Antiviral Therapy In Patients Research Articles

FRI-270 - Antiviral therapy in patients with chronic hepatitis C related hepatocellular carcinoma responding to palliative treatment

FRI-270 - Antiviral therapy in patients with chronic hepatitis C related hepatocellular carcinoma responding to palliative treatment

The influence of hepatic steatosis on the success of antiviral therapy for chronic hepatitis C

Background/Aim. Chronic hepatitis C and liver steatosis often appear simultaneously in the same person, and steatosis can lead to worsening of liver disease and reducing the success of the treatment of chronic hepatitis C. Treatment of one disease can influence and cause favorable impact on treatment of other diseases. The aim of this study was to determine the incidence of liver steatosis in patients with chronic hepatitis C and to examine the impact of steatosis of the liver and other predictors on the success of antiviral therapy for chronic hepatitis C. Methods. The study included 123 patients with chronic hepatitis C treated with pegylated interferon alfa 2a in combination with ribavirin. The patients were divided into two groups based on the presence of cirrhosis: the group I consisted of 43 (34.9%) patients with steatosis and the group II consisted of 80 (65.1%) patients without liver steatosis. The success of the treatment was evaluated on the basis of the stable virological response. Results. The presence of steatosis was determined in 34.96% of the patients. The overall success of antiviral therapy was found in 74.79% of the patients. The success of antiviral therapy was present in 62.79% of the patients with hepatic steatosis, and in 81.25% the patients without steatosis (p < 0.05). The success of antiviral treatments was seen in 80.95% of the patients with hepatic steatosis and the genotype of hepatitis C virus 3. The predictors of antiviral therapy success for chronic hepatitis C in our study were patient's age, duration of infection, genotype 3, steatosis and severe fibrosis or cirrhosis. Conclusion. Liver steatosis is often present in patients with chronic hepatitis C. It has negative impact on the efficacy of antiviral therapy in patients with infection with genotype non-3 hepatitis C virus. Therefore, hepatic steatosis in these patients must be eliminated or treated prior to application of antiviral therapy.

THU-274 - Lack of clinical benefit of direct acting antiviral therapy in patients with compensated hepatitis C virus-related cirrhosis

THU-274 - Lack of clinical benefit of direct acting antiviral therapy in patients with compensated hepatitis C virus-related cirrhosis

THU-220 - Early regression of liver fibrosis evaluated by non-invasive methods after successful antiviral therapy in patients with HCV genotype 1b compensated cirrhosis

THU-220 - Early regression of liver fibrosis evaluated by non-invasive methods after successful antiviral therapy in patients with HCV genotype 1b compensated cirrhosis

Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study.

The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome.

Factors affecting the purpose suppressive antiviral therapy for patients with recurrent genital herpes

Factors affecting the purpose suppressive antiviral therapy for patients with recurrent genital herpes

Impact ofIFNL4rs12979860 and rs8099917 polymorphisms on response to Peg-Interferon-α and Ribavirin in patients with congenital bleeding disorder and chronic hepatitis C

The aim of this study was to determine whether two polymorphisms of the human interferon lambda 4 (IFNL4) gene (rs12979860 and rs8099917) can predict sustained virologic response (SVR) following antiviral therapy in patients with inherited bleeding disorder and chronic hepatitis C (CHC). This retrospective study was conducted on 294 patients with congenital bleeding disorder and CHC who were treated with Peg-Interferon-α (PegIFN) and Ribavirin (RBV). Baseline patient and viral parameters were measured and analyzed statistically to assess their combined and individual contributions to SVR prediction. The most prevalent variants of rs12979860 and rs8099917 identified among the study patients were CT (45.9%) and TT (57.6%), respectively. Overall, SVR was achieved in 69% of the study patients. The rate of SVR was lower in patients with HCV genotype-1 than in those with HCV genotype-3 (62% vs 88%; P<.001; OR=0.23). Multivariate analysis of SVR predictors in patients with HCV genotype-1 infection included age (<24years), BMI (<25), absence of cirrhosis, HCV RNA level (<400000IU/mL), rs8099917 TT and rs12979860 CC, all of which were associated with a higher SVR rate. In HCV genotype-3 infection, only rs12979860 CC was significantly associated with SVR. These results demonstrate that polymorphisms of the IFNL4 gene are highly associated with SVR to PegIFN and RBV combination therapy in patients with a congenital bleeding disorder and CHC. Assessment of rs12979860 and rs8099917 genotypes can guide physicians in choosing an optimal treatment regimen, including less expensive therapies that may only be available in many geographic locales.

