HCV-related Liver Disease Research Articles

Clinical and economic value of sofosbuvir-based regimens in the treatment of chronic hepatitis C in Spain.

The treatment of chronic hepatitis C virus (HCV) with direct-acting antivirals has undergone a spectacular revolution and added significant value to healthcare systems and patients. The aim of the study was to evaluate the efficiency and value of Sofosbuvir (SOF)-based regimens for a target population of 85,959 chronic HCV patients treated in Spain during 2015-2019, compared to previous therapeutic strategies (peginterferon/ and ribavirin in double/triple therapy with telaprevir or boceprevir). A previously developed lifetime Markov model was adapted to simulate the disease HCV evolution. In SOF-based regimens, all patients (100%) were treated regardless with sustained virological response (SVR) of 93-98%, obtained from real-world data. In previous therapeutic, only ≥F2 patients were treated according to clinical practice (38%) with an average SVR of 61% taken from published literature. The value was measured as clinical and economic impact in terms of avoided HCV-related mortality and liver complications; total costs and quality-adjusted life years (QALYs) applying an annual 3% discount rate. Compared to previous therapeutic, during lifetime, SOF-based regimens reduced decompensated cirrhosis by 89%, hepatocellular carcinoma by 77% and liver transplant by 84%, decreasing the cost associated to liver complications management in €770 million. SOF-based regimens also decreased liver-related mortality by 82%. Besides, SOF-based regimens gained 310,765/QALYs, saving €274 million (considering drugs, monitoring, and HCV management). For Spain, SOF-based regimens offer value for HCV patients in terms of lowering HCV-related liver disease burden and generating significant cost savings for the health system, contributing to the WHO goal.

Clinical study on the efficacy of hepatitis B vaccination in hepatitis C virus related chronic liver diseases in Egypt

BackgroundChronic hepatitis B (HBV) and C virus (HCV) infections represent significant public health issues internationally. HBV vaccination has high sero-conversion rates in patients with mild to moderate chronic liver disease but has reduced efficacy in advanced stages. Aimto evaluate the efficacy of hepatitis B vaccination in HCV-related chronic liver disease and identify possible factors that may contribute to hypo-responsiveness in those patients. MethodsOur study was a retrospective observational clinical study carried out at the tropical medicine department. It was conducted on 500 individuals (400 chronic HCV patients and 100 healthy controls). Individuals were divided into 5 groups: A (control group), B (cirrhotic patient not receiving treatment), C (chronic hepatitis patients receiving treatment), D (cirrhotic patients receiving treatment), and E (HCC patients receiving treatment). All individuals were subjected for comprehensive history taking, clinical examination, laboratory investigations, and assessment of anti-HBs titer. ResultsThere is an inverse relationship between the level of anti-HBs Abs and the duration of vaccine. Diabetes and presence of cirrhosis have statistically significant relationship with serum anti-HBs Abs titer (P = 0.007). Oral DAAs therapy is associated with reduced response to HBV vaccine (only 31.75% of the patients were protected). ConclusionHCV infection and its complications significantly impair HBV vaccine response. Levels of anti-HBs Abs decline progressively with increasing duration from the last dose in immunization schedule of HBV vaccine. Diabetes and presence of cirrhosis being the main risk factors for vaccine hypo-responsiveness, also oral DAAs therapy is associated with reduced response to HBV vaccine.

Hepatitis C active viremia over time in an ED-based testing programme: Impact, disparities and surveillance tool.

Hepatitis C virus (HCV) surveillance is a critical component of a comprehensive strategy to prevent and control HCV infection and HCV-related chronic liver disease. The emergency department (ED) has been increasingly recognized as a vital partner in HCV testing and linkage. We sought to consider active RNA HCV viremia over time in patients participating in an ED-based testing programme as a measure of local HCV surveillance and as a barometer of ED-testing programme impact. We performed a retrospective analysis of individuals participating in our ED-based HCV testing programme between 2015 and 2021. Chi-square tests were used to compare the demographic characteristics of HCV antibody positive tests with active viremia to those without active viremia. Cox proportional hazard models were used to estimate the trend in active viremia risk over time in the overall study population as well as in key subpopulations of interest. Of 5456 HCV antibody positive individuals, 3102 (56.8%) had active viremia. In the overall study population, we found that the risk of active viremia decreased by 4.8% per year during the study period (RR: 0.95, 95% CI: 0.93-0.97|p < .0001). Baby boomers experienced a 9% decrease in active viremia risk per year over the study period while non-baby boomers only had a 2% decrease in risk per year (p=.0009). Compared with insured patients, uninsured patients had a smaller decrease in risk of active HCV viremia per year (p=.003). No significant differences in the risk of active viremia over time were observed for gender (p=.4694) or by primary care provider status (p=.2208). In conclusion, this ED-based testing and linkage programme demonstrates significantly decreased active HCV viremia over time. It also highlights subpopulations, specifically non-baby boomers and uninsured patients, who may benefit from focused interventions to improve access to and adoption of definitive HCV care.

Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity

PurposeIt is well known that interferon-α (IFN-α), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations.MethodsA total of 113 HCV patients, subdivided at the time of the enrollment in naïve group (n = 64) and in IFN-α group (n = 49) previously treated with pegylated interferon-α and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20–32 weeks of DAAs.ResultsBefore starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-α group (8/49, 16.3%), while no HT cases were found in the naïve group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naïve group and 4/49 (8.2%) to IFN-α group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naïve group and 6/49 (12.2%) from IFN-α group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism.ConclusionsThis study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs.

Hepatocytes infected with hepatitis C virus change immunological features in the liver microenvironment.

Hepatitis C virus (HCV) infection is remarkably efficient in establishing viral persistence, leading to the development of liver cirrhosis and hepatocellular carcinoma (HCC). Direct-acting antiviral agents (DAAs) are promising HCV therapies to clear the virus. However, recent reports indicate potential increased risk of HCC development among HCV patients with cirrhosis following DAA therapy. CD8+ T-cells participate in controlling HCV infection. However, in chronic hepatitis C patients, severe CD4+ and CD8+ T-cell dysfunctions have been observed. This suggests that HCV may employ mechanisms to counteract or suppress the host T-cell responses. The primary site of viral replication is within hepatocytes where infection can trigger the expression of costimulatory molecules and the secretion of immunoregulatory cytokines. Numerous studies indicate that HCV infection in hepatocytes impairs antiviral host immunity by modulating the expression of immunoregulatory molecules. Hepatocytes expressing whole HCV proteins upregulate the ligands of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and transforming growth factor β (TGF-β) synthesis compared to those in hepatocytes in the absence of the HCV genome. Importantly, HCV-infected hepatocytes are capable of inducing regulatory CD4+ T-cells, releasing exosomes displaying TGF-β on exosome surfaces, and generating follicular regulatory T-cells. Recent studies report that the expression profile of exosome microRNAs provides biomarkers of HCV infection and HCV-related chronic liver diseases. A better understanding of the immunoregulatory mechanisms and identification of biomarkers associated with HCV infection will provide insight into designing vaccine against HCV to bypass HCV-induced immune dysregulation and prevent development of HCV-associated chronic liver diseases.

Apelin Association with Hepatic Fibrosis and Esophageal Varices in Patients with Chronic Hepatitis C Virus.

Portal hypertension and esophageal varices complicating hepatitis C virus (HCV)-related chronic liver diseases are some of the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) single-nucleotide polymorphism (SNP), and serum apelin level in patients with chronic HCV, and their association with liver fibrosis and esophageal varices in 112 patients with HCV-related chronic liver disease (40 with liver cirrhosis [LC]/low-grade varices, 33 with LC/high-grade varices, and 39 with fibrotic non-cirrhotic liver/no varices) and 80 healthy control subjects. Real-time polymerase chain reaction was used for apelin gene expression assay and apelin rs3761581 SNP analysis in peripheral blood samples. The serum apelin level was measured by ELISA. Apelin gene expression was undetectable in the studied samples. The SNP analysis revealed a greater frequency of the C (mutant) allele among patients compared with control subjects (P = 0.012; odds ratio, 3.67). The serum apelin level was significantly greater in patients with LC/varices (median, 31.6 ng/L) compared with patients without LC/varices (median, 2.9 ng/L; P < 0.001). A serum apelin level cutoff value of 16.55 ng/L predicted the presence of varices, with an area under the receiver operating characteristic curve value of 0.786. A positive correlation was found between serum apelin level and grade of liver fibrosis (r = 0.346, P < 0.001) and portal hypertension (r = 0.438, P < 0.001). In conclusion, the apelin rs3761581-C allele may be associated with the progression of HCV-related chronic liver disease and varices formation, and can be considered a potential therapeutic target to control fibrosis progression. The serum apelin level provided an accurate prediction of the presence of esophageal varices.

Profiling the HCV Immune Response in Patients with Chronic Liver Diseases and Hepatocellular Carcinoma by Peptide Microarray Analysis.

Chronic infection with hepatitis C virus (HCV) is among the major causes of hepatic fibrosis, cirrhosis, as well as hepatocellular carcinoma (HCC), and it is associated with a significant risk of developing lymphoproliferative disorders. The rate of clinical disease progression is variable depending on multiple host and viral factors, including immune response. To perform a comprehensive epitope mapping of anti-HCV antibodies in patients suffering from HCV-related liver or lymphoproliferative diseases, we analyzed clinical samples on a peptide microarray platform made of 5952 overlapping 15-mer synthetic peptides derived from the whole HCV proteome. We evaluated the antibody profile of 71 HCV-positive patients diagnosed with HCC, mixed cryoglobulinemia (MC), and HCV chronic infection. Antibody reactivity against virus peptides was detected in all HCVpositive patients. Importantly, the signal amplitude varied significantly within and between diverse patient groups. Antibody reactivity against C peptides were found generally low in HCV chronically infected asymptomatic subjects and increasingly high in HCC and MC patients. Moreover, we found a statistically significant higher IgG response in HCC and MC patients against specific domains of HCV C, E2, NS3, NS4A, NS4B, NS5A, and p7 compared to HCV-positive subjects. In conclusion, our data suggest that immune response against specific HCV protein domains may represent useful biomarkers of disease progression among HCVpositive patients and suggest that peptide microarrays are good tools for the screening of immunotherapy targets in preclinical HCV research.

Effect of direct-acting antiviral drugs on portal circulation hemodynamics in cirrhotic patients infected with HCV

BackgroundLiver cirrhosis (LC) is the most common cause of portal hypertension. In chronic hepatitis C patients who are treated with direct-acting antiviral therapy (DAAS), the progression of cirrhosis can be reversed with treatment. Portal hypertension is also expected to improve with a virological response.AimTo evaluate the effect of direct-acting antiviral therapy on portal circulation hemodynamics in cirrhotic patients infected with HCV.MethodsThis study included 78 consecutive patients with chronic HCV-related liver disease. They were treated by a sofosbuvir-based regimen in combination with daclatasavir. All patients were subjected to routine investigations (complete blood count, liver and renal function tests), hepatitis B surface antigen, α feto protein, PCR of HCV RNA, imaging (abdominal ultrasound and colored Doppler and duplex examination for the assessment portal hypertension) before starting treatment and after 1 year.ResultsThere was a significant improvement in Doppler parameters such as portal vein (PV) diameter, PV velocity, PV cross-sectional area, portal congestive index, splenic vein diameter, and spleen span; the decrease in portal pressure occur in about 55% of the patients; several factors are associated with non-response as a history of bilharziasis, patients from a rural area, presence of splenomegaly and varices, low HB level, low platelet count, and high level of fibrosis.ConclusionSustained virological response to direct-acting antiviral therapy is associated with a reduction in portal pressure in patients with liver cirrhosis and clinically significant portal hypertension.

