End Of Treatment Viral Response Research Articles

The efficacy of adding vitamin B12 to pegylated interferon and ribavirin treatment in Hepatitis C virus patients regarding the host and viral prognostic factors

Introduction: Hepatitis C virus (HCV) infection affects almost 180 million people around the world. Even though the development of direct acting antivirals (DAAs) has significantly improved the treatment responses to HCV infection, treatment with pegylated interferon (PegIFN) in combination with ribavirin is considered the standard of care (SOC) for chronic HCV infection treatment in countries with limited medical resources. Considering the inhibitory effect of vitamin B12 on HCV replication, we have evaluated the effect of vitamin B12 supplementation along with SOC on treatment outcomes in patients with chronic HCV infection, who were antiviral treatment-naive.
 Methods: In this regard, seventy-four HCV-infected patients, naïve to antiviral therapy, were randomly assigned to receive SOC or SOC in addition to vitamin B12 (SOC + B12). Viral response was evaluated at 4, 12, 24 and 48 weeks following the initiation of viral treatment and at 24 weeks after completing the treatment. Genotyping of the interleukin 28B (IL28B) polymorphisms was also performed. Demographic characteristics, clinical findings, fibroscan results and drug adverse effects were recorded.
 Results: Our findings showed that rapid viral response was not significantly different between the two groups; however, the rates of complete early viral response (cEVR) (p=0.033), end-of-treatment viral response (ETVR) (p=0.001) and sustained virologic response (SVR) (p=0.0001) were significantly higher in SOC + B12 patients compared to SOC patients. Besides, in SOC + B12 patients, those with a higher baseline viral load and carriers of IL28B CC genotype showed significantly higher rate of SVR.
 Conclusion: In conclusion, the addition of vitamin B12 significantly improved the rate of SVR in HCV-infected patients, who were naïve to antiviral therapy. As this treatment regimen is safe and inexpensive, it proposes an option for improving the effectiveness of the HCV treatment with SOC, particularly in resource-limited settings.

Meta-Analysis of Combination Therapy of Chinese Herbs Plus Interferon and Ribavirin in Patients with Chronic Hepatitis C.

BackgroundWe aimed to evaluate the combination therapy of Chinese herbs plus interferon and ribavirin in treatment of patients with chronic hepatitis C (CHC).Material/MethodsRelated databases were searched to identify randomized controlled trials (RCTs) that evaluated biochemical response, virological response, histological response, and/or adverse reactions to combination therapy of interferon and ribavirin with and without Chinese herbs. The RR (relative risk) with a 95% confidence interval (CI) was calculated. Sensitivity analysis was conducted by omitting one study at a time. Publication bias among the eligible studies was evaluated by Egger’s test.ResultsA total of 17 RCTs matched the selection criteria. Overall, combination therapies of Chinese herbs plus interferon and ribavirin achieved significantly higher ALT (alanine transaminase) and ETVR (the end-of-treatment viral response), and significantly lower levels of HA (hyaluronic acid), LN (laminin), PC III (procollagen iii peptide), IV-C (type IV collagen), decreased LC (decreasing leukocyte count), ATF (abnormal thyroid function), psychosis, and anemia in CHC patients compared with those treated without Chinese herbs. Sensitivity analysis showed no changes and no potential publication bias was found.ConclusionsThe current evidence suggests that combination therapy of Chinese herb plus interferon and ribavirin yields better outcome and fewer adverse events in CHC patients than that of interferon plus ribavirin therapy.

Lower Viral Response to Pegylated Interferon Alpha 2a Treatment of Chronic Hepatitis B in Roma People in Eastern Slovakia.

Aim. To evaluate the compliance and virological response to pegylated interferon alpha 2a treatment of chronic hepatitis B in Roma population compared to majority Caucasian population in Slovakia. Methods. Retrospective evaluation of a cohort of all Roma patients treated with pegylated interferon alpha 2a from 2007 to 2013 in 3 centers for treatment of chronic viral hepatitis B. The Study included 43 Roma patients with chronic viral hepatitis B and randomly selected control group. Treatment duration was 48 weeks. Viral response was evaluated after 24 weeks, at the end of treatment, and 24 weeks after the end of treatment. Results. Complete treatment course was finished by 79.1% of Roma patients compared to all patients from the control group (p = 0.0009). There was a tendency toward lower viral response rate in Roma at all time points; however significant difference was only at end of treatment viral response (51.2% Roma versus 81.4% majority, p = 0.003). We also did not find significant difference at the rate of HBsAg loss. Conclusion. Roma patients with chronic hepatitis B have significantly worse compliance to treatment with pegylated interferon and they have significantly lower rate of end of treatment viral response.

