Isolation of mucosa-associated microbiota dysbiosis in the ascending colon in hepatitis C virus post-sustained virologic response cirrhotic patients.

Background: Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients. Methods: We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR. Results: In the post-SVR group, the microbial ß-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, Blautia, Alistipes, Roseburia, Agathobaculum, Dorea, and Pseudoflavonifractor were reduced in the ascending colon of post-SVR LC patients. Conclusion: In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a lowgrade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

A Nanoparticle-Based Hepatitis C Virus Vaccine With Enhanced Potency.

Despite the emergence of new direct-acting antivirals, hepatitis C virus (HCV) chronic infection and its consequent fibrosis and hepatocarcinoma remain a significant burden for public health, thus requiring an effective preventive vaccine. Our group previously showed that a subunit vaccine based on recombinant soluble E2 (sE2) can induce broadly neutralizing antibodies. To improve the immunogenicity of sE2, we designed and produced a fusion protein (sE2-ferritin) comprising sE2 and a ferritin unit in Drosophila S2 cells, which self-assembled into a nanoparticle with sE2 displayed on the surface. The sE2 moiety on the sE2-ferritin nanoparticle not only had nearly natural conformation but also had better affinities than the unfused sE2 to neutralizing antibodies, receptor, and patient serum. Mouse immunization studies showed that sE2-ferritin was more potent than sE2 in inducing anti-HCV broadly neutralizing antibodies. Our results demonstrate that sE2-ferritin is a vaccine candidate superior to previously developed sE2, providing a new possibility for controlling HCV.

Retrospective Analysis of Chronic Hepatitis C Patients with Hepatic Iron Depletion.

OBJECTIVE: The study retrospectively analyzed the effects of hepatic iron depletion on the therapy of chronic hepatitis C patients. MATERIALS: A total of 195 patients from Hamad General Hospital were studied retrospectively. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and g-glutamyl transferase (GGT) tests were implemented; descriptive analysis and mean testing were performed to analyze the data. RESULTS: It has been observed that ferritin increases with HCV, displaying R-value =0.450 and p-value=0.182. Levels of ALT (P-value=0.812) and GGT (P-value=0.723) may increase slightly with the treatment. Chronic hepatitis C patients develop iron deficiency that can be marked by evaluating various iron markers in the body. CONCLUSION: The study identified that iron markers may decrease markedly among HCV patients; yet, researches consider the occurrence as support to management modality to improve response, delivered towards the treatment.

The impact of proton pump inhibitors on the intestinal microbiota in chronic hepatitis C patients.

Objectives: Proton pump inhibitors (PPI), a class of drugs commonly used, are known to be associated with changes in the intestinal microbiota. Published studies were done in heterogeneous cohorts which could hamper conclusions drawn as effects of diseases were not taken into consideration. We aimed to elucidate differences in the intestinal microbiota being associated to the use of PPI in a cohort study of patients with chronic hepatitis C. Material and Methods: The 16S rDNA gene was analyzed in stool samples of patients with and without PPI use. Patients with concomitant medication influencing the microbiota were excluded. Results were compared with the clinical course of hepatitis C patients with decompensated liver cirrhosis. Results: No differences in alpha diversity could be observed, while the microbial community structure differed significantly, especially in patients with liver cirrhosis. The relative abundance of Streptococcus spp., Enterobacter spp. and Haemophilus spp. was significantly increased in patients with PPI use irrespectively of the stage of liver disease. Finally, in patients with decompensated liver cirrhosis due to chronic HCV infection only in these using PPI bacterial phylotypes were isolated. Conclusions: PPI use was associated with significant alterations in the microbial community in patients with chronic hepatitis C, which were even pronounced in patients with liver cirrhosis. In patients with decompensated liver cirrhosis due to chronic HCV infection, the use of PPI may promote infections either directly or indirectly through changes in the microbial community structure. Future studies should further investigate long-term impact on the microbiota and the clinical outcome.

Helicobacter pylori infection and liver diseases: Epidemiology and insights into pathogenesis.

Both Helicobacter pylori (H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and hepatocellular carcinoma (HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, negative correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study has revealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.

The prevalence of occult hepatitis B in chronic hepatitis C patients treated with interferon-based antiviral therapy.