Beneficial Effects of Silybin Treatment After Viral Eradication in Patients With HCV-Related Advanced Chronic Liver Disease: A Pilot Study.

Introduction and Aims: HCV eradication by direct-acting antivirals (DAAs) improves liver outcomes and reduces overall liver mortality. However, patients with advanced chronic liver disease (ACLD) may experience a progression of liver disease despite viral clearance. Silybin has shown hepatoprotective effects in experimental models, but clinical data are limited. The aim of this study is to evaluate the effect of a highly bioavailable form of silybin on liver fibrosis in patients with HCV-related ACLD after viral eradication with DAAs, in comparison with the standard of care. Methods: In this multicenter and prospective study, HCV patients with ACLD achieving SVR12 were treated with the combination of silybinphospholipid complex with vitamin D and vitamin E (Realsil 100D®, Ibi Lorenzini S.p.A., Aprilia, Italy) for 12 months (R group) compared to controls (C group). Patients were submitted to transient elastography (TE) and to the enhanced liver fibrosis (ELF) test at baseline, week 24, and week 48. Results: One hundred sixteen patients were enrolled, 56 in the R group and 60 in the C group. The median age was 68 years, and 53% were male, with no differences between groups. In both groups, liver stiffness improved at 6 and 12 months compared to baseline. However, patients in the R group compared to those in the C group showed a higher reduction of liver stiffness after 6 months (−2.05, 95% CI −3.89 to −0.22, p < 0.05) and 12 months of treatment (−2.79, 95% CI −4.5 to −1.09, p < 0.01) in comparison with baseline. No significant difference in the reduction of ELF was observed between the two groups. During the follow-up, four patients developed HCC, all in the C group. Conclusions: In HCV-related ACLD, the hepatoprotective effects of silybin may represent a tool to counteract liver disease progression.

Assessment of Plasma Vitronectin as Diagnostic and Prognostic Marker of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Cirrhosis

Background: hepatitis C is an inflammatory liver disease caused by the hepatitis C infection (HCV), and without treatment, almost 50% will progress to liver cirrhosis. Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and the fourth leading cause of cancer-related mortality. Aim of the study: the objective of this study was to evaluate the serum level of vitronectin (VTN) compared to AFP and determine their role as diagnostic and prognostic markers of HCV-related liver diseases. Subject and Methods: this study involved 52 HCV patients from which 26 patients were cirrhotic, and 26 patients had HCC (on top of hepatitis C virus-related cirrhosis) plus 10 healthy people as a control group. It was carried out in Gastroenterology and Hepatology Unit, Internal Medicine Department, Zagazig University Hospitals, Egypt. All individuals in this study were subjected to physical examination, full history taking, liver function tests, assessment of serum levels of Vitronectin (VTN) and alpha-fetoprotein (AFP) before and after the intervention within three months. Results: serum level of vitronectin increased significantly in cirrhosis patients and HCC patients than controls (p = 0.0041), (p &lt; 0.001), respectively, and in HCC than cirrhosis patients (p &lt; 0.001). Significant positive correlations were observed between levels of serum VTN and AFP in all HCV patients as well as cirrhotic patients (p &lt; 0.001, p = 0.011, respectively). On the contrary, VTN and AFP didn’t show a significant correlation in HCC patients’ group. Moreover, the median serum level of VTN decreased significantly after treatment in patients with HCC (p &lt; 0.001). At cut-off 38.5 ng/mL for AFP it shows sensitivity 80.8%, specificity 76.9% to differentiate HCC from cirrhosis cases. While VTN shows 84.6% sensitivity, 96.2% specificity at cut-off 26.5 μg/mL. Regarding clinicopathological characteristics and VTN levels, half of patients were stage B, 63.9% had tumor size &gt;3 cm, 84.6% had more than one focal lesion. Conclusions: these results may allow one to speculate a potential role of Vitronectin in diagnosis and prognosis of HCC on top of cirrhosis related to HCV infection in addition to AFP and US and CT.

Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand?

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death. Although the burden of alcohol- and NASH-related HCC is growing, chronic viral hepatitis (HBV and HCV) remains a major cause of HCC development worldwide. The pathophysiology of viral-related HCC includes liver inflammation, oxidative stress, and deregulation of cell signaling pathways. HBV is particularly oncogenic because, contrary to HCV, integrates in the cell DNA and persists despite virological suppression by nucleotide analogues. Surveillance by six-month ultrasound is recommended in patients with cirrhosis and in “high-risk” patients with chronic HBV infection. Antiviral therapy reduces the risks of development and recurrence of HCC; however, patients with advanced chronic liver disease remain at risk of HCC despite virological suppression/cure and should therefore continue surveillance. Multiple scores have been developed in patients with chronic hepatitis B to predict the risk of HCC development and may be used to stratify individual patient’s risk. In patients with HCV-related liver disease who achieve sustained virological response by direct acting antivirals, there is a strong need for markers/scores to predict long-term risk of HCC. In this review, we discuss the most recent advances regarding viral-related HCC.

Role of Serum Vitamin D, Interleukin 13, and microRNA-135a in Hepatocellular Carcinoma and Treatment Failure in Egyptian HCV-Infected Patients Receiving Direct Antiviral Agents.

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.

Community-Based Assessment and Treatment of Hepatitis C Virus-Related Liver Disease, Injecting Drug and Alcohol Use Amongst People Who Are Homeless: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis addressing community-based assessment and treatment of hepatitis C virus (HCV)-related liver disease, injecting drug use (IDU) and alcohol use amongst people who are homeless (PWAH). Using systematic review methodology, databases were searched (MEDLINE/EMBASE/CINAHL) for studies combining PWAH, HCV-related liver disease and community assessment until December 2019. Studies with a sample size ≥ 30, with PWAH constituting at least 30% of the cohort were included and a quality assessment performed. Pooled estimates of key indicators were analysed using meta-analysis. We identified 39 studies (n=13,918), 37 categorised as poor quality (Newcastle-Ottawa Scale). Prevalence of homelessness ranged between 30%-100% (37 studies). Eight studies provided all of the following: HCV screening, alcohol/substance use/liver fibrosis assessment and HCV treatment. No study provided interventions for alcohol use, with two providing opioid substitution treatment. Alcohol use prevalence (24 studies) was 4%-97%, being 59% (95% CI 20%-92%) in four studies that included only PWAH. Recent IDU prevalence (16 studies) was 7%-73%, being 21% (95% CI 17%-26%) in four studies that included only PWAH. HCV seroprevalence (25 studies) was 2.5% - 58%; in 13 studies that included only PWAH, this was 20% (95% CI 12%-30%). Prevalence of F4 fibrosis (nine studies) was 6%-28%, being 7% and 16% in two studies that included only PWAH. Direct acting antiviral-based intention-to-treat sustained virological response (SVR) rates (five studies) were 82%-92%, being 92% in the one study that included only PWAH. In the only two randomised controlled trials (RCT) identified, community-based interventions (mental health/peer mentor) significantly increased linkage to care (p=0.04), HCV treatment (p=0.005) and SVR rates (p=0.018). The burden from alcohol/IDU and HCV, and consequently liver disease in PWAH needs addressing. RCT trials assessing community-based interventions to improve liver health in PWAH are needed.

