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Chronic Hepatitis C Infection (chronic + hepatitis_c_infection)
Selected AbstractsChronic hepatitis C infection: Influence of the viral load, genotypes, and GBV-C/HGV coinfection on the severity of the disease in a Brazilian populationJOURNAL OF MEDICAL VIROLOGY, Issue 1 2002Leila M.M.B. Pereira Abstract The distributions of the different genotypes of the hepatitis C virus (HCV) and GBV-C virus (GBV-C/HGV) vary geographically and information worldwide is still incomplete. In particular, there are few data on the distribution of genotypes (and their relationship to the severity of liver disease) in South America. Findings are described in 114 consecutive patients from Northeast Brazil (median age 52 years, range 18,72 years) who had abnormal levels of serum aminotransferases and seropositivity for HCV RNA. The patients were recruited from an outpatient clinic between November 1997 and April 1998. Quantitative HCV RNA and GBV-C/HGV RNA estimations were carried out by double-nested polymerase chain reaction (PCR) using primers from the 5,-untranslated regions (UTRs) of the genomes. HCV genotypes were determined by restriction fragment length polymorphism (RFLP) analysis with 5,-UTR primers and by PCR with type-specific 5,-UTR primers. GBV-C/HGV-RNA genotypes were determined by RFLP with specific 5,-UTR primers and phylogenetic trees were constructed using the Neighbour-Joining and Drawtree programs. Histological features were graded and staged according to international criteria. Of the 114 patients, 35 (30.7%) patients had cirrhosis and 22 (27.8%) had mild, 51 (64.6%) had moderate, and 6 (7.6%) had severe chronic hepatitis. Median HCV viral load was 106 genome equivalents per millilitre (range 104,109/ml). Frequencies of genotypes were 5.3% type 1a, 44.7% type 1b, 3.5% type 2, 41.2% type 3, and 5.3% mixed types. GBV-C/HGV-RNA was detected in the sera of 12 (10.5%) patients and was distributed among three phylogenetic groups. There were no significant differences between patients with the predominant HCV genotypes (1b and 3) with respect to gender, age group, viral load, severity of liver disease, or coinfection with GBV-C/HGV. J. Med. Virol. 67:27,32, 2002. © 2002 Wiley-Liss, Inc. [source] Community-based treatment for chronic hepatitis C in drug users: high rates of compliance with therapy despite ongoing drug useALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009M. WILKINSON Summary Background, Chronic hepatitis C infection is common in drug users. Treatment of injectors is possible under controlled conditions, but many have not yet been included in treatment programmes as there are concerns about their ability to comply with therapy. It is not known which factors influence compliance. Aim, To examine the hypothesis that active drug users would comply with anti-viral therapy if treatment was delivered in a convenient manner. Methods, We established a community-based treatment programme and offered anti-viral therapy to all drug users who wanted it. Few pre-treatment requirements were imposed and, by design, compliance with therapy was reviewed after 50 patients had completed treatment. Results, Of the 441 patients who were known to be HCV RNA positive and attended the specialist addiction services during the period of this study, eighty three patients considered therapy. Twenty patients did not undergo treatment: 14 declined and 6 had medical conditions that precluded it. In 60 episodes (58 patients) where treatment had been completed, compliance was greater than 80% and homelessness, active illicit drug use and pre-treatment antidepressant therapy were not associated with noncompliance. In 25 of 49 treatment episodes that were assessed 6 months after treatment cessation, a sustained virological response (51%) was seen. Conclusion, Active drug users using illicit drugs can be successfully treated in community-based clinics. [source] Bell's palsy during interferon therapy for chronic hepatitis C infection in patients with haemorrhagic disordersHAEMOPHILIA, Issue 2 2000Ogundipe Two adult patients with life-long severe haemorrhagic disorders commenced on interferon-,2b therapy for chronic hepatitis C infection. Both developed Bell's palsy several weeks after commencing therapy, They were started on steroids and, in addition, the first patient discontinued interferon-,2b therapy while the second patient elected to continue with therapy. In both cases facial paralysis improved over the ensuing weeks. Bell's palsy is often idiopathic but has been reported. in association with herpesviruses. It is not a recognised complication of chronic hepatitis B or C infection, or interferon-,2b therapy. However, the interferons are associated with numerous adverse reactions including various neuropsychiatric manifestations and neurological syndromes. There are several reports of nerve palsies, including optic tract neuropathy, occurring during interferon therapy, and immune-based mechanisms are thought to play a role in the