Concomitant Hepatitis C Virus Infection Research Articles

The impact of concomitant hepatitis C virus infection on liver and cardiovascular risks in patients with metabolic-associated fatty liver disease.

Chronic hepatitis C virus (HCV)-infected patients with hepatic steatosis are excluded from the diagnosis of nonalcoholic fatty liver disease (NAFLD). The new name and diagnostic criteria of metabolic-associated fatty liver disease (MAFLD) were proposed in 2020 to replace the original term NAFLD. The clinical outcome of MAFLD patients with concomitant chronic HCV infection requires further investigation. The participants from Taiwan bio-bank cohort were included. MAFLD is defined as the presence of fatty liver, plus any of the following three conditions: overweight/obesity, type 2 diabetes, or metabolic dysfunction. The patients with positive anti-HCV were considered chronic HCV infections. The severity of liver fibrosis was determined using the fibrosis-4 index and NAFLD fibrosis score (NFS). The risk of cardiovascular disease (CVD) was assessed using intima-media thickness (IMT) or plaques of carotid duplex ultrasound. A total of 18 907 participants (age 55.79 ± 10.42; males 31.9%) were included for final analysis. The prevalence of MAFLD and chronic HCV infections were 39.2% and 2.6%, respectively. According to the status of MAFLD and chronic HCV infection, they were distributed to four groups: 'dual etiology group', 'MAFLD alone', 'HCV alone', and healthy controls. Compared with the 'MAFLD alone' group, the 'dual etiology' group had a lower frequency of the male sex, reduced levels of serum triglyceride, total cholesterol, and LDL; but overall older age, a higher percentage of hypertension history. In addition, they had higher levels of serum aspartate aminotransferase, fibrosis-4 index, and NFS; but no difference in levels of alanine aminotransferase, gamma-glutamyl transferase, fatty liver index, IMT, and the percentage of carotid plaques. Using binary logistic regression, chronic HCV infection was associated with more severe liver fibrosis, but not with carotid plaques in MAFLD patients. MAFLD patients with concomitant HCV infection, a specific phenotype of MAFLD may include a higher risk of advanced liver fibrosis, but a similar risk of atherosclerotic cardiovascular disease compared to those without.

Emicizumab Prophylaxis in Persons with Hemophilia A, Aged ≥50 Years, with Comorbidities - Pooled Data from Four Phase III Studies (HAVEN 1, 3, and 4, and STASEY)

Emicizumab Prophylaxis in Persons with Hemophilia A, Aged ≥50 Years, with Comorbidities - Pooled Data from Four Phase III Studies (HAVEN 1, 3, and 4, and STASEY)

Effect of Active Hepatitis C Infection in Relapse-Free Survival Among Patients with HIV‐Related Diffuse Large B‐Cell Lymphoma

