Predictor Of Sustained Virological Response Research Articles

IL-28B - Predictor of Sustained Virological Response for IFN-based Regimens in Chronic Hepatitis C and Criteria for Optimizing DAAs Indication

Chronic viral infections affecting the liver represents a global burden for medical comunities. More than 170 million individuals are infected chronically with hepatitis C virus (HCV), this accounting about 2-3% of the world’s population. Despite numerous progresses aquired in viral pahogenesis and treatment, chronic hepatitis C management is influenced by a multitude of factors. Interleukin IL-28 beta subunit (IL28B) demonstrated to be involved in both sustained virological response (SVR) to treatment, but even with spontaneous viral clearance without any therapy. In the era of direct antiviral agents (DAAs) we aimed to find out what was the real influence of IL28B phenotypes over the response to Peg-IFN and Ribavirin treatment in patients with chronic hepatitis C, many of theses being non-responders or relapsers, and as consequence, to optimize the referal of patients to more expensive and efficient treatments. In a retrospectively manner, we analyzed the IL28B phenotype and its influence over the rapid viral response (RVR), early viral response (EVR) and sustained viral response (SVR), in 250 patients HCV treated patients. We made correlations between the treatment response rates and the IL28B polymorphism.TT phenotype was correlated negatively with all parameters studied, while CC phenotype was correlated with the best response rates. We concluded that IL28B phenotypes interfere with the EVR and SVR rates, IL28B phenotype being an independent prognostic factor for antiviral treatment response in our patient groups, and according to this characteristics, we created the premise to optimize the patients referal to expensive therapies as DAAs. Keywords: hepatitis C virus, IL-28 beta subunit,viral treatment

Implications of soluble E-cadherin level of antiviral treatment in patients with chronic hepatitis C virus infection

Background and aimsSoluble E-cadherin (sE-cadherin) has been observed elevated in patients with various diseases, and implicated in the occurrence and development of those diseases. The implications of sE-cadherin in chronic hepatitis C virus (HCV) infection are still unclear. The purpose of this study is to explore the significance of sE-cadherin in chronic hepatitis C infection and the correlation with treatment response. Methods87 chronic HCV infected patients and 60 healthy subjects were enrolled in this study. Blood samples from patients receiving the combined treatment of pegylated interferon-a (Peg-IFN-α) with ribavirin (RBV) were collected before treatment, during 4th, 12th therapy weeks, end of the treatment, and 24 weeks post-therapy. Plasma sE-cadherin level was detected by enzyme-linked immunosorbent assay (ELISA) and the relationship between sE-cadherin and antiviral treatment outcome was analyzed. ResultsPlasma sE-cadherin concentrations of Chronic HCV infected patients were significantly higher than that of healthy controls. A strong correlation between sE-cadherin level and the HCV viral load, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and also glutamyl transpeptidase (GGT) level was detected. Chronic HCV infected patients achieving rapid virological response (RVR) and sustained virological response (SVR) had lower baseline sE-cadherin concentrations compared with the non-RVR and non-SVR groups respectively. Univariate and multivariate regression analyses suggested that baseline plasma sE-cadherin level was predictive of therapeutic effect in patients with chronic HCV infection. ConclusionBaseline sE-cadherin level could be considered as an independent predictor of SVR with Peg-IFN-α plus ribavirin therapy in the Chinese Han population chronic HCV infection patients. Effective antiviral therapy might restore sE-cadherin at physiological levels.

The predictors of sustained virological response with sofosbuvir and ribavirin in patients with chronic hepatitis C genotype 2.