611 Ifi6 Response Predicts Outcome of Treatment for Infection With Hepatitis C Virus With Novel Method for the Quantification of Interferon-Induced mRNA in Whole Blood

Background and aims: Vitamin D plays an important role in both innate and adaptive immune systems. Recently, vitamin D deficiency has been proposed as a novel predictor of poor-response of treatment with pegylated interferon-alfa and ribavirin in patients with chronic hepatitis C. CYP27B1 or 25-hydroxyvitamin D3-1α-hydroxylase catalyzes metabolic activation of 25-hydroxyvitamin D3 into 1α, 25-dihydroxyvitamin D3, an active form of vitamin D. The CYP27B1-1260 promoter polymorphisms are known to influence 1 α, 25dihydroxyvitamin D3 serum level. This study was performed to determine the association between the CYP27B1 gene polymorphism and outcome of treatment with pegylated interferon-alpha based therapy in patients with chronic hepatitis C in Asian population. Methods: 261 patients with chronic hepatitis C treated with pegylated interferon-alfa based regimen were genotyped for the promoter (-1260) polymorphism rs 10877012 C.A of the CYP27B1 gene. The definitions of rapid viral response (RVR), early viral response (EVR), end of treatment viral response (EOT) and sustained viral response (SVR) were made according to the American Association for the Study of Liver Diseases (AASLD). Results: Of these, 177 patients (67.8%) achieved SVR. 101 patients (38.7%) were genotype 1 or 4. Baseline characteristics including age, gender, body mass index, alcohol consumption, genotypes, baseline HCV RNA viral load, serum alanine aminotransferase and advanced fibrosis were not statistically different between patients with SVR and non-SVR. The overall SVR rate were 58.9%, 72.4% and 67.1 for CC, CA, and AA genotype, respectively, p=0.20. SVR was not different in CC genotype compared to non-CC genotype (58.9% vs 70.2%, p=0.15). However, in genotype 1/4-infected patients, SVR rate was significant lower in CC genotype than nonCC genotype (36.4% vs 65.8%, p=0.016), (Figure 1). Patients with EVR had lower AA genotype than non-EVR (28.7% vs 53.8%, p=0.01). There were no association between CYP27B1-1260 promoter polymorphism and rate of RVR and EOT. In difficult-to-treat HCV genotype (1/4), proportion of CC genotype was significant higher in patients with non-SVR than SVR (34.1% vs 13.3%, p=0.01). In these cases, age and CC genotype were significantly associated with non-SVR. Multivariate logistic regression analysis found CC genotype (Odds ratio = 4.8, 95% CI = 1.61-14.54, p = 0.005) and age (Odds ratio = 1.07, 95%CI = 1.021.12, p=0.01) were independent predictor of non-SVR. Conclusions: This study suggested that in Asian population, the CYP27B1 promoter (-1260) CC polymorphism was a strong predictor of poor response of treatment with pegylated interferon-alfa based regimen in patients with difficult-to-treat genotype chronic hepatitis C.

610 The Promoter Polymorphism of Cyp27b1 Gene Predicts Poor Response to Interferon-Alfa Based Therapy in Difficult-to-Treat Chronic Hepatitis C Genotype in Asian Population

