Chronic HCV-infected Patients Research Articles

Abstract 3811: Impact of antiviral treatment status on risk of extrahepatic cancers in patients with chronic hepatitis C

Abstract Background: Eradiation of hepatitis C virus (HCV) infection has been shown to reduce risk of liver cancer among HCV patients; however, there has been spare data on the effect of antiviral treatment on the risk of extrahepatic cancers. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated whether antiviral therapy impacts the risk of extrahepatic cancers among patients with HCV. Methods: 17,485 HCV patients were included in the study, and they were followed until incidence of cancer including lung cancer, non-Hodgkin lymphoma (NHL), breast cancer or prostate cancer, death, or last follow-up. An extended landmark modeling approach was considered, which included time-varying covariates and propensity score justification for treatment selection bias and used generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk. Results: Compared to untreated patients, patients with HCV treatment had significantly lower risk of lung cancer for direct-acting antiviral (DAA) treatment (hazard ratio (HR) = 0.47, 95% CI, 0.30-0.72) and for interferon-based treatment (IFN) (HR = 0.33, 95% CI, 0.20-0.50). The risk of NHL was only reduced among patients receiving DAA treatment. There were no significant associations between HCV treatment and risks of breast and prostate cancer. Conclusion: Both DAA and IFN antiviral treatment independently reduce the risk of lung cancer, while the protective association with NHL was limited among HCV patients with DAA treatment. Our findings support the importance of timely initiation antiviral therapy in chronic HCV-infected patients. Citation Format: Menghua Tao, Jia Li, Trueman Wu, Stuart C. Gordon, Loralee B. Rupp, Sheri Trudeau, Scott D. Holmberg, Anne C. Moorman, Philip R. Spradling, Eyasu H. Teshale, Mark A. Schmidt, Yihe G. Daida, Mei Lu. Impact of antiviral treatment status on risk of extrahepatic cancers in patients with chronic hepatitis C [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3811.

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 (>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.

Molecular detection of Hepatitis C virus (HCV) genotypes and viral loads in chronic hcv infected patients in Kirkuk, Iraq

Abstract Background: Hepatitis C is a disease that has a significant global impact. The World Health Organization estimates that over 150 million people are chronically infected with the hepatitis C virus (HCV). Objectives: The purpose of the study was to make a quantitative determination of the hepatitis C viral load and genotype using real-time polymerase chain reaction (RT-PCR) and to determine how these factors relate to the HCV chronicity. Materials and Methods: A cross-sectional hospital-based study was carried out in Kirkuk city, Iraq. A total of 50 patients with chronic hepatitis C whose ages ranged from 20 to 75 years were the subjects of the study. The control group consisted of 30 apparently healthy persons admitted to the blood bank for blood donation. Five milliliters of blood were drawn for the molecular detection of HCV load and genotype by RT-PCR, detection of hepatitis C antibodies by enzyme-linked immunosorbent assay (ELISA), and biochemical analysis of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total serum bilirubin (TSB). Results: According to the research, 86% of chronic hepatitis C patients with ELISA-detected anti-HCV obtained positive PCR results. Statistically significant (P = 0.01). According to the study, more chronic hepatitis C patients (31 out of 43) had genotype 4 HCV than genotype 1a (27.91%). According to the study, genotype 4 chronic hepatitis C patients exhibited significantly higher viral loads than genotype 1a patients (1901.3 vs. 1693.41 IU/mL; P = 0.01). About 41.94% of men and 58.06% of females with chronic hepatitis C had genotype 4, whereas 33.3% of males and 66.67% of females had genotype 1a. Chronic hepatitis C patients had higher ALT, AST, ALP, and TSB levels than the control group, and the difference was very significant. ALT values were 64.69, 54.8, 285.5, and 4.33 mg/dL. This study found a connection between chronic hepatitis C viral load and ALT, AST, ALP, and TSB levels. Viral load rose as fibrosis progressed, according to this study. Patients without fibrosis had the lowest mean viral load (1235.5 IU/mL), followed by those with stage 1 fibrosis, whereas cirrhosis (stage 4) had the highest (2088.1 IU/mL). Non-fibrotic patients had the lowest virus burden. Conclusions: Genotype 4 of HCV was the most predominant genotype in Kirkuk city and there was a strong positive correlations of ALT and viral load with stages of fibrosis in patients with chronic hepatitis C.

Progression of the FIB-4 index among patients with chronic HCV infection and early liver disease

Background and aimsHistorical paired liver biopsy studies are likely to underestimate current progression of disease in patients with chronic hepatitis C virus (HCV) infection. We aimed to assess liver disease...

Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct-acting antivirals.

Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)-cell immunity. Direct-acting antivirals (DAA) effectively eliminate HCV, but the long-term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56+ NK cells of chronic HCV-infected patients before and 1 year after DAA therapy. Donor-variation was observed in NK-cell proteomes of HCV-infected patients, with 46 dysregulated proteins restored after DAA therapy. However, 30% of the CD56+ NK-cell proteome remained altered 1 year post-therapy, indicating a phenotypic shift with low donor-variation. NK cells from virus-negative cured patients exhibited global regulation of RNA-processing and pathways related to "stimuli response", "chemokine signaling", and "cytotoxicity regulation". Proteomics identified downregulation of vesicle transport components (CD107a, COPI/II complexes) and altered receptor expression profiles, indicating an inhibited NK-cell phenotype. Yet, activated NK cells from HCV patients before and after therapy effectively upregulated IFN-γ and recruited CD107a. Conversely, reduced surface expression levels of Tim-3 and 2B4 were observed before and after therapy. In conclusion, this study reveals long-term effects on the CD56+ NK-cell compartment in convalescent HCV patients 1 year after therapy, with limited abundance of vesicle transport complexes and surface receptors, associated with a responsive NK-cell phenotype.

Enolase represents a metabolic checkpoint controlling the differential exhaustion programmes of hepatitis virus-specific CD8+ T cells

ObjectiveExhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how...

Risk of adverse outcomes following treatment with direct acting antiviral drugs in HCV infected patients with liver cirrhosis

IntroductionHepatitis C virus (HCV) is the second major cause of death in Pakistan. Previously, interferon-based regimens were considered highly recommended therapy for HCV patients. Since 2015, interferon-based therapy has been replaced with interferon-free therapy also known as Direct Acting Antiviral (DAA) drugs. The treatment response of interferon-free regimens has been reported as highly effective treatment option with more than 90% sustained virological response (SVR) in chronic HCV infected patients in western countries of the world. ObjectiveThis study aims to analyze the treatment response of DAA drugs in HCV-infected Pakistani population with liver cirrhosis. MethodologyWe collected the total 94 sample of the HCV infected patients, from June 2020 to September 2020. Forty-six (46) patients were cirrhotic, and forty-eight (48) patients were non-cirrhotic. Data was analyzed using IBM SPSS version 21 software. ConclusionThe findings of our study suggest that the response rate was 82.60% in HCV cirrhotic patients and 68.75% in HCV non-cirrhotic patients. Our study showed that overall treatment response was independent of age and gender. We also observed some adverse effects such as hepatocellular carcinoma, portosystemic encephalopathy (PSE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), upper gastrointestinal bleeding (UGIB), ascites, among patients following treatment with interferon-free regimens.

Bone status and HCV infection in thalassemia major patients.

Hepatitis C virus (HCV) infection increases the risk for osteoporosis but this relationship has not been investigated among multi-transfused patients with thalassemia major (TM). We cross-sectionally explored the association of HCV infection with bone mineral density (BMD), vitamin D, and bone turnover biomarkers in TM. We considered 130 TM patients (41.89±5.49years, 67 females) enrolled in the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) Network. BMD measurements taken at the lumbar spine, femoral neck and total hip were expressed as Z-scores, with a BMD Z-score≤-2.0 indicating low bone mass. Z-scores were not associated with gender, iron overload indices, vitamin D levels, and biochemical bone turnover markers, but decreased with aging and in presence of hypogonadism and were directly correlated with body mass index (BMI). The prevalence of low bone mass was 70.7%. Three groups of patients were identified: 78 who never contracted the infection (group 0), 72 who cleared HCV (group 1), and 29 with chronic HCV infection (CHC) (group 2). All Z-scores progressively decreased according to HCV status from group 0 to group 2. Osteocalcin levels were significantly lower in groups 2 and 1 than in group 0. CHC patients were more likely to have low bone mass compared to HCV naive patients, after adjusting for age, BMI, hypogonadism, and pancreatic iron. In TM, CHC appears as one additive risk factor for low bone mass and osteocalcin may play a role in this association.

