Epidemiology of Hepatocellular Carcinoma in India - An Updated Review for 2024.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is a significant cause of morbidity and mortality, especially in patients with chronic liver disease. As a reflection of geographical variations in India, there is significant variation in the prevalence and etiological factors of HCC. In contrast to previous studies reporting viral hepatitis as the most common etiology, recent data indicates a changing etiological pattern of cirrhosis and HCC, with alcohol and metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as the foremost cause. Thus, there was a need for an updated review of the current literature and databases for the changing epidemiology and etiological spectrum of HCC in India. The review included data primarily from the National Cancer Registry Program and the Global Burden of Diseases, Injuries, and Risk Factors Study, with the inclusion of other studies from India. The highlights of the present review are summarized in the following lines. Although the current incidence (2.15 per 100,000), prevalence (2.27 per 100,000), and mortality (2.21 per 100,000) rate of HCC in India remain lower compared to the global data, the annual rates of change in these parameters are higher in India. Among Indians, the present incidence, prevalence, and mortality related to HCC are higher in males, while the annual rate of change is higher in females. The Northeastern states have higher incidence, prevalence, and mortality related to HCC, but the Western states of Gujarat, Maharashtra, Goa, and Kerala are emerging as newer hotspots with higher annual rates of change in incidence, prevalence, and mortality. The incidence of HCC related to hepatitis B is on a downtrend, while those related to alcohol and MASLD are rising. Public health initiatives, awareness campaigns, and focused treatments are all necessary to combat these changes, particularly in areas with high incidence rates.

HCV prevalence and phylogenetic characteristics in a cross-sectional, community study of young people who inject drugs in New York City: Opportunity for and threats to HCV elimination.

Background and Aims: In the United States, the opioid epidemic has led many young people who use opioids to initiate injection drug use, putting them at risk for hepatitis C virus (HCV) infection. However, community surveys to monitor HCV prevalence among young people who inject drugs (YPWID) are rare. Methods: As part of Staying Safe (Ssafe), a trial to evaluate an HCV-prevention intervention, a community-recruited sample of 439 young people who use opioids (ages 18-30) in New York City (NYC) were screened from 2018 to 2021. Screening procedures included a brief verbal questionnaire, a visual check for injection marks, onsite urine drug testing, rapid HCV antibody (Ab) testing, and dried blood spot (DBS) collection. DBS specimens were sent to a laboratory for HCV RNA testing and phylogenetic analysis to identify genetic linkages among HCV RNA-positive specimens. Multivariable logistic regression was used to assess associations between HCV status (Ab and RNA) and demographics and drug use patterns. Results: Among the 330 participants who reported injecting drugs (past 6 months), 33% (n = 110) tested HCV Ab-positive, 58% of whom (n = 64) had HCV RNA-positive DBS specimens, indicating active infection. In multivariable analysis, visible injection marks (AOR = 3.02; p < 0.001), older age (AOR = 1.38; p < 0.05), and female gender (AOR = 1.69; p = 0.052) were associated with HCV Ab-positive status. Visible injection marks were also associated with HCV RNA-positive status (AOR = 5.24; p < 0.01). Twenty-five percent of RNA-positive specimens (14/57) were genetically linked. Conclusion: The relatively low prevalence of active infection suggests the potential impact of treatment-as-prevention in reducing HCV prevalence among YPWID. Targeted community serosurveys could help identify actively infected YPWID for treatment, thereby reducing HCV incidence and future transmissions.

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus.

Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large 'cloud' of RNA genomes (quasispecies) which-by trial and error-comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.

Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

A community-based participatory research approach to evaluating and improving hepatitis C risk, knowledge, and stigma associations among people who inject substances in Indiana.

