Chronic Hepatitis C Virus Infection Research Articles

Liver stiffness and associated risk factors among people with a history of injecting drugs: a prospective cohort study

BackgroundPersons with opioid use disorders (OUD) and persons with substance use disorders (SUD) who inject substances have a reduced life expectancy of up to 25 years compared with the general population. Chronic liver diseases are a substantial cause of this. Screening strategies based on liver stiffness measurements (LSM) may facilitate early detection, timely intervention, and treatment of liver disease. This study aims to investigate the extent of chronic liver disease measured with transient elastography and the association between LSM and various risk factors, including substance use patterns, hepatitis C virus (HCV) infection, alcohol use, body mass index, age, type 2 diabetes mellitus, and high-density lipoprotein (HDL) cholesterol among people with OUD or with SUD who inject substances.MethodsData was collected from May 2017 to March 2022 in a cohort of 676 persons from Western Norway. The cohort was recruited from two populations: Persons receiving opioid agonist therapy (OAT) (81% of the sample) or persons with SUD injecting substances but not receiving OAT. All participants were assessed at least once with transient elastography. A linear mixed model was performed to assess the impact of risk factors such as HCV infection, alcohol use, lifestyle-associated factors, and substance use on liver stiffness at baseline and over time. Baseline was defined as the time of the first liver stiffness measurement. The results are presented as coefficients (in kilopascal (kPa)) with 95% confidence intervals (CI).ResultsAt baseline, 12% (n = 83) of the study sample had LSM suggestive of advanced chronic liver disease (LSM ≥ 10 kPa). Advanced age (1.0 kPa per 10 years increments, 95% CI: 0.68;1.3), at least weekly alcohol use (1.3, 0.47;2.1), HCV infection (1.2, 0.55;1.9), low HDL cholesterol level (1.4, 0.64;2.2), and higher body mass index (0.25 per increasing unit, 0.17;0.32) were all significantly associated with higher LSM at baseline. Compared with persistent chronic HCV infection, a resolved HCV infection predicted a yearly reduction of LSM (-0.73, -1.3;-0.21) from baseline to the following liver stiffness measurement.ConclusionsMore than one-tenth of the participants in this study had LSM suggestive of advanced chronic liver disease. It underscores the need for addressing HCV infection and reducing lifestyle-related liver risk factors, such as metabolic health factors and alcohol consumption, to prevent the advancement of liver fibrosis or cirrhosis in this particular population.

Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors.

Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.

Elucidating the association between direct-acting antivirals and Parkinson's disease in patients with hepatitis C virus infection

BackgroundSome epidemiological studies have found an increased association between Parkinson's disease (PD) and chronic hepatitis C virus (HCV) infection. Although a few studies have also found a decreased risk of PD with interferon-α therapy, the effect of direct-acting antivirals (DAAs) on Parkinson's disease remains unclear. The current study seeks to assess and elucidate the association between DAAs and PD in patients newly diagnosed with chronic HCV infection. MethodsWe conducted a retrospective cohort study of patients ≥18 years diagnosed with HCV using MarketScan Commercial and Medicare Supplemental database (2012–2019). Follow-up started with the initiation of DAA (or randomly assigned date for the non-DAA group) and ended at occurrence of PD, disenrollment, or end of the study period. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals. ResultsWe identified 48,356 patients diagnosed with HCV. The mean follow-up time of the cohort was 1.31 years. The incidence rate of PD was 53 per 100,000 person-years for the DAA group and 48 per 100,000 person-years for the non-DAA group. The adjusted HR was 1.24 (95% CI = 0.56–2.73). Results were consistent across sensitivity and subgroup analyses. ConclusionThis study did not find an association between DAAs and PD among patients with HCV infection.