Association between Liver Stiffness and Liver-Related Events in HCV-Infected Patients after Successful Treatment with Direct-Acting Antivirals

Background and Objectives: Direct-acting antivirals (DAAs) are highly effective for the treatment of chronic hepatitis C virus (HCV) infection, but the risk of liver-related events and hepatocellular carcinoma (HCC) remains after successful therapy. We aimed to evaluate post-treatment changes in liver stiffness (LS) and identify a cut-off LS value for predicting such events in chronic HCV-infected patients receiving DAA. Materials and Methods: A total of 185 patients who had achieved sustained virologic response (SVR) after DAA therapy were included. Baseline characteristics and laboratory results were retrospectively abstracted. LS was measured by transient elastography at baseline, 12, 24, 48, and 96 weeks after SVR. FIB-4 index was assessed at baseline and 48 weeks after SVR. Development of liver-related events (hepatocellular carcinoma (HCC), portal-hypertension-related decompensation, listing for transplantation, and mortality) after SVR were identified. The association between liver fibrosis and the occurrence of liver-related events was analyzed using Cox regression analysis. Results: Significant differences in LS values were observed between baseline and 24, 48, 72, and 96 weeks after SVR. FIB-4 index at 48 weeks after SVR was significantly lower than the FIB-4 index at baseline. During the 41.6-month follow-up time, the incidence rates of all liver-related events and HCC were 2.36 and 1.17 per 100 person-years, respectively. Age, LS ≥8 kPa, and FIB-4 ≥1.35 at 48 weeks post-SVR were significantly associated with the occurrence of any liver-related events. By multivariate analysis, LS ≥8 kPa at 48 weeks post-SVR remained significantly associated with any liver-related events, with an adjusted hazard ratio (95%CI) of 5.04 (1.01-25.26), p = 0.049. Conclusions: Despite a significant reduction in LS after SVR, patients with LS ≥8 kPa at 48 weeks after SVR should be regularly monitored for liver-related complications, particularly HCC development.

Hepatitis C micro-elimination through the retrieval strategy of patients lost to follow-up

Background and aimWorld Health Organization sets up an ambitious and attainable goal to eliminate hepatitis C (HCV) by 2030. The previous diagnosed HCV patients lost to follow-up were considered as an important target group for HCV elimination. We conducted a call back program to retrieve the lost to follow-up HCV patients and link them to care in our hospital. By analyzing and comparing our result with that from other studies, we wish to improve our retrieval strategy and provide our experience to the general communities.MethodsA list of the patients with a medical record showing seropositive for antibody to HCV (anti-HCV Ab) from 2004 to 2017 was retrieved by the department of intelligent technology of our hospital. Three dedicated staff members reviewed the patients’ electronic medical records (EMRs) and recruited the patient lost follow-up to the call back program. The staff members contacted the qualified patients by telephone and inquired about their opinions for treating their chronic HCV infection. We also informed the patients about the retrieval strategy and why we contact them. As our National Health Insurance request, we gave all patient one informed consent for hepatitis C treatment. Informed consents have been obtained from all patients. Referrals to our gastroenterology unit (GU) were arranged for the patients who would like to continue their chronic HCV care in our hospital.ResultsThere were 31,275 anti-HCV positive patients. We included 11,934 patients (38.2%) into the call back system and contacted them by telephone. Based on the response to our call, we ascertained 1277 eligible cases (10.7%) for retrieval. The patients who were younger (< 55), lived in Taoyaun City or had tested positive for anti-HCV Ab at the department of internal medicine department had an increased rate of successful call back. There were 563 patients (44.1%) returning to our GU. Of them, 354 patients (62.9%) were positive for HCV viremia. 323 patients (91.2%) received the DAAs treatment. The SVR12 with Grazoprevir + elbasvir, Glecaprevir + pibrentasvir, Sofosbuvir + ledipasvir and Sofosbuvir + velpatasvir were 97.9%, 98.8%, 100% and 97.5%, respectively.ConclusionsCall back system can expand our reach to those unaware or ignoring chronic HCV infection patients and link them to treatment.

Association between Direct-Acting Agents Adherence and Health-Related Quality of Life of Patients with Hepatitis C.

