Therapy For Chronic Hepatitis Research Articles

SAR study of bisamides as cyclophilin a inhibitors for the development of host-targeting therapy for hepatitis C virus infection

The therapy of chronic hepatitis C virus infections has significantly improved with the development of direct-acting antivirals (DAAs), which contain NS3/4A protease, NS5A, and NS5B polymerase inhibitors. However, mutations in specific residues in these viral target genes are associated with resistance to the DAAs. Especially inhibitors of NS3/4A protease and NS5A, such as grazoprevir and velpatasvir, have a low barrier to resistant mutations. As a result, the mutations influence the virological outcomes after DAA treatment. CypA inhibitors, as host-targeted agents, act on host factors to inhibit HCV replication, exhibiting a high resistance barrier and pan-genotype activities against HCV. Therefore, they can be developed into alternative, more effective anti-HCV agents. However, CypA inhibitors are natural products and analogs. Based on previous studies, bisamide derivatives were designed and synthesized to develop a novel class of CypA inhibitors. Bisamide derivative 7c is a promising compound with potent anti-HCV activity at subtoxic concentrations. Surface plasmon resonance experiments revealed that 7c directly binds to CypA. All these studies indicated that the derivative 7c is a potent CypA inhibitor, which can be used as a host-targeted agent in combination with other antiviral agents for anti-HCV treatment.

HCV GENOTYPES AND ITS ASSOCIATION WITH RESPONSE TO TREATMENT

BACKGROUND & OBJECTIVE: primary Hepatitis C is a serious public health problem and is the cause of liver cirrhosis, hepatocellular carcinoma (HCC), and numerous end-stage liver disease manifestations. The management of hepatitis C is to preclude liver cirrhosis, lessen the risk of hepatocellular carcinoma or hepatoma, and curing the extra hepatic diseases. Initially, interferon was the cornerstone for treating hepatitis C, but due to its cumbersome complications, route of administration, and limited treatment access, many patients showed noncompliance. New therapies for chronic hepatitis C have been introduced based on direct antiviral effects. Several genotypes of hepatitis C have been discovered and they are responsive to different antiviral therapies. Our objective was to assess the genotypic distribution of HCV in our local setup and their pattern of response to different combination of anti-viral therapies by assessing the sustained viral response (SVR) after 12 weeks post-treatment. To determine the most prevalent genotype of hepatics C virus in our population and pattern of the response of multiple genotypes to different antiviral regimens.
 METHODOLOGY: It is a cross-sectional study conducted for duration of six months and recruited those patients whose polymerase chain reaction (PCR) was found positive for hepatitis C virus at Islamabad Diagnostic Center. We analyzed 100 patients, both children and adults. Patients were assessed for different genotypes and then different combinations of antiviral treatments were administered. Their clinical data, hematological parameters and viral load before and after treatment were also analyzed.
 RESULTS: In a total of 100 positive hepatitis C virus-infected patients, 55% were females and 45% males. The frequencies of genotypes observed were 91 %, 06%, and 03% of genotype 3, 1a, and 1b respectively. 51 out of 91 patients with type 3 genotype, who were on antiviral therapy of sofosbuvir and ribavirin, all of them achieved SVR. 30 out of 91 patients with type 3 genotype were treated with sofosbuvir alone, the percentage of failure to achieve SVR in them was 6.7%. Treatment failure percentage of 10% was observed when a combination of Interferon (INF) alpha and ribavirin was used in type 3 genotype. Remaining six patients with type 1a and three patients of type 1b genotype achieved SVR with different regimens used.
 CONCLUSION: Although the increased load of HCV in our setup is an alarming situation the prevalence of type 3 genotype is a blessing in disguise. The success of sustained viral response after various combinations of direct antiviral therapy and interferon-free treatment is hope for the ultimate cure of the disease and avoidance of debilitating side effects related to interferon.

Can We Predict the Response to Interferon: A Therapy in Chronic Hepatitis C Patients Using Anti-Interferon-A Antibody Levels?

Can We Predict the Response to Interferon: A Therapy in Chronic Hepatitis C Patients Using Anti-Interferon-A Antibody Levels?

