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Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a standardized way, adding value to laboratory findings and helping with critical clinical decisions. This paper proposes a test report based on the practices informed by 118 laboratories in 68 countries, with recommendations from the International Consensus on ANA Patterns (ICAP) group. Major focus is placed on the report format containing endpoint titers, immunofluorescence patterns together with anti-cell (AC) nomenclature, remarks on follow-up or reflex testing, and possible other autoantibody associations. ISO 15,189 directives were integrated into the test report. Special situations addressed include serum screening dilutions and endpoint titers, relevance of immunofluorescence patterns with special attention to cytoplasmic patterns, mixed and compound patterns, and how to report different titers corresponding to multiple patterns or autoantibodies in the same sample. This paper suggests a subtitle for the HEp-2-IIFA, namely anti-cell antibodies test, which could gradually substitute the original outdated ANA nomenclature. This ICAP pro forma report represents a further step in harmonizing the way relevant clinical information could be provided by laboratories.

Pegylated Interferon (Peg-INF) therapy which has various side effects and is relatively severe. The side effects that occur in each individual are different, some patients treated with Peg-INF have experienced mild to severe side effects. Evaluation The side effects of Peg-INF on chronic hepatitis B and / or C have not been widely reported. Thus, I will conduct research on the side effects of Peg-INF therapy in chronic hepatitis B and / or C patients by combining two or more research results that can be combined to obtain new quantitative data. The purpose of this study was to determine the side effects of Peg-INF treatment in chronic hepatitis B and C patients.  This research uses the Systematic Review method. With the keyword "Efek Samping Pegylated Interferon"; "Pegylated Interferon successful treatment"; Pegylated Interferon Hepatitis in Asia”. As a result total of 19 journal articles were obtained and the side effects of Peg-INF were hematological, systemic, psychiatric, autoimmune and hearing function side effects.

Pegylated Interferon (Peg-INF) therapy which has various side effects and is relatively severe. The side effects that occur in each individual are different, some patients treated with Peg-INF have experienced mild to severe side effects. Evaluation The side effects of Peg-INF on chronic hepatitis B and / or C have not been widely reported. Thus, I will conduct research on the side effects of Peg-INF therapy in chronic hepatitis B and / or C patients by combining two or more research results that can be combined to obtain new quantitative data. The purpose of this study was to determine the side effects of Peg-INF treatment in chronic hepatitis B and C patients.  This research uses the Systematic Review method. With the keyword "Efek Samping Pegylated Interferon"; "Pegylated Interferon successful treatment"; Pegylated Interferon Hepatitis in Asia”. As a result total of 19 journal articles were obtained and the side effects of Peg-INF were hematological, systemic, psychiatric, autoimmune and hearing function side effects.

Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a standardized way, adding value to laboratory findings and helping with critical clinical decisions. This paper proposes a test report based on the practices informed by 118 laboratories in 68 countries, with recommendations from the International Consensus on ANA Patterns (ICAP) group. Major focus is placed on the report format containing endpoint titers, immunofluorescence patterns together with anti-cell (AC) nomenclature, remarks on follow-up or reflex testing, and possible other autoantibody associations. ISO 15,189 directives were integrated into the test report. Special situations addressed include serum screening dilutions and endpoint titers, relevance of immunofluorescence patterns with special attention to cytoplasmic patterns, mixed and compound patterns, and how to report different titers corresponding to multiple patterns or autoantibodies in the same sample. This paper suggests a subtitle for the HEp-2-IIFA, namely anti-cell antibodies test, which could gradually substitute the original outdated ANA nomenclature. This ICAP pro forma report represents a further step in harmonizing the way relevant clinical information could be provided by laboratories.

Pegylated Interferon (Peg-INF) therapy which has various side effects and is relatively severe. The side effects that occur in each individual are different, some patients treated with Peg-INF have experienced mild to severe side effects. Evaluation The side effects of Peg-INF on chronic hepatitis B and / or C have not been widely reported. Thus, I will conduct research on the side effects of Peg-INF therapy in chronic hepatitis B and / or C patients by combining two or more research results that can be combined to obtain new quantitative data. The purpose of this study was to determine the side effects of Peg-INF treatment in chronic hepatitis B and C patients.  This research uses the Systematic Review method. With the keyword "Efek Samping Pegylated Interferon"; "Pegylated Interferon successful treatment"; Pegylated Interferon Hepatitis in Asia”. As a result total of 19 journal articles were obtained and the side effects of Peg-INF were hematological, systemic, psychiatric, autoimmune and hearing function side effects.