Background/AimsReal-world, clinical practice data are lacking about sofosbuvir/ribavirin (SOF/RBV) treatment of Korean patients with hepatitis C virus genotype 2 (HCV GT2) infection. This study investigated the efficacy and safety of SOF/RBV in Korean patients with HCV GT2 infection and clinical factors predicting sustained virological response 12 weeks (SVR12) after the end of SOF/RBV treatment.MethodsA total of 181 patients with HCV GT2 with/without cirrhosis were treated with SOF/RBV for 16/12 weeks. Rapid virological response (RVR) was defined as non-detectable HCV RNA at 4 weeks.ResultsThe RVR rate was 80.7% (146/181), the end of treatment response rate was 97.8% (177/181) and the SVR12 rate was 92.8% (168/181). Of eight patients with relapse, four did not achieve RVR. Three patients had a history of hepatocellular carcinoma (HCC). Multivariable analysis showed that RVR (p = 0.015) and no previous history of HCC (p = 0.007) were associated with SVR12. Factors significantly contributing to RVR included cirrhosis, creatinine concentration, and pre-treatment HCV RNA level. SVR12 rate was significantly higher in RVR (+) than RVR (–) patients (95.2% vs. 82.9%, p = 0.011) and also significantly higher in patients without than with a history of HCC (94.1% vs. 72.7%, p = 0.008). During treatment, 80/181 patients (44.2%) experienced mild to moderate adverse events, with 32 (17.7%) requiring RBV dose reductions due to anemia.ConclusionsSOF/RBV treatment was effective and tolerable in HCV GT2 patients. RVR and no previous history of HCC were positive predictors of SVR12.

Real-world results of direct-acting antivirals use for the treatment of chronic hepatitis C in old patients.

Old people with chronic hepatitis C (HCV) were considered a difficult-to-treat category with more frequent adverse events until recently. Interferon-free direct-acting antivirals (DAAs) improved treatment adherence and quality of life of old patients. In this study, we aimed at reporting the real-world efficacy and safety of DAAs, in addition to predictors of sustained virological response (SVR) in old chronic HCV population. This is a prospective observational intention-to-treat analysis that included old chronic hepatitis C genotype-4 patients (> 65years) treated in a single specialized viral hepatitis treatment center in Egypt. Treatment regimens were allocated according to national guidelines for treatment of hepatitis C. Primary outcome was undetectable HCV-RNA at 12-week post-treatment by PCR. Secondary outcomes were identification of predictors of SVR and assessment of safety related issues. Our study included 864 patients (64% females) with mean age of 67.7 ± 2.8years. Overall SVR rate was 98.9% while SVR rates for sofosbuvir/daclatasvir/ribavirin, paritaprevir/ombitasvir/ritonavir/ribavirin, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir/ribavirin, sofosbuvir/simeprevir/daclatasvir/ribavirin, sofosbuvir/simeprevir, interferon/sofosbuvir/ribavirin and sofosbuvir/ribavirin were 100%, 100%, 100%, 100%, 100%, 99.3%, 98% and 94.2%, respectively. DAAs were well tolerated. None of the patients discontinued the treatment due to adverse effects. Higher albumin, higher platelet count, lower bilirubin and lower stage of fibrosis were among predictors of favourable response. Different DAAs regimens were safe and effective in old Egyptian patients with chronic HCV.

Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals

Introduction and aimData on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. Material and methodsA prospective cohort of adult patients with CHC treated in French general hospitals. ResultsData from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. ConclusionsThe high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.

Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals

Introduction and aim: Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. Methods: A prospective cohort of adult patients with CHC treated in French general hospitals. Results: Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were ≥ 64 years old (fourth quartile) and 133 were ≥73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.2-92.5 %) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261, 8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. Conclusions: The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.

Assessment of efficacy and safety of PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C