Background and aims: Vitamin D plays an important role in both innate and adaptive immune systems. Recently, vitamin D deficiency has been proposed as a novel predictor of poor-response of treatment with pegylated interferon-alfa and ribavirin in patients with chronic hepatitis C. CYP27B1 or 25-hydroxyvitamin D3-1α-hydroxylase catalyzes metabolic activation of 25-hydroxyvitamin D3 into 1α, 25-dihydroxyvitamin D3, an active form of vitamin D. The CYP27B1-1260 promoter polymorphisms are known to influence 1 α, 25dihydroxyvitamin D3 serum level. This study was performed to determine the association between the CYP27B1 gene polymorphism and outcome of treatment with pegylated interferon-alpha based therapy in patients with chronic hepatitis C in Asian population. Methods: 261 patients with chronic hepatitis C treated with pegylated interferon-alfa based regimen were genotyped for the promoter (-1260) polymorphism rs 10877012 C.A of the CYP27B1 gene. The definitions of rapid viral response (RVR), early viral response (EVR), end of treatment viral response (EOT) and sustained viral response (SVR) were made according to the American Association for the Study of Liver Diseases (AASLD). Results: Of these, 177 patients (67.8%) achieved SVR. 101 patients (38.7%) were genotype 1 or 4. Baseline characteristics including age, gender, body mass index, alcohol consumption, genotypes, baseline HCV RNA viral load, serum alanine aminotransferase and advanced fibrosis were not statistically different between patients with SVR and non-SVR. The overall SVR rate were 58.9%, 72.4% and 67.1 for CC, CA, and AA genotype, respectively, p=0.20. SVR was not different in CC genotype compared to non-CC genotype (58.9% vs 70.2%, p=0.15). However, in genotype 1/4-infected patients, SVR rate was significant lower in CC genotype than nonCC genotype (36.4% vs 65.8%, p=0.016), (Figure 1). Patients with EVR had lower AA genotype than non-EVR (28.7% vs 53.8%, p=0.01). There were no association between CYP27B1-1260 promoter polymorphism and rate of RVR and EOT. In difficult-to-treat HCV genotype (1/4), proportion of CC genotype was significant higher in patients with non-SVR than SVR (34.1% vs 13.3%, p=0.01). In these cases, age and CC genotype were significantly associated with non-SVR. Multivariate logistic regression analysis found CC genotype (Odds ratio = 4.8, 95% CI = 1.61-14.54, p = 0.005) and age (Odds ratio = 1.07, 95%CI = 1.021.12, p=0.01) were independent predictor of non-SVR. Conclusions: This study suggested that in Asian population, the CYP27B1 promoter (-1260) CC polymorphism was a strong predictor of poor response of treatment with pegylated interferon-alfa based regimen in patients with difficult-to-treat genotype chronic hepatitis C.

Therapy‐induced clearance of HCV core antigen from plasma predicts an end of treatment viral response

During viral assembly, viral proteins are released into plasma and can be used to infer viral load. The Architect hepatitis C virus (HCV) core antigen (Ag) assay is a potential alternative to HCV RNA quantification for measuring response to therapy and predicting an end of treatment viral response (EOTR). The HCVp22Ag assay was used to infer viral load in 68 window RNA-containing samples and in 284 samples from baseline to week 14 of ribavirin/interferon treatment in 23 patients with EOTR including three who relapsed, 20 not achieving EOTR and 11 controls. HCV Ag and RNA correlated well (r = 0.86) with linear dose responses on dilution. In patients on therapy and control patients, plasma HCV antigen was detected in 51 of 54 with an interpolated LOD cut off between 10(3) and 10(4) RNA IU/mL. Plasma HCV antigenaemia and plasma RNA levels were significantly different in EOTR from non-EOTR patients at 3 days after treatment start and all times thereafter. Positive and negative EOTR predictive values for HCV RNA >2 log drop and HCV Ag loss at 12 weeks were 70% and 74%, 85% and 93% respectively. HCV Ag reactivity has a linear dose response independent of genotype and correlates well with HCV RNA. The failure to clear HCV Ag is as accurate as the failure to clear HCV RNA at twelve weeks into therapy in predicting the likelihood of failure to achieve EOTR. HCV Ag potentially offers a convenient alternative to RNA measurement for defining a futility flag in HCV therapy.

Cytokine/chemokine patterns connect host and viral characteristics with clinics during chronic hepatitis C