Hepatitis C virus infection and co-infection with HIV among persons who inject drugs in 10 U.S. cities—National HIV Behavioral Surveillance, 2018

BackgroundCharacterizing acute and chronic hepatitis C virus (HCV) infection and HIV/HCV co-infection among persons who inject drugs (PWID) can inform elimination efforts. MethodsDuring 2018 National HIV Behavioral Surveillance in 10 U.S. metropolitan statistical areas (MSAs), PWID were recruited using respondent-driven sampling and offered a survey, HIV testing, and HCV antibody and RNA testing. We examined prevalence and associated characteristics of HCV infection and HIV/HCV co-infection. Associations were assessed using log-linked Poisson regression models with robust standard errors accounting for clustering by recruitment chain and adjusting for MSA and network size. ResultsOverall, 44.2% had current HCV infection (RNA detected), with 3.9% classified as acute infection (HCV antibody non-reactive/RNA detected) and 40.3% as chronic (HCV antibody reactive/RNA detected). Four percent had HIV/HCV co-infection. Current HCV infection was significantly higher among PWID who were male, White, injected >1 time/day, shared syringes in past year, and shared injection equipment in past year. PWID who were transgender, injecting >5 years, and most often injected speedball (heroin and cocaine together) or stimulants alone were more likely to have HIV/HCV co-infection. Among PWID who never previously had HCV infection, 9.9% had acute HCV infection. Among PWID who started injecting ≤5 years ago, 41.5% had already acquired HCV infection. ConclusionsAcute and chronic HCV infections were substantial among a sample of PWID in 10 U.S. MSAs. Accessibility to HCV RNA testing, promoting safer practices, and intervening early with harm reduction programs for recent injection initiates will be critical to disease elimination efforts for PWID.

Sofosbuvir (+) daclatasvir (+) ribavirin in Egyptian patients with hepatitis C virus: Therapeutic outcomes and the prognostic role of natural killer cells

BackgroundOne of the prominent causes of chronic liver disease worldwide is the hepatitis C virus (HCV). HCV believed that innate immunity contributes to a sustained virological response (SVR) to the treatment of Sofosbuvir (SOF) (+) Daclatasvir (DCV) (+) Ribavirin (RBV). This study aimed to evaluate the impact of SOF (+) DCV (+) RBV therapy and persistent HCV infection on the subset of natural killer cells (NK) in HCV genotype four patients from Egypt. Materials and MethodsOne hundred and ten patients with persistent HCV infections requiring SOF (+) DCV (+) RBV therapy were grouped, and a flow cytometry (FCM) study of the NK cell subset in peripheral blood was performed. The assessment was performed before and after three and/or six months of the cessation of viral suppression therapy when a patient had a long-term viral response (SVR). One hundred and ten volunteers from the National Liver Institute’s (NLI) blood bank were selected as controls. ResultsPatients with chronic HCV infection before therapy had considerably lower CD16+ and CD3− CD56+ cells than controls. Their levels increase during SOF (+) DCV (+) RBV therapy. In patients with SVR during treatment, CD16+ and CD3– CD56+ cells increased significantly compared to those who did not get SVR. Furthermore, CD56+ cells were significantly higher in patients with persistent infection before treatment than controls but diminished with the response to treatment. Conclusion: NK cell activation following SOF (+) DCV (+) RBV therapy and polarization to cytotoxicity occurred early in HCV antiviral therapy and was elevated in the respondents. Our data illustrated that establishing an inhibitory cytotoxic NK profile is related to therapeutic outcomes.

The Association between Urinary Alcohol Metabolites on Hepatitis C Treatment and Response

Background: Direct-acting antiviral (DAA) medications for the treatment of chronic hepatitis C virus (HCV) infection has achieved higher rates of sustained virologic response (SVR) with shorter treatment durations and no alcohol abstinence prerequisite. Previous therapies required alcohol abstinence for at least 6 months. Methods: Our retrospective cohort study in Veterans with chronic HCV infection presenting for care at the Joseph Maxwell Cleland Atlanta VA medical center (AVAMC) between 1/1/2015 – 11/29/2017 examined the relationship between alcohol use, DAA initiation, and SVR. Results: The cohort included 1763 people that were mostly males (97%) with a mean age of 63 years and 70% Black. In multivariate analysis, the odds of receiving DAA were 0.7 (95% CI: 0.674, 0.9; p=0.0013) in those with “detectable” alcohol metabolites compared with those who had “undetectable” alcohol metabolites. The odds of achieving SVR were 0.7 (95% CI: 0.5, 1.0; p=0.0525) in those with “detectable” alcohol metabolites. Overall, 86% of patients who received DAA therapy achieved SVR. Conclusions: Alcohol use categorized using urine alcohol metabolite testing, during the study period was associated with a significantly lower odds of receiving DAA therapy but had no statistical significance on the odds of achieving SVR. While patients with chronic hepatitis C should be counseled on the risks of alcohol use, it is not associated with lower likelihood of achieving SVR and should not preclude the initiation of DAA therapy

Characteristics of Hepatitis B Virus, Hepatitis C Virus, and Syphilis Coinfection in People With HIV/AIDS Contracted Through Different Sources: Retrospective Study.