The effects of the insulin resistance index on the virologic response to entecavir in patients with HBeAg-positive chronic hepatitis B and nonalcoholic fatty liver disease.

PurposeTo further observe and verify the effect of nonalcoholic fatty liver disease (NAFLD) on the response to antiviral therapy in patients with chronic hepatitis B (CHB) and investigate the relationship between the virologic response and insulin resistance.Patients and methodsA retrospective study was adopted and 61 NAFLD patients with HBeAg-positive CHB were included as the observation group (group A), and 64 patients with simple CHB were included as the control group (group B).ResultsAfter 12 weeks of treatment with entecavir, the total virologic response rate in group A was statistically significantly lower than that in group B (P<0.05). During weeks 24–96, the difference was not statistically significant (P>0.05). In weeks 48 and 96, there was no significant difference in the HBeAg seroconversion rates between the two groups (P>0.05). In weeks 12 and 24, there was also no significant difference in the alanine transaminase (ALT) normalization rate between the two groups (P>0.05). Then, in weeks 48 and 96, the ALT normalization rate of group A was obviously lower than that of group B (P<0.05). Group A patients were divided into group A1 (≤M) and group A2 (>M) according to the median value (M=2.79) of the baseline homeostatic model assessment method insulin resistance levels. In weeks 48 and 96, the ALT normalization rate of group A1 was significantly higher than that of group A2 (P<0.05). The correlation coefficient (r) of the baseline homeostatic model assessment method insulin resistance level and the severity of fatty liver in group A was 0.426 (P=0.001).ConclusionNAFLD cannot affect the long-term total virologic response rate and HBeAg seroconversion rate in CHB patients treated with entecavir but can reduce the long-term biochemical response rate, which has a positive correlation with the severity of fatty liver and the insulin resistance index.

The outcome of thyroid disease induced by interferon plus ribavirin in patients with chronic hepatitis C

Objective To explore the long-term outcome of thyroid disease occurred during and after peg-interferon plus ribavirin therapy (PR therapy) in patients with chronic hepatitis C (CHC). Methods CHC patients admitted to Henan People′s Hospital during January 2009 to December 2012 treated with peg-interferon plus ribavirin were included in this study. The thyroid functions were tested before treatment, at week 12, week 24, week 48, week 72 of treatment, and at week 24, week 48, week 96, week 144 after end of treatment. Thyroid function test frequency was increased according to the patients′ test results and medication was registered. Measurement data was analyzed using t test and count data was compared using chi square test or Fisher exact probability test. Results A total of 358 patients was included with mean age of (43±12) years (range 18 to 65 years), of whom 200 were male and 158 were female. There are 300 cases (83.8%) with HCV genotype-1 infection, 56 cases (15.6%) with genotype-2 infection and 2 cases (0.6%) with genotype 3 infection. Eighty out of 358 patients (22.3%) developed thyroid disease, among whom 71 cases (88.75%) were diagnosed with autoimmune thyroiditis and 9 cases (11.25%) were non-autoimmune thyroiditis. At week 144 after end of treatment, 21 (29.6%) cases with autoimmune thyroiditis completely recovered and 9 cases with non-autoimmune thyroiditis fully restored. The comparison between two groups had statistical significance (F=16.69, P=0.00). Patients were divided into non-thyroid disease and thyroid disease groups. The were no significant differences of baseline viral load, HCV genotype, transaminase levels and age between the two group (all P>0.05). The differences of gender, baseline levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and treatment outcome were statistically significant (all P<0.05). Conclusions Interferon-induced autoimmune thyroiditis could not be completely reversed. Some patients develop chronic thyroiditis and require long-term drug therapy. Patients with positive TPOAb and TgAb induced by interferon have high risk of developing Hashimoto′s thyroiditis and Graves′disease during follow-up. Appropriate treatment for thethyroid disease induced by interferon does not affect the antiviral treatment. Clinicians should monitor the thyroid function during and after antiviral therapy in patients with CHC. Key words: Hepatitis C, chronic; Thyroid diseases; Interferon; Thyroid Autoantibodies

Nucleos(t)ide analogs improve long-term prognosis in patients with chronic hepatitis B-associated liver failure.

Chronic hepatitis B-associated liver failure (CHB-LF) is associated with high mortality. Antiviral therapy with nucleoside and nucleotide analogs (NUCs) has been reported to improve the short-term prognosis of patients with CHB-LF. However, the long-term effects of the therapy remain unclear. We undertook a cohort study to investigate the long-term effect of NUC-based antiviral therapy in patients with CHB-LF. A total of 976 patients with CHB-LF were enrolled between January 2001 and December 2009 at the Liver Disease Center of Ningbo No. 2 Hospital (Ningbo, China). The patients were divided into the NUC treatment group (n = 412) and control group (n = 564). The propensity score matching method was used to match the patients between the two groups to equilibrate the covariates. Survival analysis was carried out using the matched samples. The Cox proportional hazard model was used for the analysis of prognostic factors. After propensity matching, 262 pairs were successfully matched. No statistically significant difference was observed in the baseline characteristics of the matching pairs (P >0.05). The long-term survival rate and survival duration of the NUC treatment group were higher than that of the control group (P <0.05). Gender, age, Model for End-stage Liver Disease values, cholinesterase levels, white blood cell counts, hepatic encephalopathy, concomitant infection, and treatment with NUCs were found to be the independent factors associated with long-term prognosis. Antiviral therapy with NUCs may reduce the mortality rate and improve the long-term prognosis of patients with CHB-LF.

Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis

Direct-acting antivirals have become widely used for patients with chronic hepatitis C virus infection with decompensated cirrhosis. Virological responses are excellent and early improvements in liver function, at least in a proportion of patients, have been observed but the longer term impact of viral clearance on end-stage liver disease complications is unclear. Prospective study of patients with decompensated cirrhosis who received 12weeks of all-oral direct-acting antivirals through the English Expanded Access Programme. Endpoints were deaths, liver transplantation, hepatocellular carcinoma, serious decompensation events, sepsis or hospitalisations, and MELD scores between start of therapy to 15months post-treatment start. An untreated cohort of patients was retrospectively studied over 6months for comparison. Amongst 317/406 patients who achieved sustained virological response at 24weeks post-treatment, there were 9 deaths (3%), 17 new liver cancers (5%), 39 transplantations (12%) and 52 with serious decompensations (16%), over 15months. When compared to the first six months from treatment start and to untreated patients, there was a reduction in incidence of decompensations [30/406 (7%) in months 6-15 and 72/406 (18%) in months 0-6 for treated patients vs. 73/261 (28%) in untreated patients]. There was no significant difference in liver cancer incidence (10/406 (2.5%) in months 6-15 and 17/406 (4%) in months 0-6 for treated patients vs. 11/261 (4%) in untreated patients). This study suggests that antiviral therapy in patients with decompensated cirrhosis led to prolonged improvement in liver function, with no evidence of paradoxical adverse impact nor increase in liver malignancy. This is a report of a large group of patients in England who have hepatitis C virus (HCV) infection with advanced liver disease. They have been treated with new anti-HCV drugs, which cured the infection in the majority. This study looks at their outcomes a year following treatment, in terms of deaths, cancers and other complications of advanced liver disease. We conclude that in most patients anti-HCV treatment is beneficial even in advanced liver disease.

Efficacy and cost-effectiveness of antiviral therapy in patients with advanced hepatitis B virus-related hepatocellular carcinoma treated with sorafenib.

e15622Background: The incidence of hepatocellular carcinoma (HCC) in China accounts for 55% of cases worldwide; 85% of Chinese HCC cases are hepatitis B virus (HBV)-related. The aim of this study w...

Early decrease of liver stiffness after initiation of antiviral therapy in patients with chronic hepatitis C indicates that lower cut-off values for liver stiffness are appropriate for monitoring liver fibrosis after initiation of antiviral treatment

Early decrease of liver stiffness after initiation of antiviral therapy in patients with chronic hepatitis C indicates that lower cut-off values for liver stiffness are appropriate for monitoring liver fibrosis after initiation of antiviral treatment

소라페닙 투여 간세포암종 환자에서 항바이러스제 치료의 생존이득

Background/Aims: Nucleos(t)ide analogues (NAs) help reduce the recurrence rate after the curative treatment of hepatitis B related hepatocellular carcinoma (HCC). Sorafenib has been shown to improve survival of advanced HCC patients. Whether antiviral therapy with NAs could help such patients is unknown. Our aim is to investigate the usefulness of antiviral therapy for advanced-stage HCC treated with sorafenib. MethodsWe performed a retrospective cohort study in advanced-stage HCC patients treated with sorafenib between June 2007 and December 2013. Patients in group A (the nonantiviral therapy group) were treated with sorafenib alone. Those in group B (the antiviral therapy group) were treated with sorafenib and NAs. Progression-free survival (PS) and overall survival (OS) were compared between these two groups. ResultsFinally, 23 patients in group A and 40 patients in group B were enrolled in the study. The mean number of days of treatment with sorafenib was 79 (34-231) days and 96 (33-449) days for group A and B, respectively (P=0.286). The mean PS of group A and B was 97 (14-449) days and 51 (0-461) days, respectively (P=0.068). The OS was 154 (44-741) days in group A and 138 (30-1,025) days in group B (P=0.665). PS and OS showed no significant difference between the two groups. ConclusionsThis study shows that there was no significant survival gain of using antiviral therapy in patients with advanced-stage HCC treated with sorafenib. In consideration of costeffectiveness, antiviral therapy may be not mandatory. (J Liver Cancer 2016;16:23-30)

Systemic inflammation and compromised intestinal barrier during successful treatment of HIV infection

The relationship between immunity disorders, destruction of intestinal barrier and development of systemic inflammation during antiviral therapy in patients with HIV infection is a topical issue in terms of suppression of virus replication and reduction of its role in the pathological process. Blood of HIV-infected patients given antiretroviral therapy (n = 21) and non-infected volunteers (n = 20). Identification of cells among CD4⁺ and CD8⁺ T-lymphocytes expressing markers of activation (CD38, HLA-DR), depletion (PD-1), and interleukin (IL) 7 receptor (CD127); measurement of blood levels of IL-6, neopterin, soluble CD14 (sCD14), intestinal fatty acid-binding peptide (I-FABP), and bacterial lipopolysaccharide. Correlation analysis of the dependence between cell immunity and systemic inflammation was performed. HIV-infected patients had more activated CD4⁺ and CD8⁺ T-lymphocytes and CD4⁺ T-cells expressing PD-1 marker than non-infected subjects but less CD4⁺ and CD8+ T-lymphocytes expressing CD127. Blood IL-6, neopterin, soluble CD14, I-FABP and bacterial lipopolysaccharide levels in the former were higher than in the latter HIV-infected patients showed significant correlation of cell immunity parameters with blood neopterin and FABP levels. The process of activation, depletion, and regeneration of T-lymphocytes in. HIV infection are related to the destruction of intestinal barrier and systemic macrophage activation.

The clinical significance of high sensitivity HBV DNA detection for the treatment of antiviral therapy in patients with chronic hepatitis B

The clinical significance of high sensitivity HBV DNA detection for the treatment of antiviral therapy in patients with chronic hepatitis B

Interleukin-21 Is Associated with Early Antiviral Response in Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) becomes a characteristic of liver disease. Interleukin-21 (IL-21) plays an important role in the control of chronic hepatitis B (CHB). We aimed to investigate the relationship between IL-21 and early (24 weeks) viral response (EVR) to antiviral therapy in patients with coexistence of CHB and NAFLD (CHB + NAFLD). A prospective study was carried out in hepatitis B e antigen (HBeAg)-positive CHB + NAFLD and CHB patients receiving Entecavir for initial antiviral therapy, by recording demographic, anthropometric, and clinical data at baseline 12 and 24 weeks. Univariate analysis, correlation analysis, and receiver operating characteristic curve (ROC) were applied to find related factors with EVR. Forty CHB + NAFLD patients and 20 CHB patients entered final analysis. At baseline, IL-21, triglyceride (TG), cholesterol (CHOL), glutanyltransferase (GGT), body mass index (BMI), and computed tomography (CT) ratio of liver/spleen showed significant difference between the 2 groups. Although no significant difference was found, EVR rates was lower in CHB + NAFLD than CHB (75% vs. 90%, P = 0.053). Baseline IL-21 was associated with BMI, CT ratio of liver/spleen, TG, CHOL, and HBeAg level in CHB + NAFLD patients, whose IL-21, alanine aminotransferase, aspartate aminotransferase, CHOL, BMI, and CT ratio of liver/spleen at baseline was associated with EVR. Only the level of IL-21 exhibited significant increase from 0 to 12 weeks, while the change line of other associated factors was nearly parallel between EVR group and non-EVR group. ROC discovered the level of IL-21 at 12 weeks implied a strong predictive value for EVR. We deduced that IL-21 was associated with EVR, and the elevated level of IL-21 at treatment week 12 can predict EVR in CHB + NAFLD patients.

Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis

All oral direct acting antivirals (DAAs) effectively treat chronic hepatitis C virus (HCV) infection, but the benefits in advanced liver disease are unclear. We compared outcomes in treated and untreated patients with decompensated cirrhosis. Patients with HCV and decompensated cirrhosis or at risk of irreversible disease were treated in an expanded access programme (EAP) in 2014. Treatment, by clinician choice, was with sofosbuvir, ledipasvir or daclatasvir, with or without ribavirin. For functional outcome comparison, untreated patients with HCV and decompensated cirrhosis who were registered on a database 6months before treatment was available were retrospectively studied. Primary endpoint was sustained virological response 12weeks post antiviral treatment (treated cohort) and the secondary endpoint (both cohorts) was adverse outcomes (worsening in MELD score or serious adverse event) within 6months. 467 patients received treatment (409 decompensated cirrhosis). Viral clearance was achieved in 381 patients (81.6%) - 209 from 231 (90.5%) with genotype 1 and 132 from 192 (68.8%) with genotype 3. MELD scores improved in treated patients (mean change -0.85) but worsened in untreated patients (mean+0.75) (p<0.0001). Patients with initial serum albumin <35g/L, aged >65 or with low (<135mmol/L) baseline serum sodium concentrations were least likely to benefit from therapy. All oral DAAs effectively cured HCV in patients with advanced liver disease. Viral clearance was associated with improvement in liver function within 6months compared to untreated patients. The longer term impact of HCV treatment in patients with decompensated cirrhosis remains to be determined.

Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma

The exact incidence and severity of hepatitis B virus (HBV) reactivation after the withdrawal of prophylactic antiviral therapy (delayed HBV reactivation) is unknown. We retrospectively analyzed 107 newly diagnosed diffuse large B cell lymphoma patients with HBV infection who received chemotherapy. The median time from the cessation of antitumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in HBsAg-positive group and 0 in HBsAg-negative/anti-HBc-positive group (P < 0.001). No HBV-related fulminant hepatitis or hepatitis-related death occurred. The multivariate analysis showed that female gender and lengthy cycles of chemotherapy (>8 cycles) were independent risk factors of HBV reactivation in HBsAg-positive patients. In conclusion, prophylactic antiviral therapy could be withdrawn 6 months after the cessation of chemotherapy in HBsAg-negative/anti-HBc-positive patients. However, a longer course of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients.

Predictive Factors for Sustained Remission after Discontinuation of Antiviral Therapy in Patients with HBeAg-positive Chronic Hepatitis B

The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to-undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9±2.6 vs. 13.2±12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (≥18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment.