Genetic influence of IFN-γ gene polymorphisms on hepatitis C progression and recovery.

Background and Aim: Interleukin-28B (IL-28B) polymorphism is a predictor of sustained virologic response (SVR), spontaneous clearance and personalizing therapy of hepatitis C virus (HCV). This study aimed to determine IL28B rs12979860 polymorphism among chronic hepatitis C (CHC) Egyptian patients as a step in personalized HCV therapy and pharmacogenomics. Methods: CHC Egyptian patients were received sofosbuvir (SOF) plus pegylated interferon (PEG-IFN) and ribavirin (RBV) for 12 weeks. A total of 82 HCV infected Egyptian patients and 27 healthy individuals were included in the present study. CHC Patients were classified as achieving SVR if plasma HCV-RNA was undetectable (group A) and non-responders if plasma HCV-RNA was detectable (group B). IL28B genotypes were analyzed and their associations with SVR were selected. Results: The end of treatment response (ETR) rate was 100%. However, SVR12 was 76.8% (group A) and 23.2% relapsed (group B). Among studied CHC patients, 50% were IL-28B TT, 40.2% CT, and 9.8% CC. while the percentage of their frequencies in the healthy persons were 18.5%, 51.8%, and 29.6%, respectively. These results showed that the frequencies of TT genotypes were more prevalent in HCV patients. The genotype CC (n=8) achieved higher rates of SVR in group A (87.5%) than relapsed patients in group B (12.5%) and it had the least prevalence in group B compared with the frequencies of CT (21.2%) and TT (26.9%) genotypes. These results showed that CC genotype was associated with SVR. Conclusions: It can be concluded that the individuals with IL28B TT genotype are more susceptible to HCV infection in Egyptian patients and relapse. Moreover, IL-28B CC is useful for pretreatment prediction of the outcome of HCV treatment. Hence, IL28B polymorphism could be considered as a pharmacogenetic predictor in personalized HCV therapy and pharmacogenomics during SOF plus PEG-IFN and RBV therapy for chronic hepatitis C Egyptian patients.

ObjectiveTo investigate the association of the rs7257062T/C polymorphism of ASP gene with coronary heart disease (CHD) and the influence of serum lipid levels in Chinese Han population patients of Xinjiang.MethodsThe...

Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.35-0.83, p = 0.005; OR = 0.26, 95% CI = 0.18-0.39, p < 0.001; and OR = 0.19, 95% CI = 0.10-0.35, p < 0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR = 1.70, 95% CI = 1.20-2.40, p = 0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR = 0.22, 95% CI = 0.14-0.33, p trend < 0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT + TT) genotypes were significantly lower in the older (OR = 0.31, 95% CI = 0.15-0.65, p = 0.002) and female (OR = 0.30, 95% CI = 0.17-0.52, p < 0.001) subgroups, and rs13170556 (TC + CC) genotypes exhibited the same effect in all subgroups (all p < 0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC + CC) genotypes were significantly more frequent in the younger (OR = 1.86, 95% CI = 1.18-2.94, p = 0.007) and female (OR = 2.38, 95% CI = 1.48-3.83, p < 0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.

Genetic variations of IL-28B and PD-1 are in association with the susceptibility and outcomes of HCV infection in Southeast China

Background: Hepatitis C virus (HCV) infection is a major health problem in the United States and breast cancer is the second most common cancer in US women. Despite these prevalent diseases, there is limited information available on the effects of a concurrent HCV infection among breast cancer patients receiving chemotherapy and the problems they face during their treatment. There are limited guidelines for chemotherapy treatment in HCV positive breast cancer patients. Methods: We performed a retrospective 2:1 matched case control analysis on breast cancer patients with a confirmed active HCV infection who received chemotherapy at Boston Medical Center between January 2000 and April 2015. Cases with HCV infection (n=6) were matched with controls (n=12) who were HCV negative. The controls were matched on age (decade) of diagnosis, stage of breast cancer, and intended chemotherapy regimen. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during the treatment period in these patients from their medical records. Statistical analysis was done using R version 3.4.0 to compare these outcomes of interest between the two groups. Fisher’s exact and Wilcoxon rank sum tests were used to compare the categorical and continuous variables respectively. Results: The HCV positive group was at a significantly higher risk of dose delays (100% vs. 33%, p = 0.01), dose changes (67% vs. 8%, p = 0.02), and hospitalization during chemotherapy (83% vs. 25%, p = 0.04) than their HCV matched controls. The risk of getting a dose delay due to hematotoxicity was significantly higher in the HCV positive group than the HCV negative group (83% vs. 8%, p = 0.003). The HCV positive patients took longer time to complete their treatment cycles than the HCV negative group. Conclusions: Chronic HCV infection in breast cancer patients receiving chemotherapy may be complicated by their active HCV infection. Treatment challenges due to dose changes, dose delays and hospitalizations were significantly more common when compared to controls. Chemotherapy delays and dose changes during breast cancer treatment has a negative consequence. In the era of curative treatment for HCV, future studies focused on the effect and treatment of concurrent HCV and breast cancer treatment is warranted. Citation Format: Saptaparni Ghosh, Minghua L Chen, Janice Weinberg, Naomi Y Ko. Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients: A retrospective chart analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-12.

