Hepatitis C Virus Related Liver Disease Research Articles

Evaluation of Metabolic Changes in HCV Diabetic Patients Treated With Direct Acting Antiviral Agents

Abstract Background Viral hepatitis is a major public health problem in need of urgent response. The prevalence of hepatitis C virus (HCV) infection in Egypt is the highest in the world. Seroprevalence was modeled to 10.6% and viraemic prevalence to 7.3% in 2014. The association between hepatitis C virus (HCV) infection and diabetes has been widely postulated. Prospective studies have demonstrated a higher risk of developing type 2 diabetes mellitus (T2DM) and insulin resistance in the HCV population. Objective to evaluate metabolic changes in HCV-positive diabetic patients following combination therapy of hepatitis C, clarifying the role of DAAs in these changes. Patients and Methods This study was conducted in Ain Shams University Hospital outpatient clinics who attended from March to December 2018. our study included 70 patients, and were subdivided into the following two groups: Group I: Easy to treat group. Contains 35 diabetic patients with HCV related chronic liver disease treated with sofosbuvir, daclatasvir. Group II: Difficult to treat group. Contains 35 diabetic patients with HCV related chronic liver disease treated with sofosbuvir and daclatasvir and ribavirin. Results Treatment was considered successful when patients became non-viraemic as identified by negative HCV RNA serum PCR at 12 weeks from the end of the treatment regimens (SVR). It was found that diabetic patients treated with DAAs achieved reduction of HbA1C by mean of (0.724±0.3%). The mean increase of serum uric acid level was (0.607±0.4 mg/dL). There were increases in Cholesterol (by mean of 16.85±3.4), HDL (by mean of 5.34±2.1) and LDL (by mean of 13.91±4.2) as well as a decrease in TG (by mean of 13.56±5.1). Conclusion Our study concludes that HCV eradication in diabetic patients leads to various metabolic changes in the form of: Reduction of serum HbA1c level. Elevation of serum uric acid. Elevation of serum cholesterol, HDL, LDL as well as a decrease in TG. Further and larger studies are needed to evaluate the full magnitude of RBV effects on the patients’ metabolism.

Interleukin-9: Investigating Its Possible Role in Liver Cirrhosis Progression and in Tumour Promotion of Hepatocellular Carcinoma in Chronic HCV Infected Patients, A Single Centre Study

Background: Cytokines play an essential role in the pathogenesis of hepatitis C virus (HCV) related cirrhosis and hepatocellular carcinoma (HCC). Interleukin-9 (IL-9) participates in inflammation, autoimmunity and tumor immunity. IL-9 was reported to affect liver fibrosis, severity and prognosis of HCV related diseases.Aim of the study: To assess the potential correlation of serum IL-9 level and its receptor with the progression and prognosis of patients having HCV related chronic liver disease and its probable association with hepatocellular carcinoma.Methods: Sixty-eight patients having HCV chronic liver disease and 20 apparently healthy controls (HCs) were enrolled in the study. The patients were grouped into 3 groups: 18 patients having compensated chronic liver disease (CCLD), 18 patients having decompensated chronic liver disease, and 32 patients having hepatocellular carcinoma (HCC). Serum IL-9 level was estimated by ELISA and IL-9 receptor (IL-9R) gene expression was assessed by RT-PCR in HCC group and HCs.Results: IL-9 level was significantly higher in patients in comparison to HCs and there was statistically significant difference between the 3 patients’ groups (p 1600pg/ml, IL-9 had the ability to differentiate between CCLD group and HCC group with 75% sensitivity and 94.44% specificity. There was a highly significant statistical difference between HCC group and HCs in IL-9R gene expression (p < 0.001).Conclusion: Serum IL-9 level is higher in chronic HCV infected patients than in HCs. IL-9R gene expression is higher among HCC patients than in HCs.

