Advanced Hepatitis C Virus Research Articles

Individualized HCC surveillance using risk stratification scores in advanced fibrosis and cirrhotic HCV patients who achieved SVR: Prospective study.

Several HCC risk stratification scores were developed; however, none has been prospectively validated. The primary aim is to validate the clinical utility of six HCC risk scores in large prospective study of F3-4 patients achieving SVR following DAAs according to EASL guidelines. The secondary aim is to explore whether individualized risk stratification improves detection of HCC at early stages amenable to curative treatment. This prospective study included two cohorts: Egyptian Liver Research Institute and Hospital (ELRIAH) cohort of 463 chronic HCV patients with advanced liver disease (F3 and F4) achieved SVR with a follow-up every 6 months according to EASL guidelines using 6 simple HCC risk scores and Tanta cohort of 492 comparable patients where individualized surveillance intervals were tailored based on HCC risk assessments using GES score as follows: low-risk patients were followed yearly, intermediate-risk every 6 months and high-risk every 2-3 months. All scores, except Watanabe post, successfully stratified patients into low-, intermediate- and high-risk groups, with log-rank p-value of 0.001 and Harrell's C ranging from 0.669 to 0.728. Clinical utility of these scores revealed that the highest percentage of patients classified as low risk was 42.5% using the GES, while the lowest was 8.9% using the aMAP. ELRIAH cohort, 25 patients developed HCC with 52% diagnosed at BCLC 0 and A. Tanta cohort, 35 patients developed HCC, with 80% diagnosed at BCLC 0 and A. Individualized risk stratification using HCC risk scores was associated with improved early-stage detection and receipt of curative treatment.

Identify, screen and treat via electronic pathway: a semiautomated approach to retriaging a liver clinic waitlist.

Long specialist outpatient waiting lists are a source of clinical risk. Triage assignment is based on subjective assessment of referrals and fails to account for dynamic changes in disease status while patients await clinical review. To pilot an innovative triage method using a trifold approach to conduct noninvasive assessment of fibrosis and to determine the feasibility of reflex hepatitis C virus (HCV) polymerase chain reaction (PCR) testing. A total of 1006 patients awaiting an initial liver clinic appointment at a tertiary Australian hospital were sent a short message service (SMS) requesting a blood test be completed. The first 60 patients received an SMS only, and the subsequent 946 patients also received a phone call from a Liver Care Guide (LCG), a nonclinician employed to increase patient engagement. Liver fibrosis assessment through noninvasive testing was performed using an aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB4) score. Patients with an APRI ≥1, FIB4 ≥3.25 or positive HCV PCR were retriaged to Category 1. Four hundred ninety (49%) patients completed testing and 40 (4%) were triaged to Category 1. Subanalyses demonstrated increased response rates with LCG input (P = 0.012). Retriaged patients had been on the waitlist for a median of 216 days, exceeding initial category recommendations. This study successfully implemented a semiautomated strategy that prioritises patients with probable advanced liver disease or active HCV, demonstrating enhanced patient engagement with LCG support. It highlights the burden of patients referred for specialist care and the need for innovative strategies for monitoring and objective risk stratification.

Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study.

Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population. We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment. From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38-1.77). Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data.

Effect of dietary branched chain amino acids on liver related mortality: Results from a large cohort of North American patients with advanced HCV infection.

Branched chain amino acids (BCAA) supplementation may reduce the incidence of liver failure and hepatocellular carcinoma in patients with cirrhosis. We aimed to determine whether long-term dietary intake of BCAA is associated with liver-related mortality in a well-characterized cohort of North American patients with advanced fibrosis or compensated cirrhosis. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. The analysis included 656 patients who completed two Food Frequency Questionnaires. The primary exposure was BCAA intake measured in grams (g) per 1000 kilocalories (kcal) of energy intake (range 3.0-34.8 g/1000 kcal). During a median follow-up of 5.0 years, the incidence of liver-related death or transplantation was not significantly different among the four quartiles of BCAA intake before and after adjustment of confounders (AHR 1.02, 95% CI 0.81-1.27, P-value for trend = 0.89). There remains no association when BCAA was modeled as a ratio of BCAA to total protein intake or as absolute BCAA intake. Finally, BCAA intake was not associated with the risk of hepatocellular carcinoma, encephalopathy or clinical hepatic decompensation. We concluded that dietary BCAA intake was not associated with liver-related outcomes in HCV-infected patients with advanced fibrosis or compensated cirrhosis. The precise effect of BCAA in patients with liver disease warrants further study.

Abstract 2265: HCV seroprevalence and RNA detection rates across Florida, 2015-2018

Abstract Chronic hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma in the U.S. While there is no vaccine to prevent HCV, current treatment can cure >90% of infections. About 3 million US residents have been exposed to HCV and 65%-75% remain chronically infected. In response to increasing incidence of HCV infection in younger ages, the US Preventive Services Task Force and the Centers for Disease Control and Prevention (CDC) broadened HCV screening recommendations from baby boomers (born 1945-1965) to all adults aged 18-79 in 2020. Florida has the third highest number of individuals living with HCV in the U.S. (n=151,000). Therefore, our study aimed to identify current high-risk groups that may require advanced HCV screening and targeted HCV management using the OneFlorida Clinical Research Consortium, a state-wide health database representing a diverse set of more than one million individuals for the years 2015-2018. All HCV antibody and viral RNA tests ordered and completed during the study period were used to describe HCV seroprevalence (evidence of current/past HCV infection) and HCV viral load (active infection). Logistic regression was used to determine the odds of HCV seroprevalence or active infection. Analyses were adjusted for sex, race/ethnicity, birth cohort, and HIV status, then stratified by birth cohort and HIV status. Overall, HCV seroprevalence and active infection rates were highest among white/non-Hispanics, males, and baby boomers. However, stratified results revealed distinct risk groups across year and race/ethnicity. Odds of a positive HCV antibody test were higher among Black/non-Hispanic individuals born before 1945 (aOR: 2.74; 95% CI: 1.98-3.78) and 1945-1965 (aOR: 1.46; 95% CI: 1.36-1.56) when compared to white/non-Hispanics. However, in individuals born after 1966, Black/non-Hispanics had lower odds of a positive HCV antibody test (1966-1985, aOR: 0.28; 95% CI: 0.25-0.32; after 1985, aOR: 0.15; 95% CI: 0.13-0.18), with white/non-Hispanics having the highest HCV seroprevalence in younger birth cohorts. The same was observed for HCV active infection. When stratified by HIV status, odds of HCV seroprevalence were highest among baby boomers, regardless of HIV status. However, odds of an active HCV infection across birth cohorts differed by HIV status. Among people living with HIV, active infection was lower in people born after 1985 compared to baby boomers (aOR: 0.45; 95% CI: 0.24-0.86). In contrast, active infection was higher among individuals born after 1985 (aOR: 1.48; 95% CI: 1.28-1.70) for HIV-uninfected individuals in Florida. Patterns of seroprevalence and active HCV infection identified in our study support the recent shift form age and risk based screening guidelines to universal screening. This study provides further guidance to support a strategy for early detection and treatment of HCV to prevent hepatocellular carcinoma among diverse populations. Citation Format: Brittney L. Dickey, Anna E. Coghill, Richard R. Reich, Julie Rathwell, Susan T. Vadaparampil, Shannon M. Christy, Richard Roetzheim, Elizabeth Shenkman, Anna R. Giuliano. HCV seroprevalence and RNA detection rates across Florida, 2015-2018 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2265.

Determination of Risk Factors Associated with the Failure of 12 Weeks of Direct-Acting Antiviral Therapy in Patients with Hepatitis C: A Prospective Study.

Introduction Direct-acting antivirals (DAAs) have significantly improved the efficacy and tolerability of the treatment of hepatitis C virus (HCV). However, studies conducted on actual patients with the aim of predicting the risk associated with treatment failure are lacking. Methods Our study enrolled 334 new HCV patients and assessed the effectiveness of treatment and predicted the risk of failure to achieve sustained virological response (SVR) by developing a multiple logistic model. Our study compared the variables between the two groups, those who did (group 0, n = 239) and did not achieve SVR (group 1, n = 95). Results The cure rate of HCV at 12th week in our study was 71.56%. We found that advanced cirrhosis, HCV genotype, HBV coinfection, rapid virological response (RVR), fibrosis index (FIB-4) score, serum levels of AST, ALP, hemoglobin, and viral load before treatment were prognostic factors associated with rate of failure to achieve SVR at week 12 of DAA therapy. In the multiple logistic model, eight significant predictors including advanced cirrhosis status, HCV genotype, RVR, AST/ALP levels, FIB-4 score, and viral load before treatment predicted the risk of failure with excellent model performance (area under the receiver operating characteristic curve (AUCROC) [95% CI] =0.986 (0.971-0.999)). RVR and advanced cirrhosis were the two strongest predictors with odd ratios (95% CI) =9.72 (2.8, 39.28) and 51.54 (6.39, 139.82), respectively. Conclusion The multiple logistic regression model included significant factors to estimate the probability of failure to achieve SVR, which could improve HCV treatment strategy.

Mathematical Modelling of HIV-HCV Coinfection Dynamics in Absence of Therapy.

Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals coinfected with HIV and latent HCV. Therefore, HIV and latently HCV-infected individuals need to seek early treatment so as to slow down the progression of HIV to AIDS and latent HCV to advanced HCV.

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

Introduction: Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological response (SVR), with all-oral direct-acting antiviral agents (DAAs). Methods: Prospective study of 60 HIV/HCV-coinfected and 30 HCV-monoinfected patients with advanced HCV cirrhosis (liver decompensation or liver stiffness measurement (LSM) ≥ 25 kPa, hepatic liver pressure gradient (HVPG) ≥ 10 mmHg, or Child–Pugh–Turcotte (CPT) ≥ 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after HCV treatment. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. Results: In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p < 0.001), had lower body mass index (BMI) (p = 0.002), and had been exposed less frequently to interferons (p = 0.011). In addition, they were more frequently men (p = 0.011), smokers (p = 0.005), prior intravenous drug users (IVDUs) (p < 0.001), and alcohol abusers (p = 0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients, both at baseline (p < 0.001), and at the end of follow-up (p = 0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p < 0.001), especially in those patients with compensated cirrhosis (p < 0.001). Conclusion: HCV eradication with all-oral DAAs was associated with an increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group.

Characteristics of HCV infection in oncohematological patients

Objective: clinical and laboratory characteristics of HCV infection in patients with oncohematological malignancies. Materials and Methods: The study included 106 patients with a positive serum HCV antibody (anti-HCV) test result, who were examined or treated in 5 specialized oncohematological units of different hospitals in Saint Petersburg in 2018–2019.Laboratory tests included: ALT and AST activity, qualitative (with sensitivity of 60 IU/ml) and quantitative determination of HCV RNA, as well as HCV genotyping by real-time PCR. The presence and the grade of liver fibrosis according to the METAVIR scale were evaluated by indirect elastography on Fibroscan. Results: Men were predominant (62,2%), and most of patients (67%) were of young and middle age (18-59 years old). HCV infection was confirmed in 68% patients, and in 41.7% of them HCV genotype 3 was detected. HCV RNA was not detected in 32% cases, suggesting the spontaneous clearance of the virus. Severe liver fibrosis (F3) or cirrhosis (F4) were found in 40% patients with confirmed viremia. In most patients, the normal ALT activity level was registered. 86% patients diagnosed with HCV infection were followed up by an infectious disease specialist until the present study. 19% patients received antiviral therapy for HCV infection. Conclusion: A significant proportion of patients with advanced liver fibrosis and HCV 3 genotype, causing the greatest difficulties in antiviral treatment for HCV infection, was revealed. Prescription of direct-acting antiviral agents in the early terms after establishment of the diagnosis is reasonable.

Proteomic study of advanced cirrhosis based on HCV to reveal potential biomarkers.

We aimed to carry out proteomic assessment of long-term effects of hepatitis C on liver. Cirrhosis isa condition where liver is damaged and loses its efficiency, and has the high rate of mortality in the world. Proteome profiling may help to identify important proteins and find the pathogenesis Cirrhosis isa condition where liver is damaged and loses its efficiency, and has the high rate of mortality in the world. Proteome profiling may help to identify important proteins and find the pathogenesis. Here, by the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), combined with (MALDI-TOF-TOF MS), proteome profile of decompensated HCV cirrhosis is determined compared to healthy matched controls. Furthermore, Cytoscape has used network analysis. The proteome comparison between two groups identified proteins with significant expression changes (p<0.05 and fold change ≥ 1.5). We found upregulation of IGHA1, C3, A1BG, IGKC and one isoform of HP. Also, lower expression of APOA4 and the other spot of HP in advanced cirrhosis patients were revealed based on HCV compared to matched controls. According to network analysis, ALB has been introduced as a key protein, which may play an important role in pathogenesis. Integration of the proteomics with protein interaction data led to the identification of several novel key proteins related to the immune system that may reflect the long-term effects of hepatitis C virus on the liver, and can introduce as therapeutic targets for advanced HCV- cirrhosis.

Aminopyrine breath test predicts liver-related events and death in HCV-related cirrhosis on SVR after DAA therapy.

In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13 C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation - defined as Child A6 (N=22, 44%) or previous decompensation (N=7, 14%) - or Child B cirrhosis (N=21, 42%) eligible for DAA-based antiviral therapy. ABT was performed at baseline and 12weeks after the end of antiviral therapy. Patients received sofosbuvir-based regimens. Aminopyrine breath test was available for all 50 patients at baseline. The 120' cumulative dose was directly associated at regression analysis only with albumin levels (P=.001). ABT was available at follow-up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2months (range 12.2-32.1months). Lower Ʌ ABT - defined as changes of 120' cumulative dose from FUW12 to baseline - (HR 0.97, 95% CI 0.94-0.99; P=.02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16-310.3; P=.03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of Ʌ ABT was good (0.87, 95% CI 0.75-0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver-related events/death (P<.001). In patients with advanced HCV cirrhosis who achieve SVR with DAA, Ʌ ABT assists in assessing the residual likelihood of liver-related events and deaths after viral cure.

Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy.

Hepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis

Introduction and aim. Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an open-label multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection.Material and methods. All patients received coformulated OBV/ PTV/r daily + DSV twice daily (3-DAA). GTIa-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/ RBV nonresponders with cirrhosis who were treated for 24 weeks. GTIb-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12).Results. The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event.Discussion. The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis

Introduction and aim: Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an open-label multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. Materials and methods: All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA &lt;15 IU/mL) at post-treatment Week 12 (SVR12). Results: The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1–98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event. Conclusion: The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).

The road map toward an hepatitis C virus-free transplant population.

Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)-based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN-based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second-generation direct-acting antiviral agents (DAAs) with superior tolerability and efficacy to IFN-based therapy. These agents have the potential to reduce the number of patients developing HCV-related complications requiring LT and retransplantation, as well as reducing the demand for donor organs. We discuss the pros and cons of pretransplant, peritransplant, and posttransplant therapy with current DAAs, citing available data from clinical trials and real-world experience.

Screening for hepatitis C virus infection among Minia city school students

BackgroundHepatitis C virus (HCV) infection is a global health problem. Cirrhosis and end stage liver disease are considered main complications among adults and children. Egypt show higher level of anti HCV antibodies than other countries. The current study aimed at screening school children for the presence of HCV antibodies. Research designA cross-sectional research design was used to achieve the aim of this study. Subject and methodsTwo randomly selected schools at Minia district (one urban and one rural) were included in the study, 750 school students were included out of 862 with response rate 87%. A structured interviewing questionnaire that included demographic data and risk factors associated with HCV infection such as history of taking any injectable medications drug use, history of blood transfusion, history of hospital operation… etc. Thorough clinical examination andabdominal U/S were done for those who have history suggestive of hepatic illness. All volunteer participants were subjected to rapid HCV antibody test. ResultsThe mean age of the study sample was 15.18 ± 1.95 years, regarding to results of advanced quality rapid HCV antibody test, only 0.7% of school students were positive anti HCV. Regarding relation between risk factors and percentage of anti HCV among school students, blood transfusion, sharing shaving instruments and tooth brush are statistically significant (p = 0.029, 0.031, 0.002 respectively). ConclusionThe study concluded that the percentage of school students (aged 12–18) years old who are probably infected with HCV was 0.7% (5 out of 750) in Minia district.

Depression, fatigue and neurocognitive deficits in chronic hepatitis C.

Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood-brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.

Sofosbuvir-Based Therapy in the Pre-Liver Transplant Setting: The Canadian National Experience

Introduction and aim. Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status.Material and methods. A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status.Results. 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported.Conclusions. SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list.

Daclatasvir-sofosbuvir combination therapy for chronic hepatitis C virus infection: progress in clinical studies

All-oral, pan-genotypic combination of direct-acting antiviral agents is currently clinically prescribed trends in the management of chronic hepatitis C virus infection. The combination of daclatasvir and sofosbuvir has proven strong antiviral activity across all common genotypes in clinical trials and real world studies. Furthermore, it can be safely used in patients with advanced liver disease, HCV/HIV co-infection, or HCV recurrence after liver transplantation, more patients will gain clinical benefits. We aim to summarize the clinical progress about this combination.

Screening for hepatitis C virus infection among school children

Background: Hepatitis C virus (HCV) infection is a global health problem. Cirrhosis and end stage liver disease are considered main complications among adults and children. Epidemiologically, Egypt show higher level of anti HCV antibodies than other countries. The current study aimed to screen (HCV) infection among school children. Research design: A cross-sectional research design was used to achieve the aim of this study. Sample: Two randomly selected schools at Minia district (one urban and one rural) were included in the study, 750 students were included out of 862 with response rate 87%. Tools: A structured interviewing questionnaire that includes part one: demographic data related to studied group, part two: included risk factors associated with HCV infection such as history of taking any injectable medications drug use, history of blood transfusion, history of hospital operation... etc. while part three was a rapid HCV antibody test. Results: The mean age of the study sample was 15.18 ± 1.959 years, regarding to results of advanced quality rapid HCV antibody test, only 0.7% of school children were positive anti HCV. The most prevalent risk factors among studied school children were ear piercing, history of taking injectable medications from informal care provider, circumcision, scarification and history of dental procedure 99.3, 94.9, 88.8, 88.5, and 62.5% respectively. Regarding relation between risk factors and percentage of anti HCV among school children, blood transfusion, sharing shaving instruments and tooth brush are statistically significant. Conclusion: The study was concluded that the percentage of school children (aged 12-18) years old who are probably infected with HCV was 0.7% (5 out of 750) in Minia district. Recommendations: Future studies should focus on the screening of HCV and methods of prevention in some other nearby communities at Minia governorate to make early detection and provide proper treatment.