Therapy For Chronic Hepatitis C Research Articles

Commentary on: The optimal Dose of Ribavirin for Chronic Hepatitis C: From Literature Evidence to Clinical Practice

Commentary on: The optimal Dose of Ribavirin for Chronic Hepatitis C: From Literature Evidence to Clinical Practice

Spontaneous Weight Change during Chronic Hepatitis C Treatment: Association with Virologic Response Rates

Objective: We examined weight changes during chronic hepatitis C (CHC) therapy and association with virologic response.Methods: Weight changes were compared between subjects achieving rapid, early, and sustained virologic response rates (RVR, EVR, and SVR). RVR, EVR and SVR were compared among patients with or without weight loss of ≥ 0.5 body mass index (BMI) units (kg/m2) at 4, 12, 48 weeks.Results: CHC therapy was initiated in 184 cases. Median pretreatment BMI was 27.7 (18.4-51.3) with 38% overweight and 31% obese (BMI ≥25 and ≥ 30, respectively). Among patients with liver biopsies (n = 90), steatosis was present in 31.6%; fibrosis grade of 1-2/6 in 46%, 3-4 in 37.3% and 5-6 in 14.7%. Mean weight loss at 4, 12, 24 and 48 weeks of therapy were 1.2, 2.6, 3.8 and 3.3 kg, respectively. After 4 and 12 weeks of treatment, 38% and 54.3% had a BMI decrement of ≥ 0.5 kg/m2. For genotype 1, weight loss at 4 weeks was associated with significantly higher EVR (90.0% vs. 70%, p = 0.01) and a tendency towards better RVR and SVR (42.9% vs. 26.0% and 55.2% vs. 34.8%, respectively, p = 0.08). In multivariate analysis, weight loss at 4 weeks was independently associated with EVR (OR 6.3, p = 0.02) but was not significantly associated with RVR or SVRConclusions: Spontaneous weight loss at 4 and 12 weeks of CHC therapy was associated with improved EVR. Weight loss at 4 weeks was an independent predictor of EVR but not SVR.

Insulin resistance and early virological response in chronic HCV infection

Studies revealed that insulin resistance is associated with fibrosis progression and has negative impact on sustained virological response after standard antiviral therapy in patients with chronic hepatitis C (CHC). To assess the role of IR on progression of liver fibrosis and early virological response (EVR) rates in patients with chronic hepatitis C infection. The study population comprised 79 subjects who underwent combination therapy for CHC. Laboratory investigations in the form of glucose, insulin, bilirubin, alanine aminotransferase (ALT), cholesterol and triglycerides and liver biopsy were done for all patients. Insulin resistance was calculated using the homeostasis model of IR (HOMA-IR). IR was increased (>2 IU) in 31 (40.7%) of patients. Early virological response was achieved among 37 patients (48.7%). No difference in EVR, viral load or grade of liver fibrosis between patients with and without IR. A significant positive correlation was found between IR and liver steatosis. Insulin resistance is a common finding in CHC, it is associated with increase liver steatosis. However it has no impact on EVR to combined interferon ribavirin therapy, viral load or necroinflammation.

Identification of Novel HCV Deletion Mutants in Chronic Hepatitis C Patients

The HCV genome consists of a positive 9.6 kb single-strand of RNA. Nucleotide substitutions in the HCV genome are common and a 2 kb deletion has been reported. A total of 117 chronic hepatitis C (CHC) patients who were treated with pegylated interferon plus ribavirin combination therapy were enrolled in this study. Total RNA was extracted from the patients' sera and reverse transcription and PCR were performed. Statistical analysis was performed to evaluate the effects of HCV deletion mutants on treatment with combination therapy. By amplifying entire HCV genomes using long-distance PCR, novel large deletion mutants were identified. Sequence analysis revealed that these deletions extended approximately 6 kb from the core/E2 region to the NS5A region and that there are three kinds of deletions that are identical at their 3' and 5' extremities. The subgenome virus particles appeared to coexist with full-genome virus particles in the sera of CHC patients despite lacking essential components for HCV viral replication. These short fragments were detected in 26 of 117 patients and were associated with significantly higher HCV RNA levels (P=0.018) and poor response to combination therapy (P=0.043). Moreover, the existence of HCV deletion mutants was significantly associated with virological relapse following combination therapy (P=0.046, OR=3.4). HCV deletion mutants may affect the HCV life cycle and reduce the antiviral effects of interferon therapy for CHC.

