The high incidence of chronic infection is a characteristic of the Hepatitis C virus, a member of the Flaviviridae family of parenterally transmitted hepatitis viruses. Most patients with an acute infection have no symptoms, but over two-thirds of those infected go on to acquire a chronic infection, which leads to significant morbidity and mortality. An estimated 180 million carriers and 4 million new cases of infection occur each year, giving it a 3% global prevalence. Chronic hepatitis can cause liver failure, which can then develop to liver cirrhosis. Patients with persistent HCV infection who have had cirrhosis for a long time may develop liver cancer.

HCV infected patients who develop chronic infection were previously treated by Pegylated Interferon alfa with or without Ribavirin. Sustained virological response to treatment regimens was measured as a reduction of HCV RNA to undetectable level by PCR when measured 6 months after completion of therapy. An early virological response which is reduction in HCV RNA to undetectable levels within first 12 weeks of therapy correlates well with sustained virological response as responses after this period is rare.[1,2]

Among the main causes of end-stage liver disease, hepatitis C virus (HCV) has a high propensity to develop to cirrhosis and hepatocellular carcinoma [3, 4, 5].Despite numerous efforts to determine the natural history and progression of HCV infection, a number of factors remain unclear, despite the fact that cofactors like alcohol consumption, age, gender, genotype/subtype, viral load, and mode of infection appear to be significant in the development of liver disease [6,7,8]. Understanding genotypes in chronic hepatitis C appears to be essential for determining which patients require more intensive treatment. In fact, genotypes 1 and 4 show more resistance as compared to genotypes 2 and 3 to pegylated- interferon (PEG-IFN) and ribavirin combination therapy and thus require different treatment duration and dose [9,10]

STUDY DESIGN: Prospective analytical study.

PLACE OF STUDY: Medical College and Hospital, Kolkata.

PERIOD OF STUDY: February 2020 to January 2021

STUDY SETTING AND TIME LINES:

Chronic HCV-infected patients at the Gastroenterology Department of Medical College, Kolkata were selected for the study after determining their HCV viral load and genotype. The department administered Sofosbuvir combination therapy, and the Microbiology Department monitored virological response by measuring HCV viral load at 6 weeks, 12 weeks, 6 months, and 9 months post-therapy.

INCLUSION CRITERIA:

Chronically HCV infected patients who have no contraindication for sofosbuvir combination therapy.

EXCLUSION CRITERIA:

• Acute HCV infection
• Co infection with other hepatitis virus
• Contraindication for sofosbuvir combination therapy like decompensated liver failure

SAMPLE SIZE: 70

Table 1: Association between Treatment Regimen: Genotype

Table 2: Distribution of mean Bilirubin, AST

Table 3: Distribution of mean ALT, ALP

Among the 70 patients studied, genotype 3 was the most prevalent (64.3%), followed by genotype 1a (25.7%), genotype 2 (5.7%), and genotype 1b (4.3%). The majority of patients (64.3%) received Sofosbuvir + Ledipasvir, with this regimen being most commonly used across genotypes 1a, 1b, 2, and 3. Sofosbuvir + Velpatasvir was predominantly used in genotype 3 (40%), while Sofosbuvir + Daclatasvir was administered to a smaller proportion of patients (7.1%), primarily among genotypes 1a, 1b, and 2. A statistically significant association was observed between HCV genotype and the treatment regimen received (P = 0.0112).

The study observed significant reductions in both serum bilirubin and AST levels across all HCV genotypes following DAA therapy. For genotype 1a, bilirubin levels decreased from a mean of 8.05 to 1.36 mg/dL, and AST levels from 55.22 to 41.39 U/L. In genotype 1b, bilirubin dropped from 8.47 to 1.33 mg/dL, and AST from 55.33 to 34 U/L. Genotype 2 showed a reduction in bilirubin from 8.65 to 1.58 mg/dL, and AST from 55.33 to 39.25 U/L. The most prevalent genotype, 3, demonstrated a decrease in bilirubin from 8.23 to 1.38 mg/dL, and AST from 55.62 to 39.24 U/L. All changes were statistically significant with p-values <0.0001, indicating a consistent biochemical improvement post-treatment across all genotypes.

