Raina Das

Hepatitis C Virus (HCV), particularly genotype 3 (GT-3), is highly prevalent in India and is associated with faster progression to cirrhosis, hepatocellular carcinoma, and higher treatment failure rates. Although Direct-Acting Antivirals (DAAs) have revolutionized HCV therapy, 5–10% of patients fail to achieve sustained virological response (SVR). This proteomic study aimed to identify changes in the proteomic profile before and after treatment of both responders and non-responders to HCV treatment. Paired plasma samples from HCV GT-3 infected patients were collected before and 12 weeks after initiating DAAs treatment, along with healthy controls. Quantitative proteomic analysis was performed on the paired samples. Differentially expressed proteins (DEPs) were identified and subjected to functional analysis including gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network analysis. GSEA revealed enrichment in extracellular matrix organization and innate immune pathways. Expression patterns of candidate proteins selected based on fold change and false discovery rate (FDR) criteria were further evaluated in an independent cohort. Western blot confirmed key expression trends of candidate proteins. Proteins linked to extracellular matrix remodeling and angiogenesis showed differential expression patterns. Successful validation of these candidate proteins in large independent cohorts holds potential to predict therapeutic outcomes.

Background: Manipur, a north-eastern state of India, has a high incidence of intravenous drug use with an equally high prevalence of Hepatitis C virus (HCV) infection. Objectives: This cross-sectional study aimed to evaluate the impact of certain risk factors enhancing the susceptibility of acquiring HCV. Design: A total of 1008 participants from various risk groups, from nine districts across the state, were enrolled. Blood samples along with demographic data were collected from the study participants. Methods: HCV RNA was isolated and nested RT-PCR was performed followed by Sanger sequencing for genotyping. Phylogenetic and phylogeographic studies were further conducted. Results: Of the total, 493 (48.90%) samples were HCV sero-reactive. Among the sero-reactive samples, 406 (82.35%) were HCV RNA positive. In case of the subgroup PWID + HIV, sero-reactivity (82.22%) and viremia (90.54%) were observed to be exceptionally high. It was noted that HCV sero-reactivity increased four times in people living with HIV (PLHIV) who continued to inject drugs. Three HCV genotypes and eight subtypes were circulating in this study population. Conclusion: In PLHIV who continued to inject drugs, HCV sero-reactivity increased four-fold. About 40% of the population living with HCV belonged to genotype 6, while genotype 1 showed a noticeable decline. Phylogeographic analyses and spatiotemporal reconstructions revealed that most of the subtypes migrated from far south-east Asian countries like Thailand, Malaysia, Myanmar, and Singapore.

Hepatitis C virus (HCV) infection increases the risk of mortality and morbidity among chronic kidney disease (CKD) patients. However, the advancement of HCV treatment has made this viral infection curable. Thus, the main objective of this study was to comprehend the HCV genotype (GT) distribution and the efficacy of direct-acting antivirals (DAAs) among CKD patients in West Bengal. Over five years (January 2017 to December 2021), 310 HCV sero-reactive patients were enrolled in this observational prospective study. HCV RNA was quantified using qRT-PCR. The partial amplification of the core (405 bp) and NS5B (389 bp) region was performed by nested RT-PCR followed by Sanger sequencing for HCV genotype analysis using the NCBI genotyping tool. The phylogenetic tree was constructed using the MEGA-X tool. The occurrence of HCV RNA positivity was 50.64% (n = 157), and of these 157 patients, 141 (89.81%) completed the DAAs treatment. The most important observation of the study was the prevalence of uncommon HCV genotype GT-1c (67.52%) followed by 1a, 4a, 3a, 1b, and 3b among CKD patients. The overall DAAs efficacy between January 2017 and December 2018 was ~ 97%, and in January 2019 and December 2021, ~ 95% among CKD patients. At the same time, in these two phases, DAAs efficacy among GT-1c-infected CKD patients was ˜ 96% and ˜ 93%, respectively. The prevalence of GT-1c among CKD patients was unusual in this geographic region. The overall efficacy of DAAs among the CKD population was encouraging. However, the downtrend of the DAAs efficacy in GT-1c may increase concern among this high-risk group in the future. Not applicable.

Hepatitis C virus (HCV) is a global public health problem, but advancements in HCV treatment have improved the cure rate. This study evaluated the effectiveness of direct-acting antivirals (DAAs) in HCV-infected patients from May 2021 to April 2023 in collaboration with tertiary care hospitals in West Bengal. The HCV viral load was monitored via qRT-PCR. Sanger sequencing was performed to determine the HCV genotypes. The clinicians prescribed the patient treatment regime. The maximum number of patients in the study population (N = 398) were compensated cirrhosis patients (46.28%). The overall SVR rate of the study population was 94.47%. The decompensated cirrhosis patients experienced the lowest SVR rate (88.89%). The maximum number of patients were prescribed sofosbuvir/daclatasvir (63.77%), and the lowest SVR rate (93.23%) was observed with this treatment regime. In the study population, GT-3 was the predominant (67.43%) circulating genotype, followed by GT-1 and -4. Among 398 patients, 22 (5.53%) were non-responsive to DAA treatment. Out of these 22 non-responder patients, 77.27% (n = 17) were GT-3-infected (3a:10; 3b:07), followed by GT-1 (1c: 04; 1b: 01). Thus, increasing numbers of DAA non-responsive cases among HCV GT-3-infected and decompensated cirrhosis patients may pose serious threats in the future.

Background: HCV infection is very common in multi-transfused β-thalassemia patients who need regular blood transfusions. Aim: The study was conducted to determine the epidemiology of HCV in multi-transfused β-thalassemia patients in West Bengal, India. Methods: Over a span of six years, blood samples were collected from HCV sero-reactive β-thalassemia patients and processed for viral RNA isolation followed by nested RT-PCR for qualitative viremia detection. The HCV genotype was determined by amplifying the partial HCV core gene by nested RT-PCR followed by DNA sequencing and NCBI genotyping tools. Phylogenetic and phylogeographic studies were performed with MEGA-X and BEAST software, respectively. Results: Out of 917 multi-transfused HCV sero-reactive β-thalassemia patients, 598 (65.21%) were HCV RNA positive while 250 (41.80%) had spontaneously cleared the virus. A significant percentage of male patients from rural areas (p = 0.042) and economically backward class (p = 0.002) were at higher risk of HCV infection. Female thalassemia patients and individuals belonging to ages 11–15 years had higher chances of spontaneous clearance. The most prevalent circulatory HCV genotype was 3a (78.26%) followed by 1b (12.04%). Phylogeographic analyses revealed that the 3a strains share genomic similarities with strains from Pakistan, Sri Lanka, and Thailand, whereas the 1b strains share similarities with strains from Thailand, Vietnam, Russia, and China. Uncommon HCV subtypes 3g and 3i were also detected. Conclusion: The high prevalence of HCV infection among β-thalassemia patients of West Bengal, India indicates NAT-based assays should be implemented for HCV screening in donor blood to eliminate HCV by 2030.

Dengue fever is a self‐limiting, acute febrile illness caused by an arbovirus. This infection may be asymptomatic or symptomatic with its potential life‐threatening form as DHF/DSS. Severe dengue cases occur typically in children due to overproduction of proinflammatory and anti‐inflammatory cytokines (called cytokines storm) as well as increased microvascular permeability in them. This study aimed to find circulating dengue serotype and their clinicopathological association among pediatric patients admitted to tertiary care hospitals in Kolkata, India. Overall, 210 patients were approached, among them, 170 dengue suspected children admitted to three tertiary care hospitals were included in this study. Dengue samples were screened for the presence of dengue NS1 antigen and IgM antibodies by enzyme‐linked immunosorbent assay. Viral RNA was extracted from NS1 seropositive serum samples and subjected to molecular serotyping by semi‐nested reverse‐transcription polymerase chain reaction. All patients were followed up for clinical manifestations and biochemical parameters associated with dengue. Cocirculation of all four serotypes was observed and DENV2 was the major circulating strain. Physiological classification of associated clinical symptoms was done as per WHO guideline and represented as a percentage variable. A multivariate logistic regression approach was used for making a regression model including dengue‐associated clinical symptoms with dengue positivity or negativity as dependent variables. Thrombocytopenia was observed in 69% of patients and the commonest bleeding manifestation was petechia. Liver function profiles of infected patients were observed during follow‐up and represented using a box plot. A significant change in trends of dengue‐associated clinical manifestations and differential expression of liver functional profile with different phases of transition of dengue fever was observed in this study population.