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T cell dyscrasias that demonstrate a proclivity for the subcutaneous fat include atypical lymphocytic lobular panniculitis, lupus profundus, and primary subcutaneous T cell lymphoma, including subcutaneous panniculitis-like T cell lymphoma (SPTCL). We encountered two patients who developed fever and indurated abdominal erythema at their peginterferon alfa-2a injection sites. Biopsies showed an atypical CD8 positive, granzyme positive, CD5 negative, MXA negative lymphocytic lobular panniculitis, diagnostic of SPTCL. Peginterferon alfa-2a was held in both patients. One patient received chemotherapy with an excellent response, while the other continued to have progressive disease. Peginterferon alfa-2a is known to significantly elevate serum MXA, which may induce high levels of MXA expression at the injection site, creating a microenvironment for the development of lupus profundus, which may eventuate into SPTCL. In summation, a potential risk of peginterferon alfa-2a injections is the development of SPTCL potentially arising in a background of an exogenous interferon triggered lymphocytic panniculitis. [ABSTRACT FROM AUTHOR]

Introduction: Withdrawal of nucleos(t)ide analog (NA) therapy is associated with hepatitis B surface antigen (HBsAg) loss and sustained, off-therapy partial cure (normal ALT [≤30 U/L males, ≤20 U/L females) with HBV DNA <2000 IU/mL) but should be offered only to those most likely to benefit. HBVRNA may be useful for risk stratification., Methods: The Hepatitis B Research Network Immune-Active Trial prospectively evaluated treatment with tenofovir (TDF) for 192 weeks ± peginterferon-α (PegIFN) for initial 24 weeks followed by protocolized withdrawal of TDF amongst eligible participants (NCT01369212). HBV RNA was evaluated as predictor of ALT flares and sustained partial cure (HBV DNA<2000 IU/mL) 48 weeks after TDF withdrawal., Results: Of 93 participants discontinuing TDF (52 in TDF+PegIFN and 41 in TDF alone), 52 (55.9%) had unquantifiable HBVRNA at end-of-treatment. ALT flares (>5xULN) at 48 weeks off-therapy occurred in 33.3%, with pre-treatment age (≥35 years) and quantifiable HBV RNA at end-of-treatment, the best predictors (AUROC 0.74 and 0.85, training and test set) of ALT flare. A total of 26 (28.3%) had sustained partial cure; 3 (11.5%) with ALT flare. Non-quantifiable HBVRNA and qHBsAg <100 IU/mL at end-of-treatment were the best predictors of sustained partial cure (AUROC 0.84 and 0.93, training and test set). If HBVRNA was quantifiable at end-of-treatment, the likelihood of sustained partial cure was only 3% whereas if HBV RNA was unquantifiable and qHBsAg <100 IU/mL, this likelihood was 73%., Conclusions: HBVRNA is a useful biomarker in predicting likelihood of achieving sustained partial cure and safe withdrawal of NAs., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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Copyright of Viral Hepatitis Journal / Viral Hepatit Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The purpose of this study was to analyze the clinical characteristics of chronic hepatitis B (CHB) cured by antiviral therapy. Methods: Forty-two patients with CHB were enrolled. All patients had been treated with peginterferon (Peg-IFN) in combination with nucleoside analogue (NA) therapy for variable amounts of time, and all had been successfully cured of the disease. Results: The combined treatment time for all participants was 124.7 ± 58.8 weeks, and the average Peg-IFN treatment time was 102.6 ± 56.1 weeks. At 24 weeks, Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) had decreased more than 50% from baseline. Multivariate logistic regression analysis of the week 96 HBsAg-clearing group and the non-HBsAg-clearing group showed a statistically significant difference in baseline HBV DNA levels and week 48 HBsAg levels. Those which baseline HBV DNA was < 2.75 log10 IU/mL, and week 48 HBsAg levels were < 0.88 log10 IU/mL were more likely to achieve rapid HBsAg clearance at 96 weeks. This suggests that low levels of baseline HBV DNA and week 48 HBsAg are a predictor of rapid HBsAg clearance at 96 weeks. Conclusions: Individualized extension of combination therapy to more than 96 weeks depending on the patient’s response and adverse reaction conditions can help achieve a clinical cure. Patients with low baseline HBV DNA and low HBsAg levels at 48 weeks achieve HBsAg clearance more quickly than other populations.

This study aimed to explore the value of baseline serum exosome‐derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg‐IFN). A total of 120 treatment‐naïve HBeAg‐positive CHB patients who received Peg‐IFN therapy (48 weeks) were enrolled. Next‐generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg‐IFN treatment outcome, and qRT‐PCR was used to validate them. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers. Thirty‐three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (nonresponse group). In the identification cohort, 40 serum exosome‐derived miRNAs were differentially expressed between the response group (four patients) and the nonresponse group (four patients). In the confirmation cohort, the expression levels of serum exosomal miR‐194‐5p (p <.001) and miR‐22‐3p (p <.001) were significantly downregulated in the response group (29 patients) compared to the nonresponse group (83 patients). Multivariate analysis identified baseline serum exosomal miR‐194‐5p, miR‐22‐3p, alanine aminotransferase (ALT), and HBV DNA as independent predictors of HBeAg seroconversion (all p <.05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR‐194‐5p and miR‐22‐3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR‐194‐5p and miR‐22‐3p further improved the predictive performance with an AUROC of 0.82. Baseline serum exosomal miR‐194‐5p and miR‐22‐3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg‐IFN. Highlights: ‐Baseline serum exosome‐derived miR‐194‐5p and miR‐22‐3p were significantly lower in the Peg‐IFN treatment response group compared to the nonresponse group.‐The predictive performance of baseline serum exosomal miR‐194‐5p and miR‐22‐3p were superior to ALT and HBV DNA.‐Baseline serum exosomal miR‐194‐5p and miR‐22‐3p may serve as novel biomarkers to predict HBeAg seroconversion in HBeAg‐positive CHB patients treated with Peg‐IFN. [ABSTRACT FROM AUTHOR]

BackgroundGenetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables.MethodsHALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC).ResultsAmong 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study.ConclusionA clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC.

