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Umar et al. Hepatoma Res 2018;4:71 I http://dx.doi.org/10.20517/2394-5079.2018.31 Page 5 of 7

DISCUSSION
The availability of direct acting antivirals (DAAs) has really revolutionized the HCV treatment but their
high prices has always been an element of criticism and efforts were being made to provide patients,
[8]
especially in low income countries to get the drugs at cheap rates . Allowing generics in about 101
[9]
developing countries is one such strategy that has led to drastic decline in the prices of DAAs . But the
efficacy and safety of these generics is a big concern that needs scientific evaluation.

The findings of our study are reasonably good and quite comparable with the international data. ALLY 3+
one of the leading study evaluating the sofosbuvir and daclatasvir in genotype 3 patients showed a SVR12
of 90% (45/50) whereas in our study it is 83.33%. Similarly SVR12 in cirrhotics is 86% and treatment
[5]
experienced is 87% which in comparison with our study are 81.25% and 80% respectively . Another study
using the same combination in genotype 3 patients in a real world cohort exhibit an overall SVR12 of 88%,
[10]
in treatment naïve patients 92%, treatment experienced 84%, and cirrhotics 89% respectively .

A study from Iran also evaluated the results of generic sofosbuvir and daclatasvir in genotype 3 patients
but their results are far superior with SVR12 of 98% (40/41). Furthermore they only include cirrhotic
[11]
patients in their study and the price of generic drug is about $1,890 for a 12 week course . Our results for
cirrhotic patients are 81.25% but the cost is only $75. Several factors can be responsible for this difference
in results including the bioequivalence of generics as compared to the branded drugs, compliance, study
population and possible underlying drug resistance. For the generics it is mandatory to prove their
[11]
bioequivalence to meet WHO prequalification standards . About five different generics from Egypt
and India when compared with their originator drug (sofosbuvir or daclatasvir) proved to have similar
[12]
pharmacokinetics . However this difference is due to drug quality, underlying resistance or is purely
epidemiological, needs further probing.

The safety profile of these generic drugs is also comparable with the international data. In ALLY 3+ study
fatigue and insomnia were the major side effects. In our study apart from these major side effects patient
also complained of itching and oral ulcers. A study from Egypt using generic sofosbuvir and daclatasvir
[12]
has described itching as side effect in up to 9.8% of the patients . Oral ulcers are not a common side
effect of new DAAs. However in one of our old study regarding sofosbuvir they were present in 0.7% of
[13]
the patients , but with this combination rate of oral ulcers was 8.8%. One patient developed intractable
ulcers that didn’t respond to any supportive therapy and improved only after completion of treatment.

Only one patient was unable to tolerate the treatment and left it after 2-3 days because of worsening
decompensation. Patient was already a child class B patient with minimal ascites. After treatment patient’s
ascites worsened and patient developed encephalopathy. The complications were managed medically but
the treatment discontinued. This acute response can be due to some drug related liver injury (DILI) and a
[14]
few case reports are available in literature describing DILI in patients using sofosbuvir .
In total 6 patients were ribavirin eligible, and amongst them 2 patients developed ribavirin associated
hemolysis due to which they were shifted to sofosbuvir and daclatasvir regimen and duration extended to
6 months. Both these patients successfully eradicated the virus.

Out of 30 patients whose SVR were checked 5 patients were unable to eradicate the virus [Table 1]. Four
out of these 5 patients were males; a finding consistent with one of our previous study based on sofosbuvir
[13]
and Rabavirin . Similarly 4 out of 5 patients were treatment naïve and 1 was Interferon relapser. Our
study lacks evaluation to determine the risk factors for poor outcome. Further studies should be carried
out to determine the underlined genetic mutations for drug resistance as well as other factors like obesity
and diabetes. Our study has less number of patients with follow-up PCR at 12 weeks post treatment to
check SVR as compared to the total number of patients enrolled. This lack of follow-up is mainly due