The burden of hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis coinfections remains disproportionately high among people living with HIV/AIDS. Hubei province is located in central China, where there are distinct regional characteristics of the distribution of people living with HIV/AIDS acquired via diverse transmission routes and the AIDS epidemic itself. We aimed to estimate the magnitude of HBV, HCV, or syphilis coinfections among people living with HIV/AIDS with blood-borne transmission, which includes former paid blood donors, contaminated blood recipients, and intravenous drug users, as well as among people with sex-borne HIV transmission (including heterosexual people and men who have sex with men) and people with mother-to-child HIV transmission. From January 2010 to December 2020, people living with HIV/AIDS were tested for hepatitis B surface antigen (HBsAg), HCV antibodies, and syphilis-specific antibodies. The positive patients were further tested for HBV markers, HBV DNA, and HCV RNA, and received a rapid plasma reagin circle card test. All people living with HIV/AIDS were first divided into transmission groups (blood, sex, and mother-to-child); then, people with blood-borne HIV transmission were divided into former paid blood donors, contaminated blood recipients, and intravenous drug users, while people with sex-borne HIV transmission were divided into heterosexual people and men who have sex with men. Among 6623 people living with HIV/AIDS, rates of chronic HCV infection were 80.3% (590/735) in former paid blood donors, 73.3% (247/337) in intravenous drug users, 57.1% (444/777) in contaminated blood recipients, 19.4% (21/108) in people with mother-to-child HIV transmission, 8.1% (240/2975) in heterosexual people, and 1.2% (21/1691) in men who have sex with men. Chronic HBV infection rates were similar among all people with blood-borne HIV transmission. However, compared to heterosexual people, the chronic HBV infection rate was greater in men who have sex with men (213/1691, 12.6% vs 308/2975, 10.4%; χ21=5.469; P=.02), although HBV exposure was less common (827/1691, 48.9% vs 1662/2975, 55.9%; χ21=20.982; P<.001). Interestingly, the combination of HBsAg and hepatitis B e antigen (HBeAg) was found in 11 patients with sex-borne HIV transmission, but in 0 people with blood-borne HIV transmission (11/196, 5.6% vs 0/521, 0%; χ21=29.695, P<.001). In people with sex-borne HIV transmission, the proportions of patients with a syphilis titer ≥1:16 and neurosyphilis were 8.6% (105/1227) and 7.8% (37/473), respectively, whereas these values were 0 in people with blood-borne HIV transmission. In people living with HIV/AIDS, HCV transmission intensity was significantly associated with specific exposure modes of blood or sexual contact. The rate of chronic HBV infection among men who have sex with men was higher than in any other population. Attention should be paid to the high prevalence of neurosyphilis in people living with HIV/AIDS who contract HIV by sexual intercourse.

Real-world economic burden of hepatitis C and impact of direct-acting antivirals in France: A nationwide claims data analysis.

The economic impact of managing patients with hepatitis C virus (HCV) infection remains unknown. This study aimed to assess the economic burden of chronic HCV infection from a national health insurance perspective and the impact of direct-acting antivirals (DAAs) using nationwide real-world data. Patients with chronic HCV infection were identified from the French Health Insurance Claims Databases (SNDS) and matched for age and sex to the general population. Health resource utilization and reimbursements were summarized according to healthcare expenditure items from 2012 to 2021. The economic burden attributable to chronic HCV infection was evaluated over a 10-year period. Finally, the impact of DAAs was estimated using economic data derived from the SNDS. A total of 145 187 patients with chronic HCV infection were identified. Among the patients eligible for DAA therapy, 81.5% had received DAA by the end of 2021. Over a 10-year period, managing patients with chronic HCV infection resulted in an additional cost of €9.71 billion (95% confidence interval [CI]: €9.66-€9.78 billion) or €9191 (95% CI: €9134-€9252) per patient per year compared to the general population. After DAA therapy, patients with chronic HCV infection had a higher economic burden than the general population, with an additional cost of €5781 (95% CI: €5540-€6028) per patient at the fifth-year post-DAA therapy. A significant economic burden persists among patients with HCV infection after DAA treatment. The high proportion of patients not treated with DAA therapy supports reinforcing policies for universal access.

