Standard Therapy For Chronic Hepatitis Research Articles

Tolerability of Erythrocyte Ribavirin Triphosphate Concentrations Depends on the ITPA Genotype.

Ribavirin (RBV) is an antiviral drug that is part of the current standard therapy for chronic hepatitis C (CHC). It is enzymatically converted to ribavirin triphosphate (RTP) that inhibits the activity of viral RNA polymerase, thereby preventing viral replication. However, one of its adverse effects includes hemolytic anemia that limits its application. The variant of ITPA (inosine triphosphatase), which dephosphorylates inosine triphosphate to inosine monophosphate, is a protective factor for RBV-induced anemia. RTP is an important metabolite required for ribavirin action. This study evaluated the time-dependent association of RTP concentrations in erythrocytes, RBV-induced toxicity, and virological response to RBV treatment for hepatitis C. A total of 28 Japanese patients with CHC were treated with RBV/peg-interferon/simeprevir or RBV/sofosbuvir and were genotyped for ITPA variants (rs1127354 and rs7270101). We measured RTP concentrations in erythrocytes in a total of 76 samples collected at 4, 8, and 12 weeks from the initiation of treatment. The ITPA rs1127354 variant was found in 7 patients. This was associated with significantly higher RTP concentrations in erythrocytes than in the wild-type patients (P < 0.001). Moreover, a significant correlation was observed between RTP concentrations and decline in hemoglobin (Hb) levels from baseline values in ITPA wild type and rs1127354 variant 12 weeks after treatment initiation (P < 0.01; r = -0.618 and -0.967, respectively). Multiple regression analysis revealed that ITPA genotype and erythrocyte RTP concentrations were major factors associated with reduced Hb levels in RBV therapy for CHC. However, we did not find any association between erythrocyte concentrations and virological response. The increased tolerability to RTP concentrations in erythrocytes in the ITPA variant rs1127354 plays a role in preventing RBV-induced severe anemia in this ITPA variant.

Drug therapies for chronic hepatitis C infection: a cost-effectiveness analysis.

Before 2011, pegylated interferon plus ribavirin was the standard therapy for chronic hepatitis C. Interferon-free direct-acting antiviral agents were then approved. Although these treatments appear to be more effective, they are substantially more expensive. In anticipation of the need for information regarding the comparative cost-effectiveness of new regimens in a recent therapeutic review, we conducted the analysis to inform listing decision in Canada. A state-transition model was developed in the form of a cost-utility analysis. Regimens included in the analysis were comprehensive. The cohort under consideration had a mean age of 50 years. The cohort was defined by treatment status and cirrhosis status. Inputs for the model were derived from published sources and validated by clinical experts. For each genotype 1 population, at least 1 of the interferon-free agents appeared to be economically attractive compared with pegylated interferon-ribavirin, at a willingness-to-pay of $50 000 per quality-adjusted life-year. The drug that was the most cost-effective varied by population. For genotype 2-4 population, the direct-acting antiviral therapies appeared not to be economically attractive compared with pegylated interferon-ribavirin for the treatment-naive; however, there were direct-acting antiviral therapies that appeared to be attractive when compared with no treatment for the treatment-experienced. Public health policy should be informed by consideration of health benefit, social and ethical values, feasibility and cost-effectiveness. Our analysis assists the development of reimbursements and policies for interferon-free direct-acting antiviral agent regimens for chronic hepatitis C infection by informing the last criterion. Considering the rapid development of treatments for chronic hepatitis C, further update and expanded reviews will be necessary.

Hepatitis C virus vaccine development: old challenges and new opportunities

Abstract Hepatitis C virus (HCV), an enveloped positive-sense single-stranded RNA virus, can cause chronic and end-stage liver diseases. Approximately 185 million people worldwide are infected with HCV. Tremendous progress has been achieved in the therapeutics of chronic hepatitis C thanks to the development of direct-acting antiviral agents (DAAs), but the worldwide use of these highly effective DAAs is limited due to their high treatment cost. In addition, drug-resistance mutations remain a potential problem as DAAs are becoming a standard therapy for chronic hepatitis C. Unfortunately, no vaccine is available for preventing new HCV infection. Therefore, HCV still imposes a big threat to human public health, and the worldwide eradication of HCV is critically dependent on an effective HCV vaccine. In this review, we summarize recent progresses on HCV vaccine development and present our views on the rationale and strategy to develop an effective HCV vaccine.

Role of vitamins in gastrointestinal diseases.

A tremendous amount of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to the standard therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the positive outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychologically accepted by patients as a natural compound with relative safety and low cost, their use should be encouraged in the fields where positive data are available.

New Therapeutic Agent for Chronic Hepatitis C: Direct Acting Agent

Peg-interferon and ribavirin has been the standard therapy of chronic hepatitis C for the past 15 years in Korea. However, the treatment paradigm is changing. Direct acting agents (DAAs) are oral pills that can be easily taken. In addition, DAAs are more effective and have less adverse reactions compared to the previously used drugs. Chronic hepatitis C is hard to treat because the virus is error-prone virus. Host immunity is helpless against the hepatitis C virus since it evades the host immunity through various complex mechanisms. There are 6 genotypes. Quasispecies can co-exist even in the same patients. The treatment strategy is based on the combination of the individual drug corresponding to each step of viral replication process. NS5B nucleosides are the most powerful and effective drug available until now. Other drugs with different mechanisms of action can be used to provide synergy. NS5A and NS5B inhibition drugs currently belong to the leading group amongst many DAAs. These drugs will soon be available in Korea. We have to know the merits and adverse drug reactions of the new drug.

Predicting the outcomes of combination therapy in patients with chronic hepatitis C using artificial neural network.

Background:Treatment with Peginterferon Alpha-2b plus Ribavirin is the current standard therapy for chronic hepatitis C (CHC). However, many host related and viral parameters are associated with different outcomes of combination therapy.Objectives:The aim of this study was to develop an artificial neural network (ANN) model to predetermine individual responses to therapy based on patient’s demographics and laboratory data.Patients and Methods:This case-control study was conducted in Tehran, Iran, on 139 patients divided into sustained virologic response (SVR) (n = 50), relapse (n = 50) and non-response (n = 39) groups according to their response to combination therapy for 48 weeks. The ANN was trained 300 times (epochs) using clinical data. To test the ANN performance, the part of data that was selected randomly and not used in training process was entered to the ANN and the outputs were compared with real data.Results:Hemoglobin (P < 0.001), cholesterol (P = 0.001) and IL-28b genotype (P = 0.002) values had significant differences between the three groups. Significant predictive factor(s) for each group were hemoglobin for SVR (OR: 1.517; 95% CI: 1.233-1.868; P < 0.001), IL-28b genotype for relapse (OR: 0.577; 95% CI: 0.339-0.981; P = 0.041) and hemoglobin (OR: 0.824; 95% CI: 0.693-0.980; P = 0.017) and IL-28b genotype (OR: 2.584; 95% CI: 1.430-4.668;P = 0.001) for non-response. The accuracy of ANN to predict SVR, relapse and non-response were 93%, 90%, and 90%, respectively.Conclusions:Using baseline laboratory data and host characteristics, ANN has been shown as an accurate model to predict treatment outcome, which can lead to appropriate decision making and decrease the frequency of ineffective treatment in patients with chronic hepatitis C virus (HCV) infection.

The success of treatment of chronic hepatitis C in opiate addicts in Clinical center of Vojvodina

Chronic hepatitis C is a disease with a high prevalence in the population of intravenous drug users. Serious clinical course of the disease, which can lead to cirrhosis of the liver with all its complications, has a large epidemiological and clinical significance. This study was aimed at assessing the success of antiviral treatment of chronic hepatitis C in intravenous drug users and defining indicators of successful treatment in this population. This retrospective study included 316 patients treated with standard therapy for chronic hepatitis C, pegylated interferon and ribavirin, at the Department of Infectious Diseases, Clinical Center of Vojvodina in Novi Sad in the period from January 2007 to December 2012. The patients were divided into a group of intravenous drug users (n = 163) and a group of other modes of transmission of hepatitis C virus (n = 153). The indicators of successful treatment were measured in both groups. A total 51.57% of the subjects belonged to the group of intravenous drug users. The therapy was successful in 87.15% of cases, while the success was achieved in only 53.47% of cases in the group of patients infected otherwise. The positive effect of therapy was associated with younger age, shorter duration of infection, low levels of fibrosis and a higher percentage of infected with hepatitis C virus genotypes 2 and 3. The population of intravenous drug users can be effectively treated with the standard therapy for chronic hepatitis C, even more successfully than the population infected in some other way.