Tenofovir plus entecavir combination therapy for chronic hepatitis B with nucleos(t)ide analogue failure

Objectives: Currently, both entecavir (ETV) and tenofovir (TDF) are recommended first-line therapy for chronic hepatitis B treatment due to good tolerance, lower side-effect profile and high genetic barrier. However, mutations that may develop in the polymerase gene during treatment may result treatment failure. In this study, we aimed to evaluate the efficacy and virologic response of ETV plus TDF combination therapy in chronic hepatitis B patients with suboptimal response to nucleos(t)ide analogues (NAs) monotherapy. Methods: A total of 813 patients who were followed-up with the diagnosis of chronic hepatitis B and who were treated with TDF or ETV monotherapy were screened. Patients who had a partial or non response to monotherapy during at least 12 months and who was the presence of serum HBV-DNA levels ≥ 2000 IU/mL at the time of initiation of the ETV plus TDF combination therapy were included. Results: Ten (1.2%) patients (9 TDF, 1 ETV) were identified to have had partial response (50%) or breaktrough (40%) or virologic rebound (10%) to monotherapy. The median age was 36.8 years (range, 22-55 years), and 5/10 (50%) patients were male. Of 10 patients, nine of achieved undetectable HBV-DNA (< 15 IU/mL) levels (50% of in 6 months and 90% of in 18 months) with combination therapy. One patient showed no response. Conclusions: Our results suggest that combination therapy is superior to the antiviral change in treatment failure with NAs. In addition, it is important to conduct HBV drug resistance analyzes to prevent false drug change in treatment.

High body mass index hinders fibrosis improvement in patients receiving long-term tenofovir therapy in hepatitis B virus-related cirrhosis.

Long-term suppression of hepatitis B virus with tenofovir (TDF) induces fibrosis regression, and repeated liver stiffness (LS) measurement can indicate the improvement of fibrosis. We aimed to investigate predictors for LS improvement assessed by changes in patients receiving long-term TDF therapy in chronic hepatitis B (CHB) with liver cirrhosis. CHB patients with histologically proven liver cirrhosis who received TDF as the first-line therapy from 2012 to 2015 were recruited. LS and controlled attenuation parameter (CAP) measurements were repeated at baseline and 3years after therapy. Liver stiffness improvement was defined as a drop of LS value ≥30% from the baseline. A total of 131 patients were enrolled (mean age 51.4% and male 64.9%). After 3years of TDF therapy, the mean LS value significantly improved (from 14.7 to 8.6kPa, P<.001), and 96 (73.3%) patients have achieved LS improvement. Predictors associated with improvement of LS were low body mass index (BMI), HBeAg positivity, and low CAP value at baseline. In multivariate analysis, low BMI was a single factor independently associated with LS improvement (odds ratio 0.680, 95% CI 0.560-0.825, P<.001). Patients with BMI<23.5, had a 1.96 times more chance of achieving LS improvement compared to those with BMI≥23.5 (90.1% vs. 46.0%, P=.001). High BMI was a single significant factor hindering the fibrosis improvement in patients receiving long-term TDF therapy in CHB with liver cirrhosis. Life style modification and BMI reduction should be encouraged to enhance fibrosis improvement.

Role of Ribavirin in the Era of Direct–Acting Antiviral Therapies of Chronic Hepatitis C