Handgrip strength in prediction of sarcopenia in Chronic HCV patient

Abstract Background HCV is one of the major causes of morbidity and mortality in the world and especially in Egypt. However, there is numerous complications to HCV infection (e.g. liver cirrhosis, ascites, portal hypertension, encephalopathy …. etc.) but there is multiple unseen complication (e.g. sarcopenia, loss of electrolytes, loss of protein …etc.) Objective To evaluate value of handgrip strength in assessment of sarcopenia in HCV related chronic liver disease patients Patients and Methods This study was conducted on 64 adult persons older than 18 years. They were randomly collected from the outpatient clinics at department of internal Medicine in Ain Shams University during the period from June 2018 to August 2019. Results In our study there was a great significance relation between handgrip strength and child score in evaluating nutritional status more than anthropometric parameter. Therefore, even that several methods to evaluate nutritional and functional capacity status in patients with cirrhosis have been tested, they have reported diverse results. Conclusion Our study we can conclude that HGS is a simple, easy to be applied and more accurate method in evaluation of sarcopenia in chronic HCV patients.

Vitronectin (VTN): A Novel Diagnostic and Prognostic Marker for Hepatocellular Carcinoma (HCC) On Top Of Chronic Hepatitis C Virus Related Diseases

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the most common form of primary liver cancer. Aim of the study to study the level of serum vitronectin (VTN) compared to AFP in diagnosis and prognosis of hepatocellular carcinoma on top of HCV-related liver diseases. Patients and Methods This prospective observational study included a total number of 60 subjects who were divided into 4 groups: Group 1: include 10 normal persons. Group 2: included 10 patients who have Hepatitis C Virus infection. Group 3: included 20 cirrhotic patients. Group 4: included 20 patients with HCC (on top of hepatitis C virus related cirrhosis), in which we tested them for vitronectin before first intervention and after intervention within 3 months. Results The mean age of the cases showed high statistically significant difference between the study groups (P &amp;lt; 0.001).There were a total number of 29 males and 31 females with significant difference in the sex distribution between the study groups. 80% of the cases in HCC group were males. This sex distribution can be attributed to high prevalence of risk factors like smoking, DM and HCV in males in addition to possible role of sex hormones. On analyzing laboratory characters of the studied groups, we found statistically significant difference between cirrhosis group and non-cirrhotic groups with low platelets count, high serum creatinine, high INR, lower serum albumin, high bilirubin and higher AST. The median level of AFP in group 4 (HCC patients) was 110 IU/ml which was higher than its median value in the other study groups with high level of significance between the study groups. The median level of vitronectin levels in the different study groups didn’t reveal a statistically significant difference between the different study groups. Serum level of vitronectin in group 3 (cirrhotic patients) has no statistically significant difference between the three subgroups according to child's classification. By the analysis of serum level of AFP and vitronectin level in group IV (HCC patients) before and after treatment, the median level of AFP was significantly lower than its level before intervention, while the decrease in vitronectin level was statistically insignificant after intervention. Conclusions Chronic HCV infection and its serious complicatons specially HCC are still representing a health challenge in Egypt, reflecting wide HCV prevalence and late diagnosis. Serum AFP alone has an unreliable role in HCC surveillance as it has low sensitivity because it may be normal in up to 40% of HCC cases especially early stages of the tumor, and low specificity as its levels may be elevated in conditions other than HCC as cirrhosis or exacerbation of chronic hepatitis or even in some cases of cholangiocarcinoma. AFP is useful in clinical practice in screening and diagnosis of HCC in association with US and CT. According to our study, we can't use Vitronectin alone in diagnosis and prognosis of HCC on top of cirrhosis related to HCV +ve infection. It didn’t reveal a statistically significant difference between the different study groups ,so it may require further study and research.

Direct-acting antiviral treatment uptake and sustained virological response outcomes are not affected by alcohol use: ACANUHCanalysis.