Background: Subgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFNα-2b) vs observation randomised trials demonstrated that a treatment benefit was observed only in patients with an ulcerated melanoma without palpable nodes (hazard ratio [HR] for recurrence-free survival [RFS] was 0.69). This was confirmed by a meta-analysis of 15 adjuvant IFN trials (HR: 0.79). Patients and methods: In the EORTC 18081 trial, sentinel node-negative stage II patients with an ulcerated primary melanoma were 1:1 randomised between pegylated (PEG)-IFNα-2b at 3 μg/kg/week subcutaneously and observation, for 2 years, or until disease recurrence or unacceptable toxicity in spite of dose adjustments to maintain an Eastern Cooperative Oncology Group performance status of 0 or 1. Main end-point was RFS. Secondary end-points included distant metastasis-free survival (DMFS), overall survival, and safety (EudraCT Number: 2009-010273-20). Results: Between February 2013 and January 2017, only 112 patients were randomised, 56 in each arm. The trial was stopped early for lack of recruitment. At a 3.4-year median follow-up, the estimated HR for the PEG-IFNα-2b group compared with the observation group regarding RFS was 0.66 (95% confidence interval [CI]: 0.32–1.37), and the 3-year RFS rate was 80.0% (95% CI: 65.7–88.8%) and 72.9% (95% CI: 58.3–83.0%), respectively. DMFS was prolonged: HR: 0.39 (95% CI: 0.15–0.97), and the 3-year DMFS rate was 90.6% (95% CI: 78.9–96.0%) vs 76.4% (95% CI: 62.1–85.9%). One patient in the PEG-IFNα-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFNα-2b treatment, 16 (29%) completed 2 years of treatment, 2 (4%) stopped due to recurrence, 23 (43%) due to toxicity and 14 (25%) due to other reasons. Conclusions: The EORTC 18081 PEG-IFNα-2b randomised trial, observed a similar HR (0.69) for RFS as the previous EORTC trials (0.69). In countries without access to new drugs, adjuvant (PEG)-IFNα-2b treatment is an option for p, SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Background: Simeprevir is approved with pegylated interferon and ribavirin (PR) for chronic hepatitis C virus (HCV) genotype (GT) 1 and GT4 infection in the USA and the European Union. Methods: This 3-year follow-up study assessed the durability of sustained virologic response (SVR) (undetectable HCV RNA 12 or 24 weeks after treatment end), and evaluated the persistence of treatment-emergent NS3/4A protease inhibitor resistance in patients not achieving SVR following treatment with simeprevir plus PR in the parent study. The maintenance of SVR after the last post-therapy follow-up visit of the parent study (LPVPS) was assessed using HCV RNA measurements. The persistence of treatment-emergent NS3 amino acid substitutions in patients with no SVR at LPVPS was assessed using population sequencing. No study medications were administered. Results: Overall, 249 patients were enrolled (200 with SVR at LPVPS; 49 with no SVR at LPVPS); 40 patients discontinued prematurely (18 with SVR; 22 with no SVR). All 200 enrolled patients who achieved SVR in the parent study maintained SVR until the last available visit in this study (median follow-up time: 35.8 months). The treatment-emergent NS3 amino acid substitutions detected at time of failure in the parent study in 43/49 enrolled patients were no longer detected in 37/43 (86.0%) at the end of this study (median follow-up time: 179.9 weeks [41.3 months]). Conclusion: This 3-year follow-up study provides evidence for the long-term durability of SVR (100%) after successful treatment with simeprevir plus PR. Treatment-emergent NS3 amino acid substitutions became undetectable in the majority of patients. Trial registration: NCT01349465; ClinicalTrials.gov., SCOPUS: ar.j, info:eu-repo/semantics/published

