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Chronic Hepatitis C Virus Infection (chronic + hepatitis_c_virus_infection)
Selected AbstractsPATIENT AGE IS A STRONG INDEPENDENT PREDICTOR OF 13C-AMINOPYRINE BREATH TEST RESULTS: A COMPARATIVE STUDY WITH HISTOLOGY, DUPLEX-DOPPLER AND A LABORATORY INDEX IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2006Arne RJ Schneider SUMMARY 1Noninvasive tests for the staging of chronic hepatitis C virus (HCV) infection would be an attractive alternative to liver biopsy. The 13C-aminopyrine breath test (ABT) has been proposed for the noninvasive assessment of hepatic function and partly correlates with fibrosis. We aimed to investigate causes for the lack of discriminatory power for different degrees of hepatic fibrosis. 2Eighty-three patients (median age 49 years (28,78 years)) with chronic HCV infection underwent the ABT after an oral load of 75 mg N,N-dimethyl- 13C-aminopyrine. Portal vein flow was assessed by duplex-Doppler and a laboratory index (aspartate aminotransferase to platelet ratio index or APRI) was calculated. Parameters were compared with liver histology. 3The cumulative 13C-recovery differed significantly between patients without relevant fibrosis (fibrosis score 0,2) and cirrhosis (5,6), beginning after 30 min of sampling (P < 0.05). The ABT did not discriminate patients with fibrosis scores 3,4 from the remaining two patient groups. Sensitivity and specificity for the prediction of cirrhosis was 73.4,82.8% and 63.2,68.4%, depending on the sampling time. Compared with the fibrosis score (P = 0.04), patient age was a highly significant independent predictor for the 13C-recovery (P < 0.0001). Aspartate aminotransferase to platelet ratio index and duplex-Doppler predicted cirrhosis with 76.6%vs. 87.5% sensitivity and 63.2%vs. 68.4% specificity. 4Our data suggest an age-dependent decrease of cytochrome P450 activity which probably accounts for the large overlap of ABT results that preclude clear differentiation. This is also consistent with former pharmacodynamic trials. Age-adapted reference ranges could improve ABT results. [source] Determinants of successful chronic hepatitis C case finding among patients receiving opioid maintenance treatment in a primary care settingADDICTION, Issue 12 2009Oliver Senn ABSTRACT Aims Injection drug users are at high risk for chronic hepatitis C virus infection (CHC). Opioid maintenance treatment (OMT) offers a unique opportunity to screen for CHC. This study proposed the hypothesis that a general practitioner (GP) with special interest in addiction medicine can achieve CHC screening rates comparable to specialized centres and aimed to investigate determinants for a successful CHC case finding in a primary care setting. Design and participants Retrospective medical record analysis of 387 patients who received opioid maintenance therapy between 1 January 2002 and 31 May 2008 in a general practice in Zurich, Switzerland. Measurements Successful CHC assessment was defined as performance of hepatitis C virus (HCV) serology with consecutive polymerase chain reaction-based RNA and genotype recordings. The association between screening success and patient characteristics was assessed using multiple logistic regression. Findings Median (interquartile range) age and duration of OMT of the 387 (268 males) patients was 38.5 (33.6,44.5) years and 34 (11.3,68.0) months, respectively. Fourteen patients (3.6%) denied HCV testing and informed consent about screening was missing in 13 patients (3.4%). In 327 of 360 patients (90.8%) with informed consent a successful CHC assessment has been performed. Screening for HCV antibodies was positive in 136 cases (41.6%) and in 86 of them (63.2%) a CHC was present. The duration of OMT was an independent determinant of a successful CHC assessment. Conclusions In addicted patients a high CHC assessment rate in a primary care setting in Switzerland is feasible and opioid substitution provides an optimal framework. [source] Bosentan treatment of portopulmonary hypertension related to liver cirrhosis owing to hepatitis CEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2006W. Grander Abstract Pulmonary arterial hypertension (PAH) with coexisting portal hypertension has been defined as portopulmonary hypertension (PPHTN). It is often related to liver cirrhosis of various aetiologies and is associated with a high mortality rate. Endothelin-1 (ET) is supposed to play an important role in the pathogenesis of PAH as well as portal hypertension. Therefore, therapy with an ETA/ETB receptor antagonist might be of use in the treatment of PPHTN. We report the case of a 76-year-old male with liver cirrhosis owing to chronic hepatitis C virus infection and PPHTN who was treated with the dual ETA/ETB receptor antagonist bosentan. The patient showed remarkable improvement of 6-min walking distance from 300 to 480 m after 2 weeks and to 540 m after 14 weeks, respectively. In addition, a significant decline of N-terminal pro B-type natriuretic peptide fraction (NT-proBNP) from 4928 ng mL,1 to 640 ng mL,1 was observed. Bosentan might be a promising new therapeutical option for patients suffering from PPHTN. [source] Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: Impact of obesity and ethnicity,HEPATOLOGY, Issue 1 2010Khoa D. Lam Studies using surrogate estimates show high prevalence of insulin resistance in hepatitis C infection. This study prospectively evaluated the correlation between surrogate and directly measured estimates of insulin resistance and the impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic, noncirrhotic patients with hepatitis C virus (age = 48 ± 7 years, 74% male, 44% white, 22% African American, 26% Latino, 70% genotype 1) were categorized into normal-weight (body mass index [BMI] < 25, n = 30), overweight (BMI = 25-29.9, n = 38), and obese (BMI , 30, n = 18). Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin suppression test. Surrogate estimates included: fasting glucose and insulin, glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under the curve during oral glucose tolerance test, and the Belfiore and Stumvoll indexes. All surrogate estimates correlated with SSPG, but the magnitude of correlation varied (r = 0.30-0.64). The correlation coefficients were highest in the obese. I-AUC had the highest correlation among all ethnic and weight groups (r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the normal weight group. The common HOMA-IR cutoff of ,3 to define insulin resistance had high misclassification rates especially in the overweight group independent of ethnicity. HOMA-IR > 4 had the lowest misclassification rate (75% sensitivity, 88% specificity). Repeat HOMA-IR measurements had higher within-person variation in the obese (standard deviation = 0.77 higher than normal-weight, 95% confidence interval = 0.25-1.30, P = 0.005). Conclusion: Because of limitations of surrogate estimates, caution should be used in interpreting data evaluating insulin resistance especially in nonobese, nondiabetic patients with HCV. HEPATOLOGY 2010 [source] Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: A meta-analysis and meta-regression,HEPATOLOGY, Issue 2 2008Hla-Hla Thein Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage-specific fibrosis progression rates and their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage-specific transition probabilities (F0,F1, , , F3,F4) were derived using the Markov maximum likelihood estimation method and a meta-analysis was performed. The impact of potential covariates was evaluated using meta-regression. A total of 111 studies of individuals with chronic HCV infection (n = 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage-specific transition probabilities were: F0,F1 0.117 (0.104,0.130); F1,F2 0.085 (0.075,0.096); F2,F3 0.120 (0.109,0.133); and F3,F4 0.116 (0.104,0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%,19%) for all studies, 18% (15%,21%) for cross-sectional/retrospective studies, 7% (4%,14%) for retrospective-prospective studies, 18% (16%,21%) for studies conducted in clinical settings, and 7% (4%,12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. Conclusion: Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates. (HEPATOLOGY 2008.) [source] Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infectionHEPATOLOGY, Issue 4 2001Heike Bantel Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The activation of caspase-3, caspase-7, and cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were measured by immunohistochemistry and Western blot analysis by using antibodies that selectively detect the active truncated, but not the inactive precursor forms of the caspases and PARP. We found that caspase activation was considerably elevated in liver lobules of HCV patients in comparison to normal controls. Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic morphology. The extent of caspase activation correlated significantly with the disease grade, i.e., necroinflammatory activity. In contrast, no correlation was observed with other surrogate markers such as serum transaminases and viral load. In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3. Thus, our results suggest that caspase activation is involved in HCV-associated liver injury. Moreover, measurement of caspase activity may represent a reliable marker for the early detection of liver damage, which may open up new diagnostic and therapeutic strategies in HCV infection. [source] Expression of tumour necrosis factor-related apoptosis-inducing ligand and caspase-3 in relation to grade of inflammation and stage of fibrosis in chronic hepatitis CHISTOPATHOLOGY, Issue 5 2007A Piekarska Aim:, To assess whether the distribution of the recently described proapoptotic ligand, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and the apoptosis effector, caspase-3 alters with the degree of inflammation and fibrosis present in liver biopsy specimens from patients with chronic hepatitis C virus infection. Methods and results:, Expression of TRAIL and caspase-3 