Patients with chronic hepatitis C‐associated liver disease are of an older age in southern Taiwan. PEGylated interferon‐based therapy could reduce the risk of cirrhosis and hepatocellular carcinoma and improve survival. We assessed the efficacy and safety of combination therapy with PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C. A total of 88 consecutive patients with chronic hepatitis C treated with combination therapy were analyzed retrospectively to identify factors associated with a sustained virological response (SVR). These patients were divided into two groups according to age: elderly patients ≧ 60 years (n = 43) and patients 50 to 59 years (n = 45). We compared baseline characteristics, adherence 80/80/80, dose modification, discontinuation, and adverse events profiles between these two groups. We further compared virological response rates stratified by genotype. The factors associated with an SVR were determined by total patients and different age groups. In the intent‐to‐treat analysis, the SVR rate was 61.8%. The SVR rate of elderly patients tended to be superior to that of total patients. Patients aged ≧ 60 years had a higher proportion of concomitant chronic disease, dose modification, clinical events with anorexia, depression, leucopenia, and anemia than those aged 50 to 59 years. Total patients with genotype 1 tended to have a lower SVR rate than nongenotype 1 (P = 0.067). Total patients with nongenotype 1 had a significantly higher rapid virological response (RVR) rate than genotype 1 (P = 0.009). In patients aged ≧ 60 years, the relapse rate of genotype 1 was higher than that of nongenotype 1 (P = 0.034). After stratification by HCV genotype 1, high viral load, and achievement of an RVR, the SVR rates remained similar between the two groups. The most strongly predictive factors of an SVR of total patients were the achievement of an RVR (OR: 49.744; 95% CI: 6.979‐354.574; P < 0.001), followed by breakthrough (OR: 0.018; 95% CI: 0.002‐0.195; P = 0.001). The factor mostly predictive of an SVR in age ≧ 60 years group was achievement of an RVR (OR: 12.779; 1.430‐114.180; P = 0.023). Elderly patients had a greater frequency of adverse events. Genotype 1 is independently associated with lower SVR and RVR rates and high relapse rates. Attainment of an RVR is the most powerful predictor of SVR in elderly patients.

Influence of pegylated interferon and ribavirin on insulin resistance and metabolic factors in chronic hepatitis C

Abstract Background In this study it was aimed to evaluate the effect of pegylated interferon alfa-2a/2b and ribavirin, which are used for treatment of chronic hepatitis C (CHC), on insulin resistance and metabolic factors. Materials and methods A total of 104 CHC patients aged 20–75 years with available serum insulin data at 0 and 48 weeks, and hepatitis C virus (HCV)-RNA data at 0, 12, 24, 48 and 72 weeks were included in the study. All clinical para-meters were assessed according to the therapy response. Results Among 104 patients, sustained virologic response (SVR) was achieved in 55 cases. A statistically significant difference was noted between SVR and non-SVR groups regarding γ-glutamyltranspeptidase (GGT), insulin level plus homeostasis model assessment (HOMA) score and insulin resistance at week 48, log HCV-RNA and stage of fibrosis. Conclusion Insulin resistance is accepted to have a negative effect on SVR. Insulin resistance may improve once SVR is achieved. Presence of IR at week 48 has been found associated with SVR. In this context, it can be advocated that insulin resistance at week 48 may be a predictive factor for prediction of SVR at week 72.

Advanced liver fibrosis effects on the response to sofosbuvir-based antiviral therapies for chronic hepatitis C.

Sustained virological response (SVR) rates for the treatment of chronic hepatitis C virus (HCV)-infected patients have drastically improved with the use of direct-acting antiviral (DAA) therapies; however, a small minority of patients still fails to eradicate the virus. We analyzed factors associated with SVR in DAA therapy and the effect of age and liver fibrosis on treatment response. Nine hundred and eighteen patients with chronic HCV infection were treated with 24 weeks of daclatasvir plus asunaprevir (DCV + ASV) or 12 weeks of sofosbuvir plus ledipasvir (SOF + LDV), ombitasvir, paritaprevir plus ritonavir (OMB + PTV + r) or sofosbuvir plus ribavirin (SOF + RBV). Multivariate logistic regression analysis was used to identify factors associated with SVR. The effect of age and liver fibrosis on SVR was analyzed. The overall SVR rate was 95.4% (876 of 918 patients), and rates by DAA regimen were 93.4%, 95.7%, 100%, and 95.0% in DCV + ASV-treated, SOF + LDV-treated, OMB + PTV + r-treated, and SOF + RBV-treated patients, respectively. Patients older than 75 years achieved a similar SVR rate with those aged 75 years or younger (96.4% and 94.8%, respectively). Multivariate logistic regression analysis identified absence of DAA therapy history (odds ratio [OR], 3.868 for presence; P = 0.002) and FIB-4 index of less than 3.25 (OR, 5.042 for ≥3.25; P = 0.001) as independent predictors for SVR. SVR rates were significantly lower in patients with FIB4 index of 3.25 or more compared with those with less than 3.25, especially in sofosbuvir-based therapies such as SOF + LDV-treated or SOF + RBV-treated patients. Both older and younger patients respond similarly to DAA therapy. Advanced liver fibrosis affects the virological response to sofosbuvir-based therapy.