• Individualized extension of combination therapy can achieve clinical cure for CHB. • Patients with low baseline HBVDNA and week 48 HBsAg achieve HBsAg clearance more quickly. • Consolidation therapy after HBsAg clearance and high HBsAb level can reduce recurrence. The purpose of this study was to analyze the clinical characteristics of chronic hepatitis B (CHB) cured by antiviral therapy. Forty-two patients with CHB were enrolled. All patients had been treated with peginterferon (Peg-IFN) in combination with nucleoside analogue (NA) therapy for variable amounts of time, and all had been successfully cured of the disease. The combined treatment time for all participants was 124.7 ± 58.8 weeks, and the average Peg-IFN treatment time was 102.6 ± 56.1 weeks. At 24 weeks, Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) had decreased more than 50% from baseline. Multivariate logistic regression analysis of the week 96 HBsAg-clearing group and the non-HBsAg-clearing group showed a statistically significant difference in baseline HBV DNA levels and week 48 HBsAg levels. Those which baseline HBV DNA was < 2.75 log 10 IU/mL, and week 48 HBsAg levels were < 0.88 log 10 IU/mL were more likely to achieve rapid HBsAg clearance at 96 weeks. This suggests that low levels of baseline HBV DNA and week 48 HBsAg are a predictor of rapid HBsAg clearance at 96 weeks. Individualized extension of combination therapy to more than 96 weeks depending on the patient's response and adverse reaction conditions can help achieve a clinical cure. Patients with low baseline HBV DNA and low HBsAg levels at 48 weeks achieve HBsAg clearance more quickly than other populations. [ABSTRACT FROM AUTHOR]

Background (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. Methods In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. Results Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= −0.74, standard error [SE] = 0.16, P = 3.44 ×10–6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10–6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. Conclusions Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. Clinical Trials Registation NCT01401400. [ABSTRACT FROM AUTHOR]

Abstract Background This Phase 3, open-label, rollover study (NCT01323244) investigated the efficacy and safety of simeprevir plus peginterferon α-2a (PegIFNα-2a) and ribavirin (RBV) in a well-characterized population of HCV genotype 1 (GT1)-infected treatment-experienced patients. Methods Patients who had failed PegIFNα/RBV treatment in the placebo arm of a previous Phase 2/3 simeprevir study (Phase 2/3 group, n = 125), or had been exposed to HCV direct-acting antivirals (simeprevir or other) for up to 14 days in a selected Phase 1 study (Phase 1 group, n = 16), were eligible. Phase 2/3 group patients were classified according to prior relapse, breakthrough, or non-response (null response, partial response, non-classifiable non-response) to PegIFNα/RBV. Eight patients in the Phase 1 group received short-term (≤14 days) simeprevir. Treatment comprised simeprevir 150 mg once daily (QD) plus PegIFNα-2a/RBV for 12 weeks followed by PegIFNα-2a/RBV for 12 or 36 weeks (using response-guided therapy [RGT] to determine total treatment duration in Phase 2/3 prior relapsers or breakthrough) or 36 weeks fixed (Phase 2/3 group non-responders and Phase 1 group). The primary endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Results Phase 2/3 group: SVR12 rate was 69.6% (87/125) overall; 92.7% (51/55), 60.0% (6/10), 64.3% (18/28), and 36.7% (11/30) in patients with prior relapse, viral breakthrough, partial response, or null response, respectively. SVR12 rates were similar for patients with HCV GT1a (66.0% [33/50]) and GT1b infection (72.0% [54/75]) and among HCV GT1a-infected patients with/without a baseline Q80K polymorphism (66.7% [8/12] and 65.8% [25/38], respectively). The majority of RGT-eligible patients (prior viral relapse or breakthrough) met RGT criteria (89.2% [58/65]); of these, 89.7% (52/58) achieved SVR12. Overall, 16.0% (20/125) of patients experienced on-treatment failure and 14.4% (18/125) experienced post-treatment failure (15 relapses, 3 missing data). Phase 1 group (simeprevir-naïve and -experienced patients combined): SVR12 rate was 37.5% (6/16). Safety and tolerability findings were comparable to those of the feeder studies. Conclusions The majority of RGT-eligible patients met criteria for shortening treatment to 24 weeks in total. Simeprevir 150 mg QD with PegIFNα-2a/RBV led to a high SVR rate among prior relapsers with HCV GT1 infection. No new safety signals were noted. Trial registration NCT01323244 . (date of registration: March 24, 2011).