Serum ferritin levels in chronic hepatitis C patients during antiviral therapy and prediction of treatment response

Increased serum ferritin (SF) levels are encountered in various conditions, such as inflammatory syndromes and haemochromatosis. Interferon alpha is one of the stimulants of SF. In this study we aimed to evaluate SF changes in patients with chronic hepatitis C (CHC) during antiviral therapy, and the relationship between SF and treatment response. Data from a total of 97 patients who had received peginterferon (PEG-IFN) plus ribavirin combination therapy for CHC, and who had been followed up for more than 6 months after treatment, were analyzed retrospectively. Patients who had undetectable hepatitis C virus RNA at 6 months after the completion of antiviral therapy were regarded as having achieved a sustained viral response (SVR), while the remaining patients were categorized as non-SVR. Differences in SF levels during therapy between SVR patients and non-SVR patients were examined. We found that patients who achieved SVR had lower baseline ferritin levels. It was observed that SF levels increased dramatically in both the SVR and non-SVR groups after starting therapy, remained high until the end of the treatment period, and returned to baseline levels after completion of treatment. However the SF rise was found to be significantly higher in patients who achieved an SVR than in those without SVR at each time-point during treatment. SF levels increase during PEG-IFN-based therapy for CHC. A lower SF level before starting treatment and higher SF levels during therapy appear to be associated with a favourable treatment response. Therefore, rises in SF, especially during the early phase of treatment, could be a predictor of SVR.

PMO-158 RS12979860 CC genotype is associated with baseline high numbers of CD56bright NK-cells, low numbers of CD3-CD56-CD16+ cells, low IL-10 HCV-specific production in CH-C therapy responders

IntroductionIL28B gene single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 help to predict treatment response in chronic hepatitis C (CH-C). Strong immune responses control HCV infection. Little is known on the...

The Era of Direct-Acting Antivirals: The Evolving Role of Interferon and Ribavirin for the Treatment of chronic Hepatitis C

The burden of disease related to chronic hepatitis C (CHC) continues to increase annually. While our experience with treating CHC began less than 30 years, steady progress has been made in the ability to successfully treat patients, reducing morbidity and mortality. Until recently, the main players in therapy of CHC were interferon and ribavirin. Unfortunately, response to this therapy is successful only in a selected group of patients, leaving a sizeable portion of patients with CHC untreated or with ineffective retreatment options after having failed prior therapy. An in depth understanding of the hepatitis C virus has ushered in the dawn of a new era of therapy for CHC. Two drugs, telaprevir and boceprevir, have recently been approved by the Food and Drug Administration. Many others hold great promise and are in the early phases of drug development. Here, we will review the history of hepatitis C therapy, mechanism of action drugs approved for or in development, current data on clinical safety and efficacy of these agents as well as the role of patient preference in CHC therapy. We will conclude with current recommendations for the treatment of patients with CHC and the evolving role of interferon and ribavirin.

Pharmacogenomics of hepatitis C infections: personalizing therapy

It is a widely held view that drug response genes have not proved as useful in clinical practice as anticipated at the start of the genomic era. An exception is in the treatment for chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon α and ribavirin. In 2009, four independent genome-wide analyses identified IL28B polymorphisms that predict drug response in chronic hepatitis C (CHC). This discovery had immediate clinical impact. First, the IL28B genotype could be used to personalize therapy. In the 2 years since discovery, most of the more than 100,000 CHC patients commencing therapy for CHC in the West will have considered IL28B genotype testing. Second, the discovery has supported clinical trials for the use of the protein encoded by the gene known as interferon lambda. Third, it is expected that new insights into HCV pathogenesis will follow from studies of how IL28B affects HCV viral clearance and, ultimately, this will lead to new therapeutic strategies for CHC. This review discusses how IL28B genotyping is now used in personalizing therapy and, with the dramatically changing clinical landscape in CHC, with the advent of direct-acting antivirals, the prospects ahead.