Introduction: Diffuse-large B cell lymphoma (DLBCL) is the most common lymphoma associated with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). During the past decades, the incidence of HIV-related lymphomas has declined; however, it still remains a major cause of morbidity and mortality in this population. Before highly effective antiretroviral therapy for HIV was introduced, individuals with HIV-related DLBCL had worse complete response and survival rates compared to their uninfected counterparts. Additionally, recent studies have shown that relapse rates are lower for DLBCL patients that achieve HCV sustained virological response (SVR). Nevertheless, outcomes in patients with active HCV infection among patients with HIV-related DLBCL have not been reported yet. This study is aimed to compare the clinical outcomes in HIV-related DLBCL among patients with and without active HCV infection. Methods: Patients with HIV infection and newly diagnosed DLBCL between 2005 and 2017 at Montefiore Medical Center/Albert Einstein College of Medicine were identified using the institutional software Clinical Looking Glass. Cases were grouped into concomitant HIV and HCV infection (HIV + HCV) or HIV alone (HIV) based on HCV antibody and viral load counts at DLBCL diagnosis. Patients with active hepatitis B infection were excluded. Data regarding demographics, laboratory parameters, HCV treatment, lymphoma treatment and clinical outcomes including complete response (CR), progression of disease (POD) and relapse were collected by manual chart review and compared among groups. SVR was defined as undetectable HCV RNA level 12 weeks after HCV treatment completion. Clinical outcomes were compared between patients with and without active HCV at the time of outcome evaluation. For this purpose, patients that achieved SVR for HCV were analyzed in the HIV group. Kaplan-Meier curves were plotted to compare 12-months relapse-free survival (RFS) among groups. Statistical analysis was performed using Stata 14.1. Results: A total of 63 patients were identified, of whom 45 (71.4%) had HIV alone (HIV) and 18 (28.6%) had concomitant active HCV and HIV infection (HIV + HCV). The median age was 49 years (IQ: 40-54), there were 39 (61.9%) males, 27 (42.9%) were Non-Hispanic Black and 27 (42.9%) were Hispanic. At DLBCL diagnosis, the majority of cases had advanced stages (stage 3: 15; 25% and stage 4: 40; 66.7%), the median CD4 count was 117 (IQ: 65-217) and 45 (72.6%) had AIDS. Baseline characteristics did not differ among groups. Of 63 patients, 53 (84.1%) were treated for DLBCL. Treatment regimens included DA-EPOCH (28; 50.9%), CHOP (22; 40%) and others (3; 9.1%). Rituximab was given to 33 cases (57.9%). Within the HIV + HCV group, only 3 (16.7%) patients received treatment for HCV; all of them were treated with ledipasvir/sofosbuvir and achieved SVR. In the full cohort, CR was achieved in 17 (32.1%) treated patients and 19 (35.9%) had POD. The CR rate was lower for patients with active HCV + HIV compared to HIV alone (7.1% vs. 41%, p=0.02) and there was no difference in POD among groups (28.6% vs. 38.5%, p=0.37). Patients with active HCV + HIV had a significantly lower 18-month RFS compared to those with HIV (62.9% vs. 87.4%, p=0.035). In a multivariate model adjusted for stage, AIDS and rituximab use; active HCV + HIV was a predictor for relapse (OR:6.36, 95% CI: 1.01 - 39.9, p=0.048). Conclusions: Despite available and effective treatment against HCV infection, only a minority of patients with DLBCL-related HIV received HCV treatment. Active HCV seems to play a role in the outcomes of patients treated for DLBCL and was found to be a predictor for relapse. Hence, HCV treatment should be considered for patients with HIV-related DLBCL. Disclosures Shah: Physicians' Education Resource: Honoraria. Friedman:Incyte pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Interferon alpha, gamma, and lambda 2: are they possible culprits in the association between psoriasis and hepatitis C virus?

Background High prevalence of hepatitis C virus (HCV) infection among patients with psoriasis has been reported. Interferons (IFNs) play pivotal roles in both the pathogenesis of psoriasis and the immunological response to HCV. Objective To study serum levels of IFN-α, IFN-γ, and IFN-λ2 in psoriatic patients with concomitant HCV infection in comparison with their levels in patients with psoriasis alone and in healthy control. Patients and methods The study included 20 patients with concomitant psoriasis vulgaris and chronic HCV infection, 25 patients with only psoriasis vulgaris, and 24 healthy controls. Serum levels of IFN-α, IFN-γ, and IFN-λ2 were assessed using enzyme-linked immunosorbent assay technique. Results Psoriatic patients with HCV infection showed significantly higher serum IFN-α, IFN-γ, and IFN-λ2 compared with controls (P=0.028, 0.001, and 0.007), higher serum IFN-λ2 levels compared with patients with psoriasis alone, yet significantly lower serum IFN-α and IFN-γ levels in comparison with psoriasis only patients. A significant positive correlation was found between IFN-α and IFN-λ2 levels in psoriatic patients with HCV (r=0.536, P=0.015). Conclusion IFN-α and IFN-γ play important roles in the pathogenesis of psoriasis, yet they are not likely to be the cause of development of psoriasis in chronic HCV-infected patients. High levels of IFN-λ2 among psoriatic patients with HCV infection but not in patients with psoriasis alone point to its possible safety in the treatment of HCV in psoriatic patients.

Pretransplant diabetes mellitus predicts worse outcomes of liver transplantation: evidence from meta-analysis.

It has been demonstrated that the prognosis of liver transplantation (LT) is significantly influenced by pretransplant factors, such as diabetes mellitus (DM). However, inconsistent observations are obtained. We comprehensively searched PubMed, Embase and Web of Science to identify eligible cohort studies to evaluate the impact of preexisting DM on LT prognosis. Overall mortality and graft loss, as the most frequently observed parameters, were used to evaluate the outcomes of LT. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were pooled to assess the effect of DM. 15,768 diabetic LT recipients and 60,176 non-diabetic LT recipients from 13 populations were included in this meta-analysis. Preexisting DM increased the risk for overall death of LT by 40% (95% CI 1.22-1.61), compared with DM-free patients. In addition, the risk for graft loss was also elevated by pretransplant DM (HR 1.28, 95% CI 1.07-1.54). Both analyses showed high heterogeneities (I 2=85.2 and 93.2%, respectively) and their sources were not identified by meta-regression analyses. In terms of the additive effect of hepatitis C virus (HCV) infection on poor outcomes of diabetic LT recipients, stratified meta-analyses were conducted. It was demonstrated that HCV infection increased the risk for mortality by 73% (95% CI 1.64-1.83), relatively higher than non-HCV recipients (HR 1.32, 95% CI 1.25-1.39) and general population (HR 1.40, 95% CI 1.22-1.61). Preexisting DM predicts worse patient and graft survivals of LT. Concomitant HCV infection would further deteriorate this unfavorable impact. Given the high heterogeneities and the insufficient evidences, more studies are still warranted to support these observations.

Brief Report: Coordinated Modulation of Circulating miR-21 in HIV, HIV-Associated Pulmonary Arterial Hypertension, and HIV/Hepatitis C Virus Coinfection.

Dysregulation of microRNA-21 (miR-21) is independently associated with HIV infection, pulmonary arterial hypertension (PAH), and hepatitis C virus (HCV) infection. To assess the expression of miR-21 in these overlapping comorbidities, we measured plasma miR-21 in HIV with and without PAH and then stratified by concomitant HCV infection. MiR-21 was increased in HIV and HIV-PAH versus uninfected subjects, but it did not differ between these groups. HIV/HCV coinfection correlated with even higher miR-21 levels within the HIV-infected population. These data reveal specific regulation of plasma miR-21 in HIV, HIV/HCV coinfection, and PAH and suggest that miR-21 may integrate complex disease-specific signaling in the setting of HIV infection.

Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment.

There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but <37 copies/ml), and quantifiable HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA <37 copies/ml. Most of them (59/90, 65.6%) had full suppression, with the remaining (31/90, 34.4%) showing low-level viremia (median: 11.9 copies/ml; IQR 7.4-16.3). Among the 17 women with quantifiable viral load, median HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection should be considered at higher risk of having quantifiable HIV-RNA at the end of pregnancy.

Study of the impact of viral load of hepatitis C on patients with concomitant psoriasis vulgaris