was assessed immunohistochemically in liver biopsy specimens obtained from 89 adults with chronic hepatitis C. Expression of TRAIL in hepatocytes correlated inversely with stage of fibrosis (P = 0.001), classified according to the Scheuer score; expression of caspase-3 in hepatocytes correlated with grade of inflammation (P = 0.012). Expression of TRAIL in hepatocytes was not correlated with grade of inflammation (P > 0.05); expression of caspase-3 was not correlated with stage of fibrosis (P > 0.05). Maximum expression of proapoptotic TRAIL protein was observed in cases with low grade inflammation (G0) and low stage fibrosis (S1). Maximum expression of caspase-3 in hepatocytes was observed in cases with high grade inflammation (G3,4) and high stage fibrosis (S3), but not with liver cirrhosis (S4). Conclusions:, There is a significant decrease in TRAIL expression with increasing grade of inflammation, whereas caspase-3 expression is significantly increased with advanced fibrosis, short of cirrhosis. [source] Natural history of hepatic fibrosis progression in chronic hepatitis C virus infection in IndiaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Syed S Hissar Abstract Background and Aim:, The rate of fibrosis progression per year can predict the time for the development of cirrhosis in chronic hepatitis C (CHC). We assessed the rate of fibrosis progression and the predictors of disease severity in Indian CHC patients. Methods:, Of the 355 treatment-naïve, histologically-proven CHC patients, the precise duration of infection (from the time of exposure to HCV until liver biopsy) could be determined in 213 patients (age = 41.6 ± 14.7 years, male : female = 139 : 74, genotype 3 = 75%). The rate of fibrosis progression per year was calculated. The correlation of the advanced degree of fibrosis and age, duration of infection, age at the onset of infection, sex, mode of infection, hepatitis C virus (HCV) genotype, histological activity index (HAI), and the presence of diabetes mellitus were studied. Results:, The median rate of fibrosis progression per year was 0.25 (0.0,1.5) fibrosis units. The fibrosis progression rate was higher in patients who acquired infection at > 30 years of age, those < 30 years (0.33 vs 0.15; P < 0.001), and those who acquired HCV infection with a history of blood transfusion than with other modes of transmission (0.25 vs 0.19; P = 0.04). The median time to progress to cirrhosis was 16 years. The multivariate analysis found that the HAI score (odds ratio [OR]= 14.03; P < 0.001) and the duration of infection > 10 years (OR = 4.83; P < 0.001) correlated with severe liver disease (fibrosis , 3). Conclusion:, The median rate of fibrosis progression per year in Indian CHC patients is 0.25 fibrosis units. A higher HAI and longer duration of infection are associated with a significant risk of advanced liver disease, and merit early therapeutic interventions. [source] Interferon-induced retinopathy and its risk in patients with diabetes and hypertension undergoing treatment for chronic hepatitis C virus infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009J. D. PANETTA Summary Background, Ocular complications are amongst many side-effects of interferon based therapy for hepatitis C virus (HCV) infection. Some suggest that diabetic and hypertensive patients are at increased risk of these complications. Aim, To determine the frequency of ophthalmological complications related to interferon use. Methods, Retrospective analysis of patients undergoing HCV treatment with pegylated interferon ,-2a, ,-2b or consensus interferon plus ribavirin between 2005 and 2007. All patients underwent a baseline eye examination and any visual complaints during treatment prompted a repeat examination. Data recorded included HCV genotype, treatment duration, interferon type, pre-treatment and on treatment visual complaints, known ocular pathology, and retinal findings at baseline and at follow-up. Results, Of 183 patients, 29 (16%) had diabetes and 85 (46%) had hypertension. Seventy-one (38%) received interferon ,-2a, 100 (55%) ,-2b, and 12 (7%) consensus interferon. Seven (3.8%) had retinal changes on follow-up and treatment was discontinued in 3 (1.6%). Of seven with ocular changes two had hypertension and one had both hypertension and diabetes. Conclusion, The incidence of symptomatic retinopathy in HCV patients undergoing interferon therapy appears low and treatment cessation is rarely needed. Furthermore, patients with hypertension and diabetes may not be at higher risk for interferon-induced retinopathy. [source] Review article: investigational agents for chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009A. J. V. THOMPSON Summary Background, The need for effective treatment for chronic hepatitis C infection has driven the development of novel antiviral agents that target specific steps in the viral replication cycle. Aim, To evaluate the current literature concerning investigational agents for chronic hepatitis C virus infection. Methods, Resources