Symbolic representation of Hepatitis C eradication in Pakistan.

Curing Hepatitis C in Pakistan: How New Antiviral Drugs Offer Hope

Nico Varela in Health & Wellness November 2025 • 5 min read.

"A look at direct-acting antiviral agents (DAAs) and their impact on treating Hepatitis C virus (HCV) infection in Pakistan, where the disease burden is high."

Pakistan faces a significant challenge with hepatitis C virus (HCV) infection, ranking second-highest globally in terms of disease burden. This widespread chronic hepatitis has long been a major public health concern. Until recently, treatment options were limited to interferon-based combination therapy with ribavirin, a regimen known for its severe side effects and high failure rates against various HCV genotypes.

The landscape of HCV treatment has dramatically changed with the introduction of interferon-free, all-oral direct-acting antiviral agents (DAAs). These drugs, approved by the FDA, target different genotypes of HCV with remarkable efficiency. They have proven effective for a wide range of patients, including those who are newly diagnosed, those who have experienced treatment failure, those who have relapsed, and individuals with both compensated and decompensated cirrhosis.

However, the availability and use of DAAs remain limited in developing countries. In Pakistan, sofosbuvir (SOF), a uridine nucleotide analogue that inhibits the HCV-encoded NS5B polymerase, has become a widely accessible and utilized DAA. Daclatasvir has also recently been added to the list of available treatments. With documented results showing promise, there is growing optimism that HCV can be effectively cured in Pakistan, although certain concerns persist. This article reviews the effectiveness of DAAs and the current status of treatment against HCV genotype 3 infection in Pakistan, examining factors associated with sustained virological response (SVR), the limitations of current treatment regimens, and potential future implications.

DAAs: A New Era in Hepatitis C Treatment

Symbolic representation of Hepatitis C eradication in Pakistan.

Basic research into the structure and replicative cycle of HCV has driven the development of DAAs, boosting SVR rates from 40–50% to over 95%. First-generation DAAs targeting NS3/4A protease inhibitors (boceprevir and telaprevir) were approved in 2011. Triple therapy (PEG-IFN/RBV plus boceprevir or telaprevir) achieved SVR in 60–70% of patients with HCV genotype 1.

Revolutionary changes in HCV treatment have led to FDA approval of several second-generation DAAs:

Simeprevir (NS3/NS4A protease inhibitor): Effective for genotypes 1 and 4.
Sofosbuvir (NS5B inhibitor): Effective for genotypes 1, 2, 3, and 4 in treatment-naïve, treatment-experienced, compensated cirrhosis, and HCC patients.
Daclatasvir (NS5A inhibitor): Effective for genotypes 1, 2, 3, and 4.
Glacaprevir with pibrentasvir (NS3/NS4A protease and NS5A inhibitor): approved for all genotypes.
Sofosbuvir and daclatasvir (NS5B and NS5A inhibitor): approved for genotypes 1, 2, 3, and 4.
Sofosbuvir with velpatasvir (NS5B and NS5A inhibitor): approved for all genotypes with compensated and decompensated liver.
Sofosbuvir with ledipasvir (NS5B and NS5A inhibitor): approved for genotype 1 with renal impairment.
Elbasvir with grazoprevir (NS5A and NS3/NS4A protease inhibitor): approved for all genotypes and patients with severe renal impairment.
Ombitasvir with paritaprevir and ritonavir (NS5A, NS3/NS4A inhibitor and HIV antiretroviral drug): approved for genotype 1 and 4 patients coinfected with HIV.
Paritaprevir, ombitasvir, and dasabuvir with ritonavir (NS3/NS4A, NS5A, NS5B inhibitor with HIV antiretroviral drug): approved for genotype 1 patients coinfected with HIV.

SOF's introduction has been groundbreaking. In the liver, its phosphorylated form targets the NS5B polymerase active site, halting viral RNA replication. SVR rates have improved, reaching 100% for genotype 2 and 65–80% in genotype 3, for both treatment-naïve and treatment-experienced patients.