Alcohol use and hepatitis C virus (HCV) are two leading causes of liver disease. Alcohol use is prevalent among the HCV-infected population and accelerates the progression of HCV-related liver disease. Despite barriers to care faced by HCV-infected patients who use alcohol, few studies have analyzed uptake of direct-acting antiviral (DAA) treatment. We compared rates of treatment uptake and sustained virological response (SVR) between patients with and without alcohol use. Prospective data were obtained from the Canadian Network Undertaking against Hepatitis C (CANUHC) cohort. Consenting patients assessed for DAA treatment between January 2016 and December 2019 were included. Demographic and clinical characteristics were compared between patients with and without alcohol use by means of t-tests, χ2 tests, and Fisher's Exact Tests. Univariate and multivariate analyses were used to determine predictors of SVR and treatment initiation. Current alcohol use was reported for 217 of 725 (30%) patients. The proportion of patients initiating DAA treatment did not vary by alcohol use status (82% versus 83%; p= 0.99). SVR rate was similar between patients with alcohol use and patients without alcohol use (92% versus 94%; p= 0.45). Univariate and multivariate analysis found no association between alcohol use and SVR or treatment initiation. Patients engaged in HCV treatment have highly favourable treatment uptake and outcomes regardless of alcohol use. Public health interventions should be directed toward facilitating access to care for all patients irrespective of alcohol use. Research into high-level alcohol use and DAA outcomes is needed.

Adherence to clinical follow-up recommendations for liver function tests: A cross-sectional study of patients with HCV and their associated risk behaviors

This study examined whether patients with Hepatitis C virus (HCV) infection adhered to their physicians’ recommendation and HCV clinical guidelines for obtaining a regular liver function test (LFT), and whether high-risk behaviors are associated with behavioral adherence. A cross-sectional survey was administered to 101 eligible patients with HCV who were recruited from health centers in New Jersey and Washington, DC. Adherence outcomes were defined as the patients’ self-report of two consecutive receipts of LFTs in accordance with their physicians’ recommended interval or the clinical guidelines for a LFT within 3–6 months. 67.4% of patients (66/98) reported a receipt of their physicians’ recommendation for a LFT. The rate of adherence to physician recommendation was about 70% (46/66), however over 50% (52/101) of patients with HCV did not obtain regular LFTs. 15.8% (16/101) of patients continued to use injection drugs. Patients who used injection drugs had 0.87 (adjusted odds ratio (aOR) = 0.13, 95% confidence interval 0.03–0.59) times lower odds adhering to their physician recommendation, relative to non-users. Patients with HIV co-infection had increased odds of adhering to the clinical guidelines (odds ratio 3.41, 95% confidence interval 1.34–8.70) vs. patients who did not report HIV co-infection. Additionally, patients who had received a physician’s recommendation had 7.21 times (95% confidence interval of 2.36–22.2) greater odds adhering to the clinical guidelines than those who had not. Overall, promoting HCV patient-provider communication regarding regular LFTs and reduction of risk behaviors is essential for preventing patients from HCV-related liver disease progression.

Abstract 836: Immunologic markers and the progression of liver disease in HCV-positive individuals

Abstract Background: Host immune response and chronic inflammation associated with chronic hepatitis C virus (HCV) infection play a key role in the progression of liver disease from cirrhosis to hepatocellular carcinoma (HCC). We evaluated a large panel of circulating immunologic markers to better understand the natural history of HCV-related liver disease. Methods: We sampled 94 HCC, 68 cirrhotic and 100 non-cirrhotic controls from a Taiwanese prospective cohort study of chronically HCV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis as compared to controls and those who developed HCC. P-values for individual markers were corrected for multiple testing using a false discovery rate of 10%; a p-value&amp;lt;0.05 was used to determine significance in CDA. Receiver operating characteristic curves were used to compare the predictive ability of marker groups from both analyses. Results: After adjusting for age, sex, years of follow-up, serum alanine aminotransferase level, alcohol and smoking, DEFA-1 (p-trend: &amp;lt;0.0001), ITGAM (p-trend: &amp;lt;0.0001), CCL18 (p-trend: 0.002) and ARTN (p-trend: 0.003) were all found to be positively associated with the development of cirrhosis when compared to non-cirrhotic controls; the same four markers were shown to be associated with HCC when compared to cirrhotic participants. Taken together, these four markers predicted cirrhosis and HCC development with 79% and 88% accuracy, respectively in adjusted models. CDA models isolated a twelve-marker signature that included DEFA1, CCL18, and ARTN, improving predictability of cirrhosis development to 91% accuracy in adjusted models. Using the same methods, a fourteen-marker signature that included DEFA-1, ITGAM, CCL18 and ARTN was found to predict HCC development with 97% accuracy when compared to cirrhotic individuals in adjusted models. Conclusion: To our knowledge, this is the first prospective study to assess immunologic markers in relation to liver disease progression in individuals chronically infected with HCV. While further validation is required, these findings highlight the importance of immunologic processes in HCV-related disease. Citation Format: Ilona Argirion, Ruth M. Pfeiffer, Zhiwei Liu, Allan Hildesheim, Ligia Pinto, Katherine A. McGlynn, Jessica L. Petrick, Tram Kim Lam, Thomas R. O'Brien, Kelly Yu, Chien-jen Chen, Hwai-I Yang, Mei-Hsuan Lee, Jill Koshiol. Immunologic markers and the progression of liver disease in HCV-positive individuals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 836.