Role of INR to Platelet Ratio (INPR) in Predicting Advanced Liver Fibrosis in Patients with Chronic Hepatitis C Infection

Background: Chronic hepatitis C (HCV) infection is a leading cause of liver fibrosis, which can progress to cirrhosis and hepatocellular carcinoma if not diagnosed and treated early. The gold standard for assessing liver fibrosis, liver biopsy, is invasive and carries risks, driving the need for reliable non-invasive diagnostic methods. The International Normalized Ratio to platelet ratio (INPR) has been proposed as a potential non-invasive marker to assess advanced liver fibrosis, but its effectiveness in patients with chronic HCV infection remains to be thoroughly evaluated. Objective: This study aimed to assess the efficacy of the INR to platelet ratio (INPR) as a non-invasive marker for predicting advanced liver fibrosis in patients with chronic hepatitis C infection. Methods: In this retrospective cohort study, 267 patients diagnosed with chronic HCV infection were evaluated at the Hepato-gastroenterology department of a tertiary care center from July 2021 to May 2023. Participants underwent comprehensive diagnostic evaluations, including liver parenchymal biopsies, shear wave elastography (SWE), and laboratory tests to calculate INPR. The diagnostic performance of INPR in detecting advanced liver fibrosis (&gt;F3) was analyzed using the area under the receiver operating characteristic (AUROC) curve, alongside sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: The study population had a mean age of 43.45 ± 12.33 years, with a gender distribution of 61.8% male and 38.2% female. Advanced liver fibrosis was identified in 57 patients (21.3%). The INPR demonstrated an AUROC of 0.81 for predicting advanced liver fibrosis, with a sensitivity of 81.2%, specificity of 60.8%, PPV of 76.7%, and NPV of 91.2%. Comparatively, the Gamma Glutamyl Transpeptidase to Platelet Ratio (GPR) showed a slightly lower diagnostic accuracy. Conclusion: The INR to platelet ratio (INPR) is a promising non-invasive marker for predicting advanced liver fibrosis in chronic HCV-infected patients. It offers a practical bedside tool for clinicians, potentially reducing the need for invasive liver biopsies. However, further large-scale prospective studies are needed to validate these findings and fully establish INPR's role in the management of liver fibrosis.

Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children.

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.

A304 EXPLORING HEPATITIS C TREATMENT COST TRENDS OVER A DECADE: A CROSS-SECTIONAL ANALYSIS WITHIN MEDICARE PART D (2012-2021)

Abstract Background Chronic hepatitis C virus (HCV) infection negatively impacts quality and quantity of life. With the onset of direct-acting antivirals (DAAs), cure rates of HCV have increased to over 95%. Despite these advancements, chronic HCV infection continues to pose a substantial health and financial burden and without drug coverage, treatment of HCV with these DAAs is unaffordable. In the United States, Medicare Part D is a voluntary drug coverage plan predominantly for individuals covered by Medicare (typically over 65 years old) which can facilitate access to these DAAs. Aims This study aims to analyze the shifts in HCV treatment and spending in the USA from 2012 to 2021 for Medicare Part D and assess the impact of generic drugs on overall expenditure. Methods A retrospective cross-sectional study was conducted using publicly available Centers for Medicare and Medicaid Services (CMS) Medicare D drug spending data from 2012 to 2021. The total expenditure and utilization of HCV drugs was calculated, and average spending per beneficiary was utilized to estimate potential cost savings if generic DAAs were employed. Results The study revealed a decline in HCV claims and beneficiaries over 65 since 2015 with a peak of 134,752 beneficiaries decreasing to 35,735 in 2021. Accordingly, spending was the highest in 2015 (8.8 billion USD) and subsequently trended downwards to 1.5 billion in 2021. Over the ten-year period, the USA spent a total of 33.1 billion USD on HCV treatment. Harvoni accounted for 53% of the spending, followed by Sovaldi (17%) and Epclusa (14%). Generic drug utilization slowly increased with the introduction of generics in 2019 with 6.4% of beneficiaries treated with generic DAAs in 2019, rising to 15.3% in 2020 and 14.8% in 2021. If all prescriptions of Harvoni and Epclusa were substituted by ledipasvir/sofosbuvir and sofosbuvir/velpatasvir, respectively, there is a potential $2.7 billion cost reduction. This translates to a potential 47.3% reduction in HCV treatment expenditures from 2019 to 2021. Conclusions The decreasing number of beneficiaries for HCV treatment among people over the age of 65 suggests a decreasing HCV prevalence in this age group. This reflects the success of DAA treatment and low reinfection rates. However, the underutilization of generic DAAs despite their lower cost highlights a missed opportunity for substantial savings. This study emphasizes the importance of policy negotiations to ensure optimal resource management, advocating for a shift towards generic drug usage to alleviate the financial burden associated with HCV treatment. Trends in total spending on DAAs for HCV and number of beneficiaries within Medicare Part D from 2012 to 2021. Annual percent changes in expenditure are shown within the data bars. Funding Agencies None

