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Chronic Hepatitis C. (chronic + hepatitis_c)
Selected AbstractsProspective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography,HEPATOLOGY, Issue 6 2009Ryota Masuzaki Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV-RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow-up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person-year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM ,10 kPa, of 16.7 (95% confidence interval [CI], 3.71-75.2; P < 0.001) when LSM 10.1-15 kPa, 20.9 (95% CI, 4.43-98.8; P < 0.001) when LSM 15.1-20 kPa, 25.6 (95%CI, 5.21-126.1; P < 0.001) when LSM 20.1-25 kPa, and 45.5 (95% CI, 9.75-212.3; P < 0.001) when LSM >25 kPa. Conclusions: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development. (HEPATOLOGY 2009.) [source] Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with genotype 1 chronic hepatitis C,,HEPATOLOGY, Issue 2 2008Stefan Zeuzem The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naïve patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFN,)-2a 180 ,g one time per week (qwk), or alb-IFN 900 or 1,200 ,g once every two weeks (q2wk), or 1,200 ,g once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intention-to-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 ,g q2wk, 55.5% (61/110) with 1,200 ,g q2wk, and 50.9% (59/116) with 1,200 ,g q4wk, and 57.9% (66/114) with PEG-IFN,-2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 ,g q2wk, 18.2% with 1,200 ,g q2wk and 12.1% with 1,200 ,g q4wk, and 6.1% with PEG-IFN,-2a (P = 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatment-associated missed workdays were significantly lower with alb-IFN 900 ,g q2wk versus PEG-IFN,-2a (1.1 versus 4.3 days; P = 0.006). Conclusion: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFN,-2a. (HEPATOLOGY 2008;48:407,417.) [source] Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C,HEPATOLOGY, Issue 3 2008Robert J. Fontana This study determined the utility of a panel of serum fibrosis markers along with routine laboratory tests in estimating the likelihood of histological cirrhosis in a cohort of prior nonresponders with chronic hepatitis C. The relationship between serum markers and quantitative hepatic collagen content was also determined. Liver biopsy samples from 513 subjects enrolled in the HALT-C trial were assigned Ishak fibrosis scores. The collagen content of 386 sirius-red stained, nonfragmented biopsy samples was quantified using computerized morphometry. Serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), amino-terminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA), and YKL-40 levels were determined using commercially available assays. Sixty-two percent of patients had noncirrhotic fibrosis (Ishak stage 2-4) whereas 38% had cirrhosis (Ishak stage 5,6). Multivariate analysis identified a 3-variable model (HA, TIMP-1, and platelet count) that had an area under the receiver operating curve (AUROC) of 0.81 for estimating the presence of cirrhosis. This model was significantly better than that derived from the cirrhosis discriminant score (AUROC 0.70), the AST-to-platelet ratio (AUROC 0.73), and a prior model developed in HALT-C patients (AUROC 0.79). Multivariate analysis demonstrated that the serum fibrosis markers correlated substantially better with Ishak fibrosis scores than with the log hepatic collagen content (AUROC 0.84 versus 0.72). Conclusion: A 3-variable model consisting of serum HA, TIMP-1, and platelet count was better than other published models in identifying cirrhosis in HALT-C Trial subjects. The stronger correlation of the serum markers with Ishak scores suggests that serum fibrosis markers reflect the pattern of fibrosis more closely than the quantity of hepatic collagen. (HEPATOLOGY 2008.) [source] Does a late evening meal reduce the risk of hepatocellular carcinoma among patients with chronic hepatitis C?HEPATOLOGY RESEARCH, Issue 9 2008Satoko Ohfuji Aim:, Some studies have suggested that nutritional support might protect against the recurrence of hepatocellular carcinoma (HCC) among postoperative HCC patients. However, no epidemiological studies have evaluated the effect of nutritional support on HCC incidence. This study aimed to investigate the association between a late evening meal and HCC. Methods:, We conducted a hospital-based, case-control study comparing 73 cases with HCC to 253 matched controls among patients with chronic hepatitis C. A questionnaire elicited information on the consumption of a late evening meal, which was defined as a snack or meal within 2 h before bedtime. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by the conditional logistic regression model. Results:, After adjustment for potential confounders, patients who consumed a late evening meal had a lower OR as compared to those who did not consume one (OR, 0.08; 95% CI, 0.01,0.48). In terms of frequency of intake, a clear inverse exposure,response relationship was observed (trend P = 0.009). In addition, a negative association between a late evening meal and HCC was more pronounced among patients with an ,-fetoprotein level of less than 20 ng/mL and those with a body mass index of less than 25 kg/m2. Conclusion:, A late evening meal might protect against HCC, particularly among patients with a normal ,-fetoprotein level and who are not obese, although these relations might be accounted for other factors, including total energy intake. Further studies with larger study sizes are needed to corroborate these findings. [source] Elevation of interleukin-18 in chronic hepatitis C: implications for hepatitis C virus pathogenesisIMMUNOLOGY, Issue 1pt2 2009Arpita Sharma Summary The outcome of hepatitis C virus (HCV) infection is determined by the interplay between the virus and the host immune response. Interleukin (IL)-18, an interferon-,-inducing factor, plays a critical role in the T helper type 1 (Th1) response required for host defence against viruses, and antibodies to IL-18 have been found to prevent liver damage in a murine model. The present study was conducted to investigate the possible role of IL-18 in the pathogenesis and persistence of HCV. IL-18 levels were measured in sera of 50 patients at various stages of HCV infection (resolved, chronic and cirrhosis) and compared with those of normal controls. IL-18 gene expression was studied in peripheral blood mononuclear cells (PBMC) from each group, and in liver biopsy tissue from patients with chronic hepatitis C. The mean levels of IL-18 in sera were markedly elevated in patients with chronic hepatitis and cirrhosis, and were reduced in patients with resolved HCV infection. The serum IL-18 concentrations were related to the Child,Pugh severity of liver disease in cirrhotic patients. There also existed a strong positive correlation of IL-18 levels with histological activity score and necrosis. IL-18 mRNA expression was significantly up-regulated in the PBMC of cirrhotic patients when compared with other groups, while in the liver, higher levels of IL-18 transcripts were expressed in patients with chronic hepatitis C. The results of our study indicate that IL-18 levels reflect the severity and activity of HCV infection, and may contribute to the pathogenesis and progression of liver disease associated with HCV. [source] Clinical trial: a randomized trial of pegylated-interferon-,-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009P. LANGLET Summary Background, The combination therapy of pegylated-interferon-,2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40,50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3. Aim, To assess whether amantadine, added to the conventional combination therapy, could improve the treatment efficacy. Methods, In all, 630 patients (intent-to-treat population) with chronic hepatitis C were randomized into two groups: 316 patients (treatment group) received pegylated-interferon-,2a (180 ,g once weekly) plus ribavirin (1000,1200 mg/daily) with amantadine (200 mg/daily); 314 patients (control group) received pegylated-interferon-,2a (180 ,g once weekly) plus ribavirin (1000,1200 mg/daily) without amantadine. The duration of the treatment was 48 weeks for genotypes 1, 4, 5 and 6, and 24 weeks for genotypes 2 and 3. Results, There was no statistically significant difference between treatments groups for any of the variables tested for. Subgroups of patients likely to take advantage of the addition of amantadine were not identified. Conclusions, This large study definitely excludes the role of amantadine in addition of conventional combination therapy in the treatment of chronic hepatitis C patients. [source] Induction doses of interferon- , -2a in combination with ribavirin and/or amantadine for the treatment of chronic hepatitis C in non-responders to interferon monotherapy: a randomized trialJOURNAL OF VIRAL HEPATITIS, Issue 2 2007J. Salmerón Summary., The benefit of the triple therapy (interferon + amantadine + ribavirim) is still unknown. The efficacy of induction doses of interferon- , -2a monotherapy or in combination with ribavirin and/or amantadine was evaluated in interferon non-responders with chronic hepatitis C. A total of 378 patients were randomized. All the groups received the same doses and duration of interferon- , -2a: (i) interferon 9 MUI/day for 4 weeks and then 3 MUI/3 t.i.w. for 44 weeks (n = 53); (ii) interferon in combination with amantadine 100 mg twice daily for 48 weeks (n = 111); (iii) interferon in combination with ribavirin 1000,1200 mg (n = 106); (iv) interferon in combination with amantadine and ribavirin (n = 108). Baseline parameters were similar in the four groups. Sustained virological and biochemical responses were 13%, 6%, 18% and 22% respectively. No significant differences were found between double ribavirin arm vs triple therapy, but the difference was significant between interferon,amantadine (P = 0.008) and triple therapy (P = 