Introduction: Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with an-tivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. Material and methods: A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylat-ed interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (=C, 2014) and utilities were obtained from literature. Results: Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to =C102,841 (strategy 1) and =C105,408 (strategy 2) in HBeAg-positive, and =C85,858 and =C93,754 in HBeAg-negative. A =C1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Interferon-based simeprevir therapy showed high efficacy and tolerability in children with genotype 1 hepatitis C virus infection. While direct-acting antivirals (DAAs) therapy are undergoing study in children, this regimen is considered an available therapeutic option for selected patients in countries where DAAs have not yet been approved.

Hepatitis C virus (HCV) is a globally prevalent and hazardous disorder that is responsible for inducing several persistent and potentially fatal liver diseases. Current treatment strategies offer limited efficacy, often accompanied by severe and debilitating adverse effects. Consequently, there is an urgent and compelling need to develop novel therapeutic interventions that can provide maximum efficacy in combating HCV while minimizing the burden of adverse effects on patients. One promising target against HCV is the NS3-4A serine protease, a complex composed of two HCV-encoded proteins. This non-covalent heterodimer is crucial in the viral life cycle and has become a primary focus for therapeutic interventions. Although peginterferon, combined with ribavirin, is commonly employed for HCV treatment, its efficacy is hampered by significant adverse effects that can profoundly impact patients' quality of life. In recent years, the development of direct-acting antiviral agents (DAAs) has emerged as a breakthrough in HCV therapy. These agents exhibit remarkable potency against the virus and have demonstrated fewer adverse effects when combined with other DAAs. However, it is important to note that there is a potential for developing resistance to DAAs due to alterations in the amino acid position of the NS3-4A protease. This emphasizes the need for ongoing research to identify strategies that can minimize the emergence of resistance and ensure long-term effectiveness. While the combination of DAAs holds promise for HCV treatment, it is crucial to consider the possibility of drug-drug interactions. These interactions may occur when different DAAs are used concurrently, potentially compromising their therapeutic efficacy. Therefore, carefully evaluating and monitoring potential drug interactions are vital to optimize treatment outcomes. In the pursuit of novel therapeutic interventions for HCV, the field of computational biology and bioinformatics has emerged as a valuable tool. These advanced technologies and methodologies enable the development and design of new drugs and therapeutic agents that exhibit maximum efficacy, reduced risk of resistance, and minimal adverse effects. By leveraging computational approaches, researchers can efficiently screen and optimize potential candidates, accelerating the discovery and development of highly effective treatments for HCV, treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hepatitis C virus (HCV) infection is an important public health problem through the high levels of morbidity and mortality that it entails. Although the virus was discovered 30 years ago, the progress made in the structure and pathogenicity of the virus resulted in the development of extreme effective treatments. However, due to the current barriers to universal use of treatment, further efforts are needed to achieve the WHO desiderate to eradicate HCV infection by the year 2030. [ABSTRACT FROM AUTHOR]

Although nucleos(t)ide analog (NA) monotherapy is effective in hepatitis B virus suppression and fibrosis regression, serological response rates are not satisfactory. Studies assessing the benefits of combination therapy with NAs and peginterferon alpha (PegIFNα) in patients with chronic hepatitis B (CHB) have produced conflicting results and mainly focused on serological outcomes. Histological changes in response to combination therapy have not been evaluated in real‐world practice. This study aimed to evaluate the histological changes in response to NA‐PegIFNα combination therapy in CHB patients and to comprehensively compare the efficacy of NA‐PegIFNα combination therapy and NA monotherapy. We conducted a retrospective analysis of data from 40 CHB patients who underwent either NA‐PegIFNα combination therapy or NA monotherapy. Changes in histology at 48 weeks after treatment initiation were evaluated. Serological characteristics were also analysed and compared between the NA‐PegIFNα combination therapy and NA monotherapy groups and between histological responders and nonresponders. Compared to baseline biopsies, both fibrosis staging and necroinflammatory grading scores were significantly lower in the second biopsies examined post‐treatment in both groups. Nearly all patients experienced a reduction in inflammation (87.5% in both groups), but there was a subgroup of patients who exhibited either no significant improvement or fibrosis progression (33.3% and 31.2% in the NA monotherapy and NA‐PegIFNα combination therapy groups, respectively). Nearly, all patients achieved ALT normalization and sustained virological response (SVR) after 48 weeks of antiviral treatment. Approximately one‐third of individuals (36.8% and 30% in the two groups, respectively) achieved HBeAg loss at 48 weeks after treatment initiation. Although there were no significant differences in overall rates of histological, biochemical, virological and serological responses between the two groups, an earlier virological response and a higher cumulative SVR rate over time were observed during long‐term follow‐up in patients treated with NA‐PegIFNα combination therapy (P = 0.0129). Trends of more rapid HBeAg loss and a higher cumulative HBeAg loss rate throughout long‐term follow‐up were also observed but were not statistically significant. The ALT normalization rates at 24 and 48 weeks after treatment initiation were associated with the histological response. Significant regression of fibrosis and resolution of necroinflammation were induced with either NA‐PegIFNα combination therapy or NA monotherapy. Significant biochemical, virological and serological responses were observed in both groups, and the response rates at 48 weeks were similar in the two groups. Over time during long‐term follow‐up, the virological and serological responses were faster and superior following the combination regimen. [ABSTRACT FROM AUTHOR]

Summary: Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D‐infected patients. We conducted an open‐label study of peginterferon alfa‐2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)‐negative, genotype D‐infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48‐week add‐on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per‐protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa‐2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5‐log10 and ≥1‐log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma‐induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa‐2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg‐negative patients with genotype D infection (ClinicalTrials.gov NCT01706575). In this open‐label study in patients with genotype D, HBeAg‐negative chronic hepatitis B receiving nucleos(t)ide analogue therapy and with HBV DNA <20 IU/mL, peginterferon alfa‐2a add‐on therapy reduced HBsAg levels, with 29/43 (67.4%) patients having a >50% decline in HBsAg at week 48. An increase in Interferon gamma‐induced protein 10 from baseline up to week 48 was significantly associated with response. [ABSTRACT FROM AUTHOR]

Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy. Spontaneous clearance of hepatitis C virus RNA can occur following antiviral failure in patients with persistently low viral loads, and virological follow-up is therefore necessary in chronic hepatitis C virus infection, even after antiviral failure.

We examined whether hepatitis C virus (HCV) genotype 1b core- and NS5A-region mutations are associated with response to peginterferon α-2b plus ribavirin combination therapy. A total of 103 patients with high HCV genotype 1b viral loads (≥100 KIU/mL) were treated with the combination therapy. Pretreatment mutations in the core region and interferon sensitivity determining region (ISDR) in the NS5A region were analyzed. In univariate analysis, arginine and leucine at positions 70 and 91 in the core region, defined as double wild (DW)-type, were associated with early virologic response (p = 0.002), sustained virologic response (SVR) (p = 0.004), and non-response (p = 0.005). Non-threonine at position 110 was associated with SVR (p = 0.004). Multivariate analysis showed the following pretreatment predictors of SVR: hemoglobin level ≥ 14 g/dL (odds ratio (OR) 6.2, p = 0.04); platelet count ≥ 14 × 104/mm3 (OR 5.2, p = 0.04); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio < 0.9 (OR 6.17, p = 0.009); DW-type (OR 6.8, p = 0.02); non-threonine at position 110 (OR 14.5, p = 0.03); and ≥2 mutations in the ISDR (OR 12.3, p = 0.02). Patients with non-DW-type, non-threonine at position 110, and

Direct-acting antivirals with or without peginterferon α (PEG-IFN α) plus ribavirin are now available for the treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals are potent inhibitors of HCV replication, but some of them occasionally possess serious adverse events. We experienced a 64-year-old female with chronic HCV genotype 1b infection who showed elevated alanine aminotransferase of 528 IU/l at week 9 after the commencement of treatment of simeprevir with PEG-IFN α-2a plus ribavirin. However, she achieved sustained virological response at week 24 after the end of treatment. In Japan, we also have to treat elderly patients infected with HCV and/or advanced hepatic fibrosis. Until an effective interferon-free regimen is established, direct-acting antivirals with PEG-IFN plus ribavirin may still play a role in the treatment for certain patients. To avoid serious results from adverse events, careful attention and follow-up will be needed in the treatment course of simeprevir with PEG-IFN plus ribavirin for chronic HCV infection.

Background/AimsChronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon α-2a plus ribavirin for CHC in hemophilia.MethodsPatients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests.ResultsEleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naïve patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis.ConclusionsPeginterferon α-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.

The first generation protease inhibitors has been the mainstay of hepatitis C treatment for the last couple of years, showing marked improvement in sustained virological response, but also increased side effects. Infection has emerged as a common complication of telaprevir and boceprevir in combination with peginterferon and ribavirin, usually caused by common pathogens. We present the case of a 65 years old man who developed a Mycobacterium abscessus pulmonary infection during treatment with telaprevir, peginterferon and ribavirin. The patient was successfully treated with amikacin, imipenem and chlarithro-mycin. The present case is relevant for increasing awareness for recognition of opportunistic infections and particularly nontuberculous mycobacterial infections in patients receiving triple therapy for chronic hepatitis C, especially in cirrhotic subjects who develop significant lymphopenia.

Introduction: The primary goals of managing chronic hepatitis B (CHB) are prevention of liver-related complications and reduction of mortality. Universal vaccination has dramatically reduced the incidence of new infection, but the management of existing CHB patients are still challenging. Areas covered: This review compares the similarities and differences among the latest published regional guidelines on the indications and choices of antiviral therapy. We have summarized advances in virological biomarkers and non-invasive tests for liver fibrosis in disease assessment. Benefits and remaining challenges of current standard of care by peginterferon and nucleos(t)ide analogs (NA) have been presented. Data on combination therapy of peginterferon and NA in seeking functional cure of the disease is also critically discussed. We have also described the improvement in the management of CHB at pregnancy and prophylaxis in patients on chemotherapy and immunosuppressants. Expert commentary: Controversies exist in the assessment of disease activity for selection patients for treatment as well as on the use of tenofovir alafenamide as a safe and cost-effective alternative to tenofovir disoproxil fumarate. Though combination therapy of peginterferon and NA has induced HBsAg seroclearance in a small proportion of patients, peginterferon is not preferred in the future trend of drug development. [ABSTRACT FROM AUTHOR]

Background: The long-term incidence and factors associated with hepatitis B surface antigen (HBsAg) loss in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients receiving peginterferon is rarely reported.Methods: From 2004 to 2016, 233 HBeAg-negative CHB patients who completed 48 weeks of peginterferon treatment from 3 medical centers in Taiwan were retrospectively enrolled.Results: During a median follow-up of 7.4 years, 27 cases achieved HBsAg loss. The cumulative incidences of HBsAg loss and HBsAg seroconversion at 3, 5, 10 years after peginterferon treatment were 4.7%, 9.4%, 14.2%, and 3.5%, 6.4%, 12.5%, respectively, in overall patients, and 15.9%, 29.1%, 37.3%, and 13.1%, 19%, 30.6%, respectively, in patients achieving sustained off-treatment virological response (SVR). By multivariate analysis, age (<35 years; hazard ratio [HR] = 3.742, P = .007), baseline HBsAg levels (<1250 IU/mL; HR = 4.849, P = .002), HBsAg decline at week 24 (≥1 log; HR = 5.660, P = .002), and achieving SVR (HR = 8.546, P = .006) were predictors of HBsAg loss. After achieving SVR, HBsAg loss rates were higher than 30% in 5 years among patients with either younger age or lower HBsAg at baseline.Conclusions: HBsAg loss rate continues to increase after peginterferon treatment in HBeAg-negative CHB patients with SVR. Age, baseline HBsAg levels, on-treatment HBsAg decline, and achieving SVR are factors associated with long-term HBsAg loss. [ABSTRACT FROM AUTHOR]

Aim: This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).Methods: This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.Results: Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.Conclusions: Early treatment with DAA should be offered when available. [ABSTRACT FROM AUTHOR]

Background: Patients with a history of intravenous drug abuse included in an official opioid substitution program represent an important subgroup of patients with chronic hepatitis C. The objective of this study was to assess the efficacy of and adherence to treatment with peginterferon and ribavirin in Austrian patients on stable opioid substitution therapy (OST). Methods: This prospective, multicenter, observational, non-interventional trial (clinicaltrials.gov identifier, NCT01416610) included treatment-naïve patients with chronic hepatitis C on OST. Treatment consisted of peginterferon alpha-2a (PEGASYS®, 180 µg/week) plus ribavirin (COPEGUS®, 1000/1200 mg/day in genotypes (GT) 1/4 and 800 mg/day in GT 2/3) for 24-72 weeks, according to GT and viral response. Results: The intention-to-treat (ITT) population comprised 88 patients. Mean duration of therapy was 6.0 ± 2.8 months. Treatment was discontinued earlier than planned in 34 out of 88 patients (39%), mainly because of poor adherence or side effects of treatment. At the end of treatment 65/88 patients (74%) were PCR negative. During follow-up, 5 patients relapsed. Only 44/88 patients (50%) could be evaluated 24 weeks after the end of treatment. Sustained virologic response 24 weeks after end of therapy (SVR24) was documented in 39/88 patients (44%). If only patients were considered who finished treatment as planned and for whom results at follow-up week 24 were available, the SVR24 rate was 89% (32/36). Conclusion: Despite favorable prognostic factors, such as young age and a high proportion of GT3, SVR rates were low in this cohort of patients receiving OST, the main reason being poor adherence; however, in those patients completing treatment, the SVR rate was high. [ABSTRACT FROM AUTHOR]

Combining peginterferon-alfa-2a (peg IFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B ( CHB) patients after 5 years of follow-up. In the initial study, 92 CHB patients (44 HBeAg-positive, 48 HBeAg-negative) with HBV DNA >100 000 c/ mL (~20 000 IU/ mL) and active hepatitis were treated for 48 weeks with peg IFN 180 μg/week and 10 mg adefovir dipivoxil daily. For the long-term follow-up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HBeAg-positive, 38 HBeAg-negative) patients remained in the study. At year 5, 19% (6/32) of HBeAg-positive patients and 16% (6/38) of HBeAg-negative patients lost HBsAg, and no HBsAg seroreversion was observed. The 5-year cumulative Kaplan-Meier estimate for HBsAg loss was 17.2% for HBeAg-positive patients and 19.3% for HBeAg-negative patients. Fourteen of sixteen patients who lost HBsAg at any time point during follow-up developed anti- HBs antibodies (>10 IU/L). At year 5, in total 63% (20/32) of HBeAg-positive and 71% (27/38) of HBeAg-negative patients were retreated with nucleos(t)ide analogues during follow-up. The cumulative Kaplan-Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow-up, 18% of CHB patients treated with peg IFN/nucleotide analogue combination therapy had durable HBsAg loss and 88% of these had developed anti- HBs antibodies. [ABSTRACT FROM AUTHOR]

ABSTRACT CONTEXT: Recurrent respiratory papillomatosis (RRP) is the most common laryngeal tumor. During childhood, it may present in extremely severe forms defined by the need for frequent surgical procedures to relieve respiratory distress and/or involvement of extralaryngeal sites such as lung involvement. Adjuvant therapies are indicated in these cases and interferon is one of the options. Pegylated interferon is more effective than conventional alpha interferon and, given its reported results in relation to treating hepatitis C over the past decade, we hypothesized that this might be more effective than conventional interferon also for treating respiratory papillomatosis. Use of a treatment strategy that eliminates the need for general anesthesia is particularly appealing, yet obtaining approval for use of medications that are not currently used for this purpose is challenging. CASE REPORT: We report the case of a child with severe RRP that had been followed for the preceding six years, who was treated with pegylated interferon after failure of other adjuvant therapies. There was noticeable improvement in the frequency of surgical procedures, which was regarded very receptively, considering the child’s history and previous response to other therapies. CONCLUSION: Pegylated interferon may be a good option for diminishing the need for surgical intervention in severe cases of recurrent respiratory papillomatosis.

The antiviral treatment of Hepatitis C virus (HCV) infection is changing rapidly. Peginterferon and ribavirin are no longer the standard of care therapy and are being replaced by new drugs with greater efficacy and fewer adverse effects. These new direct-acting antivirals (DAAs), incorporated in interferon-based or all-oral regimens, cure more than 90% of infections, even in patients before considered difficult to treat, such as cirrhotic and non-responders. These agents allow shortening the treatment duration, improving sustained response rates (SVR) and have reduced toxicity. The goal of this review is to discuss the current stage of HCV therapy. We describe the mechanisms of the new drugs, the efficacy of the therapeutic regimens, and the predictors of SVR. Individual approach should be based on the different combinations of drugs, and treatment strategy should take into account the profile of the patient, the efficacy and safety of drugs as well as the reimbursement policy.

In the review is presented evolution of sights on treatment of patients with chronic hepatitises since 70-th years of XX century to the present days. Stages of development of therapy sick of chronic hepatitises В, С and D are consistently characterised. The basic emphasis is made on acurrent state of a problem and the prospects opening before researchers. Algorithms of treatment of patients with chronichepatitises are presented.

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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 (PEGIFNa/RBV) is a standard treatment, but our aim was to determine the efficacy and safety of dual PEGIFNa/RBV therapy in treating patients infected with HCV in Iranian context. Materials 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 (INFa) 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. Results: 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. [ABSTRACT FROM AUTHOR]

Background: In addition to the observation of an increased viremia among patients with chronic hepatitis C virus (HCV) infection who undergo renal transplantation, fibrosis and necroinflammatory activity have been noted to worsen comparing pre- and post-renal transplantation liver biopsies in some of these patients. Apart from the reported reduced patient and allograft survival rates, post-transplant diabetes mellitus, de novo glomerulonephritis, and an increased overall risk of infection have been observed. However, antiviral therapy for HCV is generally considered contraindicated among patients with solid organ transplants, with the main worry being the risk of acute rejection in relation to the use of interferon. We reported the long-term outcome of four renal transplant patients with chronic HCV infection who received peginterferon-based therapy. Methods: We collected the long-term follow-up data of four patients who completed the therapy with peginterferon in combination with ribavirin. Two of them had renal impairment at baseline. Results: With treatment, they had a significant improvement in terms of serum liver transaminase level, and two patients achieved the early virological response and the other two rapid virological response. All four patients achieved sustained virological response, with neither HCV flare up nor renal dysfunction during follow-up for a mean duration of 74.3 months after therapy. Conclusions: These results suggest that sustained HCV virological response may be achieved without allograft dysfunction, in selected renal transplant patients using a peginterferon-based therapy. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B infection ( CHB) causes up to 1.0 million deaths annually. Currently, more than 90% of CHB patients worldwide are receiving indefinite nucleos(t)ide analogue ( NA) therapy. New strategies for optimizing hepatitis B surface antigen ( HBsAg) loss are required for NA-treated patients as the majority are unable to achieve HBsAg loss and may require lifelong therapy. In hepatitis B e antigen ( HBeAg)-positive patients, switching from NAs to finite peginterferon (Peg IFN) therapy can double HBeAg seroconversion rates. One in five patients who switch to Peg IFN can achieve HBsAg loss, whereas patients who continue NA therapy typically do not. In HBeAg-negative NA-treated patients, add-on Peg IFN therapy achieves higher, albeit modest, HBsAg loss rates compared with continued NA monotherapy and offers the opportunity for NA-treated patients to achieve the inactive carrier state. In the absence of curative therapies, Peg IFN represents a valuable, finite option for NA-treated patients who would otherwise require potentially lifelong therapy. [ABSTRACT FROM AUTHOR]

Background The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. Methods PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). Results SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. Conclusion The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies. [ABSTRACT FROM AUTHOR]

A proportion of chronic hepatitis B patients with normal or only minimally elevated alanine aminotransferase ( ALT) levels display significant histologic changes and would benefit from antiviral therapy. We aim to evaluate the histologic abnormalities seen in these patients and then determine which of them would most likely respond to peginterferon therapy. One hundred and thirteen hepatitis B e antigen ( HBeAg)-positive patients with a normal or minimally elevated ALT level and moderate-to-severe histologic changes in their liver tissue were selected to receive peginterferon monotherapy and participate in a follow-up analysis. A multiple logistic regression analysis indicated that increasing age ( P=.049) and lower hepatitis B virus ( HBV) DNA levels ( P=.038) were associated with significant histological abnormalities in patients with a normal or minimally elevated ALT. Our predictive model which incorporated HBeAg testing at treatment week 12 combined with hepatitis B surface antigen ( HBsAg) testing at treatment week 24 was able to identify which patients with a normal ALT level would achieve a sustained virological response ( SVR) (positive predictive value [ PPV]: 66.7%, negative predictive value [ NPV]: 90.0%). Lower HBsAg and HBeAg levels at treatment week 24 were associated with a SVR in patients with a minimally elevated ALT level ( PPV: 100.0%, NPV: 100.0%). A liver biopsy and antiviral therapy should be strongly considered when treating HBeAg-positive patients with a normal or minimally elevated ALT level, low HBV DNA level, and aged >35 years. On-treatment quantification of combined HBsAg and HBeAg test results may be useful for predicting a SVR to peginterferon monotherapy in these patients. [ABSTRACT FROM AUTHOR]

Background: This Phase 3, open-label, rollover study (NCT01323244) investigated the efficacy and safety of simeprevir plus peginterferon α-2a (PegIFNα-2a) and ribavirin (RBV) in a well-characterized population of HCV genotype 1 (GT1)-infected treatment-experienced patients.Methods: Patients who had failed PegIFNα/RBV treatment in the placebo arm of a previous Phase 2/3 simeprevir study (Phase 2/3 group, n = 125), or had been exposed to HCV direct-acting antivirals (simeprevir or other) for up to 14 days in a selected Phase 1 study (Phase 1 group, n = 16), were eligible. Phase 2/3 group patients were classified according to prior relapse, breakthrough, or non-response (null response, partial response, non-classifiable non-response) to PegIFNα/RBV. Eight patients in the Phase 1 group received short-term (≤14 days) simeprevir. Treatment comprised simeprevir 150 mg once daily (QD) plus PegIFNα-2a/RBV for 12 weeks followed by PegIFNα-2a/RBV for 12 or 36 weeks (using response-guided therapy [RGT] to determine total treatment duration in Phase 2/3 prior relapsers or breakthrough) or 36 weeks fixed (Phase 2/3 group non-responders and Phase 1 group). The primary endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12).Results: Phase 2/3 group: SVR12 rate was 69.6% (87/125) overall; 92.7% (51/55), 60.0% (6/10), 64.3% (18/28), and 36.7% (11/30) in patients with prior relapse, viral breakthrough, partial response, or null response, respectively. SVR12 rates were similar for patients with HCV GT1a (66.0% [33/50]) and GT1b infection (72.0% [54/75]) and among HCV GT1a-infected patients with/without a baseline Q80K polymorphism (66.7% [8/12] and 65.8% [25/38], respectively). The majority of RGT-eligible patients (prior viral relapse or breakthrough) met RGT criteria (89.2% [58/65]); of these, 89.7% (52/58) achieved SVR12. Overall, 16.0% (20/125) of patients experienced on-treatment failure and 14.4% (18/125) experienced post-treatment failure (15 relapses, 3 missing data). Phase 1 group (simeprevir-naïve and -experienced patients combined): SVR12 rate was 37.5% (6/16). Safety and tolerability findings were comparable to those of the feeder studies.Conclusions: The majority of RGT-eligible patients met criteria for shortening treatment to 24 weeks in total. Simeprevir 150 mg QD with PegIFNα-2a/RBV led to a high SVR rate among prior relapsers with HCV GT1 infection. No new safety signals were noted.Trial Registration: NCT01323244 . (date of registration: March 24, 2011). [ABSTRACT FROM AUTHOR]

Introduction. Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. Material and methods. A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (C, 2014) and utilities were obtained from literature. Results. Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to C102,841 (strategy 1) and C105,408 (strategy 2) in HBeAg-positive, and C85,858 and C93,754 in HBeAg-negative. A C1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications. [ABSTRACT FROM AUTHOR]

Background and Aim Clinically applicable models to predict hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) response to peginterferon (PEG-IFN) are scarce. This study aimed to develop simple scoring systems, based on multiple parameters, for predicting sustained HBeAg seroconversion to PEG-IFN. Methods Eighty-five treatment-naïve patients with HBeAg-positive CHB underwent 52-week PEG-IFN treatment and 24-week follow-up. Logistic regression analysis assessed parameters at baseline and weeks 12, 24, and 52 to predict HBeAg seroconversion at week 24 off-treatment. The best three predictors at each time point were included in prediction models of PEG-IFN therapy efficacy. Results The three most meaningful predictors were alanine aminotransferase (ALT) > 5 × ULN, HBeAg ≤ 500 S/CO, and antibody to hepatitis B core antigen (anti-HBc) > 10.7 S/CO at baseline; HBeAg ≤ 20 S/CO, anti-HBc > 11.7 S/CO, and HBeAg decline > 1 log10 S/CO at week 12; ALT > 2 × ULN, HBeAg ≤ 15 S/CO, and anti-HBc > 10.4 S/CO at week 24; HBeAg ≤ 5 S/CO, anti-HBc > 11.1 S/CO, and hepatitis B virus DNA decline > 2 log10 copies/mL at week 52. Parameters meeting optimal cutoff thresholds were scored 1 or otherwise scored 0. For total scores of 0 versus 3 at baseline and weeks 12, 24, and 52, response rates were 6.3%, 12.5%, 0%, and 0% versus 90.0%, 83.3%, 76.9%, and 86.4%, respectively. Conclusions We successfully established prediction models for PEG-IFN response in HBeAg-positive CHB. [ABSTRACT FROM AUTHOR]

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

Hepatitis B virus is the most important infectious hazard in dental profession. Vectors of HBV infection are not only blood, but also saliva, nasopharyngeal secretions, crevicular fluid.The aim of the study was to evaluate serum and salivary HBV DNA levels in subjects with chronic infection and dynamics of HBV levels during the first 3 months of peginterferon α-2a therapy to be determined. Nineteen parallel samples were tested for HBV DNA by real-time PCR assay. All nineteen sera were positive for HBV DNA with levels ranging from 494 to 6 300 000 000 cp/ml. HBV DNA was detected in all saliva samples even in patients with very low viremia. HBV DNA levels in serum and saliva were quite similar in cases with serum HBV DNA < 10 000 cp/ml. Patients with viremia higher than 10 000 cp/ml had significantly lower HBV DNA levels in saliva.The presence of HBV DNA in saliva might not be only due to transudation or exudation of fluid containing virus from the general circulation into various body fluids. These facts clearly demonstrate the role of saliva in routes of HBV transmission. Our results confirm the possibility of dentist’s particiation in infection transmission and suggests that salivary analysis holds promise as a non-invasive approach to identify biomarkers for diseases.

Background/AimsGenotype C is the principal type of hepatitis B virus (HBV) in Koreans and is associated with poor prognosis for peginterferon α-2a therapy. The efficacy of and compliance to peginterferon α-2a therapy were investigated in Koreans with hepatitis B in a real clinical setting.Methods : Hepatitis B patients treated with peginterferon α-2a from 2008 to 2011 at four university hospitals were consecutively enrolled.Results : Eighty-eight patients were enrolled; 67 were hepatitis B e antigen (HBeAg)-positive. The mean treatment period was 36.1±15.2 weeks. In 26.1% of patients, treatment was discontinued due to insufficient antiviral effects and adverse events. At 24 weeks after treatment, 10/42 (23.8%) HBeAg-positive patients achieved both HBV DNA suppression to 2×106 IU/mL.Conclusion : sPeginterferon α-2a therapy in Koreans with hepatitis B in a real clinical setting resulted in a lower virologic response, as compared to Western individuals, but a favorable durability. There is a need to reduce the high rate of premature discontinuation compared to the controlled studies.

The hepatitis C virus (HCV) genotype is an important predictive outcome parameter for pegylated interferon plus ribavirin therapy. Most published therapeutic trials to date have enrolled mainly patients with HCV genotypes 1, 2 and 3. Limited studies have focused on genotype 4 patients, who have had a poor representation in pivotal trials. Our aim was to evaluate the efficacy and safety of treatment with standard dose pegylated interferon alfa-2a in combination with weight-based ribavirin in patients with chronic hepatitis C genotype 4. In this prospective observational study, 198 patients with HCV-4 were included in this study from February 2004 to August 2005,188 patients who received at least 1 dose of drugs were included in the ITT analysis and they were treated with pegylated interferon alfa-2a and ribavirin for 48 weeks. Baseline and demographic characteristics, response to treatment at weeks 12, 48 and 72, and the nature and frequency of adverse effects were analyzed. Virological response at week 12 was achieved in 144 patients (76.6%). Virological response at the end of treatment was present in 110 patients (58.5%). At week 72, 99 patients presented SVR (52.7%). The reported adverse events were similar to those found in the literature for treatments of similar dose and duration. In conclusion, combined treatment with pegylated interferon alfa-2a and ribavirin was well tolerated and effective in chronic hepatitis C genotype 4, yielding response rates between those reported for genotype 1 and those of genotypes 2-3.

Background/AimsSustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients.MethodsThis was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860.ResultsOverall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR.ConclusionsThe SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR.

Positive serum antinuclear antibody (ANA) is not infrequent in chronic hepatitis C virus (HCV)-infected patients. This prospective study evaluated the impact of ANA on the response to and safety of peginterferon/ribavirin combination therapy for chronic hepatitis C patients in clinical practice. We enrolled 243 consecutive patients who were treated with a 24-week regimen of peginterferon-α plus ribavirin, with a 24-week follow-up period. ANA titer was determined before antiviral treatment. The primary end-point was sustained virological response (SVR), defined as HCV RNA

Chronic infection with the hepatitis C virus (HCV) is associated with impaired lipid metabolism. The aim of this study was to determine the impact of antiviral response on the serial change of serum lipids in chronic HCV patients. Methods: A total of 165 consecutive patients with HCV infection were prospectively enrolled. Serum total cholesterol (TC) and triglyceride (TG) levels in these subjects were compared with age, sex and body mass index-matched healthy individuals and 55 patients with chronic infection with hepatitis B virus (HBV). Serum lipid levels were measured in 143 patients with chronic HCV infection receiving pegylated interferon plus ribavirin therapy at baseline, at the end of treatment, and at week 24 after the end of treatment. Results: Patients with chronic HCV infection had significantly lower total TC and TG levels than normal controls (both p < 0.001). Serum TC levels were lower in HCV patients than in those infected with HBV (p < 0.001). Pretreatment serum lipid levels were not independent factors associated with sustained virological response (SVR). Among patients achieving a SVR, serum TC and TG levels significantly increased from 165 ± 30 mg/dL and 100 ± 47 mg/dL at baseline to 191 ± 36mg/dL (p < 0.001) and 116 ± 77 mg/dL (p = 0.029) at week 24 posttreatment, whereas no evident change in lipid profile occurred in the non-SVR group. Conclusion: Our data suggest that chronic HCV infection is associated with hypocholesterolemia and hypotriglyceridemia, which can be reversed by successful eradication of HCV. The clinical significance of hypolipidemia reversal among SVR patients, such as the risk of coronary artery or cerebral vascular disease, should be further investigated.