regimens are what you will actually prescribe.

This is the same guideline that explains its own design principle — that patients here "are unable to gain access to the latest DAAs at the pace, as they are available globally," so it weighs "efficacy of the drugs as well as their availability." A guideline that recommends what you cannot buy is not a guideline.

Groups worth knowing about

Children. DAAs can be offered to all HCV-infected children aged 3 and over, irrespective of disease severity, with weight-banded sofosbuvir/velpatasvir for 12 weeks. And all siblings born to the same mother should be screened, and offered hepatitis B and A vaccination.

Pregnancy. Treatment is not recommended during pregnancy or within six months before conception. Women of childbearing age need precautions during therapy, and an accidental conception on treatment needs a three-way discussion between patient, hepatologist and obstetrician.

Renal impairment. Patients with CKD, including those on haemodialysis, follow standard DAA recommendations without dose adjustment — though eGFR below 30 or dialysis means treatment at a specialised centre with a multidisciplinary team.

Hepatitis B co-infection. Treat the hepatitis C as standard and test for HIV too. A patient who is HBsAg-positive but only needs HCV therapy should have a nucleoside/nucleotide analogue as prophylaxis during treatment and for at least 12 weeks after, with monthly monitoring for reactivation once it stops. HBsAg-negative but anti-HBc positive needs monthly ALT monitoring.

Bottom line

Screen widely, because there are 9.8 million people and the programme is built to find them. Stage with FIB-4 rather than waiting for a FibroScan you may not have, and never for a biopsy you do not need. Take a real drug history and ask specifically about TB treatment, omeprazole and anything bought at a pharmacy counter. Do not plan around an 8-week regimen you cannot obtain. And tell the patient the truth, which is unusually good news: the generic tablets will almost certainly cure them.

Our hepatitis C pathway includes a working FIB-4 calculator at the guideline's own 3.25 threshold and an interaction checker that separates the hard blocks from the manageable ones. Also in the section: hypertension, type 2 diabetes, community-acquired pneumonia and urinary tract infection.

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