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Background: Hepatitis C virus (HCV) infection is a serious problem in low and middle income countries including Pakistan. Objective: To compare the efficacy of combination therapy, Sofosbuvir plus Ribavirin with and without Pegylated Interferon-α in HCV genotype 3a infected patients. Study Design: Randomized control trial Place and Duration: Department of Gastroenterology, Pakistan Institute of Medical Sciences (PIMS), Islamabad, during from 16th April 2017 to 15th October 2017. Methodology: One hundred and fifty four HCV infected patients with genotype 3a were included in this study. Detailed demographics were recorded after taking informed written consent. Patients were divided in two groups (A and B) randomly, Group A was offered with Sofosbuvir plus Ribavirin with Pegylated Interferon-α for 12 weeks and Group B was offered with Sofosbuvir plus Ribavirin for 24 weeks. The sustained virological response (SVR) after 12 weeks of therapy was compared between the study groups. Results: The frequency of SVR12 was comparatively higher in patients treated with Sofosbuvir plus Ribavirin with Pegylated Interferon-α (94.8%) than Sofosbuvir plus Ribavirin alone (84.4%) with similar trends in gender and age groups. Conclusion: The combination therapy Sofosbuvir plus Ribavirin with Pegylated Interferon-α had higher eradication rate against HCV genotype 3a in our local setting. Key Words: HCV, genotype 3a, Sofosbuvir, Ribavirin, Pegylated Interferon-α, SVR12

Infekce virem hepatitidy B (HBV) představuje stale celosvětově zdravotni problem s epidemiologii měnici se v zavislosti na řadě faktorů, předevsim na vakcinacni politice a migraci. Chronicka infekce HBV je oznaceni pro infekci trva-jici dele než 6 měsiců. Jedna se o dynamický proces, který odraži interakce mezi virovou replikaci a hostitelskou imunitni odpovědi. Ne vsichni pacienti chronicky infikovani HBV maji chronickou hepatitidu B. Vsechny osoby chronicky infikovane HBV jsou ve zvýsenem riziku progrese do jaterni cirhozy a hepatocelularniho karcinomu. Dlouhodobe podavani ucinných nukleosidových nebo nukleotidových inhibitorů reverzni transkriptazy s vysokou genetickou barierou proti vzniku rezistence (tenofovir, entekavir) představuje v soucasnosti nejucinnějsi lecbu chronicke hepatitidy B. U pacientů s mirně až středně pokrocilou lze použit k lecbě i pegylovaný interferon α.

Despite significant progress, the treatment options for myeloproliferative neoplasms (MPN) are still limited. Interferon#945; (IFN#945;) has been recognized as a substance for the treatment of MPN for more than 30 years, but its widespread use has been limited by higher frequency of short-term adverse reactions compared to conventional treatment and until recently, by its off-label indication in BCR/ABL negative MPNs. With the development of pegylated forms of IFN#945; with a more favorable toxicity and pharmacokinetic profile have renewed interest in the use of IFN#945; in the treatment of MPN. Recent studies confirm that IFN#945; is important drug capable of reducing the tumor population in MPN. Thus, IFN#945; is currently a more frequently considered drug in the treatment of MPN and has adop-ted into of some expert recom-mendations as a first-line drug for younger patients with various subtypes of MPN.

The classical myeloproliferative neoplasms (MPN) are uncommon clonal haematopoietic malignancies characterised by excessive production of mature blood cells. Clinically they are associated with thrombosis, haemorrhage, varying degrees of constitutional disturbance, and a risk of progression to myelofibrosis or acute myeloid leukaemia. Many of the disease manifestations may be ameliorated by treatment with interferon‐α (IFN) but its use in Australian MPN patients has been limited due to the inconvenience of frequent injections and side effects. The pegylated form of IFN is a long‐acting preparation which is better tolerated and its Pharmaceutical Benefits Scheme listing is likely to lead to increased usage. We review the literature on risks and benefits of IFN treatment for MPNs, suggest criteria for patient selection in each of these diseases, and discuss strategies to manage the side effects of pegylated IFN. Refereed/Peer-reviewed

Background Serum hepatitis B core-related antigen (HBcrAg) levels refect intrahepatic HBV replication activity. We aimed to study whether HBcrAg levels predict response to pegylated interferon (PEG-IFN) treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. Methods We studied HBcrAg levels in 222 HBeAg-positive patients treated with PEG-IFN with or without lamivudine for 52 weeks in a global randomized trial and compared kinetics across treatment arms and types of response. Optimal HBcrAg cutoffs for stopping therapy were compared to and combined with the currently recommended hepatitis B surface antigen (HBsAg)-based stopping-rules. Results Baseline HBcrAg levels could not discriminate between responders and non-responders ( P=0.91). HBcrAg levels of patients responding to PEG-IFN therapy showed a more pronounced on-treatment decline (mean declines 3.4 versus 1.0 log U/ml; P8.35 log U/ml at week 24 identified 19 patients (19%) of whom 1 (negative predicitve value [NPV]=95%) achieved a response. The performance of this HBcrAg-based stopping rule alone was not superior to the one based on HBsAg >20,000 IU/ml. Among patients with an HBsAg 8.35, of whom 8 achieved no response (NPV 89%). Conclusions HBeAg-positive CHB patients with a response to PEG-IFN therapy achieve a more pronounced HBcrAg decline. HBcrAg levels at week 24 of therapy could be used to identify non-responders in combination with the established HBsAg-based stopping-rules.