This observational study included all patients undergoing HCV treatment with direct-acting antiviral (DAA)-based therapy between May 2020 and September 2023 at the Dolj County Hospital, Romania. The aim was to investigate adherence to DAAs among HCV patients and the effect of this treatment on their health-related quality of life (HRQoL). Chronic HCV-infected patients were prospectively evaluated at baseline (T0), before the beginning of treatment, and 12 weeks after completing DAAs treatment (T1). The HCV-AD10 questionnaire was used to measure DAAs adherence, and HRQoL was assessed with the 15D instrument. The 15D questionnaire was administered at two time points: T0 and T1, during which the Sustained Virologic Response (SVR) was also measured. The primary outcome was DAAs adherence, with secondary outcomes including quality of life (QoL), and sustained virologic response (SVR). DAAs based therapy was initiated for 368 patients, all of whom were health insured. HRQoL and psychological state of HCV patients clinically improved. The DAAs adherence was very good (mean±SD, 91.51±8.34), being influenced by age (younger patients were much adherent, rho=-0.112, p-value=0.031) and the severity of the disease (patients with more severe hepatitis were less adherent, rho=-0.167, p-value=0.001). DAAs had a significant effect on improving HRQoL of HCV patients, but did not influence medication adherence.

Transforming Growth Factor Β as a Marker of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Virus Infection.

The Transforming Growth Factor-beta (TGF-β) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role in hepatocarcinogenesis is controversial. To highlight the role of Transforming Growth Factor β as a marker of Hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. Ninety subjects were enrolled in this study, classified into three groups: Group I (chronic HCV group) included 30 patients with chronic HCV infection; Group II (HCC group) include 30 patients having HCC and chronic HCV infection and Group III consisted of 30 age and sex-matched healthy controls. TGF-β was evaluated in all the enrollees and its levels were correlated to liver function and other clinical parameters. TGF-β was found significantly higher in HCC group than in control and chronic HCV (P<0.001). In addition, it was correlated with biochemical and clinical parameters of cancer. Patients with HCC showed increased level of TGF-β compared to chronic HCV infection patients and controls.

Chronic Hepatitis C: Acute Exacerbation and Alanine Aminotransferase Flare.

The hepatitis C virus (HCV) causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma, as well as extrahepatic manifestations such as malignant lymphoma. Currently, direct-acting antiviral agents (DAAs) against HCV infection can lead to a sustained virological response (SVR) in almost all HCV-infected patients. In this review article, we discuss acute exacerbation and alanine aminotransferase (ALT) flare in patients with chronic HCV infection. Although acute liver failure caused by HCV infection is rare, careful attention should be paid to the cases with ALT elevation during the natural course of chronic HCV infection. HCV genotype 2 infection, the use of rituximab, and a higher dose of corticosteroid are factors associated with HCV acute exacerbation and ALT flare. Treatment regimens for cancer have been interrupted or changed due to ALT flare due to HCV infection in some patients undergoing chemotherapy for cancer. The pathogenesis of HCV acute exacerbation and ALT flare could involve cellular as well as humoral immune responses. In the DAA era, the earlier introduction of DAAs may prevent chronic HCV-infected patients with acute exacerbation and ALT flare from developing into a more severe form, although DAAs may not be effective for all of them.

Performance of algorithms for identifying patients with chronic hepatitis B or C infection in the french health insurance claims databases using the ANRS CO22 HEPATHER cohort.

The validity of algorithms for identifying patients with chronic hepatitis B or C virus (HBV or HCV) infection in claims databases has been little explored. The performance of 15 algorithms was evaluated. Data from HBV- or HCV-infected patients enrolled between August 2012 and December 2015 in French hepatology centres (ANRS CO22 HEPATHER cohort) were individually linked to the French national health insurance system (SNDS). The SNDS covers 99% of the French population and contains healthcare reimbursement data. Performance metrics were calculated by comparing the viral status established by clinicians with those obtained with the algorithms identifying chronic HBV- and HCV-infected patients. A total of 14 751 patients (29% with chronic HBV and 63% with chronic HCV infection) followed-up until December 2018 were selected. Despite good specificity, the algorithms relying on ICD-10 codes performed poorly. By contrast, the multi-criteria algorithms combining ICD-10 codes, antiviral dispensing, laboratory diagnostic tests (HBV DNA or HCV RNA detection and quantification, HCV genotyping), examinations for the assessment of liver fibrosis and long-term disease registrations were the most effective (sensitivity 0.92, 95% CI, 0.91-0.93 and specificity 0.96, 95% CI, 0.95-0.96 for identifying chronic HBV-infected patients; sensitivity 0.94, 95% CI, 0.94-0.94 and specificity 0.85, 95% CI, 0.84-0.86 for identifying chronic HCV-infected patients). In conclusion, the multi-criteria algorithms perform well in identifying patients with chronic hepatitis B or C infection and can be used to estimate the magnitude of the public health burden associated with hepatitis B and C in France.