DOES INSULIN RESISTANCE IMPAIR THE VIROLOGICAL RESPONSE TO PEGINTERFERON/RIBAVIRIN IN CHRONIC HEPATITIS C GENOTYPE 3 PATIENTS?

Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.

Analysis of Host and Viral-Related Factors Associated to Direct Acting Antiviral Response in Hepatitis C Virus Patients.

Hepatitis C virus (HCV) signifies an important health issue as it is a globally prevalent pathogen and poses a great threat to human health. Direct antiviral therapy became a landmark in treatment against chronic HCV infection as they have proven to increase sustained virological response (SVR) rate, provide shortened and simplified regimens. This study aimed to evaluate efficacy of Sofosbuvir and classify factors of treatment success and their function in therapy continuation decision. We studied host and viral factors in 310 patients who received Sofosbuvir (DAA) at a dose of 400 mg daily along with ribavirin 10 mg/kg body weight for 24 weeks and followed by 12 weeks after completion of treatment. A total of 302 patients (97.42%) showed end-of-treatment response. However, 8 patients (2.58%) were virological nonresponders and 286 patients (94.70%) achieved SVR. Among 310 HCV positive, the percentage of viral genotype 3-infected patients was 89.6%, whereas only 10.32% were affected by HCV genotype 1. Multivariable analysis showed that baseline HCV RNA (≤8 × 106 IU/mL vs. >8 × 106 IU/mL) [95% confidence interval (CI), odds ratio (OR) 3.0, 2.0 to 8.4; p = 0.004], age (<50 vs. ≥50 years) (95% CI, OR 1.9, 3.0 to 10.1; p = 0.03), liver texture (normal liver vs. coarse) are related to virological response. None of the patients included in the study has S282T substitution in NS5b of HCV. No significant difference in response was observed in patients with different genotypes of rs12979860. Liver texture, age, and viral load are predictors of SVR. In this real-life data no substitution of S282T in NS5b was observed related to failure of therapy. Oral Sofosbuvir generally has a high tolerance and can effortlessly beat the safety concerns of past regimens.

THU-306 - Rapid virological response, as a predictor of sustained virological response of Sofosbuvir and Ribavirin in Korean patients with genotype 2 chronic hepatitis C virus infection

THU-306 - Rapid virological response, as a predictor of sustained virological response of Sofosbuvir and Ribavirin in Korean patients with genotype 2 chronic hepatitis C virus infection

Platelet count is associated with sustained virological response rates in treatments for chronic hepatitis C.

Background/AimsThis study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection.MethodsThis retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment.ResultsSVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 103 /µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 103 /µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001).ConclusionsYoung age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

Predictors of treatment efficacy and liver stiffness changes following therapy with Sofosbuvir plus Ribavirin in patients infected with HCV genotype 2

While the combination therapy of ribavirin (RBV) and sofosbuvir (SOF) is effective in genotype 2 HCV infection, the predictors of treatment efficacy and posttreatment changes in α-fetoprotein (AFP) and liver stiffness (markers of hepatocellular carcinoma), remain unclear. In this study, 302 patients with chronic HCV genotype 2 infection were treated with SOF (400 mg) plus RBV (400-1000 mg; based on body weight) for 12 weeks. We evaluated the efficacy and safety of treatment, as well as measured serum AFP, liver stiffness, and controlled attenuation parameter (CAP, a surrogate marker of steatosis) at baseline and within 48 weeks of treatment completion. The intention-to-treat analysis showed a sustained virological response (SVR) rate of 95.7%. None of the patients discontinued treatment due to side effects. Multivariate analysis identified pretreatment (no treatment with interferon), level of AFP (AFP; <10 μg/L), and RBV/body weight (BW) ratio (≥9.0 mg/kg) as independent predictors of SVR. The SVR rate in patients with two predictors of poor response (AFP ≥10 μg/L and RBV/BW ratio <9.0 mg/kg) was significantly lower than in other patients. In the SVR group, posttreatment AFP level and liver stiffness were significantly lower than at baseline. CAP tended to be higher after treatment than at baseline in all patients. SOF plus RBV combination therapy achieved a high SVR rate and was safe in HCV genotype 2 infected patients. Treatment reduced AFP levels and improved liver stiffness, but increased CAP.

Direct-acting antiviral treatment of chronic HCV-infected patients on opioid substitution therapy: Still a concern in clinical practice?

There is limited real-world information on the effectiveness of antiviral treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAA) in people on opioid substitution therapy (OST). This study compared sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST and non-OST patients in the German Hepatitis C-Registry (DHC-R). National multi-centre prospective real-world registry (German Hepatitis C-Registry, DHC-R). Non-OST patients comprised patients with former/current drug use (non-OST/DU) and patients never consuming drugs (non-OST/NDU). A total of 254 medical centres in Germany, including 123 centres providing OST. A total of 7747 chronic HCV patients started DAA therapy (739 OST and 7008 non-OST; 1500 non-OST/DU; 5508 non-OST/NDU) patients. Five hundred and twenty-eight OST and 5582 non-OST patients had completed antiviral therapy and at least one follow-up documentation [intention-to-treat (ITT) population]. Study outcomes were SVR, proportion of LTFU and safety of treatment. SVR (ITT) was documented in 85% (450 of 528) OST patients versus 86% (969 of 1126) in non-OST/DU (P=0.651) and 92% (4113 of 4456) non-OST/NDU (P<0.001) patients. Independent predictors for SVR (P<0.01 in multivariate analysis) included HCV genotype non-3 [adjusted odds ratio (aOR)=1.11; 95% confidence interval (CI)=1.07-1.15], female sex (aOR=1.59; CI=1.30-1.94), platelet counts >90×109/l (aOR=1.51, CI=1.14-2.01), cirrhosis (aOR=0.77; CI=0.62-0.96) and patient group (OST/DI (aOR=0.58; CI=0.42-0.78); non-OST/DU (OR: 0.63; CI=0.50-0.78). In per-protocol analysis (PP), SVR rates were ≥94% in all patient groups. In OST the proportion of LTFU was higher (10.2%) than in non-OST/DU (8.5%) and non-OST/NDU (3.2%, P<0.001) patients. Independent factors for LTFU (P<0.01) were HCV genotype non-3 (aOR=0.92; CI=0.88-0.96), female sex (aOR: 0.7; CI=0.53-0.92), pre-treatment (aOR=0.64; CI=0.50-0.82), OST/DI (aOR=3.35; CI=2.35-4.78) and non-OST/DU (aOR=2.38; CI=1.80-3.14). In Germany, direct-acting antiviral treatment of former or current drug users with or without opioid substitution therapy can achieve equally high sustained virological response rates as in patients with no history of drug use.

Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India.

Background & objectives:The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection.Methods:Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon α-2a 180 μg per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients).Results:There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74).Interpretation & conclusions:The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.

Higher expression of inhibitory CD158b and CD158e NK cell receptor and age predicts treatment response in children with chronic hepatitis C

Treatment with pegylated interferon-α and ribavirin (PEG–IFN/RBV) is the only choice for chronic hepatitis C (CHC) in children. Natural killer (NK) cells were described to play a vital role in CHC. The aim of this study was to analyze the expression of peripheral blood NK cell receptors in their relation to PEG–IFN/RBV treatment response. Study included 26 children with CHC—13 boys, age range 13.42 ± 3.28 years. Blood for biochemical, virological and cytometric testing was taken for evaluation prior to the antiviral treatment. NK cell receptors were detected by flow cytometry and the results were presented as proportion of cells and mean fluorescence intensity (MFI). Therapy consisted of PEG–IFNα-2b (60 μg/m2 s.c 1×/week) and RBV (15 mg/kg p.o. daily). Treatment duration was response-related and varied from 12 to 72 weeks. Rapid virological response (RVR) was evaluated in the 4th week and sustained virological response (SVR) 6 months after completion of the therapy. RVR children were younger (11.67 ± 3.74 vs 15.35 ± 2.42; p = 0.001) and displayed higher CD158b (3.58 ± 0.16 vs 3.45 ± 0.13; p = 0.038) and CD158e expression (4.33 ± 0.21 vs 4.03 ± 0.16; p = 0.039). Density of CD158b (logMFI = 3.68 ± 0.22 vs 3.36 ± 0.16; p = 0.036) and CD158e expression was significantly higher (4.37 ± 0.14 vs 4.12 ± 0.21; p = 0.046) and NKG2D expression significantly lower (97.50 ± 3.46 vs 94.92 ± 5.93; p = 0.049) in SVR children. SVR children were also significantly younger (12.40 ± 3.66 vs 15.13 ± 2.83; p = 0.003). Significance of the age of patients, and expression of CD158b and CD158e were confirmed in univariate and multivariate analysis. Age of patients is negatively related to RVR and SVR. NK cell phenotype with higher expression density of CD158b and CD158e receptor was a positive predictor of SVR.