BackgroundIn chronic hepatitis C virus (HCV) infection, liver tissue pathology and HCV genotype are important determinants of clinical and/or treatment-related outcome. Although consistent epidemiological and/or molecular-biological clues derived from different studies on single virus-host interactions are meanwhile published, the in vivo transcriptional responses and cellular pathways affected in >1 key aspects of the disease or treatment process are far from being understood.MethodsMicroarray analysis was performed in peripheral whole blood (PB) samples from 36 therapy-naïve HCV-infected patients with known liver histology. Linear regression analysis identified gene expression profiles significantly correlating (P < 0.015) with ≥1 out of 7 variables: sustained viral response (SVR), viral non-response (NR), end of treatment viral response (ETR), viral breakthrough (VB), HCV genotype (Gt. 1 vs. Gt. 2/3), stage of hepatic fibrosis [St. 0/1 vs. St. 2/3/4] and grade of hepatic inflammation (Gr. 0/1 vs. Gr. 2/3/4). Correlation values across all seven contrasts were considered for hierarchical clustering (HCL).ResultsA total of 1,697 genes showed ≥1 significant correlation results and genes involved in cell differentiation (183), immune response (53), and apoptosis (170) were leading fractions. HCL grouped the genes into six major clusters. Functional annotation analysis using DAVID (http://david.abcc.ncifcrf.gov) revealed that expression profiles that best linked these variables were highly enriched in cytokine/chemokine activity (Fisher-exact P < 0.0001) and specific biological module-centric algorithms finally led our focus on four out of fifty-three immune response genes: SMAD family member 3 (SMAD3), interleukin 1 receptor accessory protein (IL1RAP), tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), and chemokine ‘C-C motif’ receptor 5 (CCR5). Of those, TNFRSF1A and CCR5 showed significant correlation with two out of seven variables based on microarray and/or quantitative real-time polymerase chain reaction (qRT-PCR) data.ConclusionWe identified molecular targets of the innate and adaptive immune system and validated their transcriptional specificity in vivo suggesting significant involvement in two unique outcomes during HCV treatment.

Interferon plus Chinese herbs are associated with higher sustained virological response than interferon alone in chronic Hepatitis C: A meta-analysis of randomised trials

Background/aims Traditional Chinese herbal therapies are widely used for the treatment of chronic hepatitis C (CHC) in Asia. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing interferon therapies with Chinese herbal therapies and/or interferon plus Chinese herb therapies for the treatment of CHC. Methods The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database and China Biomedical Database were searched to identify RCTs that evaluated the virological response to interferon therapies, Chinese herbal therapies and interferon plus Chinese herb therapies in CHC patients. We statistically combined data using a random-effect meta-analysis according to the intention-to-treat principle. Results The literature search yielded 770 studies, and 26 RCTs comprising 1905 patients matched the selection criteria. Overall, the sustained virological response (SVR) was significantly higher in patients treated with interferon plus Chinese herbs than in patients treated with interferon alone (49% vs 33%, relative risk, 1.52; 95% confidence interval: 1.23–1.89; p < 0.05). Combined therapies of interferon plus Chinese herb therapies were also superior to interferon therapies alone in achieving the end-of-treatment viral response (ETVR), and resulted in fewer relapses, fewer adverse events and more rapid alanine transaminase normalisation. Interferon therapies achieved higher ETVR than Chinese herbal therapies, but they yielded a similar SVR. Conclusions The current evidence suggests that combined therapies of interferon plus Chinese herbs yielded a higher SVR, and resulted in fewer relapses and fewer adverse events than interferon therapies.

Prisons and HCV: a review and a report on an experience in New South Wales Australia

Prison populations in Western countries are characterised by a high hepatitis C prevalence. This reflects a high rate of imprisonment for drug related offences. Prison entrants who are HCV-negative face a significant risk of acquiring hepatitis C. Effective prevention strategies and successful treatment of a significant percentage of hepatitis C-positive inmates could reduce the risk of transmission in the prison context significantly. Several reports of treating hepatitis C in prisoners in major facilities have been published. We report our experience of establishing a liver clinic service in two regional prisons in New South Wales, Australia. Liver biopsy requirements to access treatment in Australia meant that only 46 of 196 reviewed patients were able to commence treatment in our 5-year experience. Treatment completion rate was 61% and end of treatment viral response was 57%. The removal of liver biopsy requirements in Australia in April 2006 has freed up access to treatment and our results encourage further effort to optimise the process of assessment and treatment in this high-risk population.