Pegylated interferon-alpha (pIFN-α) is suggested to lower human immunodeficiency virus type-1 (HIV-1) DNA load in antiretroviral therapy (ART)-treated patients. We studied kinetics of HIV-1 DNA levels in 40 HIV-1/hepatitis C virus (HCV) coinfected patients, treated with pIFN-α for HCV and categorized into 3 groups according to start of ART: chronic HIV-1 infection (n = 22), acute HIV-1 infection (n = 8), no-ART (n = 10). Total HIV-1 DNA levels in 247 peripheral blood mononuclear cell samples were stable before, during, and after pIFN-α treatment in all groups. Our results question the benefit of pIFN-α as an immunotherapeutic agent for reducing the HIV-1 reservoir.

Background Recent studies suggest that serum lipids are associated with pegylated interferon-alpha (PEG-IFN-α) treatment response in chronic hepatitis C patients. However, the role of serum lipids in influencing the outcome of HBV treatment is not well understood. This study aims to investigate the association of serum lipids with the response to interferon-alpha treatment for chronic hepatitis B (CHB) patients. Methods We dynamically measured 11 clinical serum lipid parameters of 119 hepatitis B e antigen (HBeAg)-positive CHB patients, including 53 patients who achieved sustained response (SR) and 66 patients who achieved non-response (NR) induced by PEG-IFN-α treatment for 48 weeks. Results The dynamic analysis showed that the baseline serum total cholesterol (TCHO) level was higher in the NR group than that in the SR group ( P=0.004). Moreover, the correlation analysis demonstrated a significant positive correlation between TCHO and hepatitis B surface antigen (HBsAg) at baseline ( P=0.009). In addition, CHB patients with high baseline TCHO levels exhibited higher HBV DNA, HBsAg, HBeAg and hepatitis B e antibody (HBeAb) levels during early treatment periods (weeks 0, 4, 12 and 24) than those with the low TCHO levels. Furthermore, the logistic regression analysis identified that baseline serum TCHO was a risk factor for NR achievement (OR=4.94; P=0.047). Conclusions: Our results indicated that serum TCHO was associated with PEG-IFN-α therapeutic response in HBeAg-positive CHB patients which suggested that serum TCHO could be useful as an auxiliary clinical factor to predict poor efficacy of PEG-IFN-α therapy.

Serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) level was found to be a useful prognostic marker for hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients treated with nucleoside/nucleotide analogs (NUCs) therapy, and the aim of our study is to evaluate the clinical implementation of M2BPGi level in the prediction of antiviral responses to pegylated‐interferon‐α (PEG‐IFN‐α) treatment in HBeAg‐positive CHB patients. Ninety‐six CHB patients who received PEG‐IFN‐α treatment for at least 48 weeks were recruited. The serum M2BPGi, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA levels at baseline, weeks 4, 12, and 24 after PEG‐IFN‐α treatment were determined and their associations with antiviral responses were evaluated and the virological response (VR) rate and serological response (SR) rate after 48 weeks of treatment were 65.6% and 35.4%, respectively. Baseline serum M2BPGi level was significantly different between VR and non‐VR (P = 0.002) or SR and non‐SR groups (P = 0.012). Multivariate analyses suggested that baseline serum M2BPGi level was independently associated with VR and SR of PEG‐IFN‐α treatment at week 48. The area under the ROC curve (AUC) of baseline M2BPGi was 0.682 in predicting VR, which was superior to HBsAg (AUC = 0.566) or HBV DNA (AUC = 0.567). The AUC of baseline M2BPGi in predicting SR was 0.655, which was also higher than that of HBsAg (AUC = 0.548) or HBV DNA (AUC = 0.583). These results suggested that baseline serum M2BPGi level was a novel predictor of VR and SR for PEG‐IFN‐α treatment in HBeAg‐positive CHB patients.

Aim. To evaluate the prognostic value of blood group and IL-28B genotype with respect to dynamics of liver fibrosis (LF) in patients with chronic genotype-1 hepatitis C (HCV-1) who did not respond to antiviral therapy (AVT) with pegylated interferon alpha 2 (peg-IFN-α-2) and ribavarin (RBV) Material and methods. The study included 122 primary patients with HCV-1 who underwent paired liver biopsy or elastometry steam. The main group (n=66) consisted of patients who received AVT (peg-IFN-α-2/RBV) but failed to achieve a sustainable virologic response (SVR). Control group (n=56) comprised patients treated without AVT. Results. Negative dynamics of LF in patients of the main group occurred significantly more frequently than in the placebo group (p=0.025, φ2 criterion). LF dynamic patterns in patients of the main group varied depending on the IL-28B genotype and blood group, p=0.001 and p=0.014 respectively. Factorial analysis of negative LP dynamics in the main group revealed the relationship between blood group (fr=0,931) and IL-28B genotype (fr= 0.960) while classification analysis demonstrated the predictive value of combination of gene IL-28B polymorphism and blood group (p