Sustained virological response (SVR) and safety of two direct acting anti-viral (DAA) combination therapies in Chronic Hepatitis-C infected patients of Lahore, Pakistan. A Randomized Controlled Trial

Chronic Hepatitis C (HCV) is a deadly infection affecting &gt; 185 million people worldwide and led to liver cirrhosis, hepatocellular carcinoma, or liver failure. Recently, treatment regimens of chronic HCV have entered the era of direct acting anti-virals (DAAs). Sustained virological response (SVR) rate is one of the best available tools to evaluate the efficacy of DAA treatments. Objective: To compare SVR rate and safety of two combinations of DAA treatments (Sofosbuvir and Daclatasvir vs Sofosbuvir and Velpatasvir) in chronic HCV infected patients of Lahore, Pakistan. Methods: Present randomized controlled trial was conducted at Mayo Hospital, Lahore, Pakistan and recruited 76 chronic HCV infected patients according to Consort guidelines. Registered patients were allocated in two groups by lottery method. Group A received sofobuvir with daclatasvir (SOFO + DCV) while group B received sofobuvir with velpatasvir (SOFO + VEL) treatment for 12 weeks. Response to therapy was evaluated in terms of SVR after 24 weeks and safety profile of the drug. Results: Both treatment groups showed high SVR 24 weeks after the completion of therapy. Group A (SOFO + DCV) presented 92% SVR while group B showed 97% SVR rate. Both DAA combination therapies presented good efficacy and safety profile. Few contraindications noted during the treatment included fatigue, arthritis, headache, loss of appetite and anemia. Conclusions: The efficacy of both DAA combination therapies was comparably high with &gt; 90% SVR rate. Group A proved safer as compared to group B. Studied DAA combinations are effective treatment options for chronic HCV treatment planning.

Usefulness of the SAF score to characterize NAFLD/NASH in non-cirrhotic HCV patients

BackgroundThe SAF score (steatosis, activity, and fibrosis) has been developed for the assessment of the histological severity of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the usefulness of the SAF score in a homogenous cohort of Egyptian patients with chronic HCV infection (CHC) without any alcohol consumption and without cirrhosis. We performed a prospective cross-sectional study including 70 consecutive Egyptian patients with chronic HCV infection to assess the usefulness of the SAF score to characterize NAFLD/NASH in non-cirrhotic HCV patients. The inclusion criteria included positive serum anti-HCV IgG antibody and positive HCVRNA, absence of treatment, and absence of cirrhosis (fibrosis score < F4). Patients were divided into two groups: with metabolic syndrome (MS) and without metabolic syndrome (non-MS). All patients were exposed to thorough history taking, full clinical examination, and laboratory and ultrasound assessment. Histopathologic evaluation of the liver biopsy for the assessment of steatosis, activity, grade, and fibrosis stage was assessed by 2 pathologists with experience in liver diseases.ResultsWe found that the degree of fibrosis increases with aging. Liver biopsies from CHC patients with metabolic syndrome (MS) exhibited a significantly higher stage of fibrosis than biopsies from those without MS; however, the grade of inflammation did not differ significantly between the two groups. No significant correlation was found between the SAF score and the body mass index (BMI) or serum HCV RNA. No significant relation between SAF score, fibrosis, and MS. No significant relation was found between the MS and the level of HCV viremia.ConclusionWe concluded that steatosis was associated with the fibrosis stage, independently of MS. This suggests that in this population, steatosis might be more related to HCV infection than to NAFLD and that fibrosis progression might be related, at least in part, to the steatosis process, i.e., virus-associated fatty liver disease (VAFLD).

Micro-elimination of hepatitis C in patients with chronic kidney disease: an Egyptian single-center study

Background and aimsMicro-elimination of hepatitis C in renal patients is crucial. This study aims to assess the efficacy and safety of directly acting antivirals in chronic kidney disease patients and the effect of treatment on kidney functions.ResultsThis prospective cohort study included 77 chronic HCV-infected patients with chronic kidney disease. Patients were consented and treated for 12 weeks with either sofosbuvir and daclatasvir ± ribavirin if glomerular filtration rate was > 30 mL/min per 1.73m2 or ritonavir-boosted paritaprevir-ombitasvir-ribavirin if it was < 30 mL/min per 1.73m2. Patients were divided into two categories (responders versus non-responders). Predictors of response to treatment were statistically analyzed through logistic regression analysis. Sixty-two patients received ritonavir-boosted paritaprevir-ombitasvir-ribavirin, 3 received sofosbuvir and daclatasvir, and 12 received sofosbuvir and daclatasvir plus ribavirin. Most patients were on hemodialysis (n = 36) while 31 were stage 3 kidney disease. All patients completed their treatment course; ribavirin doses were adjusted or stopped in patients who developed anemia (40%). Seventy-two patients (93.5%) achieved sustained virological response 12 weeks following end-of-treatment. Five patients (6.5%) were non-responders, 4 of whom were on hemodialysis (p = 0.179). All non-responders were on ritonavir-boosted paritaprevir-ombitasvir-ribavirin. The mean serum creatinine level at weeks 4 and 8 of treatment demonstrated significant improvement compared to pretreatment values (p < 0.001) in patients on conservative therapy.ConclusionTreatment of chronic kidney disease patients for chronic hepatitis C with directly acting antivirals is safe, efficacious with high response rates and likely to improve renal functions if started early in the course of kidney disease.