aetiopathogenesis. No reports of Bell's palsy in association with interferon therapy were identified in our literature search, although one possible case has been reported to the Committee of Safety in Medicine. Although Bell's palsy in our patients may have occurred by chance, a neuropathic effect of interferon-,2b on the facial nerve cannot be excluded and we urge physicians using interferons to be aware of this potential side-effect. [source] The role of effectively treated chronic hepatitis C infection in the development of type 2 diabetes mellitus,HEPATOLOGY, Issue 6 2009Tugrul Purnak M.D. No abstract is available for this article. [source] Treating hepatitis C in the prison population is cost-saving,HEPATOLOGY, Issue 5 2008Jennifer A. Tan The prevalence of chronic hepatitis C infection in U.S. prisons is 12% to 31%. Treatment of this substantial portion of the population has been subject to much controversy, both medically and legally. Studies have demonstrated that treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin is a cost-effective measure in the general population; however, no study has addressed whether the same is true of the prison population. The aim of this study was to determine the cost-effectiveness of hepatitis C treatment with PEG IFN and ribavirin in the U.S. prison population. Cost-effectiveness was determined via a decision analysis model employing Markov simulation. The cohort of prisoners had a distribution of genotypes and stages of fibrosis in accordance with prior studies evaluating inmate populations. The probability of transitioning from one health state to another, reinfection rates, in-prison and out-of-prison mortality rates, sustained viral response rates, costs, and quality of life weights were also obtained from the literature. Sensitivity analysis was performed. In a strategy without a pretreatment liver biopsy, treatment was cost-effective for all ages and genotypes. This model was robust to rates of disease progression, mortality rates, reinfection rates, sustained viral response rates, and costs. In a strategy employing a pretreatment liver biopsy, treatment was also cost-saving for prisoners of all ages and genotypes with portal fibrosis, bridging fibrosis, or compensated cirrhosis. Treatment was not cost-effective in patients between the ages of 40 and 49 with no fibrosis and genotype 1. Conclusion: Treatment of chronic hepatitis C with PEG IFN and ribavirin in U.S. prisons results in both improved quality of life and savings in cost for almost all segments of the inmate population. If the decision to treat hepatitis C is based on pharmaco-economic measures, this significant proportion of infected individuals should not be denied access to therapy. (HEPATOLOGY 2008.) [source] Development of novel agents for the treatment of chronic hepatitis C infection: Summary of the FDA Antiviral Products Advisory Committee recommendations,,HEPATOLOGY, Issue 6 2007Kenneth E. Sherman First page of article [source] Altered innate immunity in chronic hepatitis C infection: Cause or effect?,HEPATOLOGY, Issue 4 2007Gyongyi Szabo First page of article [source] Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment,HEPATOLOGY, Issue 2 2006Kavitha Gopal The low-density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for the hepatitis C virus (HCV). Competitive inhibition of HCV binding to the LDLR by low-density lipoprotein (LDL) has been shown in vitro. If similar inhibition occurs in vivo, an elevated serum concentration of beta- lipoproteins may reduce the efficiency of infecting hepatocytes with HCV by competitively inhibiting HCV viral receptor binding. We investigated the role of baseline lipid values in influencing the outcome of HCV treatment. We conducted a retrospective chart review of patients treated with an interferon-based regimen at our liver and gastroenterology clinics between 1998 and 2004. Of 99 patients enrolled in the study, 49 (49.5%) had HCV genotype 1 (LDL 100.2 ± 30.2 mg/dL [mean ± SD]), and 50 patients (50.5%) had genotype 2 or 3 (LDL 110.1 ± 40 mg/dL) infection. Early viral response (EVR), end-of-treatment response (ETR), and sustained viral response (SVR) were documented in 99, 88, and 77 patients, respectively. LDL and cholesterol levels prior to treatment were found to be higher in patients with positive EVR, ETR, and SVR. This difference remained significant independent of age. Multivariate analysis controlling for genotype and age showed that the higher the cholesterol and LDL levels prior to treatment, the greater the odds of responding to treatment. In conclusion, having higher serum LDL and cholesterol levels before treatment may be significant prognostic indicators for treatment outcome of those with chronic hepatitis C infection, particularly in genotypes 1 and 2. (HEPATOLOGY 2006;44:335,340.) [source] The importance of steatosis in chronic hepatitis C infection and its management: A reviewHEPATOLOGY RESEARCH, Issue 3 2010Timothy J. S. Cross Hepatitis C virus (HCV) infection is a major cause of chronic