0.0005). Hence, the induction doses of interferon in combination with ribavirin or ribavirin plus amantadine showed encouraging results in patients with chronic hepatitis C who were resistant to interferon. However, triple therapy is not superior to double. [source] Evaluating the evidence from clinical trials in chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 2006R. S. Brown Jr Summary., A number of studies are being published on investigational agents for the treatment of patients with chronic hepatitis C. Before incorporating new medications into therapy or electing to postpone therapy until an investigational agent receives regulatory approval, it is important to evaluate the following specific features of the published evidence: quality of the evidence, precision of the treatment effect, magnitude of the treatment effect, magnitude of the hazards, and other factors such as risk-benefit analysis and cost, including cost-effectiveness. Previous studies of treatment of patients with the disease allow us to establish some benchmarks and provide structure to evaluate the evidence of the efficacy and safety of these newer drugs. [source] The ,670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 6 2005J. Aguilar-Reina Summary., Evidence suggests that apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C virus (HCV) infection. One of the best characterized apoptotic pathway is that mediated by the death receptor Fas. Fas expression has been found to be up-regulated on hepatocytes in chronic HCV infection, particularly in periportal areas. Recently, two polymorphisms have been identified in the promotor region of the FAS gene, ,1377G > A and ,670A > G. We have evaluated the involvement of these variants in the susceptibility to HCV infection, the severity of liver damage and progression of fibrosis in chronic hepatitis C. A cohort of 197 patients with chronic hepatitis C and 100 controls were analysed for both polymorphisms by Fluorescence Resonance Energy Transfer using specific probes and the LightcyclerTM system. In addition, liver biopsies were taken in 167 patients and scored using the Knodell classification system. We have found that the allele frequencies and the distribution of both polymorphisms do not differ significantly in the HCV cohort and in the control population. Thus, none of the polymorphisms seems to be related with susceptibility to HCV infection. However, we have examined the possible association between the two variants and the grade of necroinflammatory activity and the stage of fibrosis and we have detected an under-representation of the ,670A > G variant among those patients with higher Knodell's scores (P = 0.049) and necroinflammatory activity (P = 0.036). The ,670A allele was associated with higher levels of periportal necrosis (P = 0.012). In conclusion, our findings suggest an association between the ,670A > G polymorphism and the grade of necrosis in periportal areas in patients with chronic hepatitis C. [source] Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemiaJOURNAL OF VIRAL HEPATITIS, Issue 1 2004K. Lindahl Summary., Ribavirin in combination with interferon alpha-2 or pegylated interferon is the standard treatment for chronic hepatitis C. The current dosage recommendations for ribavirin are based on body weight (bw). Ribavirin is mainly eliminated by the kidneys and we have recently shown that ribavirin plasma concentrations are determined primarily by renal function. It is therefore reasonable to hypothesize that side-effects of ribavirin, i.e. anaemia, should be more closely related to plasma concentrations of ribavirin than to the dose per kg bw. A total of 108 consecutive patients eligible for treatment of chronic hepatitis C were studied. Ribavirin concentrations in plasma were measured by high-performance liquid chromatography (HPLC)-UV after solid-phase extraction in trough samples taken 4, 8 and 12 weeks after the treatment commenced. A total of 213 samples were obtained and the change in the haemoglobin level and the creatinine concentration was measured in addition to ribavirin. The dose of ribavirin per kg bw did not correlate with the drop in haemoglobin level induced by ribavirin. The concentration of ribavirin was non-linearly related to the drop in the haemoglobin level as revealed by fitting a standard Hill equation type dose,response curve. The half maximal drop in haemoglobin was obtained at 4.4 ,m. The results from this study suggest that the anaemia induced by ribavirin depends primarily on the concentration of ribavirin, and not on the dose per kg bw. This lends further support to the idea that ribavirin should be dosed according to renal function. [source] A pilot study of recombinant interferon beta-1a for the treatment of chronic hepatitis CLIVER INTERNATIONAL, Issue 6 2000François Habersetzer Abstract:Aims: Interferon alpha monotherapy induces a sustained response in less than 20% of patients treated for chronic hepatitis C. Interferon