Following DAA therapy, significant reductions were observed in ALT and ALP levels across all HCV genotypes. For genotype 1a, ALT decreased from a mean of 73.11 to 53.78 U/L and ALP from 163.67 to 120.06 U/L. In genotype 1b, ALT declined from 71.33 to 59.33 U/L and ALP from 161 to 114.67 U/L. Genotype 2 showed a notable drop in ALT from 81.5 to 48.75 U/L and ALP from 162.5 to 109.75 U/L. Genotype 3 patients demonstrated a reduction in ALT from 72.31 to 52.62 U/L and ALP from 164.78 to 120.78 U/L. All changes were statistically significant with p-values <0.0001, indicating consistent biochemical improvement in liver enzyme profiles post-treatment across all genotypes.

Following the determination of their HCV viral load and HCV genotype, individuals with chronic HCV infection who were enrolled at the Gastro Enterology Department of Medical College, Kolkata, were chosen for the study. The department of gastroenterology is responsible for administering the Sofosbuvir combination therapy, and the department of microbiology measured the HCV viral load at six, twelve, six, and nine weeks following medication in order to assess the virological response.

The present study demonstrates a genotype-specific distribution of HCV among the 70 patients, with genotype 3 being the most prevalent (64.3%), consistent with prior Indian epidemiological data where genotype 3 has been commonly reported as the dominant strain, particularly in northern and eastern regions of the country [11]. Genotype 1a accounted for 25.7%, followed by genotypes 2 (5.7%) and 1b (4.3%). This genotype distribution is aligned with findings by Sood and Malvankar (2010), who reported a similar predominance of genotype 3 (67.1%) in their cohort, followed by genotype 1 (23.7%) [12].

A statistically significant association was observed between the HCV genotype and the direct-acting antiviral (DAA) regimen administered (P = 0.0112). Sofosbuvir + Ledipasvir was the most frequently prescribed regimen (64.3%), showing broad usage across genotypes 1a, 1b, 2, and 3. Sofosbuvir + Velpatasvir was preferentially used in genotype 3 patients (40%), likely due to its pan-genotypic efficacy and favorable safety profile. Sofosbuvir + Daclatasvir, though used in a smaller proportion (7.1%), was predominantly administered to genotypes 1a, 1b, and 2. Similar treatment trends were noted in a study by Feld et al. (2015), who found Ledipasvir-Sofosbuvir to be particularly effective in genotypes 1 and 4, while Velpatasvir-based regimens showed consistent pan-genotypic activity [13].

Following DAA therapy, there was a significant biochemical improvement across all genotypes. The study observed substantial reductions in serum bilirubin, AST, ALT, and ALP levels, with all changes reaching statistical significance (p < 0.0001). For instance, genotype 1a patients demonstrated a reduction in bilirubin from 8.05 to 1.36 mg/dL and AST from 55.22 to 41.39 U/L. In genotype 3, bilirubin decreased from 8.23 to 1.38 mg/dL, and AST from 55.62 to 39.24 U/L. These findings are in concordance with the study by Asselah et al. (2016), which reported that DAA therapy leads to marked improvements in liver function tests and biochemical parameters, signifying hepatic recovery following viral clearance [14].

ALT and ALP levels also decreased significantly post-treatment, with genotype 3 showing a decline in ALT from 72.31 to 52.62 U/L and ALP from 164.78 to 120.78 U/L. These biochemical improvements indicate hepatic inflammation resolution and suggest the potential for long-term reversal of liver injury. Similar improvements in liver enzymes were noted by Welzel et al. (2016) in their multicenter cohort, underscoring the hepatic benefits of achieving sustained virological response (SVR) with DAAs across diverse HCV genotypes [15].

Overall, the findings underscore the effectiveness of genotype-specific and pan-genotypic DAA regimens in achieving not only virological clearance but also meaningful biochemical recovery, reflecting improved liver function across all HCV genotypes.

We conclude that the genotypic variability of Hepatitis C virus (HCV) significantly affects treatment outcomes with direct-acting antivirals (DAAs). Different HCV genotypes and subtypes exhibit distinct patterns of viral load reduction, with some, like genotype 3, showing lower response rates. Baseline viral load is another critical factor, with higher initial levels often linked to slower viral clearance and a need for longer treatment durations. Despite these challenges, DAAs have revolutionized HCV treatment, offering high rates of sustained virologic response (SVR) across diverse genotypes. Personalizing treatment based on genotype and viral load, along with considering host factors, is key to optimizing therapy and improving patient outcomes.

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