Background and study aimConcomitant hepatitis C virus (HCV) infection and psoriasis vulgaris (PV) are not uncommon coexisting diseases, especially in areas with high viral hepatitis endemicity. To date, data about the interaction between both diseases are scarce. Therefore, we aimed to describe the possible interplay between the HCV viral load and psoriatic activity in concomitant Egyptian diseased patients. Patients and methodsBetween December 2011 and August 2013, all psoriatic patients attending Assiut University Hospital outpatient clinics were tested for HCV serologic assay. Patients with positively coexisting diseases were further reevaluated for psoriasis area severity index (PASI) score assessment, liver function tests, HCV-RNA-polymerase chain reaction (PCR) assays, and sonographic examination of the liver. For comparative purposes, another matched group (n=26) with psoriasis only (HCV-negative group) was enrolled as a control. ResultsDuring the period of the study, 20 patients with concomitant PV and HCV infection (HCV-positive group; 50% males, mean age of 44.15±10.66years) were recruited. The mean PASI score was 44.75±10.38 and clinical signs of liver dysfunction were observed in 40% (n=8), 100% had abnormal liver function tests (n=20), and 75% had sonographic findings of cirrhosis (n=15). The PASI score was significantly higher in the HCV-positive psoriatic group compared to the HCV-negative control (p<0.001). Significant correlations were detected between the PASI score and the viral loads, and also with alanine aminotransferase (ALT). ConclusionWhen HCV was found concomitantly with PV, a high possibility of severe disease pattern will be expected that entails special precautions in the treatment process.

Alcoholic hepatitis and concomitant hepatitis C virus infection.

Hepatitis C virus (HCV) infection and alcohol abuse are two most important causes of chronic liver disease in the United States. Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality. About 20% of patients presenting with alcoholic hepatitis have concomitant HCV infection. Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage. Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection. The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research.

Long-term safety of anti-TNF-α in PsA patients with concomitant HCV infection: a retrospective observational multicenter study on 15 patients

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option.

Recent trends in the epidemiology of alcoholic liver disease.

Alcohol remains the second most common cause of liver cirrhosis after hepatitis C virus (HCV) infection in the United States, contributing to approximately 20% to 25% cases of liver cirrhosis and about half of all admissions among patients with cirrhosis. Of the various factors responsible for liver disease, duration and amount of drinking alcohol is the most important factor. Pooled data from many epidemiological studies show a minimum intake of 30 g/day of alcohol in women and 50 g/day in men consumed over at least 5 years to cause liver cirrhosis. 3 Prevalence and mortality rates from cirrhosis parallel alcohol consumption prevalence rates in the population globally. Within Europe, which has the highest rate of consumption per capita in the implementation of policies on alcohol sale has resulted in changing epidemiology in different parts of Europe. Alcohol consumption rates have decreased in southern Europe, whereas they have increased in eastern Europe and some areas of northern Europe (including Ireland and the United Kingdom). 4 Because only 10% to 15% of people engaged in heavy drinking develop liver cirrhosis, other factors such as host factors and comorbidities are clearly important (Fig. 1). Women are more prone to the hepatotoxic effect of alcohol compared with men and are prone to develop liver cirrhosis at a lower amount of alcohol consumption. Type of alcohol consumed, binge drinking (five or more drinks at one time), drinking on an empty stomach, and participation in alcohol rehabilitation programs such as Alcoholic Anonymous are some of the other factors. Alcohol use and concomitant HCV infection act synergistically to cause more frequent and faster progression of fibrosis. 5 With the epidemic of obesity in the United States, prevalence rates of metabolic syndrome and visceral adiposity are increasing among alcoholics contributing to more prevalent and severe liver disease. 6 Alcohol remains the third most common preventable cause of death after smoking and hypertension. Alcohol-related mortality affects young and middle-aged population with loss of productive life years. Liver-related mortality from alcohol contributes to 4% of mortality and 5% of disability adjusted life years (DALY) globally, with highest impact in Europe, where these same figures are 7% and 12%, respectively (Fig. 2). 7 This huge disease burden has an economic impact of about €125 billion annually in Europe, about 1.3% of the gross domestic product. These figures are probably underestimates due to inaccuracies in death certificate reports, because mentioning alcohol as a contributing cause of death may have social and legal implications. Fortunately, over the last two to three decades, the mortality rates from liver cirrhosis have decreased from 20 to 25 per 100,000 population in the early twentieth century to less than 10/ 100,000 currently (Fig. 3). 8 Improved management of cir

Serum Sclerostin in Alcoholics: A Pilot Study

Sclerostin is an endogenous inhibitor of the Wnt/β-catenin pathway secreted by osteocytes, which inhibits osteoblast function, differentiation and survival. As a consequence, sclerostin tends to decrease bone mass. Alcoholics frequently present osteoporosis, mainly due to decreased bone synthesis. The behaviour of sclerostin in these patients is unknown. The aim of this work was to analyse the relationship between serum sclerostin levels and bone mineral density (BMD), ethanol consumption, nutritional status, liver function derangement and biomarkers of bone homeostasis in alcoholic patients. We included 31 alcoholic patients, of whom 11 were infected with Hepatitis C virus (HCV) and 7 age and sex-matched controls. All underwent densitometry, and serum sclerostin, osteocalcin, collagen telopeptide, parathyroid hormone (PTH), vitamin D, cortisol and testosterone were determined. Sclerostin levels were significantly higher in patients (30.95 ± 18.91 pmol/l) than controls (t = 4.4; P < 0.001), especially in non-HCV patients; they showed an inverse correlation with osteocalcin, prothrombin activity and serum albumin, and a direct correlation with bilirubin and telopeptide, but not with BMD, nutritional status or ethanol intake. Serum sclerostin was raised in alcoholic patients, and it correlated with decreased markers of bone synthesis and increased markers of bone breakdown. The elevation in sclerostin levels was clearly related with liver function, but not with ethanol intake, nutritional status or concomitant HCV infection.

Hepatitis C virus infection in patients with primary biliary cirrhosis

Background and aim. The aim of this study is to evaluate the role of hepatitis C virus (HCV) infection in patients with primary biliary cirrhosis (PBC).Material and methods. On the basis of a retrospective review of medical records, all patients consecutively diagnosed with PBC or HCV infection between 1999 and 2011 and who had a regular follow-up of at least 3 years were included in the study. Clinical characteristics, especially the severity of cirrhosis, were analyzed in PBC patients with HCV infection (PBC-HCV), PBC patients without HCV infection (PBC-only), and patients with only HCV infection (HCV-only).Results. A total of 76 patients with PBC, including 9 patients with HCV infection, were analyzed. Of the PBC-HCV patients, 7 (7/9, 77.8%) were women with a mean age of 55.11 ± 14.29 years. Age- and sex-matched PBC-only patients (n = 36) and HCV-only patients (n = 36) were used as control groups. In comparison to the PBC-only controls, PBC-HCV patients had a greater severity of cirrhosis based on Child-Pugh (p = 0.019) and Model for End-Stage Liver Disease (MELD) (p = 0.01) scores. However, no significant difference in the severity of cirrhosis was found between the PBC-HCV and HCV-only control patients (p = 0.94 in Child-Pugh scores; p = 0.64 in MELD scores).Conclusions. In PBC patients with concomitant HCV infection, aggressive management may be warranted in view of the associated more severe liver cirrhosis.

Impact of Hepatitis C Virus Infection on the in-Hospital Mortality of Patients with Alcoholic Hepatitis

Background and Aim: There is limited data on the impact of hepatitis C virus (HCV) infection on alcoholic hepatitis (AH). The present study was performed to assess the effect of HCV on inhospital mortality of AH. Methods: Using Nationwide Inpatient Sample (1998-2007), AH admissions were stratified based on the presence or absence of HCV. Results: Of 111,726 AH admissions, 7,240 (6.5%) were HCV +ve. These patients were different from HCV -ve subjects in age, race, Charlston Comorbidity index, pay source, hospital characteristics, complications, and interventions needed. In-hospital mortality from AH was higher in presence of HCV (3.8% vs. 3.1%; P=0.001). On multivariate logistic regression, HCV infection independently predicted in-hospital mortality of AH after controlling for other variables including calendar year [OR 1.29 (CI: 1.12-1.49; P=0.0005)]. Other strong predictors were hepatic encephalopathy and renal failure. Conclusion: Concomitant HCV infection is an important risk factor for in-hospital mortality in AH. Further studies with longer follow up are needed to assess the impact of HCV on AH patients at 6 months and at one year.

Response to raltegravir-based salvage therapy in HIV-infected patients with hepatitis C virus or hepatitis B virus coinfection

To define the impact of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) on viroimmunological response to raltegravir-based salvage regimens that also include new HIV inhibitors such as maraviroc, darunavir and etravirine. We used data from a national observational study of patients starting raltegravir-based regimens to compare virological suppression and CD4 cell change from baseline in patients with and without concomitant HBV or HCV infection. Overall, 275 patients (107 coinfected and 168 non-coinfected) were evaluated. Coinfected patients were more commonly former intravenous drug users and had a longer history of HIV infection and higher baseline aminotransferase levels. Both HIV-RNA and CD4 response were similar in the two groups. Mean time to first HIV-RNA copy number <50 copies/mL was 4.1 months (95% CI 3.5-4.6) in non-coinfected patients and 3.9 months (95% CI 3.3-4.5) in coinfected patients (hazard ratio 1.039, 95% CI 0.761-1.418, P = 0.766, log-rank test). The risk of developing new grade 3-4 hepatic adverse events was significantly higher in coinfected patients (hazard ratio 1.779, 95% CI 1.123-2.817, P = 0.009). The two groups of coinfected and non-coinfected patients had similar rates of interruption of any baseline drug (hazard ratio 1.075, 95% CI 0.649-1.781, P = 0.776) and of raltegravir (hazard ratio 1.520, 95% CI 0.671-3.447, P = 0.311). Few AIDS-defining events and deaths occurred. Viroimmunological response to regimens based on raltegravir and other recent anti-HIV inhibitors is not negatively affected by coinfection with HBV or HCV. Liver toxicity, either pre-existing or new, is more common in coinfected patients, but with no increased risk of treatment interruption.

The association between hepatitis C virus infection, genetic polymorphisms of oxidative stress genes and B-cell non-Hodgkin’s lymphoma risk in Egypt

Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Polymorphisms in oxidative stress genes as; superoxide dismutase (SOD2), glutathione peroxidase (GPX1), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (NOS2) may influence non-Hodgkin’s lymphoma (NHL) risk. HCV screening and polymorphisms in these five genes coding for antioxidant enzymes were studied in 100 Egyptian patients with B cell-NHL and 100 controls to clarify the association between HCV infection, oxidative stress genes polymorphisms and B cell-NHL risk. A significantly higher prevalence of HCV infection was detected among NHL patients relative to controls and this carried a 14-fold increased NHL risk (odds ratio (OR)=14.3, 95% confidence interval (CI)=5.4–38.3, p<0.0001). GPX1 and MPO genetic polymorphisms conveyed increase in B-NHL risk (OR=3.3, 95% CI=1.4–7.4, p=0.004 and OR=4.4, 95% CI=1.3–14.2, p=0.009 respectively). Further analyses stratified by HCV infection revealed that concomitant HCV infection and GPX1 gene polymorphism had a synergetic effect on NHL risk with an OR of 15 (95%CI=2.2–69.6, p<0.0001). In addition, combined HCV infection and MPO gene polymorphisms had a pronounced NHL risk (OR=9.2, 95%CI=2.5–33.9, p<0.0001). SOD2, CAT and NOS2 genetic polymorphisms were not found to confer increased NHL risk. This study revealed that HCV infection is a risk factor for NHL in Egypt. Polymorphisms in GPX1 and MPO genes may influence NHL risk in HCV infected Egyptian patients. Larger scale studies are warranted to establish this genetic susceptibility for NHL.

Effects of concomitant hepatitis C virus infection in patients with underlying lupus nephritis on long-term renal outcome

Despite recent advances in the management of lupus nephritis (LN), these unfortunate patients are at a higher risk of developing chronic kidney disease (CKD). Concomitant chronic hepatitis C virus (HCV) infection is associated with adverse outcome in patients with LN and further compounds the risk as some of these patients choose to undergo kidney transplantation in the near future. Objectives. The aim of the present study is to evaluate the long-term impact of chronic HCV infection in patients with underlying Class IV LN on renal function, progression to end-stage renal disease (ESRD) and patient survival. Retrospective analysis of the medical records of 134 nondialysis-dependent patients with biopsy-proven World Health Organization Class IV LN with chronic HCV infection was done from January 1995 to January 2008 at King Khalid University Hospital, Riyadh, Saudi Arabia. Primary and the secondary end points were death or the development of ESRD. The patients were followed over a period of 6.7 ± 3.3 (1-14.4) years. From a total of 134 biopsy-proven Class IV LN patients, 15 (11.2%) patients were HCV positive of which 2 (13.3%) patients were male and 13 (86.7%) patients were female. One hundred and nineteen (88.8%) patients were HCV negative of which 17 (14.3%) were male and 102 (85.7%) were female. The mean age was 32.47 ± 11.8 years. Eight (53.3%) patients in the HCV-positive group versus 19 (22.6%) patients in the HCV-negative group progressed to severe renal impairment with serum creatinine >350 μmol/L (P = 0.024). A total of 8 (53.3%) patients in the HCV-positive group versus 18 (17.3%) in HCV-negative group progressed to ESRD (P = 0.005). The mean creatinine clearance was higher (43.3 ± 33 mL/min) in the HCV-negative LN group at last follow-up than in the HCV-positive patients (25 ± 34.9 mL/min) with a statistically significant P-value of 0.0463. Five patients (33.3%) with HCV-positive LN died in comparison to eight (7.6%) patients who were HCV negative P = 0.03; however, the cause of hospital mortality was mainly cardiovascular disease (CVD) and infection and none of the patients died of chronic liver disease, although there was significant deterioration of the liver function at the end of the study. Kaplan-Meier survival estimates showed a significantly inferior renal function and rapid deterioration to ESRD in LN patients with concomitant HCV infection, with a dialysis free survival of 95 and 80% for the HCV-negative group and 90 and 65% for the HCV-positive groups at the end of 5 and 10 years respectively, with a highly significant P-value of <0.05 at the end of 10 years. The present study highlights that concomitant HCV infection in patients with LN is associated with worse renal outcome, higher rate of progression to ESRD and reduced patient survival.

Impact of hepatitis C virus infection on the course and outcome of patients with acute alcoholic hepatitis

Limited information is available on the impact of hepatitis C virus (HCV) infection on the clinical course and outcome of acute alcoholic hepatitis (AH), a condition with a significant mortality. We designed this retrospective study to assess effect of HCV on the outcome of patients with AH. Medical charts of patients with a discharge diagnosis of AH (defined using rigorous clinical criteria) were reviewed. Patients were stratified based on the presence or absence of concomitant HCV infection. The disease severity was estimated at admission and at day 7 using model for end-stage disease and discriminant function index scores. Patient survival at 6 months was confirmed with the county death registry. A total of 76 (29 HCV positive) AH cases were analyzed. At admission, disease severity was similar in both groups with severe disease in 53% (49% of AH alone and 59% of AH+HCV; P = 0.18). Although severity scores at day 7 were not available for all patients, disease severity tended to be worse for patients with AH+HCV. Kaplan-Meier survival curves showed a poor survival for AH+HCV compared with AH alone (69 vs. 91%; log-rank P = 0.015). Although patients with AH+HCV were treated less often compared with AH alone (27 vs. 54%; P = 0.05), HCV emerged as an independent risk factor for a poor outcome at 6 months (Cox proportional hazard ratio 8.45; P = 0.01) after controlling for patient demographics, disease severity at admission, and treatment. HCV may be a risk factor for patients with AH with a worse outcome at 6 months. If our findings are confirmed in larger databases, prospective studies are needed to examine mechanisms for this effect of HCV on the outcome of AH.