Comparative efficacy and safety of Sofosbuvir/Velpatasvir and Danoprevir for the treatment of chronic hepatitis C: the real-world data in China

BackgroundSofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV.Patients and methods178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study.ResultsDNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P < 0.05). ECS group possessed more 6a (31.91% vs.13.10%) while DNV group was provided with more 1b (48.81% vs. 22.34%) patients. Significantly poor liver function was detected in ECS group at 4-week treatment (ALT and AST) and 12-week follow-up (AST) (all P < 0.05). The SVR12 undetectable rates of both groups were 100%, and no serious event was observed during the treatment and follow-up in both groups.ConclusionIn this retrospective real-world study, the efficacy of DNV combined therapy is similar to Sofosbuvir/Velpatasvir ± Ribavirin for chronic HCV infection, and the safety is comparable. DNV based therapy is a promising regimen for chronic hepatitis C.

Efficacy and safety of DAA in children and adolescents with chronic HCV infection: A systematic review and meta-analysis.

We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines. We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach. A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes. CRD42020146752.

Rising Lysophosphatidylcholine Levels Post-Hepatitis C Clearance.

Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs) effectively treat HCV and rapidly normalize serum cholesterol. In serum, LPC species are primarily albumin-bound but are also present in lipoprotein particles. This study aims to assess the impact of HCV eradication on serum LPC species levels in patients infected with HCV. Therefore, 12 different LPC species were measured by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the sera of 178 patients with chronic HCV infections at baseline, and in 176 of these patients after therapy with DAAs. All LPC species increased at 4 and 12 weeks post-initiation of DAA therapy. The serum profiles of the LPC species were similar before and after the viral cure. Patients with HCV and liver cirrhosis exhibited lower serum levels of all LPC species, except LPC 16:1, both before and after DAA treatment. Percentages of LPC 18:1 (relative to the total LPC level) were higher, and % LPC 22:5 and 22:6 were lower in cirrhotic compared to non-cirrhotic patients at baseline and at the end of therapy. LPC species levels inversely correlated with the model of end-stage liver disease score and directly with baseline and post-therapy albumin levels. Receiver operating characteristic curve analysis indicated an area under the curve of 0.773 and 0.720 for % LPC 18:1 (relative to total LPC levels) for classifying fibrosis at baseline and post-therapy, respectively. In summary, HCV elimination was found to increase all LPC species and elevated LPC 18:1 relative to total LPC levels may have pathological significance in HCV-related liver cirrhosis.

Morphometric, biochemical and histopathological effects of sofosbuvir (sovaldi) on testes of adult male albino rats

ABSTRACT Sofosbuvir treatment regimens for chronic HCV infection have recently been linked to extra hepatic side effects. This study aimed to show how sofosbuvir affected the adult male albino rat testis. Forty adult male albino rats were used. The rats were equally split into two main groups (I and II), then each group subdivided into two subgroups (A and B). Each rat in group I (control) received 0.5 ml of distilled water every day for four weeks. Each rat in group II (sofosbuvir-treated) received 0.5 ml of distilled water containing 7.2 mg of sofosbuvir every day for four weeks. After four weeks (subgroups IA and IIA) and eight weeks (subgroups IB and IIB) of treatment, the rats were sacrificed. Histological, biochemical, and morphometric studies on the testes were conducted. The data were analyzed. Examination of testes of sovaldi treated group revealed histopathological changes. Biochemical and morphometric analysis showed reduced levels of reduced glutathione and seminiferous tubule epithelial height respectively. Following a 4-week drug withdrawal period, the testes only partially recovered. We concluded that sofosbuvir induced deteriorating changes in the adult male albino rats’ testes. These changes were proved by histological and biochemical studies. These changes were incompletely reversible after cession of treatment. Researches investigating the effect of adding drugs that have antioxidant properties during sofosbuvir therapy are recommended.