OBJECTIVES: To explore hepatitis C risk, knowledge, and stigma among individuals who inject substances in South Central Indiana. DESIGN: A cross-sectional study design was employed using a community-based participatory research approach. The community partner was a grassroots harm reduction organization. SAMPLE: Participants in this study were at least 18 years of age, current residents of Indiana, and self-identified as injection substance users (n = 179). MEASUREMENTS: The survey measured hepatitis C risk, knowledge, and stigma, as well as differences in hepatitis C risk scores among key demographic characteristics. RESULTS: Most participants identified as male (n = 106, 59%), White (n = 139, 78%), and straight (n = 143, 80%). People of color reported lower hepatitis C knowledge than White participants. Women had significantly lower hepatitis C knowledge compared with men. LGBTQ participants reported increased hepatitis C risk compared with straight participants. Increased frequency of substance use was associated with decreased stigma. Unhoused participants demonstrated significantly lower hepatitis C knowledge compared with housing-secure participants. CONCLUSIONS: Our findings increase understanding that knowledge and risk around hepatitis C are associated with demographic characteristics. Results underscore the need for tailored public health interventions to increase hepatitis C knowledge, reduce stigma, and improve testing and treatment among vulnerable populations.

Hepatitis C Virus Care Cascade by Race/Ethnicity in a Statewide Correctional Population, 2019-2023.

IMPORTANCE: Hepatitis C virus (HCV) care cascade data by race/ethnicity for US correctional populations are sparse. OBJECTIVE: To evaluate the HCV care cascade by race/ethnicity for a state correctional population. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used Connecticut Department of Correction data for incarcerated individuals tested, diagnosed, and treated for chronic HCV infection with direct-acting antivirals (DAAs) from 2019 to 2023. MAIN OUTCOMES AND MEASURES: HCV care cascade outcomes, including testing, treatment, and cure rates, were compared by race/ethnicity. Poisson regression was used to estimate prevalence ratios (PRs), with adjustment for demographic and legal status factors. RESULTS: A total of 24,867 patients tested for HCV (88.9% men, mean (SD) age 35.6 (11.8), 32.7% White, 37.9% Black, 28.4% Hispanic, 0.6% Asian, 0.4% American Indian/Alaska Native (AIAN), 34.7% sentenced ≥ 1 year). Both HCV exposure and chronic HCV were highest for White (27.1% and 15.2%) and lowest for Black individuals (4.6% and 2.6%) (P < 0.01, for both outcomes). While incarcerated, 63.2% of chronic HCV patients started DAAs, and treatment rates did not significantly differ by race/ethnicity (P > 0.05). For those treated and having post-treatment lab data available, cure rates were 98.8% or better for all racial/ethnic groups (P > 0.05). In the adjusted regression analyses, HCV treatment initiation was lower for those sentenced < 1 year (PR, 0.76; 95% CI, 0.67-0.87) and unsentenced (PR, 0.85; 95% CI, 0.80-0.91) than those sentenced ≥ 1 year. The adjusted prevalence of advanced fibrosis stage/activity grade was not significantly associated with race/ethnicity. CONCLUSIONS: In this cohort study, less than two-thirds of chronic HCV patients initiated DAA treatment during their incarceration, and for those with available data, nearly all were cured. While there were disparities in HCV exposure and chronic HCV infection, significant racial/ethnic differences were not observed for treatment initiation or cure rates. Further efforts are needed to increase HCV treatment, especially for patients with shorter incarceration periods.

Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection.

Introduction: Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs. Methods: We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8). Results: Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4+CXCR5+PD-1+ICOS+FoxP3-) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19+CD27+IgM-E2-Tet+) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3+CCR6-) subset correlated with the neutralization breadth and potency of NAbs. Conclusion: These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.

Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Immunological crossroads: The intriguing dance between hepatitis C and autoimmune hepatitis.

Delving into the immunological crossroads of liver diseases, this editorial explores the dynamic interplay between hepatitis C virus (HCV) and autoimmune hepatitis (AIH). While HCV primarily manifests as a viral infection impacting the liver, previous studies unveil a captivating connection between HCV and the emergence of AIH. The dance of the immune system in response to HCV appears to set the stage for an intriguing phenomenon-an aberrant autoimmune response leading to the onset of AIH. Evidence suggests a heightened presence of autoimmune markers in individuals with chronic HCV infection, hinting at a potential overlap between viral and autoimmune liver diseases. Navigating the intricate terrain of viral replication, immune response dynamics, and genetic predisposition, this editorial adds a layer of complexity to our understanding of the relationship between HCV and AIH. In this immunological crossroads, we aim to unearth insights into the complex interplay, using a compelling case where AIH and primary sclerosing cholangitis overlapped following HCV treatment with direct-acting antivirals as background.

