Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin.

BACKGROUND & AIMS: The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. METHODS: In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. RESULTS: Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637-7.101), low (<400,000 IU) viremia (OR 2.907; CI 2.111-4.004), F0-F2 fibrosis (OR 1.631; CI 1.122-2.372) and type 2 diabetes (OR 0.528; CI 0.286-0.972). In the alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274-9.208), IL28B CC genotype (OR 3.306; CI 2.301-4.751), low viremia (OR 2.175; CI 1.542-3.070), and F0-F2 fibrosis (OR 1.506; CI 1.012-2.242). Combining the favorable baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66 patients (6.3%, overall) with all predictors could be anticipated to reach the >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. CONCLUSIONS: A consistent subset of naïve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin.

Variation in genes encoding for interferon λ-3 and λ-4 in the prediction of HCV-1 treatment-induced viral clearance.

BACKGROUND & AIMS: In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR. RESULTS: In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860CC, rs8099917TT, and rs469415590TT/TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860CC_ss469415590TT/TT_rs8099917TT or the diplotype rs12979860CC_ss469415590TT/TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917TT SNP was associated with improved response prediction. CONCLUSION: In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations.

Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins.

UNLABELLED: Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70-kg person) were added for 8 weeks to the drinking water of rats who were being fed a high-fat, high-calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two-fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF-α), tissue transglutaminase, and transforming growth factor ß and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF-α and interferon-γ and increased anti-inflammatory interleukin-4 and interleukin-10. CONCLUSION: Our data demonstrate that coffee consumption protects the liver from damage caused by a high-fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid ß-oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation.

Current evidence in the field of the management with TNF-α inhibitors in psoriatic arthritis and concomitant hepatitis C virus infection.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory condition involving the spine, enthesis and peripheral joints, which is associated with psoriasis. PsA therapy varies from use of NSAIDs to disease-modifying anti-rheumatic agents (DMARDs). However, their use can represent a limitation in patients with concomitant hepatitis C virus (HCV) infection. In the last few decades, anti-TNF-α therapy has opened new horizons in the treatment of PsA. Hence, the purpose of this review is to explore the efficacy and safety of anti-TNF-α agents in PsA and concomitant HCV infection. AREAS COVERED: We reviewed the available medical literature to find all cases of PsA and concomitant HCV infection treated with TNF-α inhibitors. We found a total of 38 cases of patients with PsA and concomitant HCV infection in therapy with anti-TNF-α agents. EXPERT OPINION: The available literature, summarized in this review, still remains very limited. Data suggest that therapy with the anti-TNF-α agents, mainly etanercept and adalimumab, at least with short-term use, would appear efficacious and reasonably safe in the management of PsA patients with concomitant HCV infection. With regard to infliximab, efficacy and safety have been scarcely explored, whereas in the case of golimumab and certolizumab no report was found, may be due to their recent introduction on the market.

Sustained virological response: a milestone in the treatment of chronic hepatitis C.

AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico II". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that virus-eradication following interferon treatment can last up to 20 years.