Disheveled EGL-10 and pleckstrin domain-containing 5 rs1012068 T/G gene polymorphism among Egyptian chronic HCV-infected patients: disease progression and related complications

Hepatitis C virus (HCV) infection related complications including fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are influenced by host genetic factors. Identification of emerging host genetic variations is of promising value. Disheveled EGL-10 and pleckstrin domain-containing 5 (DEPDC5) rs1012068 T/G gene polymorphism has been implicated in liver disease. This study aimed to assess DEPDC5 rs1012068 T/G gene polymorphism with disease progression and related complications among Egyptian patients with chronic HCV infection. Sixty chronic HCV-infected patients and 60 apparently healthy controls were recruited in this study. Patients were classified into 20 with liver fibrosis, 20 with liver cirrhosis and 20 with HCC; all recruited from Outpatients Clinic and Tropical Medicine Inpatient Department, Faculty of Medicine, Beni-Suef University Hospital. DEPDC5 rs1012068 T/G gene polymorphism was assayed by real time-polymerase chain reaction (RT-PCR) TaqMan allelic discrimination. DEPDC5 rs1012068 GG genotype and G allele variants showed statistically significant higher frequency among patients with liver fibrosis when compared to controls (OR (95% CI) 10.500 (2.086 - 52.851), P= 0.004 and 0.388 (0.155 - 0.971), P= 0.011), respectively. DEPDC5 rs1012068G allele variant showed statistically significant higher frequency among patients with liver fibrosis when compared to HCC patients (OR (95% CI) 3.316 (1.286 - 8.550), P= 0.012) and to both HCC and cirrhosis patients (OR (95% CI) 2.579 (1.187-5.645), P= 0.016). In conclusion, our results suggest that DEPDC5 rs1012068 G allele could be considered genetic risk allele for liver fibrosis and disease progression among Egyptian patients with chronic HCV infection.

Geographic Distribution of HCV Genotypes and Efficacy of Direct-Acting Antivirals in Chronic HCV-Infected Patients in North and Northeast China: A Real-World Multicenter Study.

Objective To assess the geographic distribution of HCV genotypes, effectiveness, and safety of DAA treatment for HCV-infected patients in North and Northeast China. Methods The geographic distribution of HCV genotypes was analyzed in 2162 patients recruited from April 2018 to February 2021. Sustained virologic response rates at 12 (SVR12) or 24 (SVR24) weeks posttreatment and safety were analyzed in 405 patients who completed DAA treatment according to patient baseline characteristics and treatment. Results Four genotypes and six subtypes were identified as follows: 1b (1187, 54.90%), 2a (790, 36.54%), 3a/b (134, 6.20%), 6a/n (44, 2.04%), mixed genotypes (2a-6a or 2a-3a) (7, 0.32%). Overall, 99.01% patients achieved SVR12, while 98.43% achieved SVR24. All patients treated with elbasvir/grazoprevir (EBR/GZR), sofosbuvir/velpatasvir ± ribavirin (SOF/VEL ± RBV), and SOF/ledipasvir (LDV) achieved SVR12 or SVR24; 92.86% SVR12 and 95.83% SVR24 were observed in patients using SOF + RBV. SVR12 was higher in noncirrhosis versus compensated cirrhosis patients (100% vs. 97.09%, p=0.022). No severe drug-related adverse event was observed. Conclusions Genotypes 1b and 2a were dominant subtypes in North and Northeast China. The approved drug regimens EBR/GZR and SOF/LDV for subtype 1b and SOF/VEL for nongenotype 1b are the optimal effective and safety profile.

Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients.

Background and AimsChronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies.MethodsWe screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients’ baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment.ResultsHigh IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039).ConclusionsThere were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.