ABSTRACT Background The efficacy of adding ribavirin (RBV) to direct antivirals (DAAs) in HCV treatment is still debatable, with allegations of insecure profiles. Objectives To evaluate safety and efficacy of RBV in the era of DAAs in chronic HCV Egyptian patients. Methods In this cohort retrospective study, data of 847 HCV patients treated with different regimens of DAAs with or without RBV were recruited between June 2017 and September 2018. Cases were categorized into five groups: non-cirrhotic (318), compensated (196), decompensated liver cirrhosis (53), post liver transplantation (30), and 250 treatment experienced patients. All patients’ demographics and laboratory characteristics were evaluated at baseline, week4, 12, 24 of treatment. Ribavirin was prescribed or banned outside international guideline recommendations of HCV treatment in cases assembled from the private sector.Results: No statistically significant difference between RBV and non-RBV treated patients was documented regarding SVR12 (97.2%, 97.8%) respectively in the whole cohort (p 0.509). On grouping, adding RBV was only significant in the treatment experienced patients (96.8%, 85% in RBV and non-RBV regimens respectively) (p 0.001). Adding RBV to DAA regimens was generally associated with modest adverse events particularly anemia (8.5%), and hepatic decompensation (jaundice and ascites) (0.3%). Bilirubin, INR, and platelet counts all were found to be the most independent predictors of SVR achievement by multivariate analysis (p ≤ 0.05).Conclusion: RBV may still have an augmenting role in treatment experienced patients; permitting effectual shortening of therapy particularly in patients with cirrhosis, with modest side and adverse consequences.

Results of Direct-Acting Antiviral Therapy in Chronic Hepatitis C Patients Undergoing Hemodialysis

Results of Direct-Acting Antiviral Therapy in Chronic Hepatitis C Patients Undergoing Hemodialysis

Clinical parallels and experience of antivira l therapy in chronic hepatitis with polycystic ovary syndrome

Background. Despite the progress made in the treatment of chronic hepatitis C (CHC), there remain many unsolved problems in the treatment of patients infected with the 3rd virus genotype. This fact is mainly associated with the presence of hepatocyte steatosis due to the formation of local insulin resistance. Another important medical and social problem is polycystic ovary syndrome (PCOS), patogenetically associated with insulin resistance. Application of metformin in females to reduce insulin resistance can improve the results of antiviral therapy.Material and methods. Overall 81 females with CHC and PCOS were included in original study. The 1st group (35 patients) received metformin in dose of 20 mg/kg of body weight per day as preliminary and concomitant treatment in addition to antiviral therapy. In 14 patients of this group steatosis was revealed. In another subgroup (21 patients) steatosis was not revealed. The 2nd group (46 patients) received antiviral therapy only. Patients of this group were divided into two subgroups by presence (17 patients) or absence (29 patients) of hepatic steatosis. Interferon-α2b in a standard dose of 3 million IU3 times per week in combination to ribavirin 13 mg/kg/day for 24 wks was applied as antiviral therapy. The period of the subsequent follow-up was 24 wks.Results. Patients with hepatic steatosis had higher biochemical and histological scores of activities. In the groups of patients receiving metformin a higher incidence of a sustained virological response was observed. Additional application of metformin did not aff ect the safety profile of antiviral therapy.Conclusions. Women with CHC with the 3rd genotype and PCOS, who took metformin, had a significantly higher frequency of sustained virological response with an equal safety profile.

Incidence and predictors of hepatocellular carcinoma beyond year 5 of entecavir therapy in chronic hepatitis B patients.

PURPOSE: The study compared the incidence and predictors of hepatocellular carcinoma (HCC) within and beyond year 5 of entecavir (ETV) therapy. The study enrolled 1397 CHB patients who were naïve to nucleos(t)ide analogue (NA) treatment and had received ETV monotherapy for more than 12months. The cumulative incidences of HCC at 3, 5, and 10years of ETV treatment were 4%, 9.1%, and 15.8%, respectively. In the entire cohort, the annual incidence rates of HCC were 2.28% within the first 5years and 1.34% within 5-10years of therapy. The incidences of HCC did not differ significantly within and beyond 5years of ETV therapy (p = 0.53), including patients with cirrhosis (p = 0.85) and without cirrhosis (p = 0.47). At year 5 of treatment, the multivariate analysis showed that the fibrosis-4 (FIB-4) index and alpha-fetoprotein (AFP) levels were independent risk factors for HCC development beyond year 5. The 10-year cumulative incidences of HCC beyond year 5 in the high-risk group (FIB-4 > 2.20 and AFP > 3.21ng/mL) and low-risk group (FIB-4 ≤ 2.20 and AFP ≤ 3.21ng/mL) were 48.7% and 0%, respectively. APA-B score at 12months and year 5 had a higher C-index for the prediction of HCC beyond year 5 than the PAGE-B at baseline and year 5 (p = 0.003 and p = 0.039, respectively) CONCLUSIONS: The HCC incidence tended to decrease but did not change significantly within and beyond 5years of ETV therapy. The FIB-4 index and AFP levels at year 5 were predictive of HCC development beyond year 5 of ETV therapy.