Cytokines and liver injury in chronic HCV genotype 4 infection

Hepatitis C virus (HCV)-induced cirrhosis is the most common indication for liver transplantation (LT). However, graft reinfection is nearly universal. The choice of immunosuppression, including the calcineurin inhibitor (CNI), may have some effect on severity of recurrence and graft survival. In addition, HCV recurrence may have some impact on metabolism of immunosuppressive drugs. In this retrospective study, we examined the dose and blood levels of tacrolimus (TAC) and cyclosporin A (CYA) in HCV patients consecutively undergoing transplantation (TAC, n = 44; CYA, n = 60) and surviving 12 months post-LT. In addition, we examined the CNI dose and blood levels in an age- and gender-matched comparison group of patients who were transplanted for alcoholic liver disease (ALD) (TAC, n = 44; CYA, n = 47). During the 12-month period of observation, TAC levels were significantly higher for HCV than for ALD patients (P = 0.002). The dose of TAC decreased over time for both HCV and ALD patients (P < 0.001), but the reduction was greater for HCV patients (P = 0.03). CYA dose decreased over time for both groups (P < 0.001) but a greater reduction was observed for the HCV group (P = 0.007). For both HCV and ALD patients, CYA levels decreased over time (P < 0.001) but there was no significant difference between HCV and ALD patients. Thus, to maintain comparable blood levels, a greater reduction of dose was required for HCV than for ALD patients. In conclusion, our observations demonstrate a likely effect of HCV infection on CNI metabolism, an effect that is not clearly due to graft damage. Physicians need to be alert to this interaction and to the need to respond quickly to changes in CNI levels that may be associated with HCV infection and with HCV clearance during antiviral therapy.

Low cost detection of hepatitis C virus RNA in HCV infected patients by SYBR Green I real-time PCR

BACKGROUNDCholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus (HCV). APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection. The relationship between cholesterol, APOE alleles, and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIMTo investigate the role of APOE -ε2, -ε3, and -ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODSA total of 299 treatment-naïve HCV patients were included in this retrospective study. Patients were stratified in chronic hepatitis C (CHC) (n = 206) and spontaneous clearance (SC) (n = 93). A clinical record was registered. Biochemical tests were assessed by dry chemistry assay. APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTSTotal cholesterol, low-density lipoprotein cholesterol (LDL-c), triglycerides, and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOE ε4 allele (12.4% vs 7.3%). SC patients were overweight (54.8%). The ε4 allele was associated with SC (OR = 0.55, 95%CI: 0.31-0.98, P = 0.042) and mild fibrosis (F1-F2) in CHC patients (OR 0.091, 95%CI 0.01-0.75, P = 0.020). LDL-c ≥ 101.5 mg/dL (OR = 0.20, 95%CI: 0.10-0.41, P < 0.001) and BMI ≥ 26.6 kg/m2 (OR= 0.37, 95%CI: 0.18-0.76, P < 0.001) were associated with SC status; while ALT ≥ 50.5 IU/L was negatively associated (OR = 5.67, 95%CI: 2.69-11.97, P < 0.001).CONCLUSIONIn SC patients, the APOE ε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

BackgroundThe hepatitis C virus (HCV) infection is a candidate disease for micro-elimination. Accurate baseline HCV prevalence estimation is essential to monitor progress to micro-elimination but can be methodologically challenging in low-endemic regions like the Netherlands due to lack of disaggregated data by age or risk-groups on the number of chronic HCV patients (i.e. HCV RNA positive). This study estimates the number of patients that has had a chronic HCV infection (ever-chronic) in the Utrecht region of the Netherlands.MethodsIn the Utrecht province in the Netherlands, positive HCV tests from the period 2001–2015 from one diagnostic center and four hospital laboratories were collected. A two-source capture-recapture method was used to analyze the overlap between the two registries (with 92% HCV RNA and 8% HCV immunoblot confirmed infections) to obtain the number of ever-chronic HCV infections in the Utrecht region. The Utrecht region was defined as an area with a 25 km radius from the Utrecht city center. The current viremic HCV prevalence was calculated by taking into account the proportion of cured and deceased HCV patients from a local HCV retrieval (REACH) project.ResultsThe estimated number of ever-chronic HCV patients was 1245 (95% CI 1164–1326) and would indicate a prevalence of 0.10 (95% CI 0.09–0.10) in the Utrecht region. This is 30% (95% CI 21–38%) more than the number of known HCV patients in the records. The ever-chronic HCV prevalence was highest in the 1960–1969 age cohort (0.16; 95% CI 0.14–0.18). Since 50% of the HCV patients were cured or deceased in the REACH-project, the number of current viremic HCV patients was estimated at 623 individuals in the Utrecht region (prevalence 0.05%).ConclusionThe results of this study suggest a low ever-chronic and current HCV prevalence in the Utrecht area in the Netherlands, but other studies need to confirm this.

Health-state utilities and quality of life in hepatitis C patients

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level. The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group). The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (r(s) = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(r(s) = 0.38, P = 0.0001). The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman's rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation.

Background: Hepatitis C virus (HCV) chronically infects an estimated 170 million people worldwide. Approximately 30% of patients who develop acute hepatitis C recover spontaneously, signaled by improved symptoms, normalized liver-related chemistries, loss of HCV RNA from serum, and the development of HCV antibody. Cirrhosis rates become significant after 20 years of HCV infection. Haemodialysis is a process that uses a man-made membrane (dialyzer) to clear wastes such as urea from the blood, restore the proper balance of electrolytes in the blood and eliminate extra fluid from the body. Vascular calcification is common in patients with advanced haemodialysis and is associated with poorer outcomes. Objectives: The aim was to evaluate the possible impact of chronic HCV infection on coronary calcification in prevalent haemodialysis patients in Naval Forces hospital, Alexandria, Egypt and its relation to demographic data, haemodialysis data and other laboratory findings. Patietns and methods: This cross-sectional study was carried out on 60 patients with at least one year duration on regular haemodialysis; 30 HCV negative prevalent haemodialysis patients and 30 HCV positive prevalent haemodialysis patients. Results: Our study revealed that HCV negative patients included 25 (83.3%) males and 5 (16.7%) females, their mean age was 51.67 ± 6.91 years. The mean haemodialysis duration was 7.5 ± 1.89 years. There were statistically a high significant difference between HCV negative prevalent haemodialysis patients and HCV positive prevalent haemodialysis patients regarding AST, significant differences regarding ALT and albumin and non-significant differences regarding bilirubin, prothrombin time, international normalized ratio, cholesterol and total glycerides. But, there were no significant differences between HCV negative prevalent haemodialysis patients and HCV positive prevalent haemodialysis patients regarding CKD-MBD parameters (including PO4 and iPTH), except for calcium which exhibited statistically a significant difference. Also, there were no significant differences between HCV negative prevalent haemodialysis patients and HCV positive prevalent haemodialysis patients regarding creatinine, sodium and potassium, significant differences regarding URR, C-reactive protein and a high significant difference regarding Ca score. In HCV negative prevalent haemodialysis patients, there were statistically significant correlations regarding dialysis duration and international normalized ratio and high significant correlations between Ca score and creatinine, AST and prothrombin time. In HCV positive prevalent haemodialysis patients, there were statistically significant correlations between Ca score and dialysis duration and creatinine. Other correlations were insignificant. There were non-significant relations between Ca score and gender and dialysis vascular access. Conclusion: A very high incidence of vascular calcification was found in chronic haemodialysis patients in our study as compared to other studies. Vascular calcification is correlated with many risk factors and control of the modifiable risk factors can help to decrease prevalence of vascular calcification.

Validation of the FIB-4 index for evaluation of fibrosis in patients with recurrent hepatitis C after living donor liver transplantation: A single center experience.