AIM: To investigate interferon-γ-inducible protein-10's (IP-10) potential to anticipate rapid (RVR)- and sustained virological responses (SVR) to chronic hepatitis C (CHC) treatment. METHODS: We included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC, in patients treatment free for at least six months, with genotype 1 or 4, and in relation to 24 wk treatment for genotype 2 and 3, with pegylated interferon in combination with ribavirin. Patients had to have both a baseline IP-10 level as well as a hepatitis C virus (HCV)-RNA determination 4 wk after treatment initiation or 24 wk after end of treatment. Studies including patients with liver diseases other than CHC, human immunodeficiency virus-infection, treatment with immunosuppresents or cytostatica, alcohol dependency or active intravenous drug-use were excluded. We found 81 articles by searching the MEDLINE and EMBASE databases. Eight studies were eligible for inclusion. Their quality were assesed using an 18 point checklist for case series, developed using a modified Delphi technique. Information was extracted from the articles, and no raw data was requisitioned. The review protocol was registered at the International Prospective Register of Systematic Reviews (reg. Number: CRD42014008736). RESULTS: Three studies reported on baseline IP-10 level in association with RVR. A signigficant association was found for HCV genotype 1 infection by two studies. Only two studies reported on HCV genotype 4 infected and genotype 2 and 3 infected patients, respectively. A trend was seen for an association between RVR and baseline IP-10 for genotype 4, while no association was found for genotype 2 and 3. Seven studies provided information regarding baseline IP-10 and SVR. Following the pattern regarding rapid virological response all five studies examining SVR in relation to baseline IP-10 levels for HCV, genotype 1 infected patients showed a significant association. Likewise a significant assoc

Recently, concerns were raised of high rates of HCC recurrence in patients treated with direct-acting antivirals (DAA) for hepatitis C infection. We investigated the HCC occurrence and recurrence rates within 6 months after treatment with DAA with or without pegylated interferon (PEG-IFN) in real life. This is a retrospective, multicenter cohort trial, executed in 15 hospitals distributed across Belgium. Populations were matched based on fibrosis score (Metavir F3-F4). Patients with a Child-Pugh score ≥ B were excluded. In total, 567 patients were included, of whom 77 were treated with PEG-IFN+DAA between 2008 and 2013 and 490 with DAA without PEG-IFN between 2013 and 2015. Patients treated with PEG-IFN+DAA (53±9y) were younger than patients treated with DAA without PEG-IFN (59±12y) (P=.001). 47% of patients treated with PEG-IFN+DAA were in the F4 stage vs 67% of patients treated with DAA without PEG-IFN (P=.001). Screening was inadequate in 20% of both patient groups (P=.664). The early occurrence rate of HCC was 1.7% and 1.1% in patients treated with DAA with and without PEG-IFN, respectively (P=.540). The early recurrence rate was 0% in patients treated with PEG-IFN+DAA and 15.0% in patients treated with DAA without PEG-IFN (P=.857). There is no difference in early occurrence of new HCC between patients treated with DAA with and without PEG-IFN. We did observe a high early recurrence rate of HCC in patients treated with DAA without PEG-IFN. However, these patients were at baseline more at risk for HCC. Finally, in 20%, screening for HCC was inadequate., SCOPUS: ar.j, info:eu-repo/semantics/published

This thesis describes the safety and outcome of antiviral therapy for chronic HCV infection. In the first chapters, the authors investigated (hematological) adverse events during interferon-based therapy among patients with compensated cirrhosis. By using a patient-tailored approach, interferon-based treatment can be optimized. The authors also assessed the trends in pati

Fibrosis progression is common in hepatitis C. Both host and viral factors influence its natural history. Liver fibrosis is a key predictive factor for advanced disease including endpoints such as liver failure, cirrhosis and hepatocellular carcinoma (HCC). METAVIR fibrosis stages F3–F4 have been considered as the threshold for antiviral therapy. However, this aspect is controversial after the advent of new direct-acting antivirals (DAAs) because they show an excellent efficacy and safety profile. Moreover, in the DAA era, fibrosis stage seems not to be a predictive factor of a sustained virological response (SVR). Viral eradication decreases liver damage by improving the inflammation, as well as by regressing fibrosis irrespective of the treatment regimen. Non-invasive methods are useful in the assessment of liver fibrosis, replacing liver biopsy in clinical practice; but their usefulness for monitoring fibrosis after SVR needs to be demonstrated. Fibrosis regression has been demonstrated after the eradication of hepatitis C virus infection and is associated with a lower risk of hepatic cirrhosis and liver cancer. However, patients showing advanced fibrosis and cirrhosis must be followed-up after SVR, as risks of portal hypertension and HCC remain.

