1. Effectiveness of Sofosbuvir in terms of sustained virological response at 12 weeks after treatment (SVR12) BETWEEN treatment naïve AND treatment experienced , genotype 3 infected Hepatitis C patients.
DR SADIA AHMED
POST GRADUATE TRAINEE GASTROENTEROLOGY, HFH.
SUPERVISOR: PROFESSOR MUHAMMAD UMAR
PRINCIPAL RMC AND HEAD OF DEPARTMENT MEDICINE AND GASTROENTEROLOGY, HFH

2. INTRODUCTION
HCV is a leading cause of chronic liver disease worldwide, affecting approximately 3% of population (170 million)(1,4,6) and leads to decompensated cirrhosis and hepatocellular carcinoma in many cases.
Pakistan ranks second where approximately 10 million people are affected(2).
Genotype 3 is the most treatment-resistant, and aggressive of all the types. It tends to progress more rapidly to fibrosis and cirrhosis and have a higher incidence of development of HCC.
Sofosbuvir is a recently approved nucleotide analog, which is a highly potent inhibitor of the NS5B polymerase in all genotypes of Hepatitis C virus (HCV), therefore prevents its replication.
It offers many advantages including high potency, low side effects, high barrier to resistance and oral administration therefore improving compliance and limiting the number of hospital visits as in case of IFN based regimes.

3. Response to treatment is determined in terms of SVR at 12 weeks after completion of treatment.
Patients who achieve SVR are considered cured of HCV infection.

4. RATIONALE
This study is going to be the first of its kind to assess the effectiveness of sofosbuvir therapy in pakistani population as well as make comparative analysis of its effectiveness based on SVR between first time treated (naïve) vs previously IFN treated pakistani population.

5. OBJECTIVE
To compare SVR, 12 weeks post treatment, between treatment naïve and treatment experienced, genotype 3 infected Hepatitis C patients , receiving sofosbuvir. Hypothesis: The proportion of patients with positive SVR will not be same in treatment naïve group as compared to those who had previously received interferon.

6. MATERIALS AND METHODS Study Design: Comparative cross sectional study.
Study setting:
Study will be conducted at CENTRE FOR LIVER AND DIGESTIVE DISEASES Holy Family Hospital Rawalpindi.
Duration of study: 06 months after acceptance of synopsis.

7. Sample size: Keeping the level of confidence as 95%, power of study as 80%, expected proportion of SVR in treatment naïve group as 93% and expected proportion of SVR in patients with exposure to Interferon treatment previously as 77%, the minimally required sample size was calculated through WHO sample size calculator as 61 in each group. A total of 122 patients will be included.
Sample technique: Simple random sampling technique using random number list generated through SPSS.

8. Inclusion criteria:
Study Group A (Treatment Naïve group): All patients of HCV Genotype 3, of ages from years, who had completed sofosbuvir treatment of 6 months duration, exactly 3 months back. These patients had not received interferon therapy prior to treatment regime of Sofosbuvir.
Study Group B (treatment experienced group): All patients of HCV Genotype 3, of ages from years, who had completed sofosbuvir treatment of 6 months duration, exactly 3 months prior. These patients had previously received interferon therapy prior to treatment regime of Sofosbuvir, but either relapsed or not responded to it.
Exclusion criteria:
Concomitant infection with HBV or HIV
Patients who were not completely compliant to sofosbuvir treatment or discontinued it due to adverse effects or any other reason.
HCC

9. Data collection procedure:
After approval from Institutional Research Forum of RMC, the registry of patients who completed Sofosbuvir treatment 3 months back will be accessed.
From the list, 122 patients who fulfill the selection criteria for each study group will be randomly selected and contacted, and will be included in study after written informed consent.
PCR of each patient will be performed by standardized laboratory and the patients with negative PCR will be labeled as SVR positive and those who will have positive PCR, will be labeled as SVR negative.
The data will be entered in a structured proforma.

10. Plan for Data Analysis :
All the data will be entered and analyzed using SPSS version 19.
For all the categorical variables frequencies along with percentage will be calculated.
For continuous variables like age, time since last treatment etc, means along with standard deviations will be calculated.
To compare the proportion of patients who have attained SVR in both study groups, pearson’s chi square test at 5% level of significance will be applied. P value less than 0.05 will be considered statistically significant.
To control Effect Modifiers like gender and age, stratified analysis will also be performed.

11. PROFORMA
Effectiveness of sofosbuvir in terms of SVR in treatment naïve patients vs those who have already been treated with peg interferon in HCV genotype 3.
SERIAL NO: MR NO:
NAME:
AGE: GENDER:
ADDRESS:
ENCIRCLE APPROPRIATE OPTION
TREATMENT GROUP : GROUP A GROUP B
If group B RELAPSERS OR NON RESPONDERS:
SVR (HCV PCR AFTER 12 WEEKS OF Rx) :
POSITIVE NEGATIVE

12. THANK YOU.