May 20, 2013

Recent Advances in the Treatment of Chronic Hepatitis C Threaten to Leave Some Parts of the World Behind

Journal of Viral Hepatitis

What About Us?

Recent Advances in the Treatment of Chronic Hepatitis C Threaten to Leave Some Parts of the World Behind

F. Ahmed

J Viral Hepat. 2013;20(5):367-368.

Directly acting antiviral (DAA) agents are currently revolutionizing the treatment of chronic hepatitis C infection. The first generation of these agents have significant limitations including cost issues that are of particular concern in the developing world and a lack of efficacy in genotype 3 patients. Both of these concerns are of particular relevance in Pakistan.

One cannot attend any major international liver conference over the past 1 year and not be struck by the vast array of new directly acting antiviral (DAA) agents currently in the pipeline. Telaprevir and boceprevir have already been licensed for use in Western countries. Although these and other agents will revolutionize the treatment of chronic hepatitis C, these advances threaten to leave some parts of the world, the developing world in particular, and a large proportion of the world's hepatitis C burden, behind.

Pakistan is a case in point. Recent epidemiological data suggest that 4.9% of the Pakistani populace is chronically infected with hepatitis C.[1] With an overall population estimated at 180 million, this translates into approximately 9 million hepatitis C patients. On a positive note, >65% of these infections are genotype 3. But many patients struggle to pay for the 6-month course of standard interferon-based therapy; some having to sell their jewellery, homes and livestock to do so. The fivefold price difference between standard and pegylated interferon is an insurmountable hurdle for many patients here, where health insurance does not exist and where the average person makes $650 per year. Owing to cost considerations and comparable efficacy, the Pakistan Society of Gastroenterology recommends that the first-line therapy for these genotype 3 patients be standard interferon and ribavirin. A genotype 3 predominance, however, may also have a downside given that recent studies have suggested the genotype 3 is associated with accelerated fibrosis progression.[2] This is particularly consequential in a developing country, like Pakistan, where no liver transplantation program exists and where most cirrhotics lack the resources to travel abroad for liver transplant.

Where will these new DAA agents fit into the picture here? The minority of patients who have genotype 1 and those with genotype 3 who do not respond to conventional therapy could be considered candidates for newer therapies. However, given that patients here often struggle to pay for interferon-based therapy, the ability to pay for a third additional agent seems unlikely at best. Even if money was not an issue, in Pakistan, at least, the applicability of the first generation of direct-acting antiviral agents that have hit the market would be limited at best. In contrast to their spectacular results in hepatitis genotype 1 patients, telaprevir and boceprivir have limited activity against genotype 3.[3] It is still unclear whether other agents in development will have the same genotype barriers seen with telaprevir and boceprevir. Preliminary data suggest good activity against genotype 3 of nucleoside polymerase inhibitors and cyclophilin inhibitors, but not non-nucleoside polymerase inhibitors.[4]

Are there lessons to be learnt here? First of all, it highlights the need in Pakistan and other parts of the developing world to focus on prevention. If we cannot afford to treat these infections, perhaps the wiser approach is to try and prevent them from occurring in the first place. The vast majority of hepatitis C infections in Pakistan occur because of unsafe injections.[5] This phenomenon has also been recognized in other parts of the developing world.[6] We need to do a better job in maximizing the outcomes from the existing interferon and ribavirin regimen. Finally, hepatologists in developing countries need to do a better job of leveraging their hepatitis C patient volumes into clinical trials and perhaps drug development that is more relevant to their unique clinical scenarios.

A scenario may develop where hepatitis C is largely eradicated from the developing world but exits in large pockets in developing countries. Given current patterns of human migration, however, increasing numbers of these hepatitis C patients could be projected to arrive on the shores of Europe and North America.[7] Chronic hepatitis C is a truly global problem and needs to be addressed as such. Furthermore, if the treatment of hepatitis C evolves into a multidrug antiviral combination[8] similar to that for HIV, it is not difficult to foresee struggles over patents and intellectual property rights analogous to those that occurred in Sub-Saharan Africa in the 1990s and the early part of this decade over HIV drugs.

From my perspective, sitting in my office in Karachi, Pakistan, the new directly acting antiviral agents represent an exciting leap forward in the field of hepatitis C virology but are not obviously clinically relevant to my practice. Issues relating to cost, access and applicability will affect hepatologists in the developing world, in particular, in the coming years. Further advances in this field need to take into account the global hepatitis C burden. Perhaps most importantly, a greater emphasis on prevention is needed. My colleagues and I need to do a better job of marketing our 9 million Pakistani hepatitis C patients to make them more attractive to drug companies involved in new drug development and international aid donors, as do hepatologists in other parts of the developing world. For now, I will have to be content with marvelling at the science behind these new discoveries and envy those hepatologists who have access to new tools in the fight against this global menace.

  1. Mohsin M, Qureshi H. The first prevalence report on hepatitis B and C in Pakistan. Pak J Gasroenterol 2011; 25(1): 5–7.

  2. Bochud PY, Cai T, Overbeck K et al. Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C. J Hepatol 2009; 51: 655– 666.

  3. Foster GR, Hézode C, Bronowicki JP et al. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not 3 infections. Gastroenterology 2011; 141(3): 881–889.

  4. Soriano V, Peters MG, Zeuzem S. New therapies for hepatitis C virus infection. Clin Infect Dis 2009; 48: 313–320.

  5. Jafri W, Subhan A. Hepatitis C in Pakistan: magnitude, genotype, disease characteristics and therapeutic response. Trop Gastroenterol 2008; 29(4): 194–201.

  6. Saleh DA, Shedl FM, AL-Kamary SS et al. Incidence and risk factors for community acquired hepatitis C infection from birth to 5 years of age in rural Egyptian children. Trans R Soc Trop Med Hyg 2010; 104: 357–363.

  7. Ahmed F, Foster GR. Global hepatitis, migration and its impact on western healthcare. Gut 2010; 59(8): 1009–1011.

  8. Gane EJ, Roberts SK, Stedman CAM et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomized, double-blind, placebo-controlled, dose-escalation trial. Lancet 2010; 376: 1467–1475.



  1. Great article!! However the citations are not linking correctly please can you fix this, so that the evidence is clear and can be referenced. Thank you, kind regards Penny

  2. I replaced the link to the references with the references themselves.