Association between Presence of Esophageal Varices on Endoscopy and Extreme Degree of F4-Stage Fibrosis on Fibroscan in HCV-Related Chronic Liver Disease

Background: Hepatitis C Virus (HCV) infection is one of the causes which cause liver fibrosis, cirrhosis and carcinoma if left untreated. Patients who present with acute HCV infection, 50-70% of them develop chronic infection. This study attempted to see an association between F4 fibrosis in liver on fibroscan and esophageal varices on endoscopy in HCV related chronic liver disease (CLD) patients. Method: This study was conducted in Gastroenterology and Hepatology division of holy family hospital, Rawalpindi. Total 117 patients of 10 to 90 years were included. All patients were having HCV related CLD. Patients having F4 fibrosis stage were included while patients having fibrosis stage up to F3 fibrosis stage were excluded. All data regarding age, gender, F4 fibrosis and esophageal varices was entered and analyzed using the statistical package of social sciences while descriptive analysis was performed. Results: Amongst 114 patients who presented with F4 fibrosis stage on fibroscan 69.3% (79) of them were diagnosed for esophageal varices on endoscopy and 30.7% (35) were not having esophageal varices on endoscopy. Patients who were having esophageal varices on endoscopy 84.5% (49) of them were males and 55.9% (33) were females. Study participants having F4 fibrosis stage, 98.3% of them were males and 96.6% were females. So, there was not much difference between males and females having an extreme degree of fibrosis on fibroscan. Conclusion: Patients who were having F4 fibrosis stage on fibroscan, 2/3 of them were having esophageal varices on endoscopy. Esophageal varices were more present in males as compared to females.

Monocyte chemoattractant protein 1 released from macrophages induced by hepatitis C virus promotes monocytes migration

Hepatitis C Virus (HCV) infection usually progress to chronic liver disease and shows a significant increase in total monocyte/macrophages numbers in the liver. Monocyte chemoattractant protein-1 (MCP-1) plays a role in the recruitment of monocytes to the liver. In this study we found that MCP-1 were up-regulated in macrophages cultured with cell-culture derived infectious HCV particles (HCVcc) and promoted the migration of monocytes. IL1β, IL6 and TNFα were factors that induced MCP-1 expression, which were up-regulated in macrophages induced by HCV. Long-term of HCV incubation induced apoptosis of macrophages. Finally, we observed the effect of HCV infected macrophages on nearby liver cells. Huh7 cells continuously co-cultured with monocyte/macrophages displayed increased expression of pro-inflammatory cytokines and the morphology of Huh7 cells were greatly changed. Taken together, our study provides more information for the role of monocyte/macrophages in HCV related chronic liver disease.

Characterization of differential antibody production against hepatitis C virus in different HCV infection status.

BackgroundThe Centers for Disease Control and Prevention (CDC) issued an update on hepatitis C virus (HCV) testing approach, in which it omitted the use of recombinant immunoblot assay (RIBA) in the diagnostic algorithm and recommended that future studies are needed to evaluate the performance of HCV testing without RIBA. As Egypt has the highest prevalence of HCV worldwide, we aimed to evaluate the value of RIBA in HCV testing in a high prevalence population. Our objective was to clarify whether enzyme linked immunosorbent assay (ELISA) anti-HCV signal-to-cutoff (S/CO) ratios were able to discriminate true positive from false positive anti-HCV antibody status and to evaluate the role of RIBA in solving this problem which may lead to a redefined strategy for diagnosis of HCV infection. Our second objective was to elucidate the effects of different HCV peptides of both structural and non-structural proteins on the humoral immune response to HCV infection. MethodsThe current study drew results from 167 individuals divided into three groups: Group I: included 77 HCV antibody positive (ELISA) high risk health care workers (HCW), Group II: included 56 presumably uninfected individuals who showed normal liver enzymes, negative HCV RNA and were asymptomatic. Their ELISA HCV antibody S/C ratio ranged from 0.9 to <5. Group III: included 34 patients enrolled from outpatient clinics of Ain Shams Hospital with persistent viral replication, elevated liver enzymes, and chronic HCV related liver disease. All study participants were assessed for the presence of anti-HCV antibodies by 3rd generation ELISA which was confirmed by RIBA.ResultsInterpreting the results of both ELISA and RIBA together, false positive results were highly significantly increased in HCW when compared with the other two groups. Indeterminate and false negative results were only found in the presumably uninfected group. For differentiated antibody responses by RIBA, chronic HCV cases had the highest frequency of positive antibody response to core peptides while the presumably uninfected group had the lowest. Antibody response to E2 was found less frequently in chronic cases than Core 1, Core 2 and NS3. The specific antibody response to the different HCV peptides showed the same distribution of frequencies in both chronic HCV cases and the presumably uninfected individuals with the chronic cases having the highest frequencies. This distribution was different from the HCW. The most evident difference was the reaction towards NS3 which was the highest antibody producing peptide in chronic HCV and presumably uninfected individuals whereas in HCW Core1 was the highest.ConclusionThe HCV antibody immunoblot assay (RIBA) is still necessary for the detection of false positive cases which can occur quite frequently in countries of high prevalence as Egypt. Indeterminate RIBA results indicate a waning antibody response in elderly individuals who recovered from previous or distant HCV infection.