liver disease with approximately 180 million people infected worldwide. Hepatic steatosis is a frequent histological finding in chronic hepatitis C (CHC) infection and is 2- to 3-fold more common than would be expected by chance alone. A high body mass index with excess visceral fat distribution is associated with steatosis in patients infected with HCV genotype 1 but not genotype 3, re-enforcing the concept that in patients with CHC, some have "metabolic steatosis", predominantly HCV genotype 1, and others "viral steatosis", mainly HCV genotype 3. Accumulating evidence suggests that steatosis may contribute to progression of fibrosis in CHC. Hepatic insulin resistance appears to play a role through the pro-fibrogenic effects of compensatory hyperinsulinemia. The aim of this review was to assess the effect host and viral factors play in steatosis development in patients with CHC infection and its possible relationship with hepatocellular carcinoma. The review examines the mechanisms by which CHC infection causes hepatic steatosis, the impact hepatic steatosis has on the natural history of the disease and finally, explores if treatments leading to a reduction in the amount of steatosis might lead to improved treatment outcomes. The basic medical science of steatosis in CHC will be discussed including proposed models of steatogenesis and the influence of viral and metabolic factors at the molecular level and how these might impact on current and future therapies. [source] Non-invasive markers for the prediction of fibrosis in chronic hepatitis C infectionHEPATOLOGY RESEARCH, Issue 8 2008Timothy Cross Liver fibrosis occurs as a result of chronic liver injury and is the hallmark of chronic liver disease. The final stage of progressive liver fibrosis is cirrhosis, which is implicated in portal hypertension, end-stage liver disease and hepatocellular carcinoma. Liver biopsy has historically been the gold standard test for the assessment of liver fibrosis for liver diseases such as viral hepatitis, autoimmune hepatitis and primary biliary cirrhosis. Improved serological tests have enhanced the diagnosis of these conditions and reduced the need for liver biopsy. Liver biopsy is unpopular among patients and clinicians. It is associated with morbidity and mortality, and in addition is subject to sampling error, inter- and intra-observer variability. There is therefore a need for non-invasive markers of liver fibrosis that are accurate, reliable, cheap and easy to use. The aim of this review is to examine the different non-invasive methods that can be used to estimate the severity of fibrosis. The methods evaluated include clinical examination, routine laboratory investigations, imaging tests, specialized tests of liver function and finally serum extra-cellular matrix markers of fibrosis. The review mainly focuses on fibrogenesis in the context of chronic hepatitis C infection. [source] Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2002Jason M Hui Abstract Background: Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection. Methods: In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein,cholesterol, high-density lipoprotein,cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model). Results: By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001). Conclusions: Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C. [source] Aspartate aminotransferase : alanine aminotransferase ratio in chronic hepatitis C infection: Is it a useful predictor of cirrhosis?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2000Gordon J-H Park Abstract Background: The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST : ALT , 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST : ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. Methods: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST : ALT. Results: In 30 patients with cirrhosis, the mean AST : ALT (0.99 ± 0.06) was higher than in 123 patients without cirrhosis (0.60 ± 0.02; P < 0.001). A ratio , 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. Conclusion: Although relatively insensitive, an AST : ALT , 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients. [source] Relationship between the hepatitis C viral load and the serum interferon concentration during the first week of peginterferon-alpha-2b-ribavirin combination therapyJOURNAL OF MEDICAL VIROLOGY, Issue 10 2010Catherine François Abstract In chronic hepatitis C virus (HCV) infections, the current standard of care (combination therapy with pegylated alpha interferon (PEG-IFN,) and ribavirin) is only effective in around 50% of cases. The aim of the present study was to analyze the relationship between the HCV load and the PEG-IFN concentration during the first week of treatment. Fifteen treatment-naive patients with chronic hepatitis C infection (genotypes 1, 2, 3, and 4) underwent PEG-IFN,-2b/ribavirin combination therapy. Blood samples were collected before the first injection (T0) and then at different time points until the next injection a week later. The PEG-IFN concentration and the HCV load were assayed. The serum interferon concentration peaked 2 days after the first injection (mean value for the study population; Tmax,=,40.9,hr; Cmax,=,490,pg/ml) and a trough in viral load was seen at day 3. The PEG-IFN,-2b concentration decreased from day 2 to day 7, enabling a viral rebound in all patients. The change in viral load between day 0 and day 3 differed significantly according to whether the patients were responders at week 12 (,log,d0/d3,=,2.729,±,1.419,log10,IU/ml) or not (,log,d0/d3,=,1.102,±,0.472,log10,IU/ml). Our results emphasize the potential clinical importance of achieving viral decay immediately after initiation of interferon,ribavirin combination therapy. J. Med. Virol. 82:1640,1646, 2010. 2010 Wiley-Liss, Inc. [source] Interferon-,2b induced facial erythema in a woman with chronic hepatitis C infectionJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2002U Tursen No abstract is available for this article. [source] Review article: optimizing SVR and management of the haematological side effects of peginterferon/ribavirin antiviral therapy for HCV , the role of epoetin, G-CSF and novel agentsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010R. MAC NICHOLAS Aliment Pharmacol Ther,31, 929,937 Summary Background, Chronic hepatitis C is one of the leading causes for chronic liver disease globally. The past two decades have seen many advances in hepatitis C treatment. Despite these advances, side effects of treatment are common. Haematological complications of treatment can result in treatment cessation and suboptimal results. Recent data have suggested a role for epoetin/granulocyte colony stimulating factor (G-CSF) in optimizing sustained virological response (SVR). Aim, To investigate the nature, frequency and management of haematological side effects in the treatment of chronic hepatitis C infection. Methods, The terms hepatitis C, hepatitis C virus (HCV), treatment, side effects, interferon, peginterferon, ribavirin, anaemia, haemoglobin, neutropenia, thrombocytopenia, haematological, growth factor, erythropoietin and G-CSF were searched on MEDLINE for the period 1991,2009. References from selected articles were also included. Results, Haematological side effects such as anaemia, neutropenia and thrombocytopenia are frequent in anti-HCV treatment. The off-label use of haematological growth factors is common and effective. Conclusions, Erythropoietic agents are effective in treating anaemia, preventing ribavirin dose reduction, improving patients' quality of life, but the effect on SVR is not fully elucidated. G-CSF is effective in raising absolute neutrophil count; however, neutropenic HCV-infected patients on combination treatment may not experience increased bacterial infections. Eltrombopag, a new oral thrombopoietin mimetic, may allow combination treatment in patients with thrombocytopenia. [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] Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled studyJOURNAL OF VIRAL HEPATITIS, Issue 3 2003I. Portal Summary., Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN- ,2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN- ,2b alone for 48 weeks (R1: 42 patients) or IFN- ,2b plus ribavirin (600 mg/day) for 24 weeks and IFN- ,2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN- ,2b plus ribavirin for 24 weeks and then IFN- ,2b alone for the next 24 weeks (R3: 104 patients) or IFN- ,2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 × upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR. [source] Evaluating the cost of sustained virologic response in naïve chronic hepatitis C patients treated à la carteALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007M. BUTI Summary Background There is a tendency to individualize treatment in chronic hepatitis C patients depending on viral load and rapid clearance of HCV-RNA. Aim To evaluate the cost (,, 2006) per sustained virologic response in naïve patients with therapy à la carte compared with standard combination therapy. Methods A decision analysis model was used to compare standard therapy with peginterferon alpha and ribavirin for 24 weeks for genotype (G) 2/3, and 48 weeks for G1 and therapy à la carte with the same drugs but different durations: G1 high viral load for 48 weeks, G1 low viral load with rapid virologic response for 24 weeks, and without rapid virologic response for 48 weeks, and G2/3 with rapid virologic response for 12 weeks, and without rapid virologic response for 24 weeks. Results Sustained virologic response was similar in both strategies. The cost per successfully treated patient for standard therapy is ,17 812 and for therapy à la carte,12 313. Assuming that 13 309 patients with standard therapy and 14 450 patients with therapy à la carte achieve sustained virologic response, therapy à la carte has an overall cost-saving of ,59.13 million. Conclusion Therapy à la carte is a cost-saving strategy for chronic hepatitis C infection compared to standard