Background & Aims: There is little information regarding the extent to which difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response at week 24 (SVR24). Methods: 1078 patients with bridging fibrosis (n = 552) or cirrhosis (n = 526) diagnosed by either liver biopsy or non-invasive markers, with compensated bone marrow (neutrophils >1500/ mm3, Hb >12/13 g/dl) and liver function (Albumin >3.3 g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks, followed by a PR tail according to label. Results: Overall, 614 (57%) achieved SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The SVR24 rate to response-guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (A) F3 (odds ratio (OR) = 1.51, 95% CI 1.31- 2.00, p = 0.005), (B) subtype 1b (OR = 1.63, 95% CI 1.18-2.24, p = 0.0029), (C) alpha-fetoprotein <10 ng/ml (OR = 2.50, 95% CI 1.87-3.36, p <0.0001) and (D) any prior response other than null (OR = 3.29, 95% CI 2.40-4.52, p <0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail. Conclusions: Naïve and experienced patients with advanced fibrosis or cirrhosis d, SCOPUS: ar.j, info:eu-repo/semantics/published

Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1-coinfected previous nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment of insulin resistance >2.5 were treated with pioglitazone (PIO) for 24 weeks followed by PegIFN/RBV/PIO. Three of 19 subjects (15.8%) achieved undetectable HCV RNA at week 24 of PegIFN/RBV/PIO, which was not significantly different than the historical null rate of 10% (P = 0.29, lower limit of the exact 1-sided 90% confidence interval 5.9%). Over the 24 weeks of PIO monotherapy, alanine aminotransferase and aspartate aminotransferase declined significantly and correlated with improved metabolic parameters.

Background & Aims: There is little information regarding the extent to which difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response at week 24 (SVR24). Methods: 1078 patients with bridging fibrosis (n = 552) or cirrhosis (n = 526) diagnosed by either liver biopsy or non-invasive markers, with compensated bone marrow (neutrophils >1500/ mm3, Hb >12/13 g/dl) and liver function (Albumin >3.3 g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks, followed by a PR tail according to label. Results: Overall, 614 (57%) achieved SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The SVR24 rate to response-guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (A) F3 (odds ratio (OR) = 1.51, 95% CI 1.31- 2.00, p = 0.005), (B) subtype 1b (OR = 1.63, 95% CI 1.18-2.24, p = 0.0029), (C) alpha-fetoprotein <10 ng/ml (OR = 2.50, 95% CI 1.87-3.36, p <0.0001) and (D) any prior response other than null (OR = 3.29, 95% CI 2.40-4.52, p <0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail. Conclusions: Naïve and experienced patients with advanced fibrosis or cirrhosis d, SCOPUS: ar.j, info:eu-repo/semantics/published

Background and study aims: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. Patients and methods: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800- 1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. Results: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. Conclusions: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND AND AIM: IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort. METHODS: This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA < 2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA < 2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed. RESULTS: IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62% were HBeAg positive, and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype. CONCLUSIONS: In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.

BackgroundWe hypothesized that nitazoxanide (NTZ) added to pegylated interferon alfa-2a (PEG-IFN) and weight-based ribavirin (WBR) would improve hepatitis C virus (HCV) virologic responses in HCV treatment-naïve HIV-1/HCV genotype 1 coinfected persons.MethodsProspective, single-arm study in which subjects received 4-week lead-in (NTZ 500 mg twice daily) followed by 48 weeks of NTZ, PEG-IFN, and WBR. We compared the HCV virologic responses of these subjects to historical controls from the completed ACTG study A5178 who received PEG-IFN and WBR and had similar subject characteristics. Primary endpoints were early virologic response and complete early virologic response (EVR and cEVR).ResultsAmong 67 subjects (78% male; 48% Black; median age, 50 years), EVR was achieved in 65.7% (90% CI, 55.0%-75.3%), cEVR in 38.8% (28.8%-49.6%). and SVR in 32.8% (23.4%-43.5%). EVR was higher with NTZ (51.4% in A5178; P = .03), but the sustained virologic response (SVR) proportion was similar (27.3% in A5178; P = .24). In contrast to A5178, SVR was similar across IL28B genotypes. Overall, NTZ was safe and well-tolerated.ConclusionWhereas EVR proportion improved significantly in this pilot study, the addition of NTZ to PEG-IFN/WBR did not significantly improve SVR compared to historical controls. NTZ may be associated with an attenuation of the effect of IL28B on HCV treatment response.