Prevalence of HIV, hepatitis B and hepatitis C infections among patients with thalassemia attending a tertiary care (rural) hospital.

Introduction: The Sunderban area of West Bengal is home to tribal and religious minorities inhabiting various islands. There is a high prevalence of thalassemia among poverty-stricken residents of this region living with meagre health care facilities. This work was planned to determine the proportion of four viral transfusion-transmitted infections (TTIs): HIV-1, HIV-2, hepatitis B virus (HBV) and hepatitis C virus (HCV) among thalassemia patients attending the sole rural medical college in the region. Materials and Methods: Thalassemia patients (n = 359, age ranging from 1 year to 60 years) attending the thalassemia clinic or being admitted to the indoor facilities for better management were included in the study. Only patients diagnosed with high-performance liquid chromatography (HPLC) and with classical clinical features were included in the study. Blood samples of these patients were tested for HIV as per NACO protocol. For HBV and HCV, samples were first tested serologically; reactive samples were collected and sent in the cold chain to a higher centre for nucleic acid amplification testing (NAAT) for qualitative and quantitative estimation. Clinical and laboratory data was collected, patients were followed up for complications and hospitalisation during the study period, and statistical analysis was performed. Results: Majority of our patients had E-beta-thalassemia (245, 59.81%), followed by beta-thalassemia major (102, 28.30%). NAAT-confirmed HCV infection (14.21%) infection was the most common, followed by HBV (2.51%), and lastly by HIV-1 (0.58%) infection. Among infected thalassemia patients, the mean HCV RNA was 741063 ± 438514.67 IU/ml while the mean HBV DNA level was 4082863 ± 7298514 IU/ml. Co-infections of HIV-1 and HCV and that of HBV and HCV were noted in one patient each (0.28%). HCV-related liver disease (14.21%) and growth retardation (10.31%) were the most typical complication noted, and death occurred in five patients (1.39%) during the study period. Conclusion: Primary care physicians should know HCV infection is the most common TTI among thalassemia patients in rural eastern India.

Measures of insulin resistance and beta cell function before and after treatment of HCV infection.

The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on ß-cell function particularly in the pre-diabetic population. Here, we evaluated indices of ß-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI < 25 were enrolled in the study. Among them, 119 were successfully treated with either direct acting antiviral (DAA) drugs or pegylated interferon/ribavirin (IFN/RBV) anti-HCV therapy. Fasting state- and oral glucose tolerance test (OGTT)-derived indexes were used to evaluate ß-cell function and insulin sensitivity. Among all subjects, 19 (13%) had T2DM and 21% exhibited pre-diabetes including 8% isolated impaired fasting glucose (IFG) and 13% combined IFG and impaired glucose tolerance (IGT). Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in prediabetic CHC patients compared to HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and ß-cell function in CHC patients who achieved sustained virologic response (SVR), regardless of fasting or OGTT state. These findings emphasize the role of HCV in the development of ß-cell dysfunction, while also suggesting that viral eradication can improve insulin secretion, reverse insulin resistance, and ameliorates glycemic control. These results have important implications for managing prediabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Here we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (TREG) cells from patients with chronic HCV infection according to DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response (SVR) by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of TREG cells were investigated through flow cytometry analysis. Moreover, transcriptomic and epigenetic landscape of TREG cells were analyzed using RNA-seq and ATAC-seq analysis. RESULTS: The TREG cell population-especially the activated TREG cell subpopulation-was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA-seq analysis revealed that viral clearance did not abrogate the inflammatory features of these TREG cells, such as TREG activation and TNF signal. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of TREG cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that TREG cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded TREG cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the TREG cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of DAAs led to a high cure rate of chronic HCV infection. Nevertheless, we have demonstrated that inflammatory features of TREG cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

Post-Treatment Occurrence of Serum Cryoglobulinemia in Chronic Hepatitis C Patients.