Comparison of low‐dose pegylated interferon versus standard high‐dose pegylated interferon in combination with ribavirin in patients with chronic hepatitis C with genotype 3: An Indian experience

In chronic hepatitis C virus (HCV) infection with genotype 3, therapy with pegylated interferon (peg-IFN) alfa-2b in a dose of 1.5 mug/kg/week and ribavirin (800-1000 mg/day) is recommended for 24 weeks. Reduced doses of peg-IFN may increase compliance and decrease cost and adverse events. This study aimed to assess the safety and efficacy of two different regimens of peg-IFN alfa-2b, in combination with ribavirin, in genotype 3 patients. A total of 103 liver biopsy-proven chronic HCV patients with genotype 3, having alanine aminotransferase levels >1.2 x ULN and positive HCV-RNA were randomized into two groups: group I (n = 76; age, 43.1 +/- 11.4 years; male/female, 67/9) received peg-IFN 1.0 mug/kg/week + ribavirin 10.6 mg/kg/day, while group II (n = 27; age, 37.3 +/- 11.6 years; male/female, 21/6) received peg-IFN 1.5 microg/kg/week + ribavirin 10.6 mg/kg/day. Patients in both groups were treated for 24 weeks. End of treatment viral response (ETVR) and sustained viral response (SVR) after a 6-month follow-up period were assessed. In both groups I and II, one patient was lost to follow-up, while one patient in group II withdrew due to side-effects. ETVR was seen in 72/76 (94.7%) of patients in the low dose group and 24/27 (88.9%) of patients in the high dose group (P = 0.375). SVR was seen in 60/76 (78.9%) of patients in the low dose group and 25/27 (92.6%) of patients in the high dose group (P = 0.145). Age (Pearson correlation coefficient = 0.263; P = 0.008) and fibrosis (correlation coefficient, 0.263; P = 0.008) showed a significant correlation with the SVR. In patients with genotype 3, peg-IFN at 1.0 microg/kg/week with ribavirin is as effective as peg-IFN at 1.5 mug/kg/week with ribavirin.

Treatment of Hepatitis C in Hemodialysis Patients with Pegylated Interferon α-2a as Monotherapy

Background. The high prevalence of hepatitis C virus (HCV) infection in hemodialysis patients is of great concern because they have a higher rate of mortality than HCV-negative hemodialysis patients. The aim of the study was to evaluate the efficacy and safety of pegylated interferon α-2a monotherapy in hemodialysis patients with chronic HCV infection. Methods. Fourteen dialysis patients with chronic HCV infection were scheduled to receive 135 μg pegylated interferon α-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. Efficacy and safety were assessed by end of treatment viral response, sustained viral response, biochemical response, and adverse events. Serum HCV RNA levels were assessed using reverse transcriptase polymerase chain reaction (RT-PCR), while HCV genotype was analyzed by RT-PCR followed by hybridization of amplified products. Results. Of the 14 patients enrolled in the study, 9 completed treatment. Eight patients (57%) had undetectable levels of HCV RNA at the end of treatment, while one patient remained positive. Two (14.3%) patients were discontinued because of insufficient therapeutic response. Three patients (21.34%) did not finish treatment because serious adverse events occurred: one patient with bronchopneumonia and one with pericarditis were discontinued from treatment, while one patient died due to cerebral hemorrhage. Sustained viral response was present in 36% of the patients (5/8 patients) at the end of the follow up period. Biochemical response with normalization of serum ALT levels during treatment was observed in all treated patients (83 ± 20.1 U/L at baseline vs. 23.4 ± 4.6 U/L at week 48). The most common adverse events were flu-like syndrome, myalgia, arthralgia, and pancytopenia. Most of the adverse events were manageable. The serious adverse events were believed to be unrelated to the therapy, but rather to the co-morbidities of the hemodialysis patients. Conclusions. Pegylated interferon α-2a treatment was effective in a considerable proportion of the treated hemodialysis patients with hepatitis C, and it was reasonably safe to use.

Safety and Efficacy of Peginterferon Alfa-2a and Ribavirin for Hepatitis C in Thalassemia.

Hepatitis C virus (HCV) is an important cause of liver disease in patients with thalassemia. Standard treatment for adult patients without thalassemia is pegylated interferon-alfa (PEG) and ribavirin, but has been contraindicated in patients with thalassemia due to ribavirin-induced hemolysis, with associated increase in transfusion requirement and iron loading. This study examines whether increased iron burden accelerates liver, heart, and endocrine disease, increases the risk of antiviral treatment in these patients, and influences response to therapy. An open-label, single arm trial of PEG (180 μg/week) and ribavirin (~16mg/kg/day) was performed through the NIH-sponsored Thalassemia Clinical Research Network. Patients were treated for 24 weeks (genotypes 2&3) or 48 weeks (genotype 1). Iron burden was measured as liver iron concentration (LIC) in dry weight biopsy samples and HCV-RNA levels by using the Roche COBAS HCV Tests (qualitative and quantitative). Safety for iron-related toxicities was assessed by liver pathology, cardiac echo and ECG, fasting blood sugar and thyroid function tests. Standard PEG/ribavirin toxicities were followed using biochemical parameters, vision and hearing tests, and adverse event monitoring. 21 patients (48% male, mean age 32y, 15 genotype 1, 6 genotype 2 or 3) were enrolled and started treatment. 4 participants discontinued between weeks 4 through 12 [death from presumed sepsis, persistent cough, extreme fatigue, and pregnant spouse], and 1 participant dropped out at 36 weeks. Transfusion requirement had increased by 40% after 24 weeks (range: −5 to 68 %) in all participants and by 31% after 48 weeks (range: −2 to 77%) in participants with genotype 1. Week 48 liver biopsies were obtained in 14 /16 patients. The mean baseline LIC was 11.2 mg/g (range: 1.1 to 44.1) and did not change significantly at 48 weeks (median increase: 1.7 mg/g). LIC increased in 29% (4/14) of participants by more than 5 mg/g. Ejection fraction remained stable over 48 weeks (range: −15 to +17 %) and no pathologic arrhythmias were reported. No participants developed diabetes mellitus or thyroid disease. A ≥ 2 log HCV-RNA reduction was achieved by week 4 in all participants with genotype 2 or 3, and in 47% by week 4 and 73% by week 12 in those with genotype 1. Although end of treatment viral response (ETR) in genotype 2 or 3 was 100 % (4/4), 75% did not obtain sustained viral response (SVR; HCV undetectable in blood six months after treatment). In contrast, genotype 1 participants had ETR of 75% (9/12) and SVR of 55% (6/11). No significant correlations were found in baseline LIC, baseline HCV-RNA level, or change in transfusion requirement with ETR or SVR. In summary, baseline LIC was not a predictor of early or SVR. Response rates for participants with genotype 1 were similar to the non-thalassemia population. Genotype 2 or 3 patients appear to have a lower SVR rate after 24 weeks of therapy; therefore, 48 weeks of therapy should be considered. Despite an increase in iron burden in some participants, combination therapy did not appear to pose significant iron-related safety issues. (Study medications provided by Hoffmann-La Roche).

Pegylated versus standard interferon‐α in antiviral regimens for post‐transplant recurrent hepatitis C: Comparison of tolerability and efficacy

In the treatment of hepatitis C virus (HCV) infection, regimens including pegylated interferon-alpha are superior to those including standard interferon; the present retrospective study was performed to verify whether the same is applicable to biopsy-proven recurrent hepatitis C (genotype 1b) after liver transplantation (OLT). Twenty-four patients (16 male) were studied. Twelve had received interferon-alpha(2b) (IFN), 9 MU weekly and 12 received pegylated interferon-alpha(2b) (PEG-IFN), 0.5 microg/kg weekly. All had received oral ribavirin 600-800 mg/day. Treatment duration was intended for 12 months. A repeat liver biopsy, with evaluation of the Ishak grading and staging scores, was obtained at 1 year. Only 12/24 patients (50%) completed a full year of therapy; 17 (71%) experienced side-effects requiring a 50% dosage reduction or discontinuation of the IFN, PEG-IFN and/or ribavirin. This was observed in 6/12 patients (50%) treated with IFN in comparison to 11/12 patients (92%) treated with PEG-IFN (P < 0.05). The difference was mainly accounted for by anemia and leukopenia that were reported in 4/12 IFN patients (33%) versus 9/12 PEG-IFN patients (75%; P < 0.05), respectively. End-of-treatment viral response (ETVR) and histological response were always associated and occurred in 4/24 patients (17%), two in each treatment arm. Patients with ETVR were younger, had always completed 1 year of therapy, had had recurrent hepatitis later after transplantation and presented a higher baseline grading score. In the OLT setting, the potential benefits of antiviral treatments including PEG-IFN may be limited by the poor tolerability of the adopted drugs.