used included PubMed, conference proceedings from the American and European Liver Associations' meetings 2005,2008 and the National Institute of Health's clinical trials website (http://www.clinicaltrials.gov). The focus was restricted to investigational agents that have progressed beyond preclinical development. Results, Over 50 investigational agents for chronic hepatitis C infection are currently in clinical development. Specifically targeted anti-viral therapy for HCV (STAT-C) shows great promise with NS3/4a protease inhibitors now entering phase 3 programmes. New interferon-, and ribavirin formulations aim to optimize anti-viral efficacy yet limit toxicity. Other candidates include novel immunomodulators and therapeutic vaccines. Conclusions, A new era of therapy for chronic hepatitis C beckons, promising increased cure rates with shortened duration of therapy. However, the era will not be without challenges including viral resistance, drug toxicity and the need to optimize combination therapy in the face of a rapidly evolving therapeutic arsenal. [source] Prediction of significant liver fibrosis in kidney transplant patients with chronic hepatitis C virus infection: the TX-3 indexJOURNAL OF VIRAL HEPATITIS, Issue 6 2010L. L. Schiavon Summary., HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR , F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 ± 0.081 (0.909, when adjusted by DANA). Values ,4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 ± 0.053 vs 0.762 ± 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients. [source] Autoantibodies are commonly detected by the AIT test in patients with chronic hepatitis C virus infectionJOURNAL OF VIRAL HEPATITIS, Issue 5 2010Jung-UK Sir No abstract is available for this article. [source] Association of genetic polymorphisms with interferon-induced haematologic adverse effects in chronic hepatitis C patientsJOURNAL OF VIRAL HEPATITIS, Issue 6 2009M. Wada Summary., Interferon (IFN)-based combination therapy with ribavirin has become the gold standard for the treatment of chronic hepatitis C virus infection. Haematologic toxicities, such as neutropenia, thrombocytopenia, and anaemia, however, frequently cause poor treatment tolerance, resulting in poor therapeutic efficacy. The aim of this study was to identify host genetic polymorphisms associated with the efficacy or haematologic toxicity of IFN-based combination therapy in chronic hepatitis C patients. We performed comprehensive single nucleotide polymorphism detection in all exonic regions of the 12 genes involved in the IFN signalling pathway in 32 healthy Japanese volunteers. Of 167 identified polymorphisms, 35 were genotyped and tested for an association with the efficacy or toxicity of IFN plus ribavirin therapy in 240 chronic hepatitis C patients. Multiple logistic regression analysis revealed that low viral load, viral genotypes 2 and 3, and a lower degree of liver fibrosis, but none of the genetic polymorphisms, were significantly associated with a sustained virologic response. In contrast to efficacy, multiple linear regression analyses demonstrated that two polymorphisms (IFNAR1 10848-A/G and STAT2 4757-G/T) were significantly associated with IFN-induced neutropenia (P = 0.013 and P = 0.011, respectively). Thrombocytopenia was associated with the IRF7 789-G/A (P = 0.031). In conclusion, genetic polymorphisms in IFN signalling pathway-related genes were associated with IFN-induced neutropenia and thrombocytopenia in chronic hepatitis C patients. In contrast to toxicity, the efficacy of IFN-based therapy was largely dependent on viral factors and degree of liver fibrosis. [source] Antimitochondrial antibodies in patients with chronic hepatitis C virus infection: description of 18 cases and review of the literatureJOURNAL OF VIRAL HEPATITIS, Issue 6 2005M. Ramos-Casals Summary., To describe the clinical and immunologic patterns of disease expression of patients with chronic hepatitis C virus (HCV) infection and positive antimitochondrial antibodies (AMA). We investigated the presence of AMA in 237 consecutive HCV patients with extrahepatic manifestations from an International Registry. AMA were detected by indirect immunofluorescence in triple rat tissue (liver, stomach and kidney), aceton-fixed criosections and FITC-conjugated rabbit anti-human immunoglobulins. We found positive AMA in 18 (8%) out of 237 HCV patients. All patients were female with a mean age at protocol inclusion of 65.8 years (ranging from 37 to 87 years). Twelve (67%) patients fulfilled classification criteria for systemic autoimmune diseases (SAD), including Sjögren's syndrome (n = 7), systemic sclerosis (n = 3) and systemic lupus erythematosus (n = 2). Fourteen (78%) of the HCV-AMA patients presented at least one of the highly suggestive characteristics of primary biliary cirrhosis (PBC): 9 (50%) had a specific M2 pattern, 6 (33%) had more than twice normal levels of alkaline phosphatase, 5 (28%) had raised IgM levels and 4 (22%) a histological pattern compatible with PBC. Five (28%) patients developed neoplasia after detection of AMA. Seven (39%) patients died, due to neoplasia (n = 4), cirrhotic complications (n = 2) and hepatopulmonary syndrome (n = 1). We describe a subset of HCV patients with positive AMA who presented a broad spectrum of clinical features, including liver, autoimmune and neoplasic manifestations. Two-thirds of these patients presented an associated SAD, mainly Sjögren's syndrome or systemic sclerosis, together with a high frequency of multiple autoantibodies and an increased prevalence of cirrhosis and neoplasia. [source] Intrahepatic and peripheral blood virus-specific cytotoxic T lymphocyte activity is associated with a response to combination IFN-, and ribavirin treatment among patients with chronic hepatitis C virus infection,JOURNAL OF VIRAL HEPATITIS, Issue 2 2005A. J. Freeman Summary., This report describes an association between intrahepatic and peripheral blood cytotoxic T lymphocytes (CTL) activity present prior to receiving treatment, and a response to combination interferon- , (IFN- ,) and ribavirin therapy for chronic hepatitis C virus (HCV) infection. Recombinant vaccinia virus constructs were used to expand and detect cytotoxic effectors against the entire genotype 1a HCV polyprotein. Six patients with a sustained response to therapy were significantly more likely to display intrahepatic and peripheral blood HCV-specific CTL activity than patients who relapsed or had no treatment response. Limited longitudinal data suggested that rather than combination therapy acting to enhance the CTL response to achieve viral clearance, detectable CTL prior to treatment increases the likehood of the host responding to the direct antiviral activity of IFN- , and ribavirin. [source] Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection,JOURNAL OF VIRAL HEPATITIS, Issue 1 2005J. D. Collier Summary., Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression. [source] Treatment of chronic hepatitis C virus infection in patients with cirrhosisJOURNAL OF VIRAL HEPATITIS, Issue 5 2000Zeuzem Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20,30% of patients and to hepatocellular carcinoma (HCC) in 1,5% of patients. Rates of sustained virological response with standard interferon-, (IFN-,) are low in patients without cirrhosis (generally < 20%) and are even lower in those with cirrhosis. Combination therapy with IFN and ribavirin improves response rates in patients with chronic hepatitis C without cirrhosis, and the results from subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are encouraging. Importantly, treatment with IFN slows progression of liver fibrosis, regardless of HCV genotype or early response to therapy, and reduces the risk of HCC by two- to fivefold. The risk of development of HCC is also lower in patients who show at least a partial response to IFN therapy compared with those who show no response. There is a clear need for more definitive studies of treatment in patients with chronic hepatitis C and cirrhosis, ideally using therapies with greater efficacy. Nonetheless, based on the potential to slow the progression of liver fibrosis (regardless of treatment response) and to reduce the risk of HCC, a greater number of HCV-infected patients with cirrhosis should be considered as candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have improved virological response rates and may have additional clinical benefits in the prevention or reduction of fibrosis and retardation of progression of cirrhosis and HCC in these patients. [source] Effectiveness of pegylated interferon/ribavirin combination in ,real world' patients with chronic hepatitis C virus infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2008G. BORRONI Summary Background, Clinical trials have shown that the combination of pegylated interferon/ribavirin induces a sustained virological response in 54,63% of patients with chronic hepatitis C virus infection, but its effectiveness in day-to-day clinical practice is less clear. Aim, To verify if the efficacy of pegylated interferon/ribavirin combination in ,real world' patients is comparable to that observed in trials. Methods, The medical records of 397 consecutive naïve patients with chronic hepatitis C virus infection treated with pegylated interferon/ribavirin combination in nontertiary hospital settings were reviewed in order to assess the response to anti-viral treatment. Results, The sustained virological response rate achieved in this population was similar to that recorded in registration trials (total population: 64%; genotype 1: 46%; genotypes 2,3: 84%). Also, the premature discontinuation rate (15%) was similar to that observed in registration trials, but there were fewer dose reductions in one or both medications (26%). We confirmed the association between adherence and sustained virological response among the patients infected with hepatitis C virus genotype 1 who were treated for ,80% of the planned duration of treatment. Conclusion, The effectiveness of pegylated