BACKGROUND: Persistent cryoglobulinemia after the completion of antiviral treatment is an important consideration of clinical management in chronic hepatitis C patients. We aimed to investigate the occurrence of serum cryoglobulinemia in chronic hepatitis C patients without cryoglobulinemia at the initiation of antiviral treatment. METHODS: In total, 776 patients without cryoglobulinemia were assessed for serum cryoglobulinemia after the completion of anti-HCV treatment. Serum cryoglobulinemia precipitation was assessed upon both the initiation and the completion of the treatment and analyzed for the clinical laboratory factors associated with chronic hepatitis C. RESULTS: One hundred eighteen (118) patients were checked for serum cryo-precipitation after the completion of the treatment, and eight patients (4.6%) were positive for serum cryoglobulinemia. The patients who tested positive for cryoglobulinemia included a higher proportion of liver cirrhosis patients (4/50%, p = 0.033) and other organ cancer patients (5/62.5%, p = 0.006) than patients who showed no signs of cryoglobulinemia after treatment. In a multivariate analysis, liver cirrhosis (odds ratio [OR]-17.86, 95% confidence interval [95% CI]-1.79-177.35, p = 0.014) and other organ cancer (OR-25.17 95% CI-2.59-244.23, p = 0.005) were independently and significantly associated with positive cryoglobulinemia 3 months after antiviral treatment. CONCLUSIONS: Three months after the antiviral DAA therapy had concluded, eight patients tested positive for cryoglobulinemia, representing a 6.7% prevalence. Liver cirrhosis and other organ cancer were independently and significantly associated with positive cryoglobulinemia after antiviral treatment. Further investigation into the causes of positive cryoglobulinemia after DAA antiviral therapy is warranted.

The association between hepatitis C virus infection status and blood pressure in adults in the United States: NHANES 1999-2012.

Background: The Hepatitis C virus (HCV) infection is strongly associated with cardiovascular disease risk factors, but the relationship with blood pressure (BP) remains unclear. Objectives: To assess the association between HCV infection status and BP in US adults. Methods: Data for the study were obtained from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2012. The association of HCV infection status (including HCV infection, current HCV infection, and past HCV infection) with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were explored using logistic or linear regression analyses respectively. Results: A total of 25,850 participants (age≥18 years) were enrolled in the current study, including 14,162 participants with hypertension. After adjusting for all covariates, HCV infection/current HCV infection was not associated with hypertension and SBP compared to participants with non-HCV infection (OR: 1.34,95% CI 0.96-1.87/1.31 95% CI 0.91,1.91, ß: -0.92, 95% CI -2.7-0.86/-0.35 95% CI -2.51,1.81, respectively). HCV infection/current HCV infection was only associated with elevated DBP (ß: 4.1,95% CI 2.57-5.63/4.24,95% CI 2.27-6.21). However, there was no correlation with past HCV infection in participants with hypertension, SBP, and DBP compared to those with non-HCV infection (OR: 1.23,95% CI 0.59-2.54; ß: -3.79, 95% CI -7.67-0.08 and 2.28 95% CI -0.36-4.92, respectively). Conclusion: In a representative sample of US adults, it was found that both HCV infection and current HCV infection were independently linked to higher DBP. However, there was no association between past HCV infection and DBP.

Single-tube, single-strip lateral flow assays utilizing loop-mediated isothermal amplification for simultaneous hepatitis B and C viral detection.

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop-mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 103 genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point-of-care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources.

Involvement of ribosomal protein L17 and Y-box binding protein 1 in the assembly of hepatitis C virus potentially via their interaction with the 3' untranslated region of the viral genome.

The 3' untranslated region (3'UTR) of the hepatitis C virus (HCV) RNA genome, which contains a highly conserved 3' region named the 3'X-tail, plays an essential role in RNA replication and promotes viral IRES-dependent translation. Although our previous work has found a cis-acting element for genome encapsidation within 3'X, there is limited information on the involvement of the 3'UTR in particle formation. In this study, proteomic analyses identified host cell proteins that bind to the 3'UTR containing the 3'X region but not to the sequence lacking the 3'X. Further characterization showed that RNA-binding proteins, ribosomal protein L17 (RPL17), and Y-box binding protein 1 (YBX1) facilitate the efficient production of infectious HCV particles in the virus infection cells. Using small interfering RNA (siRNA)-mediated gene silencing in four assays that distinguish between the various stages of the HCV life cycle, RPL17 and YBX1 were found to be most important for particle assembly in the trans-packaging assay with replication-defective subgenomic RNA. In vitro assays showed that RPL17 and YBX1 bind to the 3'UTR RNA and deletion of the 3'X region attenuates their interaction. Knockdown of RPL17 or YBX1 resulted in reducing the amount of HCV RNA co-precipitating with the viral Core protein by RNA immunoprecipitation and increasing the relative distance in space between Core and double-stranded RNA by confocal imaging, suggesting that RPL17 and YBX1 potentially affect HCV RNA-Core interaction, leading to efficient nucleocapsid assembly. These host factors provide new clues to understanding the molecular mechanisms that regulate HCV particle formation. IMPORTANCE: Although basic research on the HCV life cycle has progressed significantly over the past two decades, our understanding of the molecular mechanisms that regulate the process of particle formation, in particular encapsidation of the genome or nucleocapsid assembly, has been limited. We present here, for the first time, that two RNA-binding proteins, RPL17 and YBX1, bind to the 3'X in the 3'UTR of the HCV genome, which potentially acts as a packaging signal, and facilitates the viral particle assembly. Our study revealed that RPL17 and YBX1 exert a positive effect on the interaction between HCV RNA and Core protein, suggesting that the presence of both host factors modulate an RNA structure or conformation suitable for packaging the viral genome. These findings help us to elucidate not only the regulatory mechanism of the particle assembly of HCV but also the function of host RNA-binding proteins during viral infection.

Efficacy of Sofosbuvir and Velpatasvir Combination in the Treatment of Hepatitis C Virus (HCV) in Chronic Kidney Disease (CKD) Patients.

Background Hepatitis C virus (HCV) infection is still common in patients with chronic renal failure, even those on maintenance dialysis. A bidirectional association exists between HCV infection and chronic renal disease. Objective To assess the efficacy of sofosbuvir and velpatasvir combination in the treatment of chronic HCV in chronic kidney disease (CKD) patients. Methodology This descriptive, cross-sectional study was undertaken at the departments of Gastroenterology and Nephrology Lady Reading Hospital, Peshawar, from April 7, 2021, to October 7, 2021. Patients with chronic HCV and chronic renal disease at stage 4 or 5 were included while patients with decompensated cirrhosis liver, hepatoma, hepatitis B virus/HCV (HBV/HCV) coinfection, and post liver transplant patients were excluded. HCV infection was diagnosed based on detectable HCV ribonucleic acid (HCV RNA) by PCR (polymerase chain reaction). In contrast, CKD was diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria for CKD. Sofosbuvir 400 mg orally daily and velpatasvir 100 mg orally with meals were given daily for 12 weeks. Effectiveness was defined as negative HCV RNA by PCR 12 weeks after treatment completion called sustained virological response rate 12 weeks after treatment completion (SVR12). Results A total of 73 patients including 67 (91.78%) males and six (8.22%) females between the ages of 20 years and 70 years were included in this study. The mean age of the participants was 48.77±8.0 years. Twelve weeks after the treatment completion, 69 (94.52%) had negative HCV RNA, whereas four (5.48%) patients had detectable HCV RNA. Conclusion It can be concluded from our study that a fixed-dose combination of sofosbuvir 400 mg and velpatasvir 100 mg is quite effective and recommended for treating chronic hepatitis C infection in patients with chronic renal disease in our local setup.

Modeling the impact of the COVID-19 pandemic on achieving HCV elimination amongst young and unstably housed people who inject drugs in San Francisco.

BACKGROUND: Young adult (18-30 years) people who inject drugs (PWID) face high hepatitis C virus (HCV) prevalence. In San Francisco, where >60% of PWID lack stable housing, barriers hinder HCV treatment access. We assessed progress towards the World Health Organization's (WHO) HCV elimination goal of an 80% reduction in incidence over 2015-2030, focusing on young (YPWID) and unstably housed PWID in San Francisco. METHODS: We developed a dynamic HCV transmission model among PWID, parameterized and calibrated using bio-behavioural survey datasets from San Francisco. This included 2018 estimates for the antibody-prevalence among PWID (77%) and care cascade estimates for HCV for YPWID (72% aware of their status and 33% ever initiating treatment). Based on programmatic data, we assumed a 53.8% reduction in testing and 40.7% decrease in treatment from 2020 due to the COVID-19 pandemic, which partially rebounded from April 2021 with testing rates then being 31.1% lower than pre-pandemic rates and treatment numbers being 19.5% lower. We simulated different scenarios of how services changed after the pandemic to project whether elimination goals would be met. RESULTS: Continuing post-pandemic rates of testing and treatment, the model projects an 83.3% (95% credibility interval [95% CrI]:60.6-96.9%) decrease in incidence among PWID over 2015-2030 to 1.5/100pyrs (95% CrI:0.3-4.4) in 2030. The probability of achieving the elimination goal by 2030 is 62.0%. Among YPWID and unstably housed PWID, the probability of achieving the elimination goal by 2030 is 54.8 and 67.6%, respectively. Importantly, further increasing testing and treatment rates to pre-pandemic levels by 2025 only results in a small increase in the probability (67.5%) of the elimination goal being achieved among all PWID by 2030, while increased coverage of medication for opioid use disorder among YPWID and/or housing interventions results in the probability of achieving elimination increasing to over 75%. CONCLUSION: The COVID-19 pandemic impeded progress toward achieving HCV elimination. Our findings indicate that existing partial rebounds in HCV testing and treatment may achieve the elimination goal by 2030, with an additional scale-up of interventions aimed at YPWID or unstably housed PWID ensuring San Francisco is likely to achieve elimination by 2030.

No association between hepatitis C virus infection and risk of colorectal cancer: a systematic review and meta-analysis of cohort studies.

Background and aim: There is still uncertainty regarding whether hepatitis C virus (HCV) infection is associated with colorectal cancer (CRC). This study aims to investigate the potential association between HCV infection and CRC through a systematic review and meta-analysis of cohort studies. Methods: PubMed, Embase, and Web of Science were systematically searched from the beginning of their inception to October 2023 to find relevant cohort studies on the association between HCV infection and CRC risk. The random-effect, generic inverse variance method was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC outcome among individuals with HCV infection. We also performed subgroup and sensitivity analysis. Results: A total of 8 cohort studies involving 1,939,164 participants were included in this meta-analysis. The result from the meta-analysis suggested that there was no statistically significant association between HCV and the risk of developing CRC (HR = 0.99, 95% CI: 0.82-1.88, p = 0.88) with low statistical heterogeneity (I2 = 28%, p = 0.20). Subgroup analyses that were conducted based on study design, diagnosis of HCV infection, and publication year yielded similar results. Analyses of subgroups based on study areas revealed that there was no significant association between HCV infection and CRC risk in Asia (n = 2, HR = 0.96, 95% CI: 0.71-1.29, p = 0.79; I2 = 26%), Europe (n = 3, HR = 1.06, 95% CI: 0.83-1.37, p = 0.63; I2 = 0%), and North America (n = 2, HR = 1.10, 95% CI: 0.87-1.38, p = 0.44; I2 = 0%); however, a negative correlation was found in Oceania (n = 1, HR = 0.43, 95% CI: 0.22-0.84, p = 0.01). Sensitivity analysis further reinforce the stability of our conclusion. Conclusion: Our cohort-based meta-analysis showed insufficient evidence to support the association between HCV infection and an increased risk of CRC. To gain a clearer insight into the potential association between these two conditions, it would be beneficial to conduct large, well-designed, high-quality prospective cohort studies that consider different ethnic populations and potential confounding factors.Systematic review registration: PROSPERO, identifier [CRD42023472688], https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023472688.