The aim of this study was to evaluate the factors affecting the response to treatment and how it could affect survival in a large series of genotype-1 HCV-transplanted patients. Three-hundred and twenty six genotype-1 HCV patients were enrolled. One hundred and ninety-six patients (60.1%) were nonresponders and 130 (39.9%) showed negative HCV-RNA at the end of treatment. Eighty-four of them (25.8%) achieved sustained virological response, while 46 (14.1%) showed viral relapse. Five-year cumulative survival was significantly worse in nonresponders (76.4%) compared with sustained viral response (93.2) or relapsers (94.9%). Sustained responders and relapsers were therefore considered as a single 'response group' in further analysis. Pretreatment variables significantly associated with virological response at multivariate regression analysis were the absence of ineffective pretransplant antiviral therapy, the recurrence of HCV-hepatitis more than 1 year after transplant, an histological grading ≥4 at pretreatment liver biopsy, a pretreatment HCV-RNA level <1.2 × 106IU/ml, and the absence of diabetes. As expected, also on-treatment variables (rapid and early virological response) were significantly associated to the response to antiviral treatment. In conclusion, this study shows that postliver transplant antiviral treatment results in beneficial effect on survival not only in sustained responders but also in relapsers.

Randomised controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype 1 (G1) chronic hepatitis C (CHC) patients with previous relapse (RR), partial response (PAR), and null-response (NR). We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC.

The aim of this study was to evaluate the factors affecting the response to treatment and how it could affect survival in a large series of genotype-1 HCV-transplanted patients. Three-hundred and twenty six genotype-1 HCV patients were enrolled. One hundred and ninety-six patients (60.1%) were nonresponders and 130 (39.9%) showed negative HCV-RNA at the end of treatment. Eighty-four of them (25.8%) achieved sustained virological response, while 46 (14.1%) showed viral relapse. Five-year cumulative survival was significantly worse in nonresponders (76.4%) compared with sustained viral response (93.2) or relapsers (94.9%). Sustained responders and relapsers were therefore considered as a single 'response group' in further analysis. Pretreatment variables significantly associated with virological response at multivariate regression analysis were the absence of ineffective pretransplant antiviral therapy, the recurrence of HCV-hepatitis more than 1 year after transplant, an histological grading ≥4 at pretreatment liver biopsy, a pretreatment HCV-RNA level <1.2 × 10(6 ) IU/ml, and the absence of diabetes. As expected, also on-treatment variables (rapid and early virological response) were significantly associated to the response to antiviral treatment. In conclusion, this study shows that postliver transplant antiviral treatment results in beneficial effect on survival not only in sustained responders but also in relapsers.

Uvod. Hronični hepatitis C je široko rasprostranjena, teška, evolutivna bolest koja predstavlja veliki javno-zdravstveni problem. Globalna prevalencija se procenjuje na oko 3% populacije. Aktuelni standardni tretman za hronični hepatitis C sastoji se u lečenju pegilovanim interferonom alfa, subkutano, jedanput nedeljno, u kombinaciji sa oralnim ribavirinom, koji se daje svakodnevno. Primenjuje se u trajanju od 48 ili 24 nedelje. Terapija interferonom je povezana sa značajnim psihijatrijskim neželjenim efektima, a najznačajnija je pojava depresivne simptomatologije. Ciljevi. Utvrđivanje učestalosti i težine depresivne simptomatologije kod osoba obolelih od hroničnog hepatitisa C na terapiji pegilovanim interferonom alfa-2a u kombinaciji s ribavirinom; komparacija rezultata učestalosti i težine depresivne simptomatologije kod osoba obolelih od hroničnog hepatitisa C na navedenoj terapiji tokom 72 nedelje ispitivanja i kontrolne grupe koju sačinjavaju osobe obolele od iste bolesti, a bez navedene terapije u istom vremenskom periodu ispitivanja; komparacija povezanosti faktora rizika za pojavu depresivnosti kod obe grupe ispitanika; analiza uticaja utvrđenih faktora rizika na razvoj depresivnosti kod obe grupe ispitanika; preporuke tretmana sa psihijatrijskog aspekta na osnovu dobijenih rezultata. Hipoteze. Postoji statistički značajna razlika u učestalosti i težini depresivne simptomatologije kod osoba obolelih od hroničnog hepatitisa C na terapiji pegilovanim interferonom alfa-2a u kombinaciji sa ribavirinom tokom 72 nedelje ispitivanja i kontrolne grupe u istom vremenskom periodu ispitivanja; postoji pozitivna korelacija između faktora rizika i depresivnosti kod osoba obolelih od hroničnog hepatitisa C na navedenoj terapiji; prisustvo psihijatrijskih poremećaja u anamnezi i ženski pol predstavljaju prediktore za razvoj depresivnosti kod osoba obolelih od hroničnog hepatitisa C na navedenoj terapiji..., Introduction. Chronic hepatitis C is a widely distributed severe evolutive disease that is a great public health problem. The global prevalence is estimated at 3% of the population. The current standard treatment of chronic hepatitis C consists of pegylated interferon alpha, subcutaneously, once a week combined with oral ribavirin, taken every day. It is applied in the duration of 24 or 48 weeks. Interferon therapy is associated with significant psychiatric side effects, the most of them being depressive symptomatology. Aims. The aims of the study were to establish frequency and severity of the depression in patients with chronic hepatitis C with pegylated interferon alpha-2a combined with ribavirin (PEG-IFN-α-2a+RBV); to compare the frequency and the severity of depressive symptoms in chronic hepatitis C patients in the PEG-IFN-α-2a+RBV and in the control group consisting of the patients with same disease without the PEG-IFN-α- 2a+RBV, respectively, after 72 weeks of the observation; to compare the association of the depression risk factors in chronic hepatitis C patients in the aforementioned therapy and in the control group, respectively; and to assess the effects of the predictors on the development of depression in chronic virus hepatitis C in the PEG-IFN-α-2a+RBV and in the control group, respectively. Hypothesis. There is a statistically significant difference in the frequency and severity of depression in chronic hepatitis C patients in the aforementioned therapy and the control group after 72 weeks of observation, respectively; there is a positive correlation between specific risk factors and depression in chronic hepatitis C patients in the aforementioned therapy; the presence of lifetime psychiatric disorders and female sex are significant predictors for development of depression in chronic hepatitis C patients in the aforementioned therapy...

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; p<.0001); the model also included HCV RNA (log10 IU/ml), AST∶ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (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.

Background & Aims: Adherence to HCV therapy impacts sustainedvirological response (SVR) but there are limited data onadherence, particularly among injecting drug users (IDUs). Weassessed 80/80 adherence (P80% of PEG-IFN doses, P80% treatment),on-treatment adherence, and treatment completion in astudy of treatment of recent HCV infection (ATAHC).Methods: Participants with HCV received pegylated interferon(PEG-IFN) alfa-2a (180 lg/week, n = 74) and those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n = 35), for aplanned 24 weeks. Logistic regression analyses were used toidentify predictors of PEG-IFN 80/80 adherence.Results: A total of 109 out of 163 patients received treatment(HCV, n = 74; HCV/HIV, n = 35), with 75% ever reporting IDU.The proportion with 80/80 PEG-IFN adherence was 82%(n = 89). During treatment, 14% missed P1 dose (on-treatmentadherence = 99%). Completion of 0–4, 5–19, 20–23, and all24 weeks of PEG-IFN therapy occurred in 10% (n = 11), 14%(n = 15), 6% (n = 7) and 70% (n = 76) of cases, respectively. Participantswith no tertiary education were less likely to have 80/80PEG-IFN adherence (AOR 0.29, p = 0.045). IDU prior to or duringtreatment did not impact 80/80 PEG-IFN adherence. SVR washigher among those patients with P80/80 PEG-IFN adherence(67% vs. 35%, p = 0.007), but similar among those with and withoutmissed doses during therapy (73% vs. 60%, p = 0.309). SVR inthose patients discontinuing therapy between 0–4, 5–19, 20–23,and 24 weeks was 9%, 33%, 43%, and 76%, respectively (p

The characteristics and response rate to pegylated interferon and ribavirin (PEG-INF+RBV) of patients with chronic hepatitis C infected with genotype 5 are poorly documented. A meta-analysis of two large phase III/IV prospective randomized clinical trials conducted in Belgium in patients with chronic hepatitis C (n=1,073 patients) was performed in order to compare the response to antiviral therapy of hepatitis C virus (HCV) genotype 5 with that of other HCV genotypes. A subset of HCV-1 infected patients selected from within the study database were selected to match the HCV-5 sample for known prognostic factors. In Belgium HCV-5 is responsible for a significant minority of cases of chronic hepatitis C CHC (4.5%) and is characterized by a more advanced age (58.4 years), a high frequency of cirrhosis (27.7%), a specific mode of HCV acquisition, and a particular geographic origin (66.7% of patients from West Flanders). The primary comparative analysis showed that response to treatment with PEG-INF+RBV of HCV-5 is similar to HCV-1 and lower compared to HCV-2/3. The analysis of the matched patient subgroup demonstrates that the HCV-5 "intrinsic sensitivity" to PEG-IFN+RBV therapy is identical to HCV-1, with a sustained virological response of 55% in both groups. In contrast to previous publications, this meta-analysis suggests that HCV-5 response to treatment is closer to HCV-1 than to HCV-2/3 and suggests that in Belgium HCV-5 infection should be treated with the same antiviral regimen as HCV-1. © 2011 Wiley-Liss, Inc., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

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; p<.0001); the model also included HCV RNA (log10 IU/ml), AST∶ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (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.

The characteristics and response rate to pegylated interferon and ribavirin (PEG-INF+RBV) of patients with chronic hepatitis C infected with genotype 5 are poorly documented. A meta-analysis of two large phase III/IV prospective randomized clinical trials conducted in Belgium in patients with chronic hepatitis C (n=1,073 patients) was performed in order to compare the response to antiviral therapy of hepatitis C virus (HCV) genotype 5 with that of other HCV genotypes. A subset of HCV-1 infected patients selected from within the study database were selected to match the HCV-5 sample for known prognostic factors. In Belgium HCV-5 is responsible for a significant minority of cases of chronic hepatitis C CHC (4.5%) and is characterized by a more advanced age (58.4 years), a high frequency of cirrhosis (27.7%), a specific mode of HCV acquisition, and a particular geographic origin (66.7% of patients from West Flanders). The primary comparative analysis showed that response to treatment with PEG-INF+RBV of HCV-5 is similar to HCV-1 and lower compared to HCV-2/3. The analysis of the matched patient subgroup demonstrates that the HCV-5 "intrinsic sensitivity" to PEG-IFN+RBV therapy is identical to HCV-1, with a sustained virological response of 55% in both groups. In contrast to previous publications, this meta-analysis suggests that HCV-5 response to treatment is closer to HCV-1 than to HCV-2/3 and suggests that in Belgium HCV-5 infection should be treated with the same antiviral regimen as HCV-1. © 2011 Wiley-Liss, Inc., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Objective: The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72. weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered

Background/Aims: A large multicenter trial to compare the efficacy of peginterferon alfa-2a with interferon alfa-2a, in combination with ribavirin, in chronic hepatitis C patients. Efficacy data for prior relapsers are reported because treatment recommendations for this patient population are not well defined. Patients and methods: This study was a multicenter, prospective, randomized clinical trial. The primary efficacy endpoint was sustained virologic response in naïve patients (n = 348) and relapsers (n = 95).Results: Sustained virologic response rates were similar in naïve patients and relapsers, both for non-pegylated and pegylated interferon (respectively 27 and 26% and 54 and 43%). Psegylated interferon given for 48 weeks did not improved the relapse rate: 15.9 and 27.3% for non-pegylated and 16.7 and 30.4% for pegylated interferon, naïve vs relapsers respectively. Stepwise logistic regression analysis revealed a significant association between slow response (detectable HCV RNA at week 12 and undetectable at week 24) and relapse in patients with an end-of-treatment response (55% versus 13% respectively; p = 0.02; odds ratio = 6.07). Conclusions: This trial confirms the value of using peginter- feron alfa-2a in both naïve and relapsed patients and provides support for a more tailored approach to treatment for relapsers and particulary for patients with a slow viral response. (Acta gastro enterol. belg. 2010, 73, 223-228)., SCOPUS: ar.j, info:eu-repo/semantics/published