Concerted synergy between viral-specific IgG and CD8 + T cells is critical for clearance of an HCV-related rodent hepacivirus.

Evidence assessing the role of B cells and their antibodies, or lack thereof, in the spontaneous resolution of acute HCV infection is conflicting. Utilization of a strictly hepatotropic, HCV-related rodent hepacivirus (RHV) model circumvents many of the challenges facing the field in characterizing the immunological correlates of dichotomous infection outcomes. This study seeks to elucidate the importance of B cells in the clearance of acute RHV infection. µMT mice were infected i.v. with RHV and found to develop chronic infection for over a year. Wild-type (WT) mice depleted of B cells also exhibited persistent viremia that resolved only upon B cell resurgence. The persistent infection developed by B1-8i and AID cre/cre mice revealed that antigen-specific, class-switched B cells or their antibodies were crucial for viral resolution. Virus-specific CD8 + and CD4 + T cells were characterized in these mice using newly developed major histocompatibility complex class I and II tetramers and ex vivo peptide stimulation. Immunoglobulin G (IgG) was purified from the serum of RHV- or lymphocytic choriomeningitis virus Armstrong-infected mice after viral clearance and passively transferred to AID cre/cre recipients, revealing viral clearance only in αRHV IgG recipients. Further, the transfer of αRHV IgG into B cell-depleted recipients also induced viral resolution. This ability of RHV-specific IgG to induce viral clearance was found to require the concomitant presence of CD8 + T cells. Our findings demonstrate a cooperative interdependence between immunoglobulins and the T cell compartment that is required for RHV resolution. Thus, HCV vaccine regimens should aim to simultaneously elicit robust HCV-specific antibody and T cell responses for optimal protective efficacy.

Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors

ABSTRACT Background Patients with cancer with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded from many cancer clinical trials of immune checkpoint inhibitors (ICIs). Therefore, data are limited regarding the management of HBV and HCV infections in patients with cancer treated with ICIs. To address this gap, we reviewed the literature on management of HBV and HCV infections in patients with cancer receiving ICIs. Methods We searched MEDLINE and PubMed for all original research articles, case reports, and systematic reviews published in English between Jul 2013 and Jul 2023 on patients with cancer with HBV or HCV infection receiving ICIs. Results We found 28 studies (three prospective clinical trials, seven retrospective cohort studies, nine retrospective case series, and nine case reports) that evaluated the safety of ICI therapy in patients with HBV infection and cancer. The overall rate of HBV reactivation was 1.4% (38/2799), and no HBV-related deaths were reported. The frequency of HBV reactivation in patients with chronic and past HBV infections was 2% (35/1667) and 0.3% (3/1132), respectively. The risk of HBV reactivation was significantly higher among patients with chronic HBV infection not receiving antiviral prophylaxis than among those receiving antivirals (17% vs 1%, p &amp;lt; 0.05). Based on high-quality evidence, for patients with chronic HBV infection, antiviral prophylaxis is recommended before ICI therapy initiation. For patients with past HBV infection, monitoring and on-demand antiviral treatment are sufficient. We found 11 studies (five clinical trials, five retrospective studies, and one prospective observational study) that evaluated the safety of ICI therapy in patients with HCV infection and cancer. The overall rate of HCV reactivation was 0.5% (2/387), and no HCV-related deaths were reported. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICIs are safe for HCV-infected patients with solid tumors. Conclusions Chronic HBV or HCV infection should not be considered a contraindication for ICI therapy. Specific risk assessment, monitoring, and management strategies are necessary to reduce the risk of ICI-related liver injury in patients with cancer and chronic HBV or HCV infection.