therapy, with lower investment requirement per patient to achieve sustained virologic response. [source] 13C-methacetin breath test as a quantitative liver function test in patients with chronic hepatitis C infection: continuous automatic molecular correlation spectroscopy compared to isotopic ratio mass spectrometryALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007O. GOETZE Summary Background The 13C-methacetin breath test (MBT) has been proposed for the non-invasive evaluation of hepatic microsomal activity. Aim To test a new continuous breath analysis system (BreathID) in comparison with gold-standard isotopic ratio mass spectrometry (IRMS) in patients with chronic hepatitis C infection and to assess the diagnostic performance of these validation data compared with liver biopsy for the quantification of liver fibrosis. Methods Fifty patients at different METAVIR stages received 75 mg of 13C-methacetin. Breath isotopic ratio was analysed over 90 min by BreathID (one sample/3 min; BreathID) and IRMS (one sample/10 min). Results were expressed as delta over baseline [DOB (%)] at each time interval and maximal DOB [DOBmax(%)]. Results A high linear association between both methods was observed (R2 = 0.95, P < 0.001). For all DOB and DOBmax, the limits of agreement by Bland,Altman analysis were within the predefined maximal width of s.d. <2.5%. MBT parameters in patients with high-grade fibrosis were different from patients with low-grade fibrosis (P < 0.001). Conclusion The MBT obtained by an easy to operate, automated BreathID provides results comparable with standard IRMS and differentiates fibrosis grades in patients with chronic hepatitis C infection. [source] How to modulate inflammatory cytokines in liver diseasesLIVER INTERNATIONAL, Issue 9 2006Herbert Tilg Abstract: Most acute and chronic liver diseases are characterized by inflammatory processes with enhanced expression of various pro- and anti-inflammatory cytokines in the liver. These cytokines are the driving force of many inflammatory liver disorders often resulting in fibrosis and cirrhosis. Severe alcoholic hepatitis is a prototypic tumor necrosis factor-, (TNF-,)-associated disease. This knowledge has recently led to pilot studies with promising results investigating specific anti-TNF drugs such as infliximab or etanercept in the treatment of this disease, although a recently performed controlled French study did show a potential detrimental effect of this approach. Anti-TNF treatment strategies might also improve chronic hepatitis C infection as shown by one controlled trial using etanercept administered subcutaneously for 24 weeks. Furthermore, several case reports suggest that TNF-, neutralization is not harmful to patients chronically infected with this virus. In contrast, neutralization of TNF-, worsens and might even be associated with fatalities in chronic hepatitis B infection. Anti-inflammatory cytokines such as interleukin-10 (IL-10) have also been tried in patients with chronic liver diseases. Whereas IL-10 administered to patients with chronic hepatitis C virus infection shows indeed anti-inflammatory effects in the liver, it seems to act as a proviral agent thereby limiting its clinical utility. Another cytokine with major anti-inflammatory potential is the adipokine adiponectin, as its administration is beneficial in many experimental models of liver injury. Interference with cytokine pathways and/or administration of anti-inflammatory cytokines will be of major interest in the future therapy of many liver diseases. [source] Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in Caucasian patients with chronic hepatitis CLIVER INTERNATIONAL, Issue 3 2006Sigal Fishman Abstract: Objective: Previous studies have demonstrated that CYP2D6 polymorphism is associated with liver cirrhosis. The aim of the present study was to find out whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression rate. Methods: Seventy-five Caucasian patients with chronic hepatitis C infection were recruited. They were divided into two groups, ,fast fibrosers' and ,slow fibrosers', according to Poynard's fibrosis progression curves. Sixty-two patients underwent liver biopsy. Twenty healthy neonates were included as control population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by polymer chain reaction using fluorescent hybridization probes in a lightCycler instrument. Results: Forty-two patients were classified as ,fast fibrosers' and 33 patients as ,slow fibrosers'. The frequency of CYP2D6*4 allele in the ,fast fibrosers' (34.5%) was significantly higher compared with the ,slow fibrosers' (15%) (P -value=0.007). There was no significant difference between the frequency of CYP2D6*4 in the ,slow fibrosers' (15%) compared with the controls (12.5%). Carrier state of CYP2D6*4 was the only covariate that was significantly positively correlated with fast progression to cirrhosis (odds ratio=6.5, P=0.01). Conclusion: This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients. [source] The management of