Looking Ahead: The Future of Hepatitis C Eradication in Pakistan

The use of SOF and RBV, with or without IFN, offers an efficacious and safe treatment option for CHC patients, particularly those with compensated liver disease. SOF's pan-genotypic activity, fewer adverse effects, minimal drug-drug interactions, high genetic barrier to resistance, and efficacy in patients with advanced liver disease, make it a beneficial option for treatment-naïve and treatment-experienced patients. Further studies are needed to understand associated host and viral factors, especially concerning difficult-to-treat viral variants in the Pakistani population. Triple therapy with SOF + DCV + RBV shows promise for relapsers of SOF + RBV combination, but multicenter studies are needed. Continued research and reports will improve outcomes and help eradicate HCV, addressing concerns like HCV-resistant variants, host genetic profiles, and co-infections.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3390/medicina54050080, Alternate LINK

Title: Current Status Of Direct Acting Antiviral Agents Against Hepatitis C Virus Infection In Pakistan

Subject: General Medicine

Journal: Medicina

Publisher: MDPI AG

Authors: Saba Khaliq, Syed Raza

Published: 2018-11-05

Everything You Need To Know

What are direct-acting antiviral agents (DAAs) and how have they changed Hepatitis C treatment in places like Pakistan?

Direct-acting antiviral agents (DAAs) represent a significant advancement in Hepatitis C treatment. They directly target the Hepatitis C virus (HCV) at various stages of its life cycle, disrupting its ability to replicate. Unlike older interferon-based treatments, DAAs are interferon-free, all-oral, and have fewer side effects. They have shown remarkable effectiveness against multiple HCV genotypes, leading to much higher cure rates and improved outcomes for a wide range of patients, including those with cirrhosis or treatment failure. This represents a paradigm shift in how Hepatitis C is managed, particularly in regions with high disease burdens.

How does Sofosbuvir (SOF) work to combat the Hepatitis C virus (HCV), and why is it considered a groundbreaking treatment?

Sofosbuvir (SOF) is a uridine nucleotide analogue that functions as an inhibitor of the HCV-encoded NS5B polymerase. It works by targeting the NS5B polymerase active site, which is crucial for viral RNA replication, effectively halting the virus's ability to multiply within the host. Sofosbuvir's pan-genotypic activity, along with its favorable safety profile, minimal drug-drug interactions and high barrier to resistance, makes it a cornerstone in Hepatitis C treatment regimens, particularly in resource-limited settings like Pakistan. Its introduction has significantly improved sustained virological response (SVR) rates and simplified treatment protocols.

What does achieving a sustained virological response (SVR) mean for someone with Hepatitis C, and what factors influence it?

Sustained virological response (SVR) in Hepatitis C treatment signifies the eradication of the virus from the body, essentially a 'cure.' SVR is achieved when the Hepatitis C virus is undetectable in a patient's blood for a sustained period, typically 12 or 24 weeks after completing treatment. Achieving SVR not only eliminates the virus but also prevents further liver damage, reduces the risk of liver cancer, and improves overall patient health and survival. Factors influencing SVR include the specific DAA regimen used, the patient's HCV genotype, the presence of cirrhosis, and adherence to the treatment plan. While DAAs have significantly increased SVR rates, ongoing research aims to optimize treatment strategies and address challenges like resistant viral variants.

What limitations still exist in Hepatitis C treatment despite the effectiveness of DAAs like Sofosbuvir and Daclatasvir?

While treatments like Sofosbuvir (SOF) and Daclatasvir have revolutionized Hepatitis C care, certain limitations and future challenges remain. One concern is the emergence of HCV-resistant variants, which may reduce the effectiveness of existing DAAs. Additionally, host genetic profiles and co-infections can influence treatment outcomes, necessitating personalized approaches. Although not explored here, access and affordability are significant barriers, particularly in developing countries. Future research needs to focus on understanding these factors, developing new DAAs to combat resistant strains, and improving access to treatment for all patients, ultimately aiming for the eradication of Hepatitis C.

Why are multiple direct-acting antiviral agents (DAAs) used in combination to treat Hepatitis C?

The use of multiple direct-acting antiviral agents (DAAs) like sofosbuvir, daclatasvir, ledipasvir, velpatasvir, and others in combination offers several advantages in treating Hepatitis C. These combinations often target different stages of the viral replication process, enhancing their overall efficacy and reducing the risk of resistance. For example, combining an NS5B inhibitor (like sofosbuvir) with an NS5A inhibitor (like daclatasvir or ledipasvir) can lead to higher sustained virological response (SVR) rates across various genotypes. This strategy allows for shorter treatment durations, improved tolerability, and simplified regimens, making Hepatitis C treatment more accessible and effective for a broader range of patients.