This study compares treatment completion rates and outcomes in hepatitis C virus (HCV) patients between those aged

BACKGROUND Neurofibromatosis type 1 (NF1) is autosomal dominant neurogenetic disorder characterized by progressive cutaneous, neurologic, skeletal, and neoplastic manifestations. Plexiform neurofibromas (PN) are one of the different types of neurofibromas that occur in these patients. Complete surgical resection is difficult due to the tumor infiltrative behavior. We evaluated pegylated interferon- α-2b (PI) in patients with unresectable progressive or symptomatic PN. METHODS Pediatric patients (1–21 years old) affected by unresectable PN, followed at Bambino Gesù Hospital, were treated with PI. We administered PI as a weekly subcutaneous injection at a beginning dose of 1.0 mcg/kg/wk, increased to 3.0 mcg/kg/wk if well tolerated. Paracetamol (15mg/kg) was given 30 minutes prior the dose of PI and then every 4–6 hours as needed. Patients were evaluated with Magnetic Resonance Imaging (MRI) every 12 months after treatment start in case of stable disease. RESULTS 10 patients (3 females, 7 males) were enrolled. Median age was 12 years old. The median duration of treatment was 12,6 months. Grade 3 neutropenia (30%) and increased liver transaminases level (20%) were the most common toxicity. 6/10 patients experienced an improvement about pain. 7/10 patients showed clinical response. 1/10 patient had a radiological response at MRI, 1/10 experienced progression disease and 8/10 showed a stable disease at MRI evaluation. CONCLUSIONS Our study demonstrated that PI could be a suitable treatment for unresectable PN in terms of stabilization of the tumour size due to its antitumor activity although clinical response does not correlate with radiographic changes.

Background/Aims This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. Methods Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. Results The patients’ median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. Conclusions Low-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.

Background The correlation between hepatitis B surface antigen (HBsAg) seroconversion and the characteristics of HBV quasispecies (QS) before and during pegylated interferon-α-2a (PEG-IFN-α-2a) treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) children has not yet been reported. Methods 35 patients, including 18 HBsAg seroconverters (SS) and 17 non-seroconverters (SN), were enrolled. Serum samples were collected before treatment and at weeks 12 and 24 of treatment. Sequences within the basal core promoter/pre-core (BCP/PC) and S/reverse transcriptase (S/RT) region were analysed by next-generation sequencing. Results There was no significant difference in the baseline diversity of HBV QS (Shannon entropy [Sn]; Hamming distance [HD]) in either region between the two groups. The baseline mutations A1762T/G1764A, C1913A, and T2003A/G or C2004T were correlated with non-response to therapy ( P=0.025, P=0.036, P=0.032, respectively). After 24 weeks of therapy, HBV diversity within the BCP/PC region in the SS group notably declined (Sn: P=0.002; HD: P=0.011), while that of the SN group was nearly unchanged. As for the S/RT region, 24 weeks of treatment made no significant difference on QS diversity in either group. Conclusions Our data demonstrated that the baseline viral mutations and dynamic changes in HBV QS diversity within the BCP/PC region were closely related to HBsAg seroconversion in HBeAg-positive CHB children treated with PEG-IFN-α-2a.

Introduction. Occult hepatitis C is defined by the presence of virus in the peripheral blood mononuclear cells (PBMCs) and/or liver cells, in the absence of serum viremia. Objective. To detect the persistence of occult hepatitis C in hemodialysis (HD) patients and patients without renal disease (non-renal) with treatment-induced clearance of hepatitis C virus (HCV) infection, using assays with a very low detection limit of viremia. Methods. A group of 13 HD patients and a group of 43 non-renal patients, with treatment-induced HCV infection clearance were investigated in the study. The HD patients were treated with pegylated interferon alpha (PEG-IFN-α) only, while the non-renal patients were treated with a combination therapy of PEGIFN- α and ribavirin. Detection of a possible persistence of HCV RNA in the PBMCs and plasma samples was assessed by an ultrasensitive reverse transcription polymerase chain reaction (RT-PCR) assay (2 IU/ml). Results. HCV RNA was not detected in the PBMCs and plasma samples of HD patients and of non-renal patients, when assessed by the ultrasensitive RT-PCR assay. Conclusion. When a sensitive RT-PCR assay was applied, to determine if treatment induced clearance of HCV infection had been successful, occult hepatitis C could not be detected by an ultrasensitive assay, neither in HD nor in non-renal patients.

Background Acute pancreatitis (AP) associated with interferon-α or pegylated interferon-α (AP-IFN) has been described, although the causal relation certitude remains elusive. Some recent studies suggest definite causality, although the relation is grouped in class III of Badalov classification of drug-induced AP. Objectives Perform systematic review of AP-IFN and assess causality. Methods Two reviewers independently evaluated the data and quality of studies extracted from multiple databases on March 13, 2017. Studies selection was based on a priori criteria. Naranjo scale, and Badalov classification were applied to determine causality. Results We identified 16 studies that reported AP-IFN with a total of 23 patients. Fifteen studies had moderate to good methodological quality. The frequency of AP-IFN was 7/3450 (0.2%). The median age of patients was 50 years. In most cases IFN was used for chronic hepatitis C. The latency between IFN and diagnosis of AP was (>30 days). AP was mild or moderately severe and improved with supportive management. No mortality was observed. Re-challenge was done in 5 patients and resulted in AP recurrence in 3 cases. Twenty-one cases were classified as probable and 2 cases as definitive according to Naranjo scale. Evaluations of studies confirm a status Ia for AP-IFN according to Badalov classification. Conclusion AP-IFN is rare and has a probable or definite causal relation according to Naranjo scale. The evidence supports a class Ia of Badalov classification. Hypertriglyceridemia is not a contributing factor. IFN-induced AP is usually mild or moderately severe, and responds favorably to supportive management.

Background: Hepatitis C virus (HCV) infection is a global health problem. Most cases of HCV infection do not resolve spontaneously. Combination therapy with pegylated interferon-α (PegIFN-alpha) and ribavirin (RBV) is the standard treatment for patients with HCV infection. The success of treatment is affected by several host, viral, and treatment factors. Available works have demonstrated significant role of interleukin 28B (IL28B) polymorphisms in predicting HCV infection treatment outcomes. This suggests the possibility of tailored therapy in HCV infected patients. HCV is one of the most common causes of liver disease worldwide. If untreated, this infection can develop chronic hepatitis in 50%-85% of patients. The aim of current study is to determine the association of interleukin-28B (IL-28B) rs-12979860 polymorphism in response to peginterferon-alpha (PegIFN-alpha) and ribavirin combination therapy in Iranian patients with chronic hepatitis C genotype 1 infection. Methods: This cross-sectional study was carried out on 70 Iranian patients with chronic hepatitis C infection (genotype 1) receiving PegIFN-alpha and ribavirin. DNA was extracted from blood samples. Specific primers were used to amplify targeted polymorphisms. Results: In this study, 71.4% of patients reached sustained virological response (SVR). The prevalence of CC, CT and TT genotypes were 38.6%, 42.8% and 18.6% respectively. The rate of SVR was 96.3 for CC genotype, whereas this rate was 66.7 for CT and 30.8 for TT genotypes. We found an association between end of treatment response (ETR) and IL-28B genotypes as 100% of patients bearing CC genotype reached ETR, but ETR rate was 45.85% in CT group and 10.2% in TT group. Six months follow-up showed that there was a significant difference between response to treatment in patients IL-28B-CC and TT (P < 0.001). Data regression analysis showed that CC genotype was an independent predicting factor, significantly associated with higher SVR (P = 0.005 (OR=36.1; 95% CI = 3 - 434.2)). In contrast, absence of C allele (TT genotype) was significantly correlated with the failure of response (P = 0.005 (OR = 36.1; 95% CI = 3 - 434.2)). Conclusions: The results showed that IL-28B rs12979860 was an important predictor of HCV treatment response.

Objective To investigate the efficiency of pegylated interferon α therapy for patients with HBeAg-positive chronic hepatitis B (CHB) and explore whether liver histopathological features and other factors might influence HBeAg seroconversion. Methods Total of 80 HBeAg-positive CHB patients who received liver puncture were treated with pegylated interferon α once a week for 48 weeks. The rate of HBeAg seroconversion was determined after therapy, and the factors influencing HBeAg seroconversion were analyzed. Results The rate of HBeAg seroconversion was 30.00％ at the end of treatment. The rate of HBeAg seroconversion gradually increased with the elevation of liver inflammatory activity (χ2 = 9.170, P = 0.027). But liver fibrosis has little correlation with the rate of HBeAg seroconversion (χ2 = 5.917, P = 0.116). Except HBeAg, other baseline indexes including gender, age, serum ALT and serum HBV DNA 1evels had no statistical difference between the patients with HBeAg seroconversion and the patients without HBeAg seroconversion. By binary logistic regression analysis, liver inflammation and HBeAg were influencing factors for HBeAg seroconversion. Conclusions Pegylated interferon α therapy induces a higher rate of HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with severe liver inflammation, so the liver biopsies should be performed in time.

International audience; Myeloproliferative neoplasm-related myelofibrosis is associated with cytopenic or proliferative phases, splenomegaly and constitutional symptoms. Few effective treatments are available and small series suggested that interferon could be an option for myelofibrosis therapy. We performed a retrospective study of pegylated-interferon α-2a (Peg-IFNα-2a) therapy in myelofibrosis. Sixty-two patients treated with Peg-IFNα-2a at 17 French and Belgian centres were included. Responses were determined based on the criteria established by the International Working Group for Myelofibrosis Research and Treatment. Mean follow-up was 26 months. Sixteen of 25 anaemic patients (64%) (eight concomitantly receiving recombinant erythropoietin) achieved a complete response and transfusion-independence was obtained in 5/13 patients (38*5%). Constitutional symptoms resolved in 82% of patients. All five leucopenic patients normalized their leucocyte counts, whereas a normal platelet count was obtained in 5/8 thrombocytopenic patients. Splenomegaly was reduced in 46*5% of patients, and complete resolution of thrombocytosis and leucocytosis were observed in 82*8% and 68*8% of patients, respectively. Side effects (mostly haematological) were mainly of grade 1-2. The only factor independently associated with treatment failure was a spleen enlargement of more than 6 cm below the costal margin. In conclusion, Peg-IFNα-2a induced high response rates with acceptable toxicity in a large proportion of patients with primary and secondary myelofibrosis, especially in early phases.

Aim The relationship between pegylated interferon (PEG IFN)-α-2a and growth of children with chronic hepatitis C (CHC) remains unclear. This study was to evaluate the effects of PEG IFN-α-2a on growth. Methods From 2003–2012, we prospectively analyzed the data of children with CHC through mother-to-infant transmission. They were all treatment naive and were treated with PEG IFN-α-2a monotherapy. Results Among 31 children (19 boys, 12 girls; median age, 6 years) treated with monotherapy during the study period, 21 children (13 boys, eight girls; median age, 7 years) were statistically analyzed. The median treatment period of the 21 children was 48 weeks (range, 48–72). Z-scores of height and weight before treatment, at the end of treatment and 1 year after treatment were −0.05, −0.24 and −0.12 (height), and +0.11, −0.23 and −0.05 (weight). Both Z-scores were significantly decreased at the end of the treatment. One year after treatment, Z-scores of height and bodyweight were significantly improved compared with that of end of treatment but were still lower than those before treatment, with statistical significance. Z-scores of height growth velocity was significantly increased after the treatment (+0.71), compared with that during treatment (−2.25). Conclusion PEG IFN-α-2a has an inhibitory effect on children's growth, and Z-scores of height and bodyweight were decreased at the end of treatment. Although Z-scores improved after the treatment, they had not returned to the baseline level 1 year after the treatment.

Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon (PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive HBeAg-positive patients treated with PEG-IFNα 2a at a dose of 180 μg/week for at least 24 weeks were evaluated. Their treatment response was assessed, including normalization of serum ALT, decline of serum HBV DNA and loss of HBeAg. Results We found that a decrease of HBV DNA level at the 4th week was positively correlated with the decrease of HBV DNA level at the 12th week and 24th week (r = 0.8202, P < 0.0001 and r = 0.6838, P < 0.0001, respectively). We observed that a decrease of HBsAg level at the 4th week was positively correlated with decrease of HBsAg level at the 12th week and 24th week (r = 0.4868, P = 0.0023 and r = 0.4251, P = 0.0109, respectively). A decrease of HBsAg level at the 24th week was positively correlated with the decrease of HBV DNA level at the 24th week (r = 0.5262, P = 0.0024). Serum level of IFN and IFN neutralizing antibody had no relationship with HBV DNA or HBsAg titers kinetics. Conclusions The decline of serum HBV DNA and hepatitis B surface antigen at the 4th week can be used to predict the response to PEG-IFNα 2a in patients with HBeAg positive chronic hepatitis B.

Object Previous studies of systemic and intralesional administration of nonpegylated interferon have shown efficacy against craniopharyngioma. Pegylaion of interferon-α-2b (PI) prolongs the half-life, allowing sustained exposure of the drug over time, and enhances efficacy. The authors report the results of the use of PI in 5 children with recurrent craniopharyngiomas. Methods Five children, ranging in age from 9 to 15 years, with recurrent craniopharyngiomas were treated for up to 2 years with subcutaneous injections of PI at a dose of 1–3 μg/kg/week. Tumor response was assessed using MRI. Results All patients had stable disease or better in response to PI. One patient experienced a recurrence after gross-total resection (GTR). She initially showed an increase in the predominantly cystic tumor after 3 months of treatment, followed by a complete response. She required no further intervention and remains without evidence of disease 10 years after starting treatment. Another patient experienced recurrence 3.3 years after subtotal resection (STR) and radiation therapy. He had complete disappearance of the predominantly cystic component after 4 months of treatment, and a small residual calcified mass remains 5 years later. The third patient experienced recurrence after 3 GTRs. He had a complete response after 7 months of treatment and remains without evidence of disease 19 months after starting treatment. The fourth patient experienced recurrence after 2 STRs. He had a 30% decrease in tumor size after 4 months of treatment, which was maintained for 12 months at which point the cyst began to increase in size. The final patient experienced recurrence after GTR and has stable disease 6 months after starting treatment with PI. Conclusions The use of PI in children with recurrent craniopharyngiomas can result in significant and durable responses and potentially delay or avoid the need for radiation therapy.

Hepatitis C Virus (HCV) is a major concern for most of the hepatocellular carcinoma (HCC). At present, standard therapy followed is pegylated interferon α with ribavirin but it has significant side effects and was moderately effective. Therefore, there is a necessity to introduce new drugs that interact various stages of HCV life cycle. Several herbs have been isolated for treating against HCV, and are effective in preventing HCV viral diseases. Our review precises about various mode of action of certain herbs that showed inhibition activity against HCV.