Treatment of Inflammatory Bowel Disease with Anti-TNF Agents in Patients with Chronic Hepatitis C Virus (HCV) Infection - A Systematic Review of Literature

Purpose: Anti-tumor necrosis factor (TNF) therapy has been shown to be highly efficacious in the treatment of inflammatory bowel disease (IBD). However, there is a concern that inhibition of TNF may have immunosuppressive effects leading to HCV replication and worsening of liver disease. The aim of this study was to perform a systematic review of the literature regarding the treatment of IBD with anti-TNF agents in patients with chronic HCV infection. Methods: A systematic search of the literature was performed. Databases of literature examined included MEDLINE, EMBASE and PUBMED using key words: hepatitis C, ulcerative colitis, Crohn's disease, inflammatory bowel disease, anti-TNF, infliximab, certolizumab and adalimumab. Articles searched were from 1910 to May 2010. Only full-length, English-written original studies and case-reports that described the effects of anti-TNF treatment on the course of IBD and the liver function in patients with IBD and concomitant chronic HCV infection were included in the analysis.Table: [1233]Results: The search yielded a total of 1312 articles, of which 10 were included in full review and only 3 met inclusion criteria. These 3 studies were case reports, describing a total of 4 cases of treatment with anti-TNF agent, infliximab, in patients with IBD (namely Crohn's disease [CD]) and concomitant chronic HCV infection. The excluded 7 articles were either review articles, original articles not evaluating anti-TNF treatment in patients with IBD or case report describing the disseminated aspergillosis in patient with chronic HCV infection and CD who was treated with infliximab but not providing any details on the course of CD or the hepatic biochemical tests. The findings of these studies are presented in the Table. There were no original studies identified that assessed the treatment of IBD with anti-TNF agent in patients with chronic HCV infection. Conclusion: There are limited data on the use of anti-TNF agents in patients with IBD and chronic HCV infection. The results of our systematic review indicate that therapy with anti-TNF agents does not exacerbate the course of chronic HCV infection. Further, in the limited data available, interferon based therapy has been successfully used to clear HCV infection, while not inducing a flare of liver disease. Large scale studies are needed to fully evaluate the effects of anti-TNF treatment on the course of chronic HCV infection in patients who have a background of IBD. The course of IBD while on interferon based therapy also needs to be assessed in larger studies. Disclosure: Gary R. Lichtenstein, Md Potential Conflict of Interest Declaration Abbott Corporation Consultant Alaven Consultant Bristol-Myers Squibb Research Centocor Orthobiotech Consultant, Research Elan Consultant Ferring Consultant, Research Millenium Pharmaceuticals Consultant Proctor and Gamble Consultant, Research Prometheus Laboratories, Inc. Consultant, Research Salix Pharmaceuticals Consultant, Research Schering-Plough Corporation Consultant Shire Pharmaceuticals Consultant, Research UCB Consultant, Research Warner Chilcotte Consultant, Research Wyeth Consultant.

Hepatitis C virus infection and interferon therapy in patients with Down syndrome

The clinical features of hepatitis C virus (HCV)-associated liver diseases, or the efficacy of interferon (IFN) therapy in children with Down syndrome (DS) remain to be elucidated. The purpose of the present paper was to survey the features of liver diseases in this subset of children and evaluate the efficacy of IFN treatment in those patients. A questionnaire was sent to 41 members of the Japan Society of Pediatric Hepatology. Ten of them reported on 11 patients with DS who had concomitant chronic HCV infection, providing information on liver disease and the response to IFN treatment. Interferon therapy of 24 weeks duration using natural IFN-alpha was instituted in six of the 11 patients with DS, but none of the six patients cleared HCV-RNA from their serum. Among 12 age- and sex-matched control children who were treated with IFN using the same regimen against chronic HCV infection, half of them had a favorable response to IFN therapy with a sustained clearance of HCV-RNA from their serum. The major baseline features including alanine aminotransferase levels, HCV genotype and viral load were not apparently different between the six patients with DS and the 12 controls. IFN therapy for HCV infection in patients with DS may be unfavorable as compared with non-DS children.