Background/Aims:To evaluate the possible influence of baseline insulin resistance in sustained virological response. Methods:One hundred and fifty-five consecutive individuals from a multicentric cohort of HIV/ HCV co-infected patients who underwent therapy with pegylated interferon plus ribavirin were included. The main outcome variable was sustained virological response, defined as undetectable plasma HCV RNA at week 24 after the end of the therapy. Insulin resistance was determined using the HOMA method. Results: Sustained virological response was achieved in 55 (36%) patients. Forty-two (38%) patients with aHOMA lower than 4 developed sustained virological response vs 13 (29%) of those with a HOMA above 4 (p = 0.27). Analyses restricted to patients harbouring genotype 1 or 4 showed similar rates of sustained virological response among patients with aHOMA below and above 4 [19 (27%) vs 7 (24%); p = 0.8]. In the multivariate analysis, genotype 3 [AOR 9.26; 95%CI 3.03 28.30; p < 0.0001], a baseline HCV viral load below 600.000 IU/mL [AOR 2.97; 95% CI 1.03 8.57; p = 0.04] and baseline LDL cholesterol above 100 mg/dL [AOR 6.62; 95% CI 1.97 22.19; p = 0.002] were independently associated with sustained virological response. Conclusions: Insulin resistance is not a relevant predictor of sustained virological response to pegylated interferon plus ribavirin in HIV/HCV co-infected patient

Background/Aims: A large multicenter trial to compare the efficacy of peginterferon alfa-2a with interferon alfa-2a, in combination with ribavirin, in chronic hepatitis C patients. Efficacy data for prior relapsers are reported because treatment recommendations for this patient population are not well defined. Patients and methods: This study was a multicenter, prospective, randomized clinical trial. The primary efficacy endpoint was sustained virologic response in naïve patients (n = 348) and relapsers (n = 95).Results: Sustained virologic response rates were similar in naïve patients and relapsers, both for non-pegylated and pegylated interferon (respectively 27 and 26% and 54 and 43%). Psegylated interferon given for 48 weeks did not improved the relapse rate: 15.9 and 27.3% for non-pegylated and 16.7 and 30.4% for pegylated interferon, naïve vs relapsers respectively. Stepwise logistic regression analysis revealed a significant association between slow response (detectable HCV RNA at week 12 and undetectable at week 24) and relapse in patients with an end-of-treatment response (55% versus 13% respectively; p = 0.02; odds ratio = 6.07). Conclusions: This trial confirms the value of using peginter- feron alfa-2a in both naïve and relapsed patients and provides support for a more tailored approach to treatment for relapsers and particulary for patients with a slow viral response. (Acta gastro enterol. belg. 2010, 73, 223-228)., SCOPUS: ar.j, info:eu-repo/semantics/published

Background and study aims: The combination of Pegylated (PEG)interferon 2b and ribavirin is considered to be the standard treatment for naïve chronic hepatitis C patients. Study aims are to evaluate the differences between standard interferon and PEG-interferon by conducting a multi-centre, controlled randomized trial comparing 3 groups. Group A: daily interferon alfa-2b at a dose of 4 MIU + ribavirin, Group B: PEG-interferon alfa-2b at a dose of 100 mcg/week + ribavirin; Group C: interferon alfa-2b at a dose of 3 MIU TIW + ribavirin. Patients and methods: Multicentrer, open label study including naïve chronic Hepatitis C Virus patients randomised in three groups with a ratio of 2:2:1. Group A: daily interferon α-2b (4 MIU s.c. for patients >65 kg or 0.06 MIU/kg < 65 kg) and ribavirin, group B: PEG-interferon α-2b (100 μg s.c. weekly for patients > 65 kg or 1.5 μg/kg weekly for patients < 65 kg) and ribavirin and group C (reference arm): interferon α-2b (3MIU s.c. TWI) and ribavirin. The duration of the