Pharmacodynamics and pharmacokinetics of elbasvir and grazoprevir in the treatment of hepatitis C

ABSTRACTIntroduction: Approximately 130 – 150 million people have chronic hepatitis C virus (HCV) infection and upwards of 500,000 deaths annually are attributed to HCV related liver disease worldwide. Pegylated interferon and ribavirin have been the mainstay of treatment for greater than 25 years until recent advent of protease inhibitors which has led to all oral HCV treatment regimens that have changed the outlook of hepatitis C treatment.Areas covered: This review provides summary of pharmacokinetics, pharmacodynamics, efficacy and safety of grazoprevir/elbasvir therapy for treatment of HCV infection.Expert opinion: Grazoprevir/elbasvir provides an all-oral once daily treatment option for HCV infection with high rates of efficacy and tolerability in a pangenotypic fashion. It highly efficacious in treating patients with cirrhosis, patients who have previously failed treatment with pegylated interferon and ribavirin, and patients with HIV co-infection. Grazoprevir/elbasvir has demonstrated higher barrier to resistance even in the presence of variants associated with resistance such as Q41R, F43S, R155K, V36M, T54S, and D168. It is one of only few HCV treatment regimens evaluated for use in patients with advanced chronic kidney disease and dialysis. It is a very promising regimen for treatment of HCV infection.

PTU-104 Non-invasive detection, stratification and treatment of chronic hepatic c related liver disease amongst substance users in the community: a prospective study

<h3>Introduction</h3> Despite discovery of direct acting antiviral agents (DAA), a two- three fold increase in hepatitis C virus (HCV) detection/treatment is necessary to reduce the national HCV disease burden. Ninety percent of HCV positive individuals in England are people who inject drugs (PWID) with poor engagement with health services. Our aim was to assess feasibility of non-invasive detection, stratification and treatment of HCV related chronic liver disease (CLD) in the community. <h3>Method</h3> Two-year prospective study (Dec 2013–Nov 2015) conducted at a large substance misuse service in SE England. Individuals offered dry blood spot testing (DBST), mobile transient elastography (TE), and HCV treatment (pegylated interferon/ribavirin/telaprevir). Clinically significant hepatic fibrosis: liver stiffness measurement (LSM) ≥7.5 kPa. <h3>Results</h3> To date, 165 individuals recruited, mean age 39.8 ± 8.9 yrs, 84.8% male. One hundred and forty-one (85.5%) had history of injecting drug use (IDU) and 143 (86.7%) reported alcohol use. Eighty-three (50.3%) had had a psychiatric diagnosis. Uptake of DBST was 75 (45.5%), main reason for declining being recent prior testing. Overall prevalence of positive serological markers were: HBcAb 28.8% (n = 42), HCV antibody 62.2% (n = 97) and HCV PCR 75.2% (73/97) (genotype 3a 42.8%, 1a 34.3%). Of those with a positive HCV PCR (n = 73), 62 (84.9%) underwent TE, mean LSM being 7.7 ± 6.6. kPa. Twenty-one (33.9%) had LSM ≥7.5 kPa including 13 (21%) with cirrhosis (LSM ≥12 kPa), one of whom had decompensated disease. Of the 73 with a positive HCV PCR none had had prior treatment: fifteen (20.5%) were not treatment candidates (chaotic life style), interferon was inappropriate in 35 (47.9%) with 23 (31.5%) being eligible for interferon based treatment. Thirteen have commenced therapy (nine genotype 3a, three 1a and one 2b), of whom 4 have successfully completed with 8 achieving rapid virological response. <h3>Conclusion</h3> This novel community based liver service at a substance service has shown excellent uptake of both DBST and mobile TE amongst PWID, though prevalence of a positive HCV antibody (62.2%) remains high. Additionally, despite a mean age of &lt;40 yrs about a third of PWID have clinically significant HCV related hepatic fibrosis with 1:5 having established cirrhosis. Though community based interferon therapy is feasible in PWID, it is contraindicated in approximately 50% emphasising the urgent need for interferon-free regimens in this vulnerable population. <h3>Disclosure of interest</h3> S. Verma Grant/Research Support from: Gilead, Conflict with: Travel grants from Gilead, Abbvie, Roche, BMS and Janssen, M. O’Sullivan Conflict with: salary funded by Gilead, H. Williams: None Declared, A.-M. Jones: None Declared.

Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation.

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, ≥ moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.

Evolving therapies for the treatment of HCV viral hepatitis.

Evolving therapies for the treatment of HCV viral hepatitis.

Diagnosis, treatment, and follow-up of hepatitis C-virus related liver disease. Hungarian national consensus guideline

Approximately 70 000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. Early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases (liver cirrhosis and liver cancer) and its complications. In addition, it may increase work productivity and life expectancy of infected individual, and can prevent further viral transmission. Early recognition can substantially reduce the long term financial burden of related morbidity from socioeconomic point of view. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can kill the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of two direct acting first generation protease inhibitor drugs (boceprevir and telaprevir) to the dual therapy increased the chance of sustained clearance of virus to 63-75% and 59-66%, respectively. These two protease inhibitor drugs are available and financed for a segment of Hungarian patients since May 2013. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. For initiation of treatment as well as for on-treatment decisions accurate and timely molecular biology tests are mandatory. Staging of liver damage (fibrosis) non-invasive methods (transient elastography and biochemical methods) are acceptable to avoid concerns of patients related to liver biopsy. Professional decision for treatment is balanced against budget limitations in Hungary, and priority is given to those with urgent need using a national Priority Index system reflecting stage of liver disease as well as additional factors (activity and progression of liver disease, predictive factors and other special circumstances). All naïve patients are given a first chance with dual therapy. Those with genotype 1 infection and with on-treatment or historic failure to dual therapy are eligible to receive protease inhibitor based triple therapy provided, they reach financial cutoff eligibility based on Priority Index. Duration of therapy is usually 48 weeks in genotype 1 with a response-guided potential to reduce duration for non-cirrhotic patients. Patients with non-1 genotypes are treated with dual therapy (without protease inhibitors) for a genotype and response driven duration of 16, 24, 48, or 72 week. Careful monitoring for early recognition and management of side-effects as well as viral response and potential breakthrough during protease-inhibitor therapy are recommended.

Genotype Distribution and Time Trend of Hepatitis C In South India

Background: Hepatitis C virus (HCV) shows considerable genetic heterogeneity among isolates from all over the world. Six main groups of sequence variants are recognized. Genotype 1,2 and 3 are most common in North America and Europe, genotype 4 is most common in Middle East, genotype 5 and 6 are common in South East Asia. In India, genotype 3 is most common and genotype 2 is least common. The knowledge about the genotype distribution of HCV in a geographical area may help for treatment plan and also provide clues about the outcome of HCV related liver disease in that area.

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus (HIV) positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers. Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients co-infected with hepatitis B virus (HBV). However, liver transplantation in HIV positive patients with hepatitis C virus (HCV) has poorer outcomes overall, requiring careful selection of candidates. This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management. In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.

CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV) Infection

Golgi protein 73 (GP73), which is up-regulated in hepatocellular carcinoma (HCC), has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV) infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

The prevalence of hepatitis C virus among people of South Asian origin in Glasgow – Results from a community based survey and laboratory surveillance

South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted.

