HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

BACKGROUND: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. METHODS: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. CONCLUSION: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. STUDY REGISTRATION: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Association of Metabolic Dysfunction-Associated Steatotic Liver Disease/Non-alcoholic Fatty Liver Disease With Type 2 Diabetes Mellitus: A Case-Control Study in a Tertiary Care Hospital in Pakistan.

Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels, insulin resistance, and relative insulin deficiency. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the term used to describe fatty liver (steatosis) in individuals without a history of significant alcohol intake. MASLD is progressively known as the leading cause of chronic liver disease. Dietary factors, a significant risk factor for developing T2DM and cardiovascular disease, also contribute to MASLD development. The risk of developing MASLD increases with age, particularly in patients with diabetes mellitus. This risk is notably elevated among South Asians due to their higher incidence of insulin resistance and metabolic syndrome. Importantly, MASLD is acknowledged as a component of the metabolic syndrome, with insulin resistance playing a central role in its development. Objective To determine the association between MASLD and T2DM in patients presenting at a tertiary care hospital in Pakistan. Methodology This case-control study was conducted for one year in a tertiary care hospital in Gujranwala, Pakistan. A total of 380 patients were enrolled through convenient sampling and were analyzed according to two groups: those with diabetes (case) and those without diabetes (control). All participants were assessed for serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and underwent abdominal ultrasound to determine hepatic fibrosis. A diagnosis of MASLD was made only in the presence of hepatic steatosis with AST and ALT values of more than 40 IU. The odds ratio (OR) was calculated, and stratified analysis was conducted according to gender, age, and BMI. A p-value of ≤0.05 was considered statistically significant. Results In our study, 55.53% of patients were male, while 44.47% were female. The average BMI (±SD) of the patients was 23.66±3.08 kg/m2. Among the cases group, the MASLD was noted in 91 (47.9%) patients, while among the controls group, the MASLD was noted in 64 (33.7%) patients with a statistically significant OR of 1.810 (1.19-2.74). Conclusion In conclusion, MASLD is significantly associated with T2DM, regardless of gender and BMI of patients. We recommend screening T2DM patients for the presence of MASLD at regular intervals to prevent hazardous consequences of MASLD in adult populations, particularly those with features of metabolic syndrome. Further larger-scale studies investigating the impact of T2DM on MASLD are required to reduce morbidity and decrease disease burden, especially in prevalent areas.