interferon/ribavirin therapy and factors predicting an sustained virological response in everyday clinical practice mirror those reported in randomized-controlled studies. [source] Review article: management of patients with chronic hepatitis C virus infection and ,normal' alanine aminotransferase activityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006S. ZEUZEM Summary Background Hepatitis C virus infection, a major cause of chronic liver disease, occurs with normal serum alanine aminotransferase activity in approximately 25% of patients. These patients have historically remained untreated but substantial evidence indicates liver damage, progression of disease and impaired quality of life in some individuals. Aim To review the current management of patients with chronic hepatitis C and normal alanine aminotransferase activity. Methods This review represents the summary of discussions at a Clinical Workshop with a comprehensive literature searching of available databases (PubMed and Embase). Results Current limits defining normal serum alanine aminotransferase activity are not representative of a ,healthy' status. Most patients with hepatitis C and normal alanine aminotransferase levels have histologically proven liver damage that, although generally mild, may be significant (,F2) in up to 20% of patients and progresses at approximately 50% of the rate in patients with elevated alanine aminotransferase levels. Some patients have persistently normal alanine aminotransferase activity and may have a more benign outcome, but a significant proportion (,20%) experience periods of increased serum alanine aminotransferase activity which may be associated with enhanced disease progression. Conclusions A treatment approach that considers host and virus-related variables and optimizes patient and cost benefits may therefore provide more effective management of patients with chronic hepatitis C and normal alanine aminotransferase activity. [source] Comparison of simple tests for the non-invasive diagnosis of clinically silent cirrhosis in chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2006G. BORRONI Summary Background Biopsy is the gold standard for assessing cirrhosis in patients with chronic hepatitis C virus infection, but it is expensive and at risk of complications. Alternative non-invasive methods have been developed but their usefulness remains uncertain. Aim To compare the accuracy of five non-invasive scores in detecting cirrhosis. Methods We reviewed the charts and liver biopsies of 228 consecutive, treatment-naïve, hepatitis C virus-positive patients, 13.2% of whom with histological diagnosis of cirrhosis. The five alternative scores were age-platelet index, cirrhosis discriminant score, aspartate transaminases to platelet ratio index, Pohl's index, and aspartate transaminases/alanine transaminases ratio. Results The specificities of the scores were good (87,100%), but not so their sensitivities (17,67%). Accordingly positive likelihood ratios were generally good but negative likelihood ratios were suboptimal. Combinations of the scores independently related to cirrhosis only slightly change this diagnostic accuracy. Using double cut-offs to exclude/diagnoses cirrhosis, cirrhosis discriminant score classified 21% of patients without misdiagnoses and aspartate transaminases to platelet ratio index classified 85% of case with 9% of misdiagnoses. Conclusions The five scores showed variable sensitivities and specificities in detecting liver cirrhosis, both individually and in combination. The use of double cut-off points may make the cirrhosis discriminant score and aspartate transaminases to platelet ratio index useful to reduce the number of patients submitted to liver biopsy. [source] 13C-methacetin breath test as liver function test in patients with chronic hepatitis C virus infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2005B. Braden Summary Background :,The 13C-methacetin breath test enables the quantitative evaluation of the cytochrome P450-dependent liver function. Aim :,To find out whether this breath test is sensitive in noncirrhotic patients also with chronic hepatitis C in early stages of fibrosis. Methods :,Sixty-one healthy controls and 81 patients with chronic hepatitis C underwent a 13C-methacetin breath test. In all patients, a liver biopsy was performed. The liver histology was classified according to the histology activity index,Knodell score. Results :,Delta over baseline values of the patients at 15 min significantly differed from controls (19.2 ± 9.2, vs. 24.1 ± 5.7,; P < 0.003). The cumulative recovery after 30 min in patients was 11.4 ± 4.8% and in healthy controls 13.8 ± 2.8% (P < 0.002). However, patients with early fibrosis (histology activity index IVB) did not differ in delta over baseline values of the patients at 15 min (23.2 ± 7.9, vs. 22.6 ± 7.2,; P = 0.61) or cumulative recovery (13.6 ± 3.7% vs. 13.2 ± 3.8%; P = 0.45) from patients with more advanced fibrosis (histology activity index IVC). Patients with clinically nonsymptomatic cirrhosis (histology activity index IVD; Child A) metabolized 13C-methacetin to a significantly lesser extent (delta over baseline values of the patients at 15 min: 8.3 ± 4.9,; P < 0.005 and cumulative recovery after 30 min: 5.6 ± 3.2%; P < 0.003). The 13C-methacetin breath test identified cirrhotic patients with 95.0% sensitivity and 96.7% specificity. Conclusion :,The non-invasive 13C-methacetin breath test reliably distinguishes between early cirrhotic (Child A) and noncirrhotic patients, but fails to detect early stages of fibrosis in patients with chronic hepatitis C. [source] Relapse to prior therapy is the most important factor for the retreatment response in patients with chronic hepatitis C virus infectionLIVER INTERNATIONAL, Issue 7 2007Abdurrahman Sagir Abstract Background: Treatment options for hepatitis C have developed rapidly in the past decade. The current treatment of choice is a combination of pegylated-interferon-, (PEG-IFN-,) and ribavirin. With the development of more therapy options, patients who failed in prior therapy hope to clear hepatitis C virus by undergoing a more effective retreatment regime. In this report, we investigated response rates to combination therapy [standard IFN-, or PEG-IFN-, and ribavirin] in patients who relapsed or failed in prior therapy. Methods: Ninety-three patients were included in this retrospective study. All patients failed to previous IFN-, monotherapy (n=55) or to a combination of standard IFN-, and ribavirin (n=38). Fifty-nine patients were nonresponders and 34 were relapsers. Thirty-five patients were retreated with standard IFN-, plus ribavirin and 58 received PEG-IFN-, combination therapy. Results: Sustained virologic response (SVR) was induced in 31% of all patients. The highest SVR rate (58%) was observed in relapsers to standard IFN-, combination therapy who were retreated with PEG-IFN-, combination therapy. The SVR rate in relapsers to standard IFN-, monotherapy who received a standard IFN-, combination therapy was 50%. Relapsers responded in a significantly higher proportion to retreatment than nonresponders (56% vs. 17%, P<0.001). Relapse to previous therapy was identified as an independent predictor for therapy response. The lowest SVR rate was observed in nonresponders to standard IFN-, combination therapy who were retreated with PEG-IFN-, combination therapy (1/26; 4%). Conclusions: In relapsers, retreatment with the most effective therapy regime to date a combination of PEG-IFN-, and ribavirin, is promising. However, retreatment with PEG-IFN-, combination therapy in nonresponders to standard IFN combination therapy is not effective. [source] Noninvasive serum markers in the diagnosis of structural liver damage in chronic hepatitis C virus infectionLIVER INTERNATIONAL, Issue 9 2006Edison R. Parise Abstract: Aim: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST to platelet ratio index (APRI) and ,-glutamyltransferase (GGT) levels to predict the intensity of hepatic fibrosis in patients with CHC. Patients and methods: In a total of 206 hepatitis C virus RNA-positive biopsied patients, AST, ALT, GGT levels, platelet count and serum HA concentration were determined. The APRI was calculated as the ratio of AST to platelets. Results: HA levels were best correlated with disease stage (r=,0.694; P<0.001). In the diagnosis of significant fibrosis (F2,F4), HA levels [AUC=0.879, 95% CI (0.832,0.927)] and APRI [AUC=0.824 (0.772,0.903)] were the markers with the best diagnostic accuracy. These parameters also best identified the presence of cirrhosis (F4), with an AUC of 0.908 (0.868,0.949) for HA and of 0.837 (0.772,0.903) for APRI. Conclusion: Serum HA was the parameter that alone presented the best diagnostic accuracy in the assessment of hepatic fibrosis in CHC. The APRI showed a better diagnostic sensitivity than GGT levels or the AST/ALT ratio. Its simple determination and low cost make this index a valid alternative for the noninvasive staging of CHC. [source] Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infectionLIVER INTERNATIONAL, Issue 2 2002MT Levy Abstract: Background: Activated hepatic stellate cells (HSCs), recognised by their , smooth muscle actin immunoreactivity, are primarily responsible for liver fibrosis. However, the presence of , smooth muscle actin positive HSCs is not always associated with the development of liver fibrosis. Recently, other markers of human HSCs including the gelatinase fibroblast activation protein (FAP) and glial fibrillary acidic protein have been identified. Aims: We examined the relationship between the expression of these HSC markers and the severity of liver injury in patients with chronic hepatitis C virus infection. Methods: Liver tissue from 27 patients was examined using immunohistochemistry. Linear correlation analysis was used to compare staining scores with the stage and grade of liver injury. Results,Conclusions: FAP expression, seen at the tissue-remodelling interface, was strongly and significantly correlated with