EFFICACY OF SOFOSBUVIR PLUS VALPATASVIR BASED THERAPY IN THE TREATMENT OF TREATMENT NAIVE CHRONIC HEPATITIS C GENOTYPE-3 IN KASHMIR.

Abstracts&#x0D; Objectives: Direct acting antivirals (DAAs) have dramatically changed our approach towards management of chronic hepatitis C by yielding a high sustained virological response (SVR). Genotype-3 is the most common genotype found in Kashmir (Northern India) besides having an aggressive nature with increased risk of steatosis and hepatocellular carcinoma. We assessed the efficacy and safety of sofosbuvir plus valpatasvir based therapy in chronic hepatitis C genotype-3 infection in Kashmiri population.&#x0D; Aims and objectives: An observational, prospective, open label, hospital based study was carried over a period of two years which included 230 treatment naïve chronic hepatitis-C genotype-3 patients. Patients were divided in two groups. Group-A: Non-cirrhotics who received sofosbuvir (400 mg daily) with valpatasvir (100 mg) in fixed–dose combination for 12 weeks. Group B included CPT class A cirrhotics who received sofosbuvir (400mg daily) with valpatasvir (100 mg daily) and weight based ribavarin for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.&#x0D; Results and observations: We observed 98.57 % (138/140) SVR 12 in non-cirrhotics who received valpatasvir plus sofosbuvir treatment regimen. Cirrhotics who received Sofosbuvir plus valpatasvir with ribavirin observed SVR of 96.6 % (87/90). All patients tolerated the drug regimens well without any serious adverse effect.&#x0D; Conclusion: Once daily oral Sofosbuvir plus valpatasvir based fixed dose rerimen is highly efficient and safe in treatment of both cirrhotics and non-cirrhotic hepatitis C patients.&#x0D; Keywords: Direct acting antivirals; sustained virological response; Genotype; chronic hepatitis C

Fatty liver is not independently associated with the rates of complete response to oral antiviral therapy in chronic hepatitis B patients.

Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are common liver diseases. Concurrent NAFLD may affect antiviral treatment outcomes in CHB patients. The aim of this study is to investigate the impact of NAFLD on complete viral suppression ([CVS], HBV DNA<20-100IU/mL) and/or biochemical response ([BR], ALT of≤25U/L for females; 35U/L for males) in CHB patients who received oral antiviral therapy. A retrospective study of 555 treated CHB patients (187 NAFLD; 368 non-NAFLD) from 2000 to 2016 at a USA medical centre. NAFLD was diagnosed by imaging and/or histology after ruling out secondary causes of hepatic steatosis. The majority of patients were male (60.7%), Asian (87.56%) and HBeAg-negative (66.7%). NAFLD patients compared to non-NAFLD were more likely HBeAg negative (74.3% vs 62.8%, P=.02), hypertensive (33.2% vs 22.8%, P=.009) and male (67.4% vs 57.3%, P=.02) with a higher mean BMI (25.4±4.3 vs 23.8±4.0kg/m2 , P<.001). Both cohorts achieved similar rates of CVS (86% vs 88%) and BR (38% vs 41%) during the follow-up of up to 60months (P>.05), but NAFLD had higher cumulative rates of CVS+BR, compared with non-NAFLD patients (32.5% vs 22.8%, P=.03). In multivariate analyses, NAFLD was not independently associated with CVS and/or BR outcomes. Receipt of entecavir or tenofovir (vs older therapies) and lower baseline HBV DNA or higher ALT were positively associated with achieving CVS or BR. Concomitant NAFLD had no impact on the long-term rates of CVS and/or BR in treated CHB patients.

Impact of Direct Acting Antiviral Therapy for Hepatitis C Virus Infection on Recurrence of Hepatitis C Virus Related Hepatocellular Carcinoma

Abstract Background hepatocellular carcinoma is the fifth most common tumor worldwide and the second most common cause of cancer-related death with a male-to-female predominance greater than 2:1. The presence of cirrhosis represents a key risk factor for the development of HCC. The prevalence of cirrhosis among patients with HCC has been estimated to be 85%-95% and the HCC incidence rate among patients with cirrhosis has been shown to be 2%-4% per year. HCV infection is a leading cause of liver cirrhosis and hence the development of HCC. Egypt has the highest HCV prevalence worldwide; with estimated rate of 10% of Egyptians between 15 – 59 years as reported by the Egyptian Health Issues Survey (EHIS) in 2015. Aim of the Work the aim of this study was to evaluate the impact of Direct Acting Antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection on recurrence of HCV related HCC after intervention. Patients and Methods this study was conducted on 50 patients with previously treated HCC who were treated for HCV infection using direct acting antiviral agents after confirming HCC regression and response to different treatment modalities and were followed for one year after antiviral treatment. A control group of another 50 patients with cured HCC who didn’t receive DAA therapy was included in the study to compare the recurrence rate in both groups and its relation to the antiviral therapy. Results the two groups didn’t differ as regards age, sex, biochemical profile, AFP, CBC and child score. The results of the study came to show an HCC recurrence rate of 38% in patients who received direct acting antiviral therapy after HCC intervention versus 62% in those who didn’t receive antiviral therapy. Conclusion direct acting antiviral drugs didn’t show to increase the risk of HCC recurrence in comparison to the control group. Yet it did not abolish it. So, close follow up of patients with HCC receiving antiviral therapy is highly recommended.

Entecavir versus Tenofovir for the Prevention of Hepatocellular Carcinoma in Treatment-Naïve Patients with Chronic Hepatitis B in Korea: A Retrospective Cohort Study with Nationwide Claims Data

Background: Preventing hepatocellular carcinoma (HCC) is a major concern of antiviral therapy in chronic hepatitis B. There are conflicting reports about the effects of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on HCC prevention. Here, we assessed these two antivirals on prevention of HCC. Methods: A retrospective cohort study was conducted using Korean Health Insurance Review and Assessment Service database. We included treatment-naive 55 488 adults who started ETV or TDF between 2013 and 2017. The ETV and TDF groups were 1:2 matched on the basis of age, sex, comorbidities, hospital type, and year of the index date. Patients were followed until December 2018. The outcome was the development of HCC. Findings: The matched participants (18496 in the ETV and 36992 in the TDF group) was followed for a mean of 41·2 months. The incidence of HCC was not significantly different between the ETV (1·46 per 100 patient-years [PY]) and the TDF group (1·36 per 100 PY) (hazard ratio, 0·93; 99% confidence interval [CI], 0·84 to 1·03). Interpretation: In this study, we could not find ETV treatment resulted in a higher rate of HCC than TDF among patients with chronic hepatitis B. Funding Statement: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: The authors stated: None exist. Ethics Approval Statement: The HIRA provide the claims data with concealed individual identification of patients. This study was approved by the Institutional Review Board of HIRA (approval number: B2019-025). Informed consent from patients was waived by the Board.

Timing disparity of hepatocellular carcinoma (HCC) recurrence in a patient receiving interferon and subsequent direct antiviral agent (DAA) therapy for chronic hepatitis C

Timing disparity of hepatocellular carcinoma (HCC) recurrence in a patient receiving interferon and subsequent direct antiviral agent (DAA) therapy for chronic hepatitis C

Sarcoid-like syndrome as a complication of the combined antiviral therapy of chronic hepatitis C1b genotype using Russian pegylated interferon

A description of the clinical case of a rare complication of combination therapy of chronic hepatitis C - lung sarcoid syndrome, the formation of noncaseating granulomas, and the involvement of several intrathoracic lymph nodes in the process of using Russian interferon alpha 2b.

48 weeks outcome after cessation of nucleos(t)ide analogue therapy in chronic hepatitis B patients

Introduction and objectiveThe aim of the present study was to investigate the significance of serum HBsAg levels in treatment cessation of nucleoside analogues (NAs) in patients with chronic hepatitis B (CHB) infection. MethodsIn 158 CHB patients with long-term NAs treatment, 74 patients were in HBeAg negative and had a HBsAg level <1500IU/mL, 36 of whom were informed and consented to cease NAs. HBsAg, HBV DNA and liver function were examined in the 1st, 3rd, 6th, 9th and 12th month after treatment cessation. ResultsThe sustained response rate was 88.89% (32/36) within one year after NAs cessation. Sub-group analysis was based on HBsAg levels of patients with NAs cessation, there was no relapse case in 11 patients whose HBsAg <50IU/mL, and the negative predictive value (NPV) was 100%. Seroconversion of HBsAg occurred in 3 patients. 2 patients from 21 cases whose HBsAg was between 50IU/mL and 1000IU/mL relapsed. 2 of 4 patients whose in HBsAg >1000IU/mL relapsed. HBsAg of patients with a sustained response decreased slowly. In contrast, HBsAg levels increased gradually in relapsed patients, and the increase of HBsAg was precedent to relapses of HBV DNA and ALT. Multivariate analysis suggested that only HBsAg level showed a close correlation with HBV DNA relapses. ROC curve analysis suggested that the increase of HBsAg level in the 3rd and 6th month after NAs cessation had a great predictive value for relapses. ConclusionMonitoring of base line HBsAg level can predict outcomes of NAs cessation in HBeAg-negative chronic hepatitis B. HBsAg <50IU/mL has higher predictive values of better sustained responses in HBeAg-negative CHB patients.

Predict of the development of lipid distress syndrome in patients with a sustained response to antiviral therapy of chronic hepatitis C

The aim. is to develop a method, for predicting the development of lipid, distress syndrome in patients with a sustained, response to antiviral therapy of chronic viral hepatitis C on the basis of clinical and laboratory data. Materials and. methods . The outcomes of lipid, distress syndrome were studied in 235 patients with a sustained vi-rological response to antiviral therapy of chronic hepatitis C during the follow-up period, from 1 to 10 years. Results. On the basis of discriminant analysis of the data of complex examination of 135 patients, a discriminant model of predicting the development of lipid distress syndrome in patients with a sustained response to antiviral therapy of chronic hepatitis C. On the basis of the data of the survey of other 100 patients, cross-checking the accuracy of the prediction. was carried out. Conclusion. Developed, diskriminantnaja model allows by identifying 5 of biochemical and. immunological parameters of blood (low-density lipoproteins cholesterol, homocysteine, interleukin. 4 and. 10, TNF) to predict the development of lipid distress syndrome in patients with sustained response to antiviral therapy for chronic hepatitis С . The sensitivity, specificity, predictive value of positive and. negative results of forecasting and precision index developed forecasting model of Fisher discriminant lipid, distress syndrome equal 100%. The proposed, method, should, be used, in clinical practice to predict development of lipid, distress syndrome in patients with sustained, response to antiviral therapy for chronic hepatitis C.

Therapy for Chronic Hepatitis E Virus Infection-Current Recommendations and Future Aspirations.

Therapy for Chronic Hepatitis E Virus Infection-Current Recommendations and Future Aspirations.

Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response.

Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1–5% of patients who achieved an SVR after treatment with interferon. We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy. The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment and 70 CH patients were assessed using microarray analysis. We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning. Twenty-five of 69 patients had HCC recurrence. The expression of four exosomal miRNAs predicted HCC recurrence with 85.3% accuracy. Fifteen of 70 patients had HCC occurrence. The expression of four exosomal miRNAs predicted the onset of HCC with 85.5% accuracy. The expression patterns of miR-4718, 642a-5p, 6826-3p, and 762 in exosomes were positively correlated with those in the liver, and downregulation of these miRNAs induced cell proliferation and prevented apoptosis in vitro. Aberrant expression of four miRNAs, which was used for prediction, was associated with HCC onset after HCV eradication. Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC.

Новые направления в терапии хронического гепатита В

Новые направления в терапии хронического гепатита В