BACKGROUND AND STUDY AIMS: Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders. PATIENTS AND METHODS: This retrospective cross-sectional study was conducted in CHC patients who had previously received IFN-based antiviral therapy. Serum samples of 100 HBsAg negative CHC patients were tested for HBV DNA, anti-HBc IgG, anti-HBs, ALT and AST. The presence of OBI was compared between 50 IFN responders and 50 IFN non-responders. Patients with a history of previous HBV infection, patients with evidence of cirrhosis and patients who had received IFN therapy within the last one year were excluded from the study. RESULTS: Anti-HBc IgG positivity was determined in 53% of the patients. HBV DNA positivity, indicating OBI was determined in 1 (1%) patient. This patient was anti-HBc IgG positive, anti-HBs negative, ALT and AST levels were normal. The HBV DNA and anti-HBc IgG positivity rates were higher in the non-responder group than in the responder group, but the difference was not statistically significant (p = 0.31 and p = 0.07 respectively). CONCLUSION: According to the results of this study, the prevalence of OBI is lower than expected amongst CHC patients in Turkey and it may not be necessary to apply routine screening to IFN non-responders for OBI infection before DAA therapy. However, there is a need for multicentre studies with larger patient series.

Can we go for a shorter treatment course in chronic hepatitis C? More inspiring cases.

Current interest in HCV therapy with direct acting antivirals is focused on shortening treatment length. We managed two cirrhotics who achieved virological cure after 4 weeks of ombitasvir/paritaprevir/ritonavir, dasabuvir, ribavirin treatment. Analysis to identify potential predictive factors for a successful outcome with a shorter treatment course was conducted.

Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls.

BACKGROUND & AIMS: The importance of the intestinal microbiota for the onset and clinical course of many diseases, including liver diseases like non-alcoholic steatohepatitis and cirrhosis, is increasingly recognized. However, the role of intestinal microbiota in chronic hepatitis C virus (HCV) infection remains unclear. METHODS: In a cross-sectional approach, the intestinal microbiota of 95 patients chronically infected with HCV (n=57 without cirrhosis [NO-CIR]; n=38 with cirrhosis [CIR]) and 50 healthy controls (HC) without documented liver diseases was analysed. RESULTS: Alpha diversity, measured by number of phylotypes (S) and Shannon diversity index (H'), decreased significantly from HC to NO-CIR to CIR. S and H' correlated negatively with liver elastography. Analysis of similarities revealed highly statistically significant differences in the microbial communities between HC, NO-CIR and CIR (R=.090; P<1.0×10-6 ). Stratifying for HCV genotypes even increased the differences. In addition, we observed distinct patterns in the relative abundance of genera being either positive or negative correlated with diseases status. CONCLUSIONS: This study shows that not only the stage of liver disease but also HCV infection is associated with a reduced alpha diversity and different microbial community patterns. These differences might be caused by direct interactions between HCV and the microbiota or indirect interactions facilitated by the immune system.

Simeprevir with peginterferon α-2a/ribavirin for chronic hepatitis C virus genotype 1 infection in treatment-experienced patients: an open-label, rollover study.

BACKGROUND: This Phase 3, open-label, rollover study (NCT01323244) investigated the efficacy and safety of simeprevir plus peginterferon α-2a (PegIFNα-2a) and ribavirin (RBV) in a well-characterized population of HCV genotype 1 (GT1)-infected treatment-experienced patients. METHODS: Patients who had failed PegIFNα/RBV treatment in the placebo arm of a previous Phase 2/3 simeprevir study (Phase 2/3 group, n = 125), or had been exposed to HCV direct-acting antivirals (simeprevir or other) for up to 14 days in a selected Phase 1 study (Phase 1 group, n = 16), were eligible. Phase 2/3 group patients were classified according to prior relapse, breakthrough, or non-response (null response, partial response, non-classifiable non-response) to PegIFNα/RBV. Eight patients in the Phase 1 group received short-term (≤14 days) simeprevir. Treatment comprised simeprevir 150 mg once daily (QD) plus PegIFNα-2a/RBV for 12 weeks followed by PegIFNα-2a/RBV for 12 or 36 weeks (using response-guided therapy [RGT] to determine total treatment duration in Phase 2/3 prior relapsers or breakthrough) or 36 weeks fixed (Phase 2/3 group non-responders and Phase 1 group). The primary endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). RESULTS: Phase 2/3 group: SVR12 rate was 69.6% (87/125) overall; 92.7% (51/55), 60.0% (6/10), 64.3% (18/28), and 36.7% (11/30) in patients with prior relapse, viral breakthrough, partial response, or null response, respectively. SVR12 rates were similar for patients with HCV GT1a (66.0% [33/50]) and GT1b infection (72.0% [54/75]) and among HCV GT1a-infected patients with/without a baseline Q80K polymorphism (66.7% [8/12] and 65.8% [25/38], respectively). The majority of RGT-eligible patients (prior viral relapse or breakthrough) met RGT criteria (89.2% [58/65]); of these, 89.7% (52/58) achieved SVR12. Overall, 16.0% (20/125) of patients experienced on-treatment failure and 14.4% (18/125) experienced post-treatment failure (15 relapses, 3 missing data). Phase 1 group (simeprevir-naïve and -experienced patients combined): SVR12 rate was 37.5% (6/16). Safety and tolerability findings were comparable to those of the feeder studies. CONCLUSIONS: The majority of RGT-eligible patients met criteria for shortening treatment to 24 weeks in total. Simeprevir 150 mg QD with PegIFNα-2a/RBV led to a high SVR rate among prior relapsers with HCV GT1 infection. No new safety signals were noted. TRIAL REGISTRATION: NCT01323244 . (date of registration: March 24, 2011).

Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies.

BACKGROUND: The development of direct-acting antivirals in recent years has dramatically enhanced rates of viral eradication to >90% in patients with chronic hepatitis C virus (HCV) infection. To determine true treatment efficacy and define the most appropriate retreatment, it is important to distinguish virologic relapse from reinfection when patients in whom HCV is eradicated during treatment become infected with a new HCV strain after treatment. METHODS: We investigated the prevalence of late recurrent viremia (patients with sustained virologic response 12 weeks after the end of treatment but detectable HCV RNA at follow-up week 24) and used refined phylogenetic analysis of multiple HCV genes to distinguish virologic relapse from reinfection. RESULTS: Across 11 phase 3 clinical trials of ledipasvir-sofosbuvir (SOF) and SOF, only 12 of 3004 patients had detectable HCV RNA following sustained virologic response 12 weeks after the end of treatment. Of these 12 patients with late recurrent viremia, 11 had the same HCV genotype/subtype at baseline and at recurrence. Phylogenetic analysis demonstrated that 58% (7 of 12) of these patients were successfully treated with the SOF-based regimen, with HCV eradication achieved, but became reinfected with a different HCV strain after treatment. The remaining 5 patients with late recurrent viremia had virologic relapse in which the HCV present at baseline persisted in the liver or another compartment and reemerged in the blood 24 weeks after treatment. CONCLUSIONS: The incidence of late recurrent viremia was low. Distinguishing reinfection from virologic relapse has implications for determining true treatment efficiency and selecting optimal retreatment strategies.

The Association of Chronic Hepatitis C with Respiratory Microbiota Disturbance on the Basis of Decreased Haemophilus Spp. Colonization.

BACKGROUND Haemophilus species are the most common microbiota in humans. The aim of this paper was to investigate Haemophilus spp., mainly H. parainfluenzae prevalence, in the upper respiratory tract of chronic hepatitis C (CHC-positive) patients with or without therapy using pegylated interferon alfa and ribavirin. MATERIAL AND METHODS We collected 462 samples from 54 healthy people and 100 CHC-positive patients at various stages: before (group A), during (group B), and after (group C) antiviral therapy. Identification of bacterial isolates including biotypes and antimicrobials susceptibility was accomplished by means of standard microbiological methods. RESULTS In 70.4% of healthy people (control group) and in 27.0% of CHC-positive patients, the presence of haemophili, mainly H. parainfluenzae was observed, and those differences were statistically significant (p<0.0001). Statistically significant differences in Haemophilus spp. colonization were also observed among healthy people and CHC-positive patients from group A (p=0.0012) and from B or C groups (p<0.0001). Resistance to ampicillin in beta-lactamase-positive isolates and multidrug resistance (MDR) of H. parainfluenzae was detected mainly in group A. CONCLUSIONS The obtained data suggest that chronic hepatitis C, together with antiviral therapy, may influence the respiratory tract microbiota composition as found using haemophili, mainly H. parainfluenzae.

Squamous cell lung cancer in a male with pulmonary tuberculosis.

Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.

Low levels of microbial translocation marker LBP are associated with sustained viral response after anti-HCV treatment in HIV-1/HCV co-infected patients.

BACKGROUND: Microbial translocation (MT) contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) could predict anti-HCV treatment outcome. METHODS: Plasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART) treatment) were categorized into sustained viral responders (SVR; n = 21) or non-responders (NR; n = 15) based on treatment outcome. ART starting subjects--were categorized into chronically HCV-infected (CH; n = 24) and mono-infected (HIV; n = 18), based on the HCV infection status. Samples were collected before start (at baseline) of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV) or antiretroviral-therapy and two years after treatment start (at follow up). χ2-test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers. RESULTS: Plasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06-0.31, p = 0.004) and multivariate analysis (OR: 1.43, 95% CI: 1.1-1.86, p = 0.07). CONCLUSION: In HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART) may be a more relevant MT marker than LPS and sCD14.