Management of Hepatitis C in Patients with Chronic Kidney Disease

Chronic kidney disease represents a global health problem. Chronic hepatitis C virus (HCV) infection is prevalent in patients with end stage renal disease (ESRD) on hemodialysis (HD) and in renal transplant recipients with significant impact on morbidity and mortality. Furthermore, HCV can cause various forms of glomerulopathy with the predominant type being cryglobulinemia associated membranoproliferative glomerulonephritis. Liver enzymes are traditionally used as markers of liver injury; however, there is wide variation in aminotransferase levels in patients with ESRD. Therefore, diagnosis of chronic hepatitis C (CHC) in patients with ESRD is based on HCV antibody testing and further confirmation with polymerase chain reaction testing. Current standard therapy for CHC is composed of pegylated interferon and ribavirin. However, this combination is challenging in patients with ESRD due to its tolerability. We describe in this review relevant issues in epidemiology, diagnosis and management of CHC in ESRD, HD and renal transplant recipients.

Association of Interleukin-28B and Hepatitis C Genotype 1 with a High Viral Load and Response to Pegylated Interferon plus Ribavirin Therapy

Background: Pegylated interferon (PEG-IFN) plus ribavirin therapy is the current standard treatment for chronic hepatitis C (CHC) genotype 1 with high viral load. A common genetic variation near the IL28B gene has been found to affect the response to PEG-IFN plus ribavirin therapy for CHC. The aims of this study were to analyze the association between the rs8099917 genotype and treatment response in a cohort study of CHC. Methods: This study evaluated clinical and laboratory parameters retrospectively in a cohort of 122 patients with chronic hepatitis C with genotype 1 and a high viral load who received PEG-IFN plus ribavirin therapy. We carried out univariate and multivariate statistical analyses of parameters and clinical responses. Results: Sixty-three of 122 patients (51.6%) had sustained virological responses (SVRs). Patients with the rs8099917 genotype TT achieved significantly higher SVR rates (p < 0.01). Univariate analysis revealed that SVRs were associated with BMI, fibrosis, albumin, total cholesterol, PEG-IFN dose, ribavirin dose and the rs8099917 genotype. Multivariate analysis revealed that the rs8099917 genotype (odds ratio 7.434, 95% CI 2.278–24.257, p = 0.001) and total PEG-IFN dose (odds ratio 7.162, 95% CI 1.565–18.15, p = 0.007) were significant factors. Conclusions: The rs8099917 genotype and total PEG-IFN dose were associated with SVR in patients with hepatitis C virus genotype 1.

Genetic Variants of Interferon-Stimulated Genes and IL-28B as Host Prognostic Factors of Response to Combination Treatment for Chronic Hepatitis C

Chronic hepatitis C (CHC) is a worldwide health problem that is highly related to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The achievement of response to the current standard of care-pegylated interferon plus ribavirin-has recently been described to be associated with single-nucleotide polymorphisms (SNPs) near the IL-28B gene. Additionally, baseline expression levels of genes involved in interferon (IFN)-stimulated genes (ISGs) have been found to be related to treatment outcome. In the present study, 285 patients were genotyped for 63 SNPs within genes of the IFN signaling pathway (IPGs) and ISGs. Two ISG polymorphisms-OASL rs12819210 (odds ratio (OR)=2.1, P=0.03) and IFIT1 rs304478 (OR=2.5, P=0.01)-were found to be independent predictive factors of sustained virological response (SVR) after adjusting for other clinical covariates. Furthermore, the predictive value of IL-28B SNP was notably improved by simultaneous genotyping of rs12819210 and rs304478, particularly in patients with the worst prognosis (viral genotype 1, area under the curve (AUC)=0.74). In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy.

Weight Loss Prior to Hepatitis C Therapy Improves Virological Response Rates at 1 and 3 Months

Purpose: Obesity is a modifiable risk factor for non-response to chronic hepatitis C (CHC) treatment. We examined the effect of pre-treatment weight loss by nutrition education and exercise intervention, during 6 weeks prior to CHC therapy, on rapid and early virological responses (RVR, EVR). Methods: RVR and EVR were compared among treatment naïve HCV Genotype 1 infected patients divided into 3 groups: 1: BMI <25; 2: BMI >25 who received one time 15-minute weight loss instructions and pamphlets (standard of care); 3: weekly one hour nutrition and physical exercise education immediately after initial evaluation+ monthly follow up (n = 23, 25, 17), respectively. All patients received weight based ribavirin + Peg-IFNα2b or Peg-IFNα2a, 6 weeks after their initial evaluation. Results: Out of 65 patients referred to a tertiary center (UPMC) for HCV management who provided consent to the study, 46 completed at least 1 month of HCV therapy and were included in the analysis. Data were missing in patients due to inability to start CHC therapy (n=8) or noncompliance with nutrition management program (n=11). Fifty one percent had BMI >25, 62% were males, 60% Caucasians, 23.8% African American, 16% other races. Compliance in group 3 (attending at least 3 pre-treatment sessions) was 30%. There was no significant difference in RVR and EVR for groups 1,2,3 (54%, 61%, 60% and 45%, 77%, 80%, respectively). There was no difference in the percentage of patients with loss of >0.5 BMI in group 2 vs group 3, at start of IFN therapy,weight loss (WL) (76% VS 80%) respectively. Among group 2 and 3, WL was associated with higher RVR and EVR compared to patients with no pre-treatment weight loss, (81% vs 41 % and 72% vs 33% respectively, p < 0.05). Conclusion: One-time 15-minute nutrition education session and three 1-hour nutrition and exercise education program were equally effective in inducing weight loss in our CHC patients. However, compliance with aggressive weight loss regimen was low. Weight loss of > 0.5 BMI prior to IFN+ribavirin therapy was associated with significantly higher virological response at 1 and 3 months of IFN therapy.

The Effect of Antiviral Therapy on Serum Cholesterol Levels in Chronic Hepatitis C

Background/AimsThe aims of this study were to evaluate the effect of antiviral therapy on serum total cholesterol (TC) levels and to investigate the factors related to serum TC changes in chronic hepatitis C (CHC) patients.MethodsA total of 94 CHC patients, the majority of whom were infected with genotype 1 or 2 and were receiving antiviral therapy, were consecutively enrolled. TC levels before treatment, at week 4, at the end of treatment (EOT), and at 24 weeks after the EOT were analyzed, along with factors related to pre- and post-treatment TC levels.ResultsPretreatment TC levels in the sustained virologic response (SVR) group (167±3.6 mg/dL) and the non-SVR group (158±8.3 mg/dL) were similar, and both decreased during antiviral therapy. The TC levels at 24 weeks after the EOT significantly increased in the SVR group (183±4.7 mg/dL), but not in the non-SVR group (160±7.1 mg/dL, p=0.044) after adjusting for the pretreatment TC levels. The grade of hepatic fibrosis, as measured by the METAVIR score or the aspartate aminotransferase-platelet ratio index (APRI), but not viral load (p=0.119), was an independent variable associated with the pretreatment TC levels (METAVIR score, p=0.011; APRI, p=0.033). After adjusting for the presence of a SVR by longitudinal data analysis using generalized estimating equations, the independent variable APRI was associated with the serum TC level after antiviral therapy (p=0.014), whereas a SVR was associated with the serum TC level only with marginal statistical significance (p=0.084).ConclusionsSerum TC levels increased in the SVR group after antiviral therapy for CHC; however, this was probably due to an improvement in liver fibrosis rather than the eradication of virus.