Hepatitis C virus and HIV type 1 co-infection

Around 33 million people worldwide are living with Human Immunodeficiency Virus (HIV) infection, and approximately 20-30% of HIV-infected individuals are also infected with Hepatitis C virus (HCV). The main form of HCV transmission is via the blood borne route; high rates of co-infection are found in intravenous drug users with HCV prevalence rates as high as 90%. Introduction of effective antiretroviral therapy (ART) has led to a significant decline in HIV-related morbidity, but at the same time the incidence of HCV related liver disease is increasing in the co-infected population. Meta analysis has revealed that individuals who are co-infected with HIV/HCV harbor three times greater risk of progression to liver disease than those infected with HCV alone. Increased risk of progression to Acquired Immunodeficiency Syndrome (AIDS) and AIDS-related deaths is shown among the co-infected patients by some studies, suggesting that HCV infection may accelerate the clinical course of HIV infection. HCV may also affect the incidence of liver toxicity associated with ART, affecting the management of HIV infection. There is a lack of optimal therapeutic approaches to treat HCV infection in HIV co-infected patients. This review discusses recent literature pertaining HIV/HCV co-infection, in addition to providing a snapshot of impact of co-infection on human genome at the level of gene expression and its regulation by microRNAs (miRNAs).

HGV-HCV/HBV co-infection in India: A pilot study

Background:Hepatitis G virus (HGV) is newly identified virus, transmitted by infected blood and blood products. Effect of HGV infection on liver diseases is not well known.Aims:Co-infection of HGV with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection has been reported however; very limited data is available from India. Therefore, we have performed a pilot study for the presence of co-infection of HGV in chronic liver disease patients.Setting and Design:The study was performed in research laboratory at P.D. Hinduja National hospital and Medical research center, Mahim, Mumbai. Prospective study was designed.Methods and Materials:Forty HBV, HCV related chronic liver disease patients were studied. Forty randomly selected voluntary healthy blood donors visiting our blood bank were included as controls. Serum bilirubin, alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were estimated. HGV infection was detected by using reverse transcriptase molony murine leukemia virus (M-MLV) with the help of HGV 340/625IC kit (Sacace, Italy).Results and Conclusion:One HCV positive patient had infection with HGV among 40 HBV/HCV chronic liver disease patients.

Serum Mannan-Binding Lectin in Egyptian Patients With Chronic Hepatitis C: Its Relation to Disease Progression and Response to Treatment

Chronic hepatitis C virus (HCV) infection is a major worldwide public health problem. Egypt has the highest prevalence of adult HCV infection in the world, averaging 15%-25% in rural communities. Mannan-binding lectin (MBL) is a liver-derived pluripotent serum lectin that plays a role in the innate immune system of the host. It is an acute-phase protein that is involved in the activation of the classical complement pathway. MBL may play a defensive role in HCV infection. To investigate the relationship between MBL concentration and HCV infection in Egyptian patients suffering chronic hepatitis C. Serum samples obtained from 35 Egyptian hepatitis C patients and 30 normal controls were assayed for MBL. MBL concentrations were correlated to disease characteristics and treatment response. Serum MBL was significantly higher in HCV patients than in controls, but no relationship was found between MBL concentration and disease progression in terms of hepatic fibrosis and inflammation. Responders to interferon (INF)-based therapy had significantly higher serum MBL than non-responders. We found no association between serum MBL concentration and progression of HCV related liver disease. Responders to INF-based therapy had significantly higher serum MBL than non-responders.

Serum Mannan-Binding Lectin in Egyptian Patients With Chronic Hepatitis C: Its Relation to Disease Progression and Response to Treatment

: Background: Chronic hepatitis C virus (HCV) infection is a major worldwide public health problem. Egypt has the highest prevalence of adult HCV infection in the world, averaging 15%–25% in rural communities. Mannan-binding lectin (MBL) is a liver-derived pluripotent serum lectin that plays a role in the innate immune system of the host. It is an acute-phase protein that is involved in the activation of the classical complement pathway. MBL may play a defensive role in HCV infection.Objectives: To investigate the relationship between MBL concentration and HCV infection in Egyptian patients suffering chronic hepatitis C.Patients and Methods: Serum samples obtained from 35 Egyptian hepatitis C patients and 30 normal controls were assayed for MBL. MBL concentrations were correlated to disease characteristics and treatment response.Results: Serum MBL was significantly higher in HCV patients than in controls, but no relationship was found between MBL concentration and disease progression in terms of hepatic fibrosis and inflammation. Responders to interferon (INF)-based therapy had significantly higher serum MBL than non-responders.Conclusions: We found no association between serum MBL concentration and progression of HCV related liver disease. Responders to INF-based therapy had significantly higher serum MBL than non-responders. Implication for health policy/practice/research/medical education:MBL may be considered as a predictor of response to antiviral therapy in HCV patients and MBL replacement therapy may improve the response to antiviral therapy in these patients. Please cite this paper as:Esmat S, Omran D, Sleem GA, Rashed L. Serum Mannan-Binding Lectin in Egyptian Patients With Chronic Hepatitis C: Its Relation to Disease Progression and Response to Treatment. Hepat Mon. 2012;12(4):259-64. DOI: 10.5812/hepatmon.704 Copyright © 2012 Kowsar Corp. All rights reserved.

Hepatitis C Treatment Response in Liver Transplant Recipients

BackgroundHepatitis C virus (HCV)–related end-stage liver disease is the leading indication for liver transplantation (LT). HCV recurrence after LT is universal leading to accelerated recurrence of cirrhosis. Therapeutic response to currently available regimen is reported lower compared to treatment of HCV in non LT patients.ObjectiveEvaluate the response of HCV treatment in LT recipients.MethodsIt was a retrospective study in which medical records of subjects who underwent liver transplant for HCV related liver disease from September 1991 to August 2009 were reviewed.ResultsOne hundred ninety-five subjects with HCV LT recipients charts were reviewed, 139 were excluded as there were not treated. Fifty-six subjects were treated with pegylated interferon and ribavirin standard dose. Mean age was 60 years, predominantly males (82%). Twenty-eight (50%) were white, 18 (32%) were Hispanic and 10 (18%) were African American. Average body mass index was 28, and genotype (GT) 1 was predominant (84%). Median METAVIR fibrosis score was 2. Overall sustained virological response (SVR) in this cohort was 32%. Hispanics and Whites had similar SVR rates (50%) but none of the African Americans achieved SVR and had 40% relapse rate. There were no deaths in subjects who achieved SVR whereas 4 died in non SVR group.ComplicationsSVR group: one subject underwent re-transplantation due to hepatic artery issues, 6 had acute cellular rejection (ACR) during treatment and one had chronic rejection. Overall, 16% received blood transfusions, 21% required erythropoietin respectively for anemia.ConclusionTable 1Treatment Response According to GenotypeGT-1 (n = 47)GT-2 (n = 2)GT-3 (n = 7)SVR13 (28%)5 (71%)No SVR17 (36%)Relapser14 (30%)1 (50%)2 (29%)Treatment intolerant3 (6%)1 (50%)GT, genotype; SVR, sustained virological response. Open table in a new tab BackgroundHepatitis C virus (HCV)–related end-stage liver disease is the leading indication for liver transplantation (LT). HCV recurrence after LT is universal leading to accelerated recurrence of cirrhosis. Therapeutic response to currently available regimen is reported lower compared to treatment of HCV in non LT patients. Hepatitis C virus (HCV)–related end-stage liver disease is the leading indication for liver transplantation (LT). HCV recurrence after LT is universal leading to accelerated recurrence of cirrhosis. Therapeutic response to currently available regimen is reported lower compared to treatment of HCV in non LT patients. ObjectiveEvaluate the response of HCV treatment in LT recipients. Evaluate the response of HCV treatment in LT recipients. MethodsIt was a retrospective study in which medical records of subjects who underwent liver transplant for HCV related liver disease from September 1991 to August 2009 were reviewed. It was a retrospective study in which medical records of subjects who underwent liver transplant for HCV related liver disease from September 1991 to August 2009 were reviewed. ResultsOne hundred ninety-five subjects with HCV LT recipients charts were reviewed, 139 were excluded as there were not treated. Fifty-six subjects were treated with pegylated interferon and ribavirin standard dose. Mean age was 60 years, predominantly males (82%). Twenty-eight (50%) were white, 18 (32%) were Hispanic and 10 (18%) were African American. Average body mass index was 28, and genotype (GT) 1 was predominant (84%). Median METAVIR fibrosis score was 2. Overall sustained virological response (SVR) in this cohort was 32%. Hispanics and Whites had similar SVR rates (50%) but none of the African Americans achieved SVR and had 40% relapse rate. There were no deaths in subjects who achieved SVR whereas 4 died in non SVR group. One hundred ninety-five subjects with HCV LT recipients charts were reviewed, 139 were excluded as there were not treated. Fifty-six subjects were treated with pegylated interferon and ribavirin standard dose. Mean age was 60 years, predominantly males (82%). Twenty-eight (50%) were white, 18 (32%) were Hispanic and 10 (18%) were African American. Average body mass index was 28, and genotype (GT) 1 was predominant (84%). Median METAVIR fibrosis score was 2. Overall sustained virological response (SVR) in this cohort was 32%. Hispanics and Whites had similar SVR rates (50%) but none of the African Americans achieved SVR and had 40% relapse rate. There were no deaths in subjects who achieved SVR whereas 4 died in non SVR group. ComplicationsSVR group: one subject underwent re-transplantation due to hepatic artery issues, 6 had acute cellular rejection (ACR) during treatment and one had chronic rejection. Overall, 16% received blood transfusions, 21% required erythropoietin respectively for anemia. SVR group: one subject underwent re-transplantation due to hepatic artery issues, 6 had acute cellular rejection (ACR) during treatment and one had chronic rejection. Overall, 16% received blood transfusions, 21% required erythropoietin respectively for anemia. ConclusionTable 1Treatment Response According to GenotypeGT-1 (n = 47)GT-2 (n = 2)GT-3 (n = 7)SVR13 (28%)5 (71%)No SVR17 (36%)Relapser14 (30%)1 (50%)2 (29%)Treatment intolerant3 (6%)1 (50%)GT, genotype; SVR, sustained virological response. Open table in a new tab GT, genotype; SVR, sustained virological response.