Evaluation of bacterial translocation in patients with chronic HCV infection.

INTRODUCTION: The factors involved in the progression of liver disease towards decompensated cirrhosis are not completely elucidated. It seems that bacterial translocation (BT) from the gut to the systemic blood flow has an important role in the disease progression, but literature data are controversial. Our objectives were to evaluate the presence of BT in patients with chronic HCV infection and to assess the correlation between BT and liver fibrosis stages and inflammatory state. METHODS: We conducted a cross-sectional study on patients with chronic HCV infection in a tertiary care hospital between January and July 2013. Blood samples were collected for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), total cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, platelets, lipopolysaccharide (LPS) and tumor necrosis-alpha (TNFα). Plasma LPS were measured by ELISA (Kamiya Biomedical Company Seattle, SUA) and TNFα by DIAsource ImmunoAssay (Louvain-la-Neuve, Belgium) kits. Liver fibrosis was evaluated by means of FibroMax (BioPredictive, Paris, France) in all patients. RESULTS: We enrolled 116 patients with CHC, with a sex ratio M/F of 0.55 and a median age of 54 (45-61) years. Most of the patients (32) had compensated cirrhosis (F4). LPS levels were higher in patients with mild fibrosis--median value of 60.34 (32-91.7) ng/mL, than in cirrhotic patients--median value 40.39 (20.2-74.4) ng/mL (p = 0.051). We found no statistical correlation between LPS levels and fibrosis (p = 0.068) or TNFα levels (p = 0.097) CONCLUSIONS: There was BT in patients with CHC but it was not correlated with liver fibrosis stages or systemic inflammation. This may suggest that LPS evaluation may not be the best technique to assess baterial translocation, but further studies are needed.

Short-term probiotic therapy alleviates small intestinal bacterial overgrowth, but does not improve intestinal permeability in chronic liver disease.

AIM: : Although numerous animal studies suggest that probiotic therapy has beneficial effects in various liver diseases, the evidence for beneficial effects in human liver disease is controversial. This study was carried out to investigate the efficacy of probiotic therapy in alleviating small intestinal bacterial overgrowth (SIBO) and permeability in chronic liver disease. METHODS: Fifty-three patients with chronic liver disease were randomized to either probiotic therapy or placebo. Six bacterial species were used: Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. After 4 weeks, changes in the composition of fecal bacteria, SIBO, intestinal permeability, and clinical symptoms were examined. RESULTS: Three of the six probiotic species, B. lactis, L. rhamnosus, and L. acidophilus, increased in the feces of the probiotic therapy group (P<0.001), whereas there was no change in fecal microbiota in the placebo group. SIBO disappeared in many individuals of the probiotic therapy group, but none in the placebo (24 vs. 0%, P<0.05). General gastrointestinal symptoms also improved more in the probiotic group and improvement in intestinal permeability was slightly but not significantly more frequent in the probiotic arm than the placebo arm (50 vs. 31.3%, P=0.248). Numbers of lactobacilli in stool were correlated negatively with intestinal permeability (P for trend<0.05). Liver chemistry did not improve significantly in either group. CONCLUSIONS: We conclude that short-term probiotic administration in chronic liver disease is effective in alleviating SIBO and clinical symptoms, but ineffective in improving intestinal permeability and liver function.

Altered functionality of anti-bacterial antibodies in patients with chronic hepatitis C virus infection.

BACKGROUND: Using comparative glycoproteomics, we have previously identified a glycoprotein that is altered in both amount and glycosylation as a function of liver cirrhosis. The altered glycoprotein is an agalactosylated (G0) immunoglobulin G molecule (IgG) that recognizes the heterophilic alpha-gal epitope. Since the alpha gal epitope is found on gut enterobacteria, it has been hypothesized that anti-gal antibodies are generated as a result of increased bacterial exposure in patients with liver disease. METHODS: The N-linked glycosylation of anti-gal IgG molecules from patients with fibrosis and cirrhosis was determined and the effector function of anti-bacterial antibodies from over 100 patients examined. In addition, markers of microbial exposure were determined. RESULTS: Surprisingly, the subset of agalactosylated anti-gal antibodies described here, was impaired in their ability to mediate complement mediated lysis and inhibited the complement-mediated destruction of common gut bacteria. In an analysis of serum from more than 100 patients with liver disease, we have shown that those with increased levels of this modified anti-gal antibody had increased levels of markers of bacterial exposure. CONCLUSIONS: Anti-gal antibodies in patients with liver cirrhosis were reduced in their ability to mediate complement mediated lysis of target cells. As bacterial infection is a major complication in patients with cirrhosis and bacterial products such as LPS are thought to play a major role in the development and progression of liver fibrosis, this finding has many clinical implications in the etiology, prognosis and treatment of liver disease.

Anemia management in patients with chronic viral hepatitis C.

OBJECTIVE: To review the literature regarding current strategies for the management of anemia associated with treatment for chronic viral hepatitis C (HCV) in adults. DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases were searched (January 1980-October 2012) for articles in English using the search terms anemia, ribavirin, dose reduction, erythropoietin stimulating agents, hepatitis C, HIV, liver transplant, telaprevir, and boceprevir. STUDY SELECTION AND DATA EXTRACTION: All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search. DATA SYNTHESIS: Standard of care for patients infected with HCV genotype 1 now requires a triple therapy regimen including an HCV NS3 protease inhibitor. These regimens lead to significantly higher rates of anemia compared to prior dual therapy regimens. Development of an optimal management strategy should begin with risk stratification. Ribavirin dose reductions have been recommended in the package inserts for the pegylated interferon products and studies have demonstrated the need for maintenance of 80% of the initial ribavirin dose to achieve optimal sustained virologic response (SVR) with dual therapy. The use of erythropoietin-stimulating agents has been shown to be effective for anemia caused by peginterferon and ribavirin without compromising SVR rates. Limited data have been published regarding the management of anemia with triple therapy; however, efficacy studies for boceprevir and telaprevir have used ribavirin dose reduction and erythropoietin-stimulating agents to successfully manage anemia. CONCLUSIONS: Anemia is a common adverse event associated with the use of ribavirin, and, more recently, the new HCV protease inhibitors. Ribavirin dose reduction should continue to be used as an initial anemia management strategy, with the use of erythropoietin alfa 40,000 units once weekly reserved for patients whose hemoglobin does not adequately respond to initial management strategies.

Association between chronic hepatitis C virus infection and high levels of circulating N-terminal pro-brain natriuretic peptide.

The association between HCV infection and myocardial disorders remains unclear. This study aimed to assess whether or not HCV infection influences myocardial dysfunction by the use of NT-proBNP, a sensitive marker of myocardial dysfunction. A total of 198 participants [99 patients with chronic HCV infection (aged 46-68 years) and 99 anti-HCV-negative sex and age matched controls] were examined. Serum HCV-RNA level and HCV genotype were tested and liver biopsy was done only for the patient group. The NT-proBNP concentration of the HCV patients (mean 71.6 ± 79.1 pg/ml; median 46.0 pg/ml, range 5.0-400.0) was significantly higher than that of the controls (mean 39.8 ± 24.4 pg/ml; median 35.8 pg/ml, range 7.0-108.0) (P < 0.05). 20.0 % of the HCV patients and 0.6 % of the controls had high NT-proBNP (higher than 125 pg/ml; the single cut off point for patients under 75 years of age) (P < 0.05). Stepwise multiple regression analysis revealed that chronic HCV infection was independently correlated with NT-proBNP level after adjustment for parameters that might influence NT-proBNP (P = 0.005). Our data suggest that chronic HCV infection is associated with increased NT-proBNP, indicating that chronic HCV infection might induce myocardial dysfunction.

Bacterial DNA translocation and liver disease severity among HIV-infected patients with chronic hepatitis C.

We carried out a cross-sectional study to explore whether bacterial 16S ribosomal DNA (bactDNA) shows association with severity of liver disease among human immunodeficiency virus/hepatitis C virus coinfected patients. Patients with advanced fibrosis (F3/F4), moderate activity grade (A2/A3), and high fibrosis progression rate (FPR > 0.15) had higher values of plasma bactDNA levels than did patients without these markers of liver disease (P < 0.05). The chance of having a fibrosis stage or activity grade increased was 1.20 [95% confidence interval (CI) = 1.0 to 1.44, P = 0.045] and 1.22 (95% CI = 1.1 to 1.45, P = 0.029) times greater for every 100 copies per microliter of plasma bactDNA. Likewise, the odds of having values of FPR > 0.15 was 1.18 (95% CI = 0.98 to 1.42, P = 0.089). In addition, patients with high bactDNA levels (≥175 copies per microliter) had the highest odds of having high values of Metavir score and FPR (P < 0.05). Our data show that bacterial translocation is associated with severe liver disease among human immunodeficiency virus-infected patients with chronic hepatitis C.