Recent Advancement in the Treatment of Chronic Hepatitis C

Currently, the most widely prescribed standard therapy for chronic hepatitis C consists of pegylated-interferon combined with ribavirin. Although the response rate to interferon-based treatments has improved since interferon monotherapy was first combined with ribavirin, and then pegylated-interferon was adopted, patients eligible for this treatment are limited; the side effects are unbearable in some patients, and the response rates are still unsatisfactory for those who have unfavorable clinical features. Achievements in molecular research have led to the discovery of enormous molecules with anti-hepatitis C virus (HCV) activity. Telaprevir, boceprevir, simeprevir, and sofosbuvir have already been approved by the U.S. Food and Drug Administration and many new drugs are being evaluated in ongoing clinical trials. We review the clinical efficacy of approved new anti-HCV drugs, along with many promising treatment options under development. (Korean J Med 2014;86:563-569)

Drug-Drug Interactions in the Treatment of HCV Among People Who Inject Drugs

Boceprevir and telaprevir are inhibitors and substrates of the cytochrome P450 3A4 family. With the use of these HCV protease inhibitors as part of standard therapy for chronic hepatitis C genotype 1 infection, drug-drug interactions with multiple medications being inductors, inhibitors, or substrates of cytochrome P450 3A4 can be expected. Due to the complexity of these interactions, predicting the expected magnitude and sometimes even the direction of the effect has proven to be difficult. Pharmacokinetic studies should be carried out to evaluate drugs with clinical relevance and possible interactions. This review focuses on the data available regarding drugs that are frequently used in the setting of addiction or used by patients with addiction. In addition to highlighting relevant drug-drug interactions, alternative drugs that can be safely used are suggested.

Pegylated Interferon and Ribavirin in the Retreatment of Chronic Hepatitis C in Korea

Background/Aims Pegylated interferon (peginterferon) and ribavirin is the current standard therapy for chronic hepatitis C. The aims of this study were to evaluate the efficacy of peginterferon and ribavirin and to identify predictors of a sustained virological response (SVR) to the retreatment of chronic hepatitis C in Korea.MethodsThe clinical records of 91 patients with chronic hepatitis C who were retreated with peginterferon and ribavirin were retrospectively analyzed. None of the patients had previously attained a SVR, and the patients were categorized according to their previous responses (nonresponder, relapser, or inadequate treatment) to conventional interferon/ribavirin.ResultsThe overall SVR rate was 54.9%. Independent predictors of a SVR were genotypes 2 and 3, relapse, an adherence to peginterferon of over 80%, and an early virological response (EVR). For genotype 1 patients, an adherence to peginterferon of over 80% was an independent predictor of a SVR.ConclusionsPeginterferon and ribavirin therapy is effective for the retreatment of Korean chronic hepatitis C patients who have failed interferon/ribavirin, especially in patients with genotypes 2 and 3, relapse, an adherence to peginterferon over 80%, and an EVR. For genotype 1 patients, retreatment was effective in patients with an adherence to peginterferon over 80%.

Analysis of Associative Classification for Prediction of HCV Response to Treatment

objective of this research is the analysis of predicting the response for treatment in patient with hepatitis C virus. The Interferon Alfa (IFN) in combination with ribavirin (RBV) is used as a standard therapy for chronic hepatitis C (CHC), it is very expensive and accompanied with great side effects, with that it fails in more than half cases. For the prediction of treatment response, a knowledge discovery framework including two main phases: pre- processing and data mining was developed. In pre- processing phase, the cleaning and selection of suitable features from patients' data were done. In data mining phase the selected patients' features were mined using Associative Classification (AC) technique to generate a set of Class Association Rules (CARs). The most suitable rules from the generated CARs were selected to build a classifier, which predicts patients' response for treatment. Using our classification model, 220 patients treated with IFN plus RBV were analyzed, 92 patients resulted responders and 128 non- responders at the end of treatment and during the follow up. 170 cases had been used to train our intelligent models and 50 patients had been used to test the models. The experiment results showed that the proposed technique is an effective classification technique with high prediction accuracy reach up to 90%.