Serum MicroRNA profiles in chronic hepatitis C Egyptian patients before and after combined sofosbuvir and daclatasvir treatment

BackgroundMicroRNAs (miR) are small sequence of nucleotides that can affect multiple genes involved in the hepatitis C virus (HCV) life cycle and disease development. The purpose of the present study was to investigate the clinical significance of serum microRNA profiles in a cohort of Egyptian patients with chronic HCV infection before and after combined sofosbuvir and daclatasvir treatment, as well as to gain a better understanding of the exact interaction mechanism in HCV transcriptional activity via differentially expressed miRNAs. For 12 weeks, 50 patients were eligible for and received sofosbuvir (400 mg daily) and daclatasvir (60 mg daily) treatment. Each patient’s blood was obtained twice: once before therapy began and again three months afterwards.ResultsThe current study found that serum levels of circulating miR-122, miR-221, miR-23a, miR-125, miR-217, miR-224, and miR-181a were high in HCV pre-treatment patients, but after 12 weeks of direct-acting antiviral (DAAs) treatment, there was a statistically significant reduction in expression levels of miR-122, miR-221, miR-23a, miR-125, miR-217, and miR-224 (p < 0.001). There is no statistical significance for miR-181a.ConclusionThe key differentially expressed microRNAs before and after the direct-acting antiviral (DAA) regimen were connected to the dynamics of chronic HCV infection, suggesting their potential as predictive biomarkers for HCV clearance after sofosbuvir and daclatasvir therapy.

Evaluation of serum thioredoxin as a hepatocellular carcinoma diagnostic marker

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent and fatal malignancies worldwide. Following an increase in reactive oxygen species (ROS), cancer cells enter an oxidative stress state. As a result, these cells experience an increase in antioxidant activity to counteract oxidative stress. The thioredoxin (TRX) system is a ubiquitous mammalian antioxidant system that neutralizes ROS and maintains intracellular reduction oxidation (redox) balance, which is essential for HCC growth. However, the role of TRX protein in HCC remains largely unknown. Hence, we aimed to assess the diagnostic utility of serum TRX in patients with HCC. A total of 50 patients were consecutively recruited in this observational study. They were classified into three groups: an HCC group (25 patients), a cirrhosis group (15 patients with liver cirrhosis on top of chronic HCV infection), and a control group (10 healthy individuals). Serum TRX levels were measured using ELISA.ResultsHigher serum TRX levels were detected in the HCC group than in the cirrhosis and control groups (140.96 ± 12.70 vs 88.33 ± 10.34 vs 73.10 ± 13.22 ng/mL, respectively; P < 0.001). TRX was independently associated with the presence of HCC (P < 0.001). Regarding the detection of HCC, TRX at a cut-off value of 114 ng/mL had superior diagnostic performance to AFP with an AUC of 1.000, sensitivity of 100%, and specificity of 100%, whereas AFP at a cut-off value of 20.5 ng/mL had an AUC of 1.000, sensitivity of 100%, and specificity of 47%.ConclusionThioredoxin has the potential to be an HCC diagnostic marker. The clinical significance of thioredoxin in HCC requires further investigation.

Cytokines in hepatitis C-infected patients with or without opioid maintenance therapy.

Both chronic hepatitis C virus (HCV) infection and opioids cause altered blood levels of cytokines. Previous studies have investigated levels of selected groups of cytokines in patients on opioid maintenance treatment. Little is known about the levels of multiple cytokines in patients with chronic HCV infection on opioid maintenance treatment. Our aim was to investigate the cytokine profile in patients with active HCV infection with and without opioid maintenance treatment. We conducted a cross-sectional study in an out-patients population included upon referral for antiviral hepatitis C infection treatment. The level of 27 cytokines was measured in serum using multiplex technology. Patients were interviewed using a modified version of the European addiction severity index. Data pertaining to weight, height, current medication, smoking habits, allergies, previous medical history and ongoing withdrawal symptoms were collected. Non-parametric testing was used to investigate differences in levels of cytokines between the two groups. A 3-model hierarchical regression analysis was used to analyse associations between cytokines and confounding variables. Out of 120 included patients, 53 were on opioid maintenance treatment. Median duration of opioid treatment was 68.4 months. There were no demographical differences between the two groups other than age. IL-1β was lower and eotaxin-1 higher in the group on opioid maintenance treatment than in the non-opioid group. No other inter-group differences in the remaining cytokine levels were found. In HCV infection patients, the impact of chronic opioid administration on peripheral circulating cytokine level is minimal.