beta represents a potential therapeutic alternative for the treatment of chronic hepatitis C. The aim of this pilot study was to evaluate the efficacy and tolerance of recombinant interferon beta-1a administered subcutaneously. Methods: Twenty-one drug-naive patients with chronic hepatitis C were treated with recombinant interferon beta-1a administered, subcutaneously, for 24 weeks using two different regimens: 9 MU, three times per week (n=11) and 12 MU, three times per week (n=10). Results: At the end of the treatment period, nine (43%) patients had a biochemical and virological response (i.e. normal ALT and absence of hepatitis C virus RNA by PCR). Four of these patients were in the 9 MU group and five in the 12 MU group. A biochemical and virological sustained response occurred in four (19%) patients, all in the 9 MU dose group. The 4 patients with a sustained response maintained their response during a follow-up period of 33 to 58 months. Side effects were mild and 19 (90%) patients completed the treatment period. Conclusions: The results of this pilot study indicate that interferon beta-1a administered subcutaneously is an effective therapy for some patients with chronic hepatitis C, and suggest that interferon beta-1a deserves further evaluations in larger trials especially in combination with ribavirin. [source] Serum Autoantibodies Against Cytochrome P450 2E1 (CYP2E1) Predict Severity of Necroinflammation of Recurrent Hepatitis CAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009C. Rigamonti We previously reported that autoantibodies against cytochrome P4502E1 (CYP2E1) are frequent in patients with chronic hepatitis C. As autoimmune reactions are increasingly detected after orthotopic liver transplantation (OLT), this study investigates prevalence and significance of anti-CYP2E1 autoantibodies in 46 patients with post-OLT recurrent hepatitis C. IgG against recombinant human CYP2E1 above the control threshold was detected in 19 out 46 (41%) sera collected immediately before OLT and in 15 out 46 (33%) sera collected at the time of the 12 months follow-up liver biopsy. Although anti-CYP2E1 reactivity was not modified by OLT, the patients with persistently elevated anti-CYP2E1 IgG (n = 12; 26%) showed significantly higher prevalence of recurrent hepatitis with severe necroinflammation and fibrosis than those persistently negative or positive only either before or after OLT. Moreover, the probability of developing severe necroinflammation was significantly higher in persistently anti-CYP2E1-positive subjects. Multivariate regression and Cox analysis confirmed that the persistence of anti-CYP2E1 IgG, together with a history of acute cellular rejection and donor age >50 years, was an independent risk factor for developing recurrent hepatitis C with severe necroinflammation. We propose that autoimmune reactions involving CYP2E1 might contribute to hepatic damage in a subgroup of transplanted patients with recurrent hepatitis C. [source] Dialysis Reduces Portal Pressure in Patients With Chronic Hepatitis CARTIFICIAL ORGANS, Issue 7 2010Sandeep Khurana Abstract The purpose of this study was to characterize changes in hepatic venous pressures in patients with chronic hepatitis C. The histology and laboratory data from patients with chronic hepatitis C who underwent a transjugular liver biopsy (TJLB) and hepatic venous pressure gradient measurement were analyzed. Portal hypertension was defined as hepatic venous pressure gradient ,6 mm Hg. A single pathologist masked to hepatic venous pressure gradient scored liver sections for inflammation and fibrosis. The patients with high-grade inflammation (relative risk [RR] 2.82, P = 0.027, multivariate analysis) and late-stage fibrosis (RR 2.81, P = 0.022) were more likely to have a hepatic venous pressure gradient ,6 mm Hg, while the patients on dialysis (RR 0.32, P = 0.01) were less likely to have a hepatic venous pressure gradient ,6 mm Hg. The patients on dialysis (n = 58) had an elevated serum blood urea nitrogen and creatinine when compared with those who were not (n = 75) (47.6 ± 3.3 and 7.98 ± 0.4 vs. 25.9 ± 2.0 and 1.66 ± 0.22 mg/dL, respectively; P < 0.001). While the hepatic venous pressure gradient increased with the rising levels of liver fibrosis in the latter group (P < 0.01), it did not change in the patients on dialysis (P = 0.41). The median hepatic venous pressure gradient was especially low in late-stage fibrosis patients on dialysis when compared with the latter group (5 vs. 10 mm Hg, P = 0.017). In patients on dialysis, serum transaminases were low across all levels of fibrosis. Twenty-three of the 92 patients with early fibrosis had a hepatic venous pressure gradient ,6 mm Hg. In patients with chronic hepatitis C, concomitant TJLB and hepatic venous pressure gradient measurement identify those who have early fibrosis and portal hypertension. Long-term hemodialysis may reduce portal pressure in these patients. [source] | |||||||||||||||||||