Dilip Ratnam, Anouk Dev, Tin Nguyen, Vijaya Sundararajan, Hugh Harley, Wendy Cheng, Alice Lee, Ferry Rusli, Robert Chen, Sally Bell, Stephen Pianko and William Sievert

九州大学病院ではいくつかの診療科で肝疾患患者を診療している. 内科系では総合診療科がウイルス性肝炎を, 膠原病・免疫・感染症内科では自己免疫性肝炎を, 肝臓・膵臓・胆道内科では肝臓癌を中心に診療しているが, 必ずしも完全に疾患別にはなっていない. 現在, わが国の慢性肝疾患の大部分はC型肝炎ウイルス（hepatitis C virus : HCV）によるものであり, それに対してはinterferon（IFN）療法が行われている. 九州大学病院としては各科ごとに治療し, その成績を各科ごとにまとめても, 症例数が少なく臨床研究として価値ある報告ができず, 他の研究施設の後塵を拝することになる. そこで, 2003年9月に「九州大学病院における肝臓病治療の新しい試み」として座談会を行ない, C型慢性肝炎に対するpegylated（PEG）IFN αとribavirin（RBV）併用療法について, 九州大学の関連病院で肝臓疾患の診療に従事している医師にも協力を依頼し, 大規模多施設共同臨床研究を開始することとした. その研究組織として九州大学関連肝疾患研究会（Kyushu Liver Disease Study : KULDS）を立ち上げ, 世界に通用する症例数の多い臨床研究を目指した. したがって, 本稿に述べる内容は九州大学総合診療科（九州大学大学院感染環境医学分野）での独自の研究もあるが, 主としてKULDS の成績をまとめたものもある. 前置きが長くなったが, わが国は世界的にみてもHCV の高浸淫国であり, 感染者は150-200万人いると推定されている. その60％以上は程度の差こそあれ慢性肝疾患に罹患していると考えられ, また, C型慢性肝炎患者は年間5-6％に肝癌を発症することが判明している. HCV感染者が癌年齢に達してきた現在, わが国における肝癌による年間死亡者数は1970 年頃の約10, 000人から, この30年間に3倍に増加し, 現在では34, 000人に達し, 悪性新生物の中では胃癌, 肺癌とほぼ肩を並べている. 肝癌発症抑制のための最も有効な手段は, 感染者からHCV を排除することと考えられ, IFNはその唯一の原因療法の薬剤である. 本稿では, 2004年から保険適応となったPEG-IFN α-2b ＋ RBV 併用療法の治療成績から得られたこと, さらにそれから派生した臨床研究について述べる.

Summary Background Interleukin (IL) 28B single nucleotide polymorphisms can predict sustained virological response (SVR) in hepatitis C virus (HCV) patients following pegylated interferon-alpha (PEG IFN-α) and ribavirin treatment. Aim To design a meta-analysis to determine IL28B genotypes', rs12979860 CC and rs8099917 TT, correlation with SVR in PEG IFN-α/ribavirin-treated HCV patients. Methods Meta-analysis was performed in 17 studies of rs12979860 CC vs. CT/TT and 17 of rs8099917 TT vs. TG/GG. Odds ratios (OR) and confidence intervals (95% CI) were calculated by fixed- or random-effects models. Heterogeneity, sensitivity analysis and publication bias were also assessed. Results Of 4252 Asian, Caucasian and African HCV patients analysed for rs12979860, SVR was more frequent in CC (vs. CT/TT; OR = 4.76, 95% CI: 3.15–7.20). Moreover, CC was associated with SVR for HCV genotype-1 or -4 infections (ORgenotype 1 = 5.52, 95% CI: 3.74–8.15; ORgenotype 4 = 8.11, 95% CI: 4.13–15.93), regardless of ethnicity. Of 4549 Caucasian and Asian HCV patients analysed for rs8099917, SVR was more frequent in TT (vs. TG/GG; OR = 3.31, 95% CI: 2.39–4.59). Moreover, TT was associated with SVR for HCV-1 (ORgenotype 1 = 4.28, 95% CI: 2.87–6.38). Rs8099917 TT predictive value was stronger in Asians (ORAsians = 8.09, 95% CI: 5.63–11.61; ORCaucasians = 3.00, 95% CI: 2.03–4.45). Ethnicity stratification revealed that rs8099917 TT had slight predictive value in Asian HCV-2/3 patients (OR = 1.99, 95% CI: 1.09–3.62). Conclusions IL28B rs12979860 CC and rs8099917 TT are strong SVR predictors for PEG IFN-α/ribavirin-treated HCV-1 patients, regardless of ethnicity. In HCV-2/3, rs12979860 CC has no SVR predictive value, but rs8099917 TT was slightly associated with SVR in Asians.

Highlights ► We modeled drug responses using decision tree learning based on SNPs in a genome-wide association study. ► We can predict the drug responses of a new patient with HCV genotype 1. ► Responsiveness to pegylated interferon α (PEG-IFN-α) plus rebavirin (RBV) treatment was predicted. ► We can predict with 93% probability whether a new patient with HCV genotype 1 will be helped by drug treatment., The recommended treatment for patients with chronic hepatitis C, pegylated interferon α (PEG-IFN-α) plus rebavirin (RBV), does not provide a sustained virologic response in all patients, especially those with hepatitis C virus (HCV) genotype 1. It is therefore important to predict whether or not a new patient with HCV genotype 1 will be cured by the recommended treatment. We propose a prediction method for a new patient using a decision tree learning model based on SNPs evaluated in a genome-wide association study. By the decision tree learning for 142 Japanese patients with HCV genotype 1 (78 with null virologic response and 64 with virologic response), we can predict with high probability (93%) whether or not a new patient with HCV will be helped by the recommended treatment.

Introduction: Treatment of chronic hepatitis C (CH-C) with peginterferon α (Peg-IFN) and ribavirin leads to a sustained virological response (SVR) in 50% of patients and depends on HCV and host factors. Polymorphism of the IL28B gene is associated with eradication of HCV and SVR. Aim: The objective of this study was to examine patients from the region of southern Poland and determine whether CH-C therapy depends on the genetic variants of IL28B and whether this polymorphism may predict SVR. Material and methods: One hundred forty-two patients with CH-C and the genotype 1b HCV were treated with PegIFN and ribavirin for 48 weeks. IL28B rs12979860 polymorphisms (C/T) were tested by PCR-RFLP. The HCV-RNA and alanine aminotransferase (ALT) levels were measured before treatment and after 12, 48 and 72 weeks. Results: Viral load before and after 12 weeks of therapy was higher in the genotypes T/C and T/T than in C/C. 71.1% of patients with the genotype C/C achieved SVR vs. 41.4% with the genotype T/C and 23.5% with T/T. Patients with the genotype C/C responded better to treatment as compared to subjects with the genotypes T/C and T/T, and achieved better early response (12 weeks), at the end of treatment (48 weeks) and SVR. Alanine aminotransferase activity was similar among the groups. Tolerance of therapy was similar and independent of the genotypes. Conclusions: The study confirmed the dependence of response to standard treatment of CH-C caused by the genoStreszczenie Wstep: Leczenie przewleklego zapalenia wątroby typu C (PZW-C) pegylowanym interferonem α (Peg-IFN) z ryba wiryną powoduje tzw. trwalą odpowiedź wirusologiczną (sustained virological response – SVR) u blisko 50% chorych. Odpowiedź ta ściśle zalezy od HCV i czynnikow genetycznych chorego. Wykazano, ze polimorfizm genu IL28B wiąze sie z eradykacją wirusa i SVR. Cel: Zbadanie, czy wyniki leczenia PZW-C u chorych z regionu Polski Poludniowej zalezą od wariantow genetycznych IL28B, a polimorfizm moze byc czynnikiem predykcyjnym SVR. Material i metody: Sto czterdzieści dwie osoby z PZW-C spowodowanym genotypem 1b HCV leczono standardowo PegIFN z rybawiryną przez 48 tygodni. Polimorfizmy rs12979860 IL28B (C/T) badano metodą PCR-RFLP. HCV-RNA i aktywnośc aminotransferazy alaninowej (ALT) w surowicy mierzono przed leczeniem i po 12, 48 i 72 tygodniach terapii. Wyniki: Wiremia HCV-RNA przed terapią i po 12-tygodniowym leczeniu byla wyzsza u chorych z genotypem T/C i T/T. Trwalą odpowiedź wirusologiczną osiągnelo istotnie wiecej chorych z genotypem C/C (71,1%) w porownaniu z 41,4% z genotypem T/C i 23,5% T/T. Chorzy z genotypem C/C lepiej reagowali na leczenie w porownaniu z osobami z genotypami T/C i T/T, osiągali wyzsze wskaźniki odpowiedzi wczesnej (12 tygodni), na koniec leczenia (48 tygodni) i SVR. Aktywnośc ALT nie roznila sie istotnie podczas terapii pomiedzy grupami. Tolerancja leczenia byla podobna i nie zalezala od genotypow C/C, T/C i T/T. Przegląd Gastroenterologiczny 2012; 7 (1) type 1b HCV on the patient's genetic predisposition. In contrast to some other reports, poor prognosis was observed in T/T homozygotes of IL28B. Wnioski: Wyniki badania potwierdzily zaleznośc odpowiedzi na standardowe leczenie PZW-C spowodowanego genotypem 1b HCV od predyspozycji genetycznej chorego, jednak w przeciwienstwie do niektorych doniesien zle rokowanie obserwowano u homozygot T/T IL28B.

Novel approaches are urgently needed to achieve the next level of control of HIV infection beyond antiretroviral medications that will lead to the ultimate goal of curing HIV infection. Exploiting the innate immune system control of HIV is one possible component of that strategy with pegylated interferon α representing a well-characterized agent that is being applied to this effort.In this review, the authors summarize the history of interferon α treatment in the setting of HIV infection with a focus on clinical trials that examined the downstream effects on innate immune responses. More recently, clinical trials that administered pegylated interferon α-2a have demonstrated which interferon-stimulated genes are associated with its antiviral effects and which of these host-restriction factors may play a role in limiting the magnitude of the HIV reservoir.The potential to exploit interferon α as part of a cure strategy is provocative. Whether key interferon-induced antiviral factors can be upregulated sufficiently to affect the reservoir is unknown. Additional research employing pegylated interferon α-2a is needed to identify which innate immune pathways are candidate targets for novel biological therapies for the potential cure of HIV infection.

Aim: To investigate the efficacy and safety of a pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) combination treatment for patients with chronic hepatitis C virus (HCV) infection who have persistently normal alanine aminotransferase (NALT). Methods: This multicenter study included 989 patients with HCV genotype 1 (114 with NALT and 875 with elevated ALT) who received weight-based doses of PEG-IFN α-2b plus RBV for 48 weeks. We compared the sustained viral response (SVR) rates of patients with NALT and elevated ALT who received at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target RBV (minimum acceptable dosage). Results: No significant difference was found in the overall SVR rate between the NALT (42.1%) and elevated ALT groups (37.3%). No significant difference in the SVR rates was found between NALT (63.3%) and elevated ALT group (61.6%) patients who received minimum acceptable dosage. Multivariate analysis showed that age (

Aim: Elevation of alanine aminotransferase (ALT) levels during pegylated-interferon (peg-IFN) plus ribavirin therapy in patients with chronic hepatitis C [CHC] is a problem that cannot be disregarded. The aim of this study is to assess the frequency and to characterize clinical parameters of this phenomenon. Methods: Two hundred and thirty-five (235) CHC patients with genotype 1b receiving peg-IFN α-2b plus ribavirin therapy were analyzed. Clinical parameters that may be associated with abnormal ALT values during treatment and therapy outcomes were evaluated statistically. One hundred and sixteen (116) patients treated with peg-IFN α-2a plus ribavirin were also included for partial analysis. Results: Abnormal ALT values during treatment were observed in 23.0% of patients. It was observed in 14.5% of those with sustained virological response (SVR) and 17.8% of those with relapse, in whom viral clearance was observed during therapy. Multivariate logistic regression analysis revealed that pretreatment ALT values, therapy outcome, and body mass index (BMI) were significant factors related to abnormal ALT values during treatment. Abnormal ALT values during treatment became normal in SVR patients at 6 months after the completion of treatment, but not in NR (non-response) patients. Mean ALT values were significantly higher at some time points during treatment in patients treated with α-2a when compared to those treated with α-2b. Conclusion: Abnormal ALT values during peg-IFN plus ribavirin treatment are observed relatively frequently, even in patients without detectable HCV RNA. Direct or indirect involvement of drugs is considered as one possible cause.

Background The development of more sensitive HCV RNA assays might necessitate re-evaluation of the rules for stopping treatment (for example, HCV RNA negativity at week 24 during treatment with pegylated interferon-α and ribavirin for chronic hepatitis C). The aim of this study was to assess discordance between the week 24 HCV RNA test results of two PCR-based assays (Amplicor and Taq-Man) and the transcription-mediated amplification (TMA) HCV RNA qualitative assay. Methods A total of 89 week 24 samples that were negative using PCR-based assays during treatment were retested with the TMA qualitative assay to investigate discordance between tests results. All week 24 samples were HCV RNA negative by Amplicor or by TaqMan. Results Of the 89 patients, 46 (52%) achieved sustained virological response (SVR). Viral breakthrough or relapse occurred in 43 patients (48%). All 89 HCV RNA negative week 24 samples were retested with the qualitative TMA assay. Eleven out of 89 samples had detectable HCV RNA (12%). All patients with detectable HCV RNA experienced breakthrough or relapse (negative predictive value 100%). Of the 78 patients with undetectable HCV RNA at week 24 using the TMA assay, 46 achieved SVR. This resulted in a positive predictive value (PPV) of 59% for the TMA assay compared with a PPV of 52% for the PCR-based assays. Conclusions All patients with detectable HCV RNA at week 24 using the TMA assay eventually relapsed. On the basis of these results, the use of this more sensitive HCV RNA assay could lead to the prevention of unnecessary treatment.

A 41-year-old woman with chronic hepatitis C was treated with pegylated-interferon (PEG-IFN)-alpha-2b plus ribavirin for 24 weeks. She had hepatitis C virus (HCV) genotype 2a (1600 KIU/mL), and her liver histology showed mild inflammation and fibrosis. Four weeks after the start of the therapy, she achieved a rapid virological response (RVR) and then a sustained virological response (SVR). Serum alanine aminotransferase (ALT) levels remained within normal ranges and HCV RNA continued to be negative. However, ALT levels flared with the re-emergence of HCV RNA in the serum 1.5 years after discontinuation of therapy. HCV RNA obtained from sera before therapy and after relapse shared a 98.6% homology with the E2 region, and phylogenetic analyses indicated that they were the same HCV strain. These results eliminated the possibility of a re-infection and strongly indicated a late relapse of the disease. Therefore, follow-up is necessary for chronic hepatitis C patients after SVR, even if they respond well to therapy, including RVR.

This study assessed the effect of a 3-month course of pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) in 3 liver transplant patients with chronic active hepatitis E. A virological response was sustained for 6 and 5 months in 2 patients after Peg-IFN-alpha-2a therapy was completed. A relapse was observed in the third patient.

INowadays the standard of care for hepatitis C therapy is based on Pegylated interferon alpha and ribavirin (Peg IFN/RBV). This combination has led to a sustained virological response rate (SVR) of 50 to 80% depending on genotype. This is still low, considering the side effects, overall costs and duration of therapy. So far, strategies to foresee SVR have been described such as genotype, fibrosis stage, viral load and gamma-glutamyltransferase. In addition, new data has recently been provided on predictive factors of SVR like genetic polymorphism related to race, insulin resistance and viral kinetics. This review aims to discuss these predictive factors of therapy that might help the decision about starting or discontinuing therapy in chronic HCV infected patients.