Study of the effect of antiviral therapy on homocysteinemia in hepatitis C virus- infected patients

BackgroundHepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease (CLD). About 80% of those exposed to the virus develop a chronic infection. Hyperhomocysteinemia, which is an independent risk factor for atherosclerotic vascular disease and thromboembolism, may develop in HCV-infected patients although altered alanine amino transferase (ALT) enzyme levels are generally associated with damage to liver cells. The gold standard therapy for chronic hepatitis C patients is pegylated interferon combined with an anti-viral drug (ribavirin). The current study aimed to investigate the effect of antiviral therapy on plasma homocysteine (Hcy) levels in HCV patients in addition to other parameters.Methods532 HCV-infected patients and 70 healthy controls were recruited for the study. All patients were subjected to laboratory investigations including HCV-RNA levels, complete blood cell counts, serum levels of homocysteine, ALT, alkaline phosphatase (ALP), lipid profile and liver ultrasonographic examination. The outcome of treatment with pegylated interferon α plus ribavirin treatment and sustained virologic response (SVR) was determined 6–9 months post-therapy.ResultsHyperhomocysteinemia was found in 91.35% of HCV-infected patients. The difference in plasma Hcy concentrations reached statistical significance between the patient and control groups. ALT, cholesterol and triglycerides (TGs) levels were found higher than normal in the patients group. After receiving a combined therapy for 24 weeks, 43.66% patients showed an SVR (responders); 30.98% patients were non-responders while 25.35% patients initially responded to therapy but again retrieved positive status of HCV infection six months post-therapy (relapse-cirrhotic patients). The mean levels of plasma Hcy, ALT and ALP were significantly reduced in responders within 10 weeks of therapy when compared with non-responders and relapse-cirrhotic patients.ConclusionElevated homocysteine levels in serum due to HCV infection can be reduced to normal range with the standard interferon α plus ribavirin treatment. This study highlights the significance of the measurement of serum homocysteine levels in the diagnosis and monitoring of HCV infection treatment in addition to other laboratory parameters.

Impaired STAT4 phosphorylation is associated with non-response to PEG-IFN plus Ribavirin treatment in chronic HCV Hepatitis patients

Background: The standard therapy for chronic hepatitis C (CHC) is combination of PEG- IFN and ribavirin that results sustained viral clearance in only half of HCV1 genotype patients. It is known that PEG-IFN induces upregulation of IFN-stimulated genes (ISG) transcription by activating the Jak-STAT pathway and promotes Th1 type cytokine production. While activated STAT4 regulates Th1 cell development, STAT6 is important in the activation of IL-4 and Th2 cytokine induction. Increased Th2 type cytokine production was associated with non-response to PEG-IFN. To investigate the underlying molecular mechanisms of non-response to PEG-IFN, we compared IFNalpha-induced STAT4/STAT6 signaling pathways in PEG-IFN responder and non-responder CHC patients.

T-52 Interferon-stimulated gene expression and IL28B genotype predict rapid viral response during standard therapy for chronic hepatitis C

T-52 Interferon-stimulated gene expression and IL28B genotype predict rapid viral response during standard therapy for chronic hepatitis C

Efficacy of Peginterferon and Ribavirin Combination Therapy of Chronic Hepatitis C: A Pooled Analysis

A combination of peginterferon and ribavirin is the standard therapy for chronic hepatitis C (CHC). However, the respective study has not been carried out in a large scale in Korea. The purpose of this study was to collect the studies that have been reported in Korea in order to analyze the therapeutic effect of combination therapy and compare to find racial difference. Twenty-eight papers related to the therapeutic effect of combination therapy in CHC patients were analyzed based on pooled analysis. Based on the analysis for genotype 1 in Korea, early virologic response (EVR), end of treatment response (ETR), and sustained virologic response (SVR) were 79.6% (125/157), 80.1% (166/207), and 62.7% (341/543). The EVR, ETR, and SVR for genotype 2 and 3 were 89.4% (119/133), 92.2% (203/220), and 84.1% (434/516). Data from other Asians showed that EVR and SVR for genotype 1 were 88.9% (290/326) and 64.4% (491/762) respectively and 88.8% (135/152), and 79.4% (151/190) for genotype 2 and 3 respectively. In Western, EVR and SVR for genotype 1 were 51.3% (1,981/3,860) and 42.4% (1,798/4,231) respectively, and for genotype 2 and 3 were 87.7% (350/399) and 77.8% (533/685) respectively. Based on the comparative analysis, no statistical difference in SVR between Koreans and other Asians (p=0.955) was observed; However, the SVR of Koreans was higher with significance than that of Westerns (p<0.001) On the other hand, there was no difference what so ever, in SVR for genotype 2 amongst the different races. The SVR of combination therapy for the Korean chronic hepatitis C patients was similar to other Asians but higher than Westerns.

Adding to the toolbox: Receptor tyrosine kinases as potential targets in the treatment of hepatitis C

Adding to the toolbox: Receptor tyrosine kinases as potential targets in the treatment of hepatitis C

Durability of sustained virologic response in chronic hepatitis C: analysis of factors related to relapse after sustained virologic response with peginterferon plus ribavirin combination therapy

Pegylated interferon plus ribavirin combination therapy has been the standard of therapy for patients with chronic hepatitis C. Although previous studies have reported long term durability after the sustained virologic response (SVR) with standard therapy for chronic hepatitis C, it is still unclear in Korea. The aim of this study was to evaluate the relapse rate and related factors after SVR to pegylated interferon therapy in Korean patients with chronic hepatitis C. A total of 119 chronic hepatitis C patients were treated with pegylated interferon plus ribavirin, and 73 patients achieved SVR (61.3%). Among 73 patients who achieved SVR, 68 patients (genotype 1, n=40; genotype non-1, n=28) were evaluated for virological response after SVR. SVR rate in genotype 1 and genotype non-1 were 52.5%, and 65.1%, respectively. Relapse after SVR occurred in 5 patients (7.4%) with genotype 1, and the median time to relapse from SVR was 10 months. Univariate analysis revealed that the dose reduction of pegylated interferon (p=0.005) and cirrhosis (p=0.03) were significantly associated with relapse. These results suggested that the relapse could occur even after SVR achievement in Korean patients with chronic hepatitis C, and the dose reduction of pegylated interferon during treatment or having cirrhosis may increased the risk for relapse.

Durability of a sustained virologic response in patients with chronic hepatitis C treated with peginterferon and ribavirin

A Sustained virologic response is durable in patients with chronic hepatitis C with peginterferon alfa-2a and ribavirin. Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, Abergel A, Pessoa MG, Lin A, Tietz A, Connell EV, Diago M. Gastroenterology 2010;139(5):1593-1601. The current standard therapy for chronic hepatitis C virus (HCV) infection is the combination of pegylated interferon and ribavirin. The ultimate goal of treatment in patients with chronic HCV infection is to completely eradicate HCV in infected hosts, and prevent liver-related morbidity and mortality. However, these goals are difficult to measure and it takes long time to assess the achievement of these goals. A sustained virologic response (SVR) has been used as a surrogate marker of these ultimate goals in treatment of chronic hepatitis C. An SVR is defined as undetectable serum HCV RNA at 24 weeks after the end of treatment. To be a useful surrogate marker, achievement of SVR should result in the reduction of liver-related morbidity and mortality, complete eradication of HCV in infected hosts, and no late virologic relapse. Achievement of SVR has been associated with improvement in liver histology and health-related quality of life, as well as a reduced risk of hepatocellular carcinoma and liver-related mortality.1-3 The survival of patients who achieved SVR was reported to be comparable to that of general population, matched for age and sex.4 However, the development of hepatocellular carcinoma was reported despite achievement of SVR in patients with chronic hepatitis C and advance fibrosis.5 There is some debate as to whether achievement of SVR results in complete eradication of HCV. In a study of 2089 patients with chronic hepatitis C from 3 clinical trials, hepatic HCV RNA was found to correlate with serum HCV RNA in all cases, and 98% of sustained virologic responders had undetectable hepatic HCV RNA.6 Several small studies have described patients who achieved SVR but have residual HCV RNA detected in peripheral blood mononuclear cells with highly sensitive reverse transcription and nested polymerase chain reaction assays.7,8 Whether these findings represent a replication-competent virus or have any clinical significance is unclear. Several small studies reported SVR achieved with conventional interferon alone or in combination with ribavirin was durable. In these reports, serum HCV RNA remained undetectable in 92-100% of patients who achieved SVR with 2 to 13 years of follow-up.4,5,9-12 However, there are limited data on the durability of SVR achieved with peginterferon in patients with chronic hepatitis C. Swain et al. studied the durability of SVR achieved with peginterferon in 1343 patients.13 They analyzed the durability of SVR in large cohort of patients who were enrolled in one of 9 randomized controlled clinical trials,14-22 which evaluated the efficacy of peginteferon alfa-2a alone or in combination with ribavirin. Total 1343 treatment-naive patients who achieved SVR and had at least one post-baseline HCV RNA evaluation were assessed. One thousand three hundred thirty one of 1343 patients (99.1%) remained HCV RNA undetectable in serum at mean of 3.9 years after completion of treatment. The durability of SVR in this study was independent of patient characteristics such as HCV mono-infection, HCV-HIV co-infection, or ALT level. The durability of SVR also appeared to be unaffected by the type of treatment. HCV RNA was detected in the serum of 12 patients who obtained SVR in their original studies at mean of 666 days after completing treatment. Among the 12 patients with reappearance of HCV RNA, there were no baseline or treatment factors associated with reappearance of HCV RNA including HCV genotype, sex, age, race, risk factor for infection, or baseline viral load. It was unknown whether these cases reflect relapse or re-infection because of the paucity of paired samples. The findings of this study were comparable with those reported from smaller studies with conventional interferon. There was one domestic report on the durability of interferon-based therapy in patients with chronic hepatitis C.23 In this study, 73 patients who achieved SVR with conventional interferon or peginterferon in combination with ribavirin were included. HCV RNA reappeared in 8 of 73 (11%), but persistent viremia remained only in one patient (1.4%). Transient positive tests probably represent false-positive test, and the durability of SVR in Korean patients with chronic hepatitis C appears to be similar with those reported in other studies. In conclusion, this study showed SVR achieved with peginterferon alfa-2a alone or in combination with ribavirin is durable in 99% of patients for at least 4 years after completion of therapy and is independent of patient or treatment characteristics.

Durability of Sustained Virologic Response in Chronic Hepatitis C: Analysis of Factors Related to Relapse after Sustained Virologic Response with Peginterferon Plus Ribavirin Combination Therapy

Pegylated interferon plus ribavirin combination therapy has been the standard of therapy for patients with chronic hepatitis C. Although previous studies have reported long term durability after the sustained virologic response (SVR) with standard therapy for chronic hepatitis C, it is still unclear in Korea. The aim of this study was to evaluate the relapse rate and related factors after SVR to pegylated interferon therapy in Korean patients with chronic hepatitis C.A total of 119 chronic hepatitis C patients were treated with pegylated interferon plus ribavirin, and 73 patients achieved SVR (61.3%). Among 73 patients who achieved SVR, 68 patients (genotype 1, n=40; genotype non-1, n=28) were evaluated for virological response after SVR.SVR rate in genotype 1 and genotype non-1 were 52.5%, and 65.1%, respectively. Relapse after SVR occurred in 5 patients (7.4%) with genotype 1, and the median time to relapse from SVR was 10 months. Univariate analysis revealed that the dose reduction of pegylated interferon (p=0.005) and cirrhosis (p=0.03) were significantly associated with relapse.These results suggested that the relapse could occur even after SVR achievement in Korean patients with chronic hepatitis C, and the dose reduction of pegylated interferon during treatment or having cirrhosis may increased the risk for relapse.

Amino acid substitutions in core and NS5A regions of the HCV genome can predict virological decrease with pegylated interferon plus ribavirin therapy

The current standard therapy for chronic hepatitis C is pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, it has been reported that amino acid (aa) substitutions in the core region, as well as the IFN-sensitivity-determining region (ISDR), were predictive of non-virological response (NVR), sustained virological response (SVR) and early virological response. Despite the importance of these two predictive factors for combination therapy, their interaction is poorly understood. A total of 117 patients who were treated with PEG-IFN-α2b plus RBV combination therapy were selected for participation in this study. We determined the aa sequences in the core region and ISDR by direct sequencing and analysed them along with clinical data to identify predictive factors for therapeutic response. The aa sequences in the core region and γ-glutamyl transpeptidase (GTP) levels were associated with SVR and NVR, but aa sequences in the ISDR were not. However, substitutions at both aa 70 and aa 91 in the core region without substitutions in the ISDR and higher levels of γ-GTP were independent predictive factors for NVR. Wild-type aa 70 and aa 91 in the core region, higher platelet counts and lower levels of γ-GTP were independent predictive factors for SVR. These results indicate that analyses of aa substitutions in both the core region and the ISDR are useful for predicting the effectiveness of combination therapy, and could help to avoid therapy exposure for patients who have a low probability of SVR.