The treatment outcome and impact on blood transfusion demand of Peg-interferon/ribavirin in thalassemic patients with chronic hepatitis C.

Hepatitis C virus (HCV) prevails in patients with thalassemia. We aimed to investigate the efficacy, safety, and impact on red blood cells (RBC) transfusion demand of pegylated interferon (Peg-IFN)/ribavirin therapy in thalassemic patients with HCV. This retrospective study included 18 thalassemic patients (16 with HCV-1b, one HCV-1b/2b, and one HCV-2b) and 54 consecutive sex- and genotype-matched controls. Patients with HCV-2, or HCV-1 or mixed HCV-1/2 with lower viral loads plus rapid virological response (RVR) received 24-week Peg-IFN/ribavirin; whereas HCV-1 or mixed HCV-1/2 with higher viral loads or without RVR received 48-week regimens. The rates of RVR, complete early virological response, and sustained virological response (SVR) in thalassemic patients were 72.2% (13/18), 94.1% (16/17), and 77.8% (14/18), which resembled those of controls (63.0%, 94.4%, and 81.5%, respectively). RVR was the only significant factor associated with SVR in thalassemic group, and was the strongest predictor for SVR among both groups (OR/95% CI=14.7/2.20-98.6), followed by male gender and lower viral loads. More proportion of interleukin-28B-TT carriage were observed among thalassemic patients with SVR versus non-SVR (78.6% vs. 50.0%). Thalassemic patients experienced significantly less 80/80/80 adherence, more ribavirin reduction and serious adverse events than controls. Notably, there was a decreased post-treatment RBC transfusion demand versus baseline in thalassemic patients with SVR (5.21 vs. 5.64units/month, p=0.05), but not in those without SVR (6.33 vs. 6.56units/month, p=0.54). Peg-IFN/ribavirin was effective and tolerable for thalassemic HCV patients. Successful antiviral therapy might have extra benefit of reducing the post-treatment transfusion demand.

The Sustained Virologic Response and Adverse Effects of Peg Interferon Alfa and Ribavirin in the Treatment of Patients with Chronic Hepatitis C: A Study from Iran

Background: Hepatitis C infection is a worldwide problem. In Iran, hepatitis C virus (HCV) infection prevalence is about 1-2%. A combination therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a standard treatment, but our aim was to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating patients infected with HCV in Iranian context. M aterials and Methods: This study is a cross sectional conducted among 98 HCV infected patients who were admitted to Labbafinezhad Hospital (Tehran, Iran) for treatment from April 2014 to September 2016. Patients were medicated with Peg Interferon Alfa (INFα) and Ribavirin (RBV). Lab tests were monitored through the study and dose modification was done. We also assessed treatment responses at the defined time points. The incidences of adverse events were determined either. We investigated independent predictors of sustained virologic response (SVR) in the participants. Finally, data were gathered and statistical analysis was completed. R es ults: Eighty-eight percent of patients were male and 11.2% were female. Mean age was 43.44 years. Patients were mostly male, single, with nongovernmental business and low level of education. Risk factors were known to be addiction with non-injectable substances and phlebotomy. Myalgia, fatigue and malaises were the most common complications and suicide intention was the least one. SVR was estimated 76.7%. AST and ALT were significantly reduced in treatment period. Conclusion: Peg INFα and RBV are effective in treating HCV infection.

Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals.

In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7)mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60)mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28mg/L was the optimal lower cut-off for achieving SVR and 3.61mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin<10g/dL). In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR.