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Background None of the current guidelines recommend antiviral therapy for inactive hepatitis B virus (HBV) carriers (IHCs). Methods In this real-world, multicenter, nonrandomized study, 32 participants meeting the inclusion criteria were enrolled 1:1 for treatment with peginterferon α-2b or monitoring without treatment based on participant preference. The expected treatment duration was 48 weeks. The primary end point was hepatitis B surface antigen (HBsAg) loss. The HBV vaccine could be injected after HBsAg loss. Results All patients had HBsAg levels of <20 IU/mL. The mean baseline HBsAg levels were 6.6 IU/mL and 5.8 IU/mL in the treated and untreated groups, respectively. Fifteen (93.8%) participants achieved HBsAg loss, 5 obtained HBsAg seroconversion after undergoing a mean of 19.7 weeks of therapy in the treated group, and no one in the follow-up group achieved HBsAg loss during a mean follow-up time of 12.6 months (P <.0001). Generally, the therapy was well tolerated. Nine of 11 individuals who exhibited HBsAg loss benefited from receiving the HBV vaccine. Conclusions This study provides justification for further studies of short-course peginterferon α-2b for the functional cure of IHCs with low HBsAg levels. Additionally, HBV vaccine injection is beneficial after interferon-induced HBsAg loss. [ABSTRACT FROM AUTHOR]

Objective: To investigate the the clinical efficacy, safety and effects of entecavir combined with peginterferon α-2 b in the treatment of hepatitis B E antigen(HBeAg) positive hepatitis B. Methods: 97 cases of HBeAg positive hepatitis B patients enrolled in our hospital from October 2015 to October 2017 were divided into control group(n=48) and observation group(n=49) by random number table methods. The control group was treated with subcutaneous injection of peginterferon α-2 b, while the observation group was treated with entecavir combined with peginterferon alpha-2 b. The clinical efficacy, the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT) and hepatitis B virus DNA(HBV-DNA), the conversion rate of HBeAg serological, the seroconversion rate of hepatitis B virus deoxyribonucleic acid(HBV-DNA), and the incidence of adverse reactions of the patients in the two groups after treatment was compared. Results: The total effective rate of observation group was 91.84%, which was significantly higher than that of control group(x2=8.50, P<0.05). After treatment, the contents of ALT, AST and HBV-DNA in observation group was significantly lower than those in control group(P <0.05), the repetition rate of ALT, the conversion rate of HBeAg serological,the seroconversion rate of HBV-DNA rate was significantly higher than those of the control group(P<0.05). After treatment, the incidence of adverse reactions in the observation group was 30.61%, compared with 29.17% in the control group, the difference was not statistically significant(P>0.05).Conclusion: The efficacy of entecavir combined with peginterferon α-2 b in the treatment of HBeAg positive hepatitis B is better than that of interferon alone, it can reduce the contagiousness and has a good safty. [ABSTRACT FROM AUTHOR]

Objectives: Interferon (IFN) treatment has many neuropsychiatric side effects such as depression and anxiety disorder. Although untreated depression is a major contributor to dosage reduction or premature discontinuation of the IFN treatment, it is found that depressive symptoms among patients undergoing hepatitis C virus (HCV) treatment are commonly overlooked during routine clinical interviews. Besides depression, anxiety disorders are shown to affect adherence to pegylated IFN (Peg-IFN) treatment in patients with hepatitis C. Despite the occurrence of neuropsychiatric side effects of IFN treatment being widely reported in patients with hepatitis C, there are few studies studying patients infected with hepatitis B virus (HBV). The aim of this prospective study was to evaluate the incidence and risk factors of depressive and anxiety disorders that occur during Peg-IFN treatment of patients with HBV. Methods: The sample consisted of volunteer patients who were diagnosed with HBV infection and who were decided to receive IFN treatment. During the study period, all consecutive patients with HBV infection and who would have IFN treatment were informed about the study and invited to participate. Thirty-seven chronic hepatitis B (CHB) patients were recruited for the study, but four of them were excluded due to psychiatric diagnosis at the initiation of the treatment. Therefore, the sample consisted of 33 patients with CHB, meeting the inclusion criteria. The participants had psychiatric assessment before the treatment and at 1st, 3rd, 6th, and 12th months. At each visit, the subjects were assessed with Clinical Global Impressions Scale, Hamilton Rating Scale for Depression (HRSD), and Hamilton Anxiety Rating Scale (HAM-A). Results: Among the 33 patients with HBV, 22 (66.7%) were men. Mean age was 35.97 ± 10.73 years. While follow-up, 6 patients dropped out from the study. Also, 13 patients were excluded from the study as they developed depression and/or anxiety disorder. Mean baseline HRSD and HAM-A scores were smaller than the following visits’ scores. The difference was not statistically significant only for the 12th month assessments. Totally 14 (42.4%) patients developed depression/anxiety disorder during 1 year follow-up. Six (42.86%) of them received the diagnosis at the 1st month, 3 (21.43%) at the 3rd, 4 (28.57%), at 6th months, and 1 (7.14%) at the 12th month. When we compared the patients who developed depression/anxiety disorder with the patients who did not develop any psychiatric disorder, we found that the mean baseline HRSD score (t = 2.303, p = .028) and female percentage (p = .017) were statistically significantly higher in the depression/anxiety disorder group. Conclusions: There is an incidence of 42.4% for depression and/or anxiety disorders during Peg-IFN treatment. Females and patients with subsyndromal depressive symptoms should be referred to a psychiatrist and closely monitored especially for the first three months of the IFN treatment.

Objective: Treatment of chronic hepatitis C virus (HCV) infection with pegylated interferon (PeglFN) and ribavirin causes haematological side effects such as anemia, neutropenia and trombocytopenia. This study aimed to evaluate and compare the haematological side effects of PeglFN α-2a and PeglFN α-2b with ribavirin in the treatment of chronic HCV infection. Methods: 103 patients treated with PeglFN α-2b plus ribavirin and 70 patients treated with PeglFN α-2a plus ribavirin were included in this retrospective study. Patients' haematological parameters in first and third month's visits were compared with pretreatment test results. Results: ln all patients, 21.2% had anemia (haemoglobin <10 g/dL), 3.8% had neutropenia (<750/mm²) and 6.2% had thrombocytopenia (<75x109/L) at the end of the third month. When compared with initial levels, significant decreases in haemoglobin, neutrophil and thrombocyte counts were observed at first and third months in both groups. There wasn't a significant decrease in thrombocyte counts in the first month between two groups, however, a more significant decrease in thrombocyte counts were observed in patients who received PeglFN α-2a plus ribavirin than the patients receiving PeglFN α-2b plus ribavirin during the third month. Conclusions: PeglFN α-2b seems to have similar haematologic side effects, compared with PeglFN α-2a except the effects on the thrombocyte counts during the third month. [ABSTRACT FROM AUTHOR]

The ideal approach to treat chronic hepatitis B remains controversial. This pilot study aimed to evaluate the effectiveness of peginterferon (PEG-IFN) α-2b and entecavir hydrate (ETV) as a combination therapy for patients with chronic hepatitis B, particularly in the context of virological response and the reduction of intrahepatic covalently closed circular DNA (cccDNA). A total of 17 patients with hepatitis B virus (HBV) genotype C were enrolled in this study. All subjects were treated with this combination therapy for 48 weeks and observed for an additional 24 weeks. All patients underwent liver biopsy before and after the therapy period. Changes in cccDNA levels and liver histology were monitored between biopsies. Among the 11 patients who exhibited pre-therapy hepatitis B e antigen (HBeAg), 8 (73%) showed evidence of HBeAg seroconversion by the end of the follow-up period. Serum HBV DNA levels decreased by 5.2 and 3.3 log copies/ml (mean) by the end of the therapy and follow-up periods, respectively. In addition, intrahepatic cccDNA decreased significantly to 1.4 log copies/µg (mean) by the end of the therapy period. Among the 11 patients who did not experience viral relapse, only 2 (18%) exhibited high levels of cccDNA (>4.5 log copies/µg) by the end of the treatment period. In contrast, all relapsed subjects exhibited significantly higher levels of cccDNA than subjects who did not relapse ( P = 0.027). The combination regimen is a promising approach to treat chronic hepatitis B and may achieve significant reduction in serum HBV DNA and intrahepatic cccDNA. J. Med. Virol. 85: 987-995, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients. Methods: A total of 201 PegIFN-naïve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180 μg) or PegIFNα-2b (60-150 μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B ( IL28B) gene (rs8099917). Results: PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P = 0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19-15.50, and odds ratio 7.31; 95% CI 3.45-4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P = 0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60 kg, women, and patients aged >60 years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively). Conclusions: PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype. [ABSTRACT FROM AUTHOR]

Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patient's lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patient's own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinib's effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-γ-producing-CD8, -CD4, -NK cell, and IFN-γ-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types. [ABSTRACT FROM AUTHOR]

Background: Antiviral therapy for chronic hepatitis D (delta) is not yet satisfactory, although it appears to be the only means to alter the progressive natural course of chronic hepatitis D virus (HDV) infection. Aim: To assess safety and efficacy, evaluated by virological, biochemical and histological end-of-treatment (EOT) and end-of-follow-up (EOF) response to Peg-Interferon α-2b 1.5μg/kg body weight weekly in a Romanian cohort of naïve patients with chronic hepatitis delta. Results: 49 Caucasian patients (55.1% men, 44.9% females) with a mean age of 37.95 years received study medication; per-protocol population consisted of 36 subjects. Virological EOT response was present in 33.3% and EOF response was maintained in 25% of patients. 50% of study population showed normalization of ALT level at EOT and 25% at EOF. A combined biochemical and virological response was observed in 19.4% of patients at EOT and in 16.7% at EOF. At baseline, the necroinflammation quantified by histological activity index (HAI) score was 9.72 and the mean fibrosis score was 2.03; there was a significant decrease of HAI score to 7.44 (p=0.01) at EOT, but not for fibrosis score (1.33, p=0.37). However, only 8.3% of patients at EOT and 19.4% at EOF had progressive histological disease. Conclusions: Treatment with Peg-Interferon α-2b succeeded in obtaining a negative HVD RNA in 25% of patients after 104 weeks of follow-up, although combined biochemical and virological response was present in only 16.7%. Necroinflammation decreased significantly in treated patients. Longer treatment periods with pegylated interferon or combination regimen peginterferon-nucleotide analogues should be tested in order to increase efficacy. [ABSTRACT FROM AUTHOR]

Purpose: High-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon α-2b in patients with high-risk melanoma. Methods: For PK analysis, 32 patients received peginterferon α-2b 6 μg/(kg week) subcutaneously for 8 weeks (induction) then 3 μg/(kg week) for 4 weeks (maintenance). PK profiles were determined at weeks 1, 8, and 12. Exposure-response relationships between peginterferon α-2b and absolute neutrophil count (ANC) and alanine aminotransferase (ALT) level were also studied. Results: Peginterferon α-2b was well-absorbed following SC administration, with a median T of 24 h. Mean half-life estimates ranged from 43 to 51 h. The accumulation factor was 1.69 after induction therapy. PK parameters showed moderate interpatient variability. PK profiles were described by a one-compartmental model with first-order absorption and first-order elimination. Toxicity was profiled and was acceptable; observed side effects were similar to those previously described. Dose reduction produced proportional decreases in exposure and predictable effects on ANC in an Imax model; however, a PK/pharmacodynamic (PK/PD) relationship between peginterferon α-2b and ALT could not be established with high precision. Conclusions: Peginterferon α-2b was well-absorbed and sustained exposure to peginterferon α-2b was achieved with the doses tested. These data confirm and extend previous PK observations of peginterferon α-2b in melanoma and solid tumors. Our PK/PD model of exposure and ANC effect provides useful information for prediction of peginterferon α-2b-related hematologic toxicity. [ABSTRACT FROM AUTHOR]

Background: The standard treatments for chronic infection with the hepatitis C virus (HCV) are peginterferon α-2a or α-2b plus ribavirin, but it remains unclear if one has a better efficacy and safety profile. Objective: The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing peginterferon α-2a and α-2b (in combination with ribavirin) treatments for chronic HCV. Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, Science Citation Index, and EMBASE were searched (1966–April 2010) to identify RCTs that evaluated the sustained virologic response (SVR) to peginterferon α-2a and peginterferon α-2b in patients with chronic HCV. The inclusion criteria were: RCT studies designed to compare the therapeutic effects of peginterferon α-2a (180 μg/wk) and peginterferon α-2b (1.5 μg/kg/wk) for treatment-naive patients with chronic HCV; patients treated for ≥24 weeks if infected with HCV genotypes 2 or 3 and for ≥48 weeks if infected with genotypes 1 or 4, with 24-week follow-ups; and publications written in any language. Reports of duplicated studies were excluded by examining the author list, parent institution, sample size, and results. The primary outcome was the SVR, and the other measures included the liver-related morbidity, all-cause mortality, and adverse events leading to treatment discontinuation. Results: The literature search yielded 5580 studies, and 7 RCTs comprising 3212 patients matched the inclusion/exclusion criteria. Overall, the SVR rate was significantly higher in patients treated with peginterferon α-2a than in patients treated with peginterferon α-2b (50% vs 46%, respectively; relative risk [RR] = 1.11; 95% CI, 1.02–1.20; P < 0.05) and varying levels of ribavirin treatment. The subgroup analysis found that, in patients with genotypes 1 or 4, the difference between SVR rate in patients treated with peginterferon α-2a and patients treated with peginterferon α-2b was not statistically significant (43% vs 39%; RR = 1.25; 95% CI, 0.99–1.57). A significantly higher SVR rate was achieved in the HCV patients with genotypes 2 or 3 treated with peginterferon α-2a compared with the patients treated with peginterferon α-2b (86% vs 77%; RR = 1.11; 95% CI, 1.02–1.22; P = 0.02). The meta-analysis of adverse events leading to treatment discontinuation revealed no significant differences between the 2 treatments. Conclusions: The evidence reviewed in this meta-analysis suggests that peginterferon α-2a treatment was associated with a higher SVR rate than peginterferon α-2b treatment in patients with chronic HCV also treated with ribavirin. However, the available evidence on adverse events was insufficient to make recommendations. [Copyright &y& Elsevier]

In patients with chronic hepatitis C, rapid virological response (RVR) at week 4 of treatment seems to be strongly associated with a high probability of achieving a sustained virological response (SVR). The aim of this study was to investigate the outcome of different pegylated interferon-α2b (Peg-IFN-α2b) dosages plus ribavirin (RBV) in patients with RVR. Forty-five naïve patients chronically infected with hepatitis C virus (HCV)-1b started Peg-IFN-α2b (1.5 μg/kg/week) in combination with weight-based RBV doses (800–1200 mg/day). Thirty-one patients (68.9%) attained RVR at week 4 of therapy, while four further patients showed negative HCV-RNA values for the first time at week 12 and were considered early virological responders (EVR). The 31 RVR patients were randomized to receive either RBV plus 1.5 μg/kg/week (17 pts) or 1.0 μg/kg/week (14 pts) of Peg-IFN-α2b for the remaining 44 weeks. The two groups were matched for age, sex, baseline alanine aminotransferase levels, viral load and fibrosis score. After 6 months of post-treatment follow-up, the prevalence of SVR was 94.1% (16/17) among RVR patients treated with 1.5 μg/kg/week and 92.8% (13/14) in RVR patients treated with 1.0 μg/kg/week ( P = not significant). A high-baseline viral load ( P = 0.01) and bridging fibrosis/cirrhosis ( P = 0.02) negatively influenced the likelihood of achieving RVR. On the contrary, the ability of RVR patients to achieve SVR did not correlate with these baseline characteristics in either of the treatment group. Finally, the SVR rate among EVR patients who responded after more than 4 weeks of treatment was significantly lower than among RVR patients (1/4 = 25% vs 29/31 = 93.5%; P = 0.0058), because of a high prevalence of post-treatment relapse among patients with EVR. [ABSTRACT FROM AUTHOR]

Current models used to predict response to peginterferon plus ribavirin treatment, based on viral decline during the first 12 weeks of therapy, have focused on creating an early stopping rule to avoid unnecessary prolongation of therapy. We developed a multivariate model that predicted sustained virological response and nonresponse at baseline and during the first 12 weeks of therapy using collected data from 186 unselected patients with chronic hepatitis C treated with peginterferon plus ribavirin. This model employed ordinal regression with similarity least squares technology to assign the probability of a given outcome. Model variables include sex, age, prior treatment status, genotype, baseline serum alanine aminotransferase levels, histologic necroinflammation and fibrosis scores and serum hepatitis C virus RNA concentration at baseline and weeks, 4, 8, and 12. A multivariate model demonstrated high performance values at all time points. At baseline, the model demonstrated a negative predictive value (NPV) and a positive predictive value (PPV) of 91% and 95%, respectively. At week 4, these values improved to 97% and 100%, respectively, with 95% sensitivity, 89% specificity and 93% accuracy. At week 4, the model was equally efficient for naïve or previously treated patients. Internal validation demonstrated 90% PPV, 94% NPV, 95% sensitivity, 88% specificity and 92% accuracy. A week 4 stopping rule for patients with chronic hepatitis C treated with peginterferon with ribavirin might be proposed by using the model developed in our study. [ABSTRACT FROM AUTHOR]

Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy-proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferonα-2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group,n = 76) or 3 MU of interferonα-2b t.i.w. plus ribavirin (IFN group,n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN (65.8%vs41.0%,P = 0.019), but no difference was found in genotype non-1 patients (PEGvsIFN: 68.4%vs86.8%,P = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG-IFNα2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNα2b ribavirin. [ABSTRACT FROM AUTHOR]

Gallegos-Orozco JF, Loaeza-del Castillo A, Fuentes AP, García-Sandoval M, Soto L, Rodríguez R, Gutiérrez-Ruíz MC, Gutiérrez-Reyes G, Bonder A, Olivera MA, Kershenobich D. Early hepatitis C virus changes and sustained response in patients with chronic hepatitis C treated with peginterferonα-2b and ribavirin.Liver International 2005: 25: 91–95.© Blackwell Munksgaard 2005Interferon-based therapy induces changes in viral dynamics in chronic hepatitis C (CHC) patients.The aim of this study was to assess early hepatitis C virus (HCV)-RNA changes and evaluate its predictive value to achieve sustained viral response (SVR) in patients with CHC treated with peginterferonα-2b weekly plus ribavirin daily for 48 weeks.HCV-RNA was measured at baseline, 48 h, 4, 12, 24 and 48 weeks of treatment and 24 weeks after treatment.Eighteen HCV genotype 1 patients were included (13 male, five female) with a mean age of 44.4±11.9 years. Nine patients achieved SVR (50%). Viral decline occurred as early as 48 h; the magnitude of decline was statistically different between both groups (P<0.01). Responders had a≥1 log10 drop in HCV-RNA at 48 h (positive predictive value (PPV) of 89% to achieve SVR) that persisted at week 4. By week 12, serum HCV-RNA was undetectable (PPV 100%).Our data indicate that peginterferonα-2b plus ribavirin treatment produces significant changes in HCV dynamics that can be detected as early as 48 h after the first dose of peginterferonα-2b and that these changes are useful in predicting response to therapy in CHC patients. [ABSTRACT FROM AUTHOR]