Comparative Study of Compliance between Sofosbuvir and Interferon in the Management of Viral Hepatitis at Tertiary Care Hospital of Gambat, Sindh, Pakistan

Introduction: Hepatitis can be defined as inflammation of the liver. Hepatitis may be acute or chronic. It is estimated that in 2017, approximately 15 million people suffered from Hepatitis in Pakistan suffering from hepatitis. 150–200 million people, or approximately ~3% of the world's population, are living with chronic Hepatitis C. Methodology: A descriptive cross-sectional study was conducted on 300 patients selected by purposive sampling who were reported with Hepatitis-C and co infection of Hepatitis-C + HepatitisB, at a tertiary care hospital Gambat. A series of questions were asked from reported patients regarding symptoms and compliance. Original Research Article Ali et al.; JPRI, 33(24A): 1-8, 2021; Article no.JPRI.66910 2 Results: The results were analyzed by using SPSS-22. Among the 300 patients some were on sofosbuvir (n=150, 50%), which the others were on interferon (n=150, 50%). The findings showed that most of the patients on interferon were non-compliant (n=125,83.3%), and only (n=25, 16.7%) are compliant. Among non-compliant factors, fear from injection was reported in (n=42, 33.6), technique for injection (n=38, 30.4%), prolong duration of action (n=35, 28%), adverse drug reaction (n=26, 20.8%). Better compliance was observed with sofosbuvir (n=93, 62.8%) and noncompliant were (57, 38%). Conclusion: This study concluded that better compliance was achieved with sofosbuvir as compared to interferon, rate of ADR’S were also less with sofosbuvir.


INTRODUCTION
Hepatitis can be defined as inflammation of the liver [1]. Hepatitis may be acute or chronic [2]. It is estimated that in 2017, approximately 15 million people suffered from Hepatitis in Pakistan suffering from hepatitis. 150-200 million people, or ~3% of the world's population, are living with chronic hepatitis C [3]. The cases of hepatitis c are also increasing in USA as well [4]. In 2014, approximately 19659 peoples died due to hepatitis C in America [5]. It is caused by the hepatitis C virus (HCV) [6]. The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years [7]. It can be transferred by intravenous administration of drugs, blood transfusion, Organ Transplant without HCV screening, Sexual/household exposure to anti-HCV-positive contact etc. Hepatitis-C can be treated by using interferon and antiviral agent [8][9]. Compliance can be defined as the degree to which a patient correctly follows medical advice [10]. Most commonly, it refers to medication or drug compliance, but it can also apply to other situations such as medical device use, self care, self-directed exercises, or therapy sessions [11]. Both the patient and the health-care provider affect compliance, and a positive physicianpatient relationship is the most important factor in improving compliance, although the high cost of prescription medication also plays a major role [12][13]. Non-compliance can be defined as failure or refusal to comply. In medicine, the term noncompliance is commonly used regarding a patient who does not take a prescribed medication or follow a prescribed course of treatment [14]. The primary factors affecting patient compliance fall into one of two groups: External influencers, or Patient experience [15]. External influencers are all the factors outside of a patient's control that have the potential to impact compliance. All the factors that contribute to a patient's experience using prescriptions are known as patient experience [16][17].
Hepatitis is a chronic and long-term disease, which is influencing the majority of population of Pakistan including Gambat and all over the world. Studies have shown already that onset of hepatitis drug requires prolonged treatment, the therapy may continue from 12-16 weeks sometimes 24 weeks time is needed to show its response. Patients who find the side effects of any hepatitis drug with increased symptoms causes discontinue his/her medicine without informing the prescriber. Some time when patients observed that symptoms are not reduced at initial dose may cause discontinuation of medicines. Sometimes initial dose of interferon may cause anemia, high fever, depression and nausea.
This study will provide best choice or option for the management of hepatitis C that which of the drug either sofosbuvir or interferon has fast and early onset of action to overcome the problem of hepatitis with low symptoms.

METHODOLOGY
This study was started by sitting in the hepatitis outdoor patients department and the patients who were suffering with the sign and symptoms of hepatitis C like, Fatigue, dark urine, pale stool, abdominal pain, loss of appetite, unexplained weight loss, yellow skin and eyes, which may be signs of jaundice etc. A predesigned questionnaire for clinical assessment of compliance and non-compliance of patients on sofosbuvir and interferon, during the management of hepatitis C was used to record patient's disease history, habits, medication regimen, complaints and necessary information. 300 patients having hepatitis C participated in the current study. All patients were randomly given Interferon and sofosbuvir. 150 patients were given sofosbuvir 400mg once a day, 150 patients were prescribed with Interferon alpha 2b, 300 million international units three times a week. Patients were asked, not to change their diet, exercise and medication routine during the study. Study patients were enrolled via purposive sampling (non-probability sampling). The total collected data was analyzed with the help of Statistical Package for Social Science (SSPS) software version 21 for interpreting the data.

Inclusion Criteria
Patients were selected from the ages of 25-65 years, Patients having co infection of HCV and HBV were included in the study, Patients having co infection of HCV and HIV were included in the study, only those patients were included, who were either on interferon or on sofosbuvir.

Exclusion Criteria
Children were not included in the study, Study was not only comprising on same gender of patients, Patients whose age was less than 25 years were not included in the study, and patients whose age more than 65 years were excluded from the study. Hepatitis patients who were on drugs other than sofosbuvir or Interferons were not included in study.

RESULTS
In Table 1, occupational status of study subjects is described in which indoor job holders were high 101(33.7%).
In Table 2, distribution of hepatitis C and co infection patients were described, which shows that out of 300 study subjects 281 (93.4%) study subjects were suffering from hepatitis c only, 13 (4.3%) patients were of HCV+HBV and 07 (2.3%) study subjects were of HCV+HIV.
In Table 3, management of hepatitis C was described, which shows that out of 300 patients 150 (50%) were on interferons and 150 (50%) were on sofosbuvir.
In Table 4, distribution of gender of patients who were on interferon was described, which shows that out of 150 patients 90 (64.7%) were male and 53 (53.7%) were females. Among study subjects who were on interferon male patients were more as compared to female.
In Table 5, compliance and non-compliance among study subjects who were on interferon was described, which shows that out of 150 patients 125 (83.3%) study subjects were non compliant with interferon where as 25 (16.7%) study subjects were compliant with interferon. This study shows that majority of study subjects were non-compliant with interferon. In Table 6, non-compliant factor fear from injection was dominant, which shows that out of 125 non-compliant study subjects 42 (33.6%) study subjects were non compliant because having fear from injection.
In Table 7, non-compliant factor duration of therapy among non compliant study subjects was described, which shows that out of 125 non compliant study subjects 35 (28%) patients were non compliant due to prolong therapy of interferon.
In Table 8, non-compliant factor technique by which interferon was injected among non compliant study subjects who were on interferon was described, which shows that out of 125 non compliant study subjects 38 (30.4%) study subjects were non compliant with interferon due to technique of injection.
In Table 9, non-compliant factor adverse drug reaction which were reported among non compliant study subjects who were on interferon was described, which shows that out of 125 non compliant study subjects 26 (20.8%) study subjects were non compliant with interferon due to appearance of adverse drug reactions.
In Table 10, distribution of gender of patients who were on sofosbuvir was described, which shows that out of 150 patients 95 (63.4%) were male and 55 (36.7%) were females. Among study subjects who were on sofosbuvir male patients were more as compared to female.
In Table 11, compliance and noncompliance among study subjects who were on sofosbuvir was described, which shows that out of 150 patients 57 (38%) study subjects were noncompliant with sofosbuvir where as 93 (62%) study subjects were compliant with sofosbuvir. This study shows that majority of study subjects were compliant with sofosbuvir.
In Table 12, non-compliant factor taste of sofosbuvir was described, which shows that out of 57 non compliant study subjects 32 (56.2%) study subjects were non compliant because taste of sofosbuvir. In Table 13, non-compliant factor adverse drug reaction of sofosbuvir was described, which shows that out of 57 non-compliant study subjects 12 (21.1%) study subjects were non compliant adverse drug reaction of sofosbuvir. In Table 14, non-compliant factor prolong duration of therapy with sofosbuvir was described, which shows that out of 57 noncompliant study subjects 24 (42.1%) study subjects were non compliant due to prolong duration of therapy with sofosbuvir.
In Table 15, comparison of compliance and noncompliance was described. In this study, patients were more compliant with sofosbuvir as compared to interferon.
In Table 16, statistical analysis of compliance with gender of those patients who were on interferon was done. On applying Chi-Square Test result shows both variables are independent on each other.
In The study concluded that an increased SVR results were observed in a large proportion of patients with Hepatitis C Virus with Pegylated interferon. The researchers has observed that the two forms of PEG-IFN have been proved to be a key element in creating a competition resulting in lower prices. Thus, a careful analysis must be made when trying to decide which PEG-IFN provides best results, and in our opinion, the debate is still ongoing to manage the HCV patient in a better way so that the patient get maximum efficacy, less toxicity and it must be cost effective or available in reasonable price [18]. Our study providing insight that sofosbuvir is best choice to treat patients who are suffering from chronic as well as acute hepatitis C has better patients acceptability for infections of hepatitis C plus hepatitis b, because in the current study which compared interferon and sofosbuvir, it was observed that sofosbuvir got more compliance among study subjects than interferon with less adverse drug reactions were reported with sofosbuvir as compared with interferon. Vincent Leroy et al, 2016, conducted a study to assess the response of oral anti viral agents such as daclatasvir along with sofosbuvir and ribavirin, they concluded that the oral antivirals were well tolerated and their  [19]. There study is similar to current study because current study also proves that the sofosbuvir is well tolerated their compliance rate is more than interferons and less adverse drug effects reported with sofosbuvir hence it could be safe as well.
Surakit Pungpapong et al, 2015, a multicenter study for the assessment of effectiveness, tolerance and safety profile of Sofosbuvir was conducted along with or without ribavirin in the management of hepatitis C genotype 1 virus, after liver transplantation, they summarized their findings which was conducted on multiple centers as all-oral without interferon or interferon free antiviral regimen using simeprevir and sofosbuvir along with or without RBV for 12 weeks. They were very well tolerated and resulted in excellent SVR12 rates in LT recipients who were diagnosed with HCV genotype 1 infection [20]. As compared to above studies in the current study the safety and compliance of 300 patients were assessed and divided into two groups of 150 patients. Sofosbuvir is appears to be safe as compared to interferon and compliance rate of sofosbuvir was more than interferon. However, a more elaborate my study revealed the extent of the findings.
Younossi et al 2016, conducted a study to assess the adherence to treatment of chronic hepatitis c with different interferon and interferon free anti HCV regimen [21]. Their findings were similar with the current study because in that study patients who were on interferon therapy their adherence and compliance score was smaller as compared with sofosbuvir based therapy, similarly in current study rate of compliance was better achieved with sofosbuvir.

CONCLUSION
It was revealed that out of 300 study subjects, 100 patients were doing indoor job, 70 were outdoor job, 43 jobless and 86 house wives. Out of 300 patients, 280 patients were having hepatitis C virus infection only, 13 Hepatitis C+B and 7 have HCV+HIV. The compliance rate among study subjects was better with sofosbuvir i.e. 62% as compared to interferon alpha 2b where the rate of compliance among study subjects was only 16.7%. This study concluded that compliance rate of sofosbuvir was 45.3% more than interferon and 26% less adverse drug reaction reported with sofosbuvir, means sofosbuvir is safer than interferon.

CONSENT
As per international standard or university standard, patients' written consent has been collected and preserved by the author(s).

ETHICAL APPROVAL
As per international standard or university standard written ethical approval has been collected and preserved by the author(s).