High Predictivity of IL28B Genotype for Natural Clearance of HCV-RNA in Patients with Hemoglobinopathies

AbstractAbstract 2070 Background and Aim.Patients with transfusion-dependent hemoglobinopathies, as thalassemia major (TM) and sickle/β-thalassemia (S/βThal), have an high risk to be infected by hepatitis C virus (HCV), developing chronic hepatitis C (CHC).Current standard-of-care therapy for CHC consists of pegylated interferon-α 2 and ribavirin (PEG-IFN- α/RBV). A genome-wide association study (GWAs) identified a single nucleotide polymorphism (SNP), on chromosome 19, 3 kilobases (kb) upstream of the IL28B gene (IL28B -3kb C>T). This SNP is associated to the natural clearance of HCV-RNA. The IL28B -3kb C>T SNP is in strong linkage disequilibrium with a non-synonymous variant in the exon2 of IL28B gene (213A>G, K70R). Because of in these patients the PEG-IFN-α/RBV treatment of chronic HCV infection could be complicated by severe side adverse events, i.e. ribavirin-associated hemolysis, it is noteworthy to predict the spontaneous C virus clearance by investigate these two IL28B DNA variants. Therefore, in a cohort of 42 patients with hemoglobinopathies, it was analyzed the two mentioned DNA variants to evaluate their allele frequencies and to eventually correlate them to the C virus clearance. Patients and Methods.Forty two patients with hemoglobinopathies, not-treated with PEG- IFN-α/RBV, were included in this study. Molecular analysi:. Genomic DNAs were extracted from peripheral blood mononuclear cells. DNA variants, IL28B -3kb C>T e K70R, were investigated by direct genomic sequencing (CEQ880-Beckman), endonuclease digestion and reverse dot-blot hybridization. PCR primers, specific for the investigated DNA regions, were designed in our laboratory on the basis of IL28B gene map (GENATLAS) and FASTA SNP sequences. According to literature, the genotype IL28B -3kbCC/K70RAA was considered most frequently associated with the spontaneous HCV-RNA clearance, whereas the genotypes IL28B 3kbTT/K70R GG and -3kbCT/K70R AG were considered most frequently associated with a persistent infection. Result:Allele frequencies of -3kbC>T polymorphism were 63,1% for the favourable C allele and 36,9% for the T allele. Allele frequencies for the K70R variant were 63.1% for the A allele and 36,9% for the G allele. Twenty of 42 studied patients (47,6%) showed a spontaneous HCV-RNA clearance: 15/20 (75%) had IL28B genotype -3kbCC/K70R AA, 5/20 (25%) had IL28B genotype -3kbCT/K70R AG. Twenty two of 42 studied patients (52,4%) showed HCV-RNA persistence: 13/22 (59,1%) showed viral genotype 1b and IL28B genotype -3kbCT/K70R AG; 4/22 (18,2%) showed viral genotype 1b and IL28B genotype -3kbCC/K70R AA; 4/22 (18,2%) showed IL28B genotype -3kbTT/K70R GG (3 had viral genotype 2a2c and one viral genotype 1b; one case had viral genotype 2a2c and was homozygous for the favourable -3kb C allele but it was heterozygous for the K70R mutation (Table 1). Conclusion:It seems that IL28B genotype has a marked impact on natural clearance of HCV-RNA: 15/20 (75%) not treated patients who showed a spontaneous HCV-RNA clearance had an IL28B genotype promoting the viral defence (IL28B-3kbCC/K70R AA) (Table 1). These data are in agreement with Thomas et al (Thomas et al. Nature 461,798-801-2009) who showed a -3kb CC genotype in the 60% of patients who clear HCV.Therefore, they may suggest that waiting and watch approach should be advised in patients with hemoglobinopathy and favourable IL28B genotype.Tab.1Effects of IL28B genotype on HCV-RNA spontaneous clearanceHCV genotype-3kbC>T genotypeK70R genotypeHCVclearance 20/42 (47′6%)15/20 (75%)1bCCAA5/20 (25%)1bCTAGHCV persistence22/42 (52,4%)3/22 (13,7%)2a2cTTGG1/22 (4,5%)1bTTGG13/22 (59,1%)1bCTAG4/22 (18,2%)1bCCAA1/22 (4,5%)2a2cCCAG Disclosures:No relevant conflicts of interest to declare.

Suicide risk in hepatitis C and during interferon-alpha therapy: a review and clinical update

Chronic hepatitis C (CHC) affects over 170 million individuals worldwide and is a growing public health concern. Despite the availability of CHC treatment, specifically interferon-α and ribavirin, treatment of CHC is limited by concerns about psychiatric side effects including risks of suicide. Although depression has been the focus of neuropsychiatric complications from interferon-alpha (IFNα), emerging evidence has contributed to our understanding of IFNα-induced suicidal ideation and attempts. Using Pubmed, we performed a literature review of all English articles published between 1989 and April 1, 2010 on suicide in untreated and IFNα-treated patients with CHC. References in all identified review articles were scanned and included in our review. A total of 17 articles were identified. Studies have suggested that the first 12 weeks of IFNα therapy are the high-risk period. Moreover, the emergence of suicidal ideation can be linked to neuropsychiatric abnormalities, specifically serotonin depletion. Pretreatment with antidepressant treatment should be reserved for high-risk groups, as this may reduce the risk of depression and thus decrease the suicide risk indirectly. Although there is a paucity of literature on suicide and suicide risk during IFNα therapy for CHC, recent studies on IFNα-induced depression have provided some potential insights into suicide in this patient population. Further research examining the effects of pharmacological and nonpharmacological interventions on suicide risk during IFNα treatment is needed.

PTU-055 Safety and tolerability of combination therapy for chronic hepatitis C: the Leeds experience: Abstract PTU-055

Introduction Combination therapy is the mainstay of treatment for chronic hepatitis C (CHC). However, some patients report debilitating adverse events (AEs), which may limit efficacy due to need for dose reduction or discontinuation of therapy. We report tolerability and safety of combination therapy in normal clinical practice, in a large cohort of CHC patients treated in a single tertiary referral centre in Leeds, UK. Methods AE data for individuals receiving combination therapy for CHC were collected prospectively between February 2001 and May 2008. Premature discontinuation of therapy due to AEs was recorded. Effect of experiencing an AE on achieving sustained viral response (SVR) 6 months after treatment end was examined by univariate analysis, with an OR and 95% CI. The association between patient demographics, type of interferon (α-2a or 2b), duration of therapy, genotype, presence of cirrhosis and likelihood of experiencing AEs was explored using multivariate analysis, and results expressed as ORs with 95% CIs. Results During the study period 356 individuals with CHC commencing combination therapy had adverse events data recorded (231 (65%) male, mean age 42 years, range 21–73). 228 (64%) reported at least one AE (Abstract 055). Therapy was discontinued due to AEs in 56 patients. Six individuals experienced decompensation, but there were no deaths related to therapy. AEs did not alter likelihood of achieving an SVR (63% (144/228) in those with an AE vs 61% (78/128) in those without (OR 1.10, 95% CI 0.69 to 1.76)). No predictors of AEs were identified. Conclusion Data from this large cohort of CHC patients treated with combination therapy demonstrate >60% experience AEs, though most are minor, do not affect completion of therapy, and do not impact on SVR at 6 months.

PTU-057 Predictors of response to combination therapy for chronic hepatitis C: the Leeds experience

Introduction Combination therapy for chronic hepatitis C (CHC) achieves sustained viral response (SVR) in randomised trials. We studied factors predicting SVR 6 months after the end of treatment (undetectable viral load by PCR) in normal clinical practice, in a large cohort of CHC patients treated in a single tertiary referral centre in Leeds, UK. Methods Data for individuals receiving combination therapy for CHC were collected prospectively between February 2001 and May 2008. Age, gender, ethnicity, type of interferon (α-2a or 2b), genotype, presence of cirrhosis, body mass index (BMI), alcohol use (none vs any), serum ferritin, and history of intravenous drug use (IVDU) or psychiatric illness were collected prior to commencing therapy. Early discontinuation of therapy was also recorded. The association between these variables and achieving an SVR was explored by univariate and multivariate analysis, with ORs and 95% CIs. Data from individuals being re-treated for CHC were not analysed. Individuals defaulting follow-up with no SVR data at 6 months were classed as treatment failures. Results During the study period 394 individuals with CHC commenced combination therapy (257 (65%) male, mean age 42 years (range 21–74)). After univariate analysis SVR at 6 months was significantly more likely in younger patients (OR per year 0.96, 95% CI 0.94 to 0.98), with interferon α-2b (OR 1.61, 95% CI 1.00 to 2.58), in genotype 2 and 3 compared with genotype 1 (OR 3.52, 95% CI 1.47 to 8.44, and OR 3.51, 95% CI 2.23 to 5.54, respectively), and significantly less likely in those with biopsy-proven cirrhosis (OR 0.24, 95% CI 0.15 to 0.39), in those consuming any alcohol (OR 0.35, 95% CI 0.22 to 0.55), those with serum ferritin >250 (OR 0.26, 95% CI 0.15 to 0.46), and those discontinuing therapy early (OR 0.22, 95% CI 0.13 to 0.39). Following multivariate analysis effect of genotype, alcohol use, presence of cirrhosis, and early discontinuation of therapy on SVR remained significant. Gender, ethnicity, BMI, and prior history of IVDU or psychiatric illness had no effect on SVR at 6 months in any of our analyses. Conclusion Data from this large cohort of patients with CHC treated with combination therapy demonstrate lower SVR rates in those consuming alcohol and those with cirrhosis. The former should be advised to cease consuming alcohol prior to embarking on therapy, and the latter should be warned of the reduced likelihood of successful therapy. A prior history of IVDU or psychiatric illness should not preclude consideration of combination therapy.

A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-alpha treatment.

Interferon-alpha (IFN-alpha) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life. Defining relevant risk factors for IFN-alpha-induced depression is essential in order to identify prophylactic treatment strategies. The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-alpha-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-alpha and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment. Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-alpha-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations. 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-alpha therapy for CHC in a population-specific manner.

A Functional Serotonin Transporter Gene Polymorphism and Depressive Effects Associated With Interferon- α Treatment

Interferon-alpha (IFN-α) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life. Defining relevant risk factors for IFN-α-induced depression is essential in order to identify prophylactic treatment strategies. The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-α-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-α and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-α-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations. 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-α therapy for CHC in a population-specific manner.

Usefulness of liver biopsy in chronic hepatitis C

Major requirements for performance of liver biopsy (LB) are the benefits for the patient and the impossibility of having the same information by less invasive procedures. In the last two decades physicians have faced the difficult task of convincing a patient positive for hepatitis C, with minimal clinical or laboratory alterations to be submitted to LB in order to evaluate the status of the disease for therapeutic management. The characteristics of the needle used for percutaneous LB interferes with the accuracy of diagnosis. In chronic hepatitis C (CHC), validity is achieved with liver fragments about 25mm in length containing more than 10 portal tracts. Morbidity due to LB is mainly related to bleeding but death is very rare. Severe complications are also uncommon, increasing with number of passes and decreasing with experience of operator and ultrasound guidance. Although CHC is a diffuse disease, the various areas of the liver may not be equally affected and sampling errors are possible. Another potential limitation of LB is the discordance between pathologists in its interpretation. To replace LB, many panels of surrogate markers have been described, aiming to identify extent of fibrosis and inflammation. All of them have used LB as their “gold standard”. Liver biopsy continues to be the most reliable method to evaluate the possibility of therapy for CHC. Universal treatment of all patients with diagnosis of CHC would be ideal. But, there are mainly three drawbacks. Overall efficacy is as low as 50%, side effects are common and may be severe and treatment is prolonged and expensive. The acceptability of the biopsy by the patient is highly dependent on the physician’s conviction of its usefulness.