Clinicopathological features and genotype distribution in patients with hepatitis C virus chronic liver disease

Hepatitis C virus (HCV) genotype influences the severity of disease and response to therapy. This retrospective study examined the clinical and histological features and the genotype distribution in biopsied patients with HCV related chronic liver disease. Of 105 biopsies from patients with HCV infection, 96 from patients with chronic liver disease were reviewed. The Ishak scoring system was used for histological analysis. Genotype 3 was most common accounting for 77.1%, and genotype 1 for 9.4% of cases. There was no significant association of transaminase levels, viral load or necro-inflammatory activity score with genotype. A severe degree of fibrosis was seen in 77.8% cases of genotype 1 and in 63.5% of genotype 3 (p=0.76). Variable degrees of steatosis were noted in 68.8% of cases. However, severe steatosis was noted only in genotype 3 (7 cases). Serum transaminase levels did not correlate with either histological activity (p=0.43) or degree of fibrosis (p=0.72). Severe fibrosis / cirrhosis was seen in 74.24% of patients above 40 years of age as compared to 33.3% of patients below 40 years (p=0.001). The frequency of Mallory hyaline was significantly different between genotypes 1 and 3 infection (P<0.001). This study confirms the preponderance of genotype 3 in Indian patients with HCV related chronic liver disease. Severe steatosis was seen only in genotype 3 and Mallory hyaline was very common in genotype 1. The small numbers of patients in non genotype 3 could be a reason for the apparent lack of histological differences between different HCV genotypes. Severe fibrosis seen in older age groups confirms that HCV infection is progressive and major acceleration of the disease process occurs after 40 years of age.