the severity of liver fibrosis. A weaker correlation was seen between glial fibrillary acidic protein expression and fibrosis stage. This contrasted with the absence of a relationship between , smooth muscle actin and the fibrotic score. A correlation was also observed between FAP expression and necroinflammatory score. In summary, FAP expression identifies a HSC subpopulation at the tissue-remodelling interface that is related to the severity of liver fibrosis. [source] Controversies in the management of hepatitis C virus infection after liver transplantationLIVER TRANSPLANTATION, Issue 11 2003Mitchell L. Shiffman Recurrence of hepatitis C virus infection after liver transplantation is universal. A significant percentage of these patients develop progressive graft injury and cirrhosis. Those factors that modulate disease progression in liver transplant recipients with recurrent hepatitis C virus infection remain controversial and are poorly understood. Treatment of recurrent hepatitis C virus after liver transplantation with either interferon or interferon and ribavirin has yielded only limited success. Regardless of this, treatment is instituted. Peginterferon is more effective than standard interferon for treatment of chronic hepatitis C virus infection in the nontransplantation setting when used either alone or with ribavirin. The effectiveness of peginterferon, both with and without ribavirin in the posttransplantation setting, is currently being explored. In this review those factors thought to affect disease progression in patients with recurrent hepatitis C virus will be discussed, strategies that have been used to treat recurrent hepatitis C virus will be reviewed, and the impact that peginterferon may have on hepatitis C virus infection in the pretransplantation and posttransplantation setting will be explored. [source] Detection of HCV-RNA in Cerumen of Chronically HCV-Infected Patients,THE LARYNGOSCOPE, Issue 3 2005Yasar Bayindir MD Abstract Objectives/Hypothesis: Viral hepatitis C is a worldwide public health problem. Hepatitis C virus is mainly transmitted by parenteral or percutaneous route. Nonparenteral transmission, such as through sexual activity, household contact, and vertical or perinatal exposure to body fluids or secretions, can occur, which has been studied before. Cerumen, however, has not been investigated for its ability to transmit hepatitis C virus. The aim of this study is to evaluate the importance of cerumen in transmission of hepatitis C virus infection. Study Design: This study was performed on 35 patients with confirmed chronic hepatitis C virus infection. Methods: Thirty-five cerumen specimens collected from the patients with hepatitis C virus RNA in their sera were prospectively analyzed for the presence of hepatitis C virus RNA by polymerase chain reaction. Results: None of the 35 cerumen specimens were positive for hepatitis C virus RNA. Conclusion: This study showed that cerumen has no risk for transmission of hepatitis C virus infection, even in patients with high hepatitis C virus RNA serum levels; however, standard infection control precautions should be applied carefully in all examinations and surgical operations of the ears. [source] Immunohistochemical expression of CD95 (Fas), c-myc and epidermal growth factor receptor in hepatitis C virus infection, cirrhotic liver disease and hepatocellular carcinoma,APMIS, Issue 6 2006A. EL-BASSIOUNI Gene product expression in normal and chronic hepatitis C virus infection was determined in an attempt to improve our understanding of the molecular events leading to the development of cirrhosis and liver carcinoma. Activation of CD95 (Fas) causes apoptosis of cells and liver failure in mice and has been associated with human liver disorders. c-myc is involved in cell proliferation and EGFR in regeneration of cells. The material of the current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 29 cases of liver cirrhosis and HCV (LC), and 19 cases of hepatocellular carcinoma and HCV (HCC) admitted to the Theodor Bilharz Research Institute (TBRI) during the years 2003,2004. Ten wedge liver biopsies , taken during laparoscopic cholecystectomy , were included in the study as normal controls. Laboratory investigations, including liver function tests, serological markers for viral hepatitis and serum alpha fetoprotein level (,-FP), were determined for all cases. Histopathological study and immunohistochemistry using monoclonal antibodies for CD95, c-myc and EGFR were also done. In CHC cases, the histological activity index (HAI) revealed more expression of Fas antigen in liver tissues with active inflammation than in those without active inflammation (p<0.01). EGFR and c-myc act synergistically in liver tumorigenesis. Upregulation of Fas in chronic hepatitis C infection and of c-myc & EGFR in malignant transformation was concluded from this study. c-myc expression may obstruct the induction of apoptosis of HCC cells and lead to uncontrolled cell growth. [source] | |||||||||||||||||||||||||