Influence of IL28B of Donors and Recipients on Liver Transplantation Due to End Stage HCV Related Liver Disease

Abstract Background: Recent studies have described a major impact of the IL28B gene polymorphism on graft survival post liver transplantation. Our study aims to investigate the impact of IL28B of donors and recipients on the natural course and outcome of liver transplantation due to end stage HCV related liver disease. Aim of Study: This study aims to investigate SNP of IL28B gene in Egyptian patients with end stage HCV related liver disease. Correlating the prevalence of IL-28b-alleles with patient and graft survival and with the progression of fibrosis for HCV-induced (graft) liver disease after liver transplantation. Also to correlate IL28B genotype with the outcome after liver transplantation. Patients and Methods: Donor and recipient IL28B rs12979860C>T single nucleotide genotype was determined in 24 patients who had undergone LT for HCV-induced end stage liver disease and received regular follow-up evaluations for two years post liver transplantation. Results: We found that the CC genotype frequency was reduced among patients with HCV related end stage liver disease while, in contrast, the frequency of CT & TT increased. No association was noted between IL 28B polymorphism of donors and recipients regarding fibrosis progression or patient and graft survival, as well as liver outcomes. Conclusions: No impact of IL 28B polymorphism on fibrosis progression, liver outcomes or patient and graft survival.

Comorbidities impact and de-prescribing in elderly with HCV-related liver disease: analysis of a prospective cohort

Management for HCV has undergone a notable change using direct-acting antiviral drugs (DAAs), which are safe and effective even in elderly. Here, we define impact of comorbidities, concomitant medication and drug–drug interactions in elder patients with HCV related disease before starting DAAs regimen. We analyzed data of 814 patients prospectively enrolled at our Unit within the web based model HCV Sicily Network. Out of 814, 590 were treated with DAAs and 414 of them were older than 65 years. We divided those 414 in two groups, one including 215 patients, aged between 65 and 74 years, and another with 199 patients, aged of 75 years and over. Charlson Comorbidity Index (CCI) was assessed for each patient; drug–drug interactions (DDI) and de-prescribing process were carried out appropriately. Within 414 patients included, percentage rates of women treated was higher than males, BMI was lower and cirrhosis was frequently reported in patients older than 75 years. Hypertension, diabetes mellitus, dyslipidemia (p < 0.0001), prostatic pathologies, kidney disease, gastrointestinal disease (p < 0.0001), osteoporosis (p < 0.01) and depression were most common co-morbidities. CCI showed lower scores in the first group as compared with the second one (p < 0.0001). Among drugs, statins were frequently suspended and anti-hypertensive often replaced. DAAs are useful and effective regardless of disease severity, comorbidities, medications and age. De-prescribing allows a stable reduction of number of medications taken with real improvement of quality of life.