side-effects during therapy for hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2004R. J. Aspinall Summary The results of interferon and ribavirin combination therapy for chronic hepatitis C infection have substantially improved in recent years, such that the majority of patients in randomized-controlled trials now achieve a sustained virological response. However, adverse effects are commonplace, often disabling and may lead to interruption or cessation of therapy with subsequent loss of efficacy. Constitutional, neuropsychiatric and haematological reactions have proved particularly troublesome. In this review, we discuss these adverse effects in more detail and highlight recent advances in their management. [source] Raised serum ferritin predicts non-response to interferon and ribavirin treatment in patients with chronic hepatitis C infectionLIVER INTERNATIONAL, Issue 3 2002S Distante Abstract: Background/Aim: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. Methods: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21,70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. Results: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 µg/L vs. 75 µg/L P < 0.001). There was no difference in transferrin saturation among the two response groups. Only 23% (4/7) of patients with Perls grade 1 in liver biopsies responded to treatment vs. 54% (122/225) patients without iron deposition (P = 0.02), however, 10/13-non-responders had HCV genotype one. Two patients (0.8%) were homozygous for the C282Y mutation, 36 patients were heterozygous (14%). Among mutation carriers 26/38 achieved sustained response compared with 102/216 non-carriers (68% vs. 48%, P = 0.02). In a multivariate analysis s-ferritin (P = 0.030) and C282Y carrier status (P = 0.012) remained independent predict of sustained response. Conclusions: Raised s-ferritin values predicate non-response to interferon-ribavirin therapy in hepatitis C patients. Response rate in C282Y mutation carriers seems greater than in non-carriers. [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] Porphyria cutanea tarda in south-east New South WalesAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2002Ian McCrossin SUMMARY Thirteen patients with porphyria cutanea tarda diagnosed between 1994 and 2000 were reviewed to evaluate the precipitating factors and associations of porphyria cutanea tarda in a regional area of coastal and rural NSW. The majority had more than one precipitating factor, with excess alcohol intake, mutations in the haemochromatosis gene, chronic hepatitis C infection and oestrogen therapy being the most common. Antibodies to the hepatitis C virus were detected in 25% and these patients presented at a younger age. Of the patients tested for the two known haemochromatosis gene mutations, six (46%) had at least one copy of the C282Y mutation. Two (15%) patients were homozygous for the C282Y mutation and two (15%) were compound heterozygous for the C282Y and H63D mutations. All patients responded to venesection, which is the treatment of choice for the majority of patients with porphyria cutanea tarda. [source] Treating cancer with PEG IntronCANCER, Issue 2 2002Pharmacokinetic profile, dosing guidelines for an improved interferon-alpha-2b formulation Abstract BACKGROUND PEG Intron (pegylated interferon-alpha-2b [IFN-,-2b]; Schering-Plough, Kenilworth, NJ) has demonstrated delayed clearance and increased area under the curve compared with native IFN-,-2b. Studies in patients with chronic hepatitis C infection and malignancies have demonstrated both biologic and clinical activity of PEG Intron and have provided empiric data to compare the pharmacokinetics (PK) and pharmacodynamics of PEG Intron and IFN-,-2b. METHODS The authors conducted a review of the available data comparing the PK and pharmacodynamic effects of PEG Intron and IFN-,-2b. Safety and efficacy data from Phase I/II studies of PEG Intron in patients with chronic myelogenous leukemia (CML) and solid tumors were also reviewed. RESULTS Data from patients with chronic hepatitis C infection suggest that exposure to IFN at a PEG Intron dose of 0.25 ,g/kg per week is similar to that observed after administration of IFN-,-2b at a dose of 3 million International Units, three times per week. PEG Intron at doses up to 6 ,g/kg per week was well tolerated and demonstrated clinical activity in patients with CML and solid tumors, including metastatic melanoma and renal cell carcinoma. CONCLUSIONS Dose intensification can be achieved safely in patients with CML and solid tumors using PEG Intron, which could improve efficacy. These results provide useful dosing guidelines to clinicians investigating the antitumor activity of PEG Intron in patients with malignancies. More data are needed to determine the optimal dose in various oncologic indications. However, these results provide a sound rationale for further investigation of PEG Intron. Cancer 2002;95:389,96. © 2002 American Cancer Society. DOI 10.1002/cncr.10663 [source] | ||||||||||||||||||||||||||||