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Page 2 of 7 Umar et al. Hepatoma Res 2018;4:71 I http://dx.doi.org/10.20517/2394-5079.2018.31

83.33% (25/30) amongst which treatment Naïve had a response rate of 84% (21/25), treatment experience 80%
(4/5), non-cirrhotics 85.71% (12/14), cirrhotics 81.25% (13/16) and decompensated chronic liver disease patients
have a SVR12 of about 83.33% (10/12) respectively. The combination was well tolerated with few side effects,
18.6% patients had itching, 10.8% had insomnia, 8.8% had oral ulcers and 6.9% had fatigue.

Conclusion: Generic sofosbuvir and daclatasvir are cheap, safe and efficacious with a SVR12 of about 83.33%
amongst genotype 3 patients. These generics will act as a pivot in the eradication of hepatitis C infection from
developing world.

Keywords: Daclatasvir, sofosbuvir, genotype 3, hepatitis C

INTRODUCTION
Eighty million people are suffering from hepatitis C globally having six known genotypes with different
distribution throughout the world. Amongst the countries with highest hepatitis prevalence, Pakistan
[1]
ranks number 2, with the prevalence rate of 6.7% and the most commonly detected genotype is 3 . Before
the availability of direct acting antivirals (DAAs), patients were treated with interferon and ribavirin with
sustained virologic response (SVR) of as low as 50% using conventional interferon and 57.6% using pegylated
[2]
interefron in Pakistani population . The advent of DAAs undoubtedly revolutionized the treatment both in
[3]
terms of safety and efficacy however genotype 3 is still thought to be difficult to treat genotype .
After approval from FDA in 2013, sofosbuvir a NS5B inhibitor was the leading DAA followed by daclatasvir
which is a NS5A inhibitor. The patent price for sofosbuvir is US$84,000 and daclatasvir is US$63,000, for a
[4]
12 week course . According to ALLY 3+ trial the combination of sofosbuvir and daclatasvir in genotype 3
patients is safe and efficacious with a SVR12 of 92% in treatment naïve and 89% in treatment experienced
[5]
patients respectively . The combination has minimal drug-drug interactions and has safely been tried in
[6]
patients with liver transplant, renal transplant and HIV co-infected patients as well .
[7]
With Pakistan being a developing nation with a population of 29.5% living below poverty line , the price
of DAAs is a major issue. With the availability of generics, a combination of sofosbuvir and daclatasvir
costs as low as US$75 for a 12 week course that makes it affordable for the majority of patients in the
country. Scarce data are available to determine the safety and efficacy of these low price generic drugs.
Our study is one such effort to establish the efficacy and safety of these generics in Pakistani population.

METHODS
This open-label, non-randomized, uncontrolled study was carried out at Centre for Liver and Digestive
Diseases, Holyfamily Hospital, Rawalpindi. Holyfamily Hospital is one of the largest tertiary care
hospitals that drain not only local population but also patients from northern Punjab, Azad Kashmir and
Khyber Pakhtunkhwa provinces. Our Centre is one of the largest gastroenterology centres of the country
with well-established liver clinics. Formal approval was conducted from the ethical review board of
Rawalpindi Medical University.

Eligible patients from March 2016 through March 2018 who were 18 years or older having chronic
hepatitis C infection with detectable polymerase chain reaction (PCR), regardless of whether they were
treatment naïve or have experienced Interferon in the past were enrolled in the study. Their cirrhosis
status was determined using non-invasive measures like Fibroscan, ultrasound and child class before
5
starting therapy. A high viral load was considered if the pretreatment PCR was ≥ 8 × 10 IU whereas a low
5
viral load was considered if PCR was < 8 × 10 IU. Patients who were of genotype other than 3, pregnant,
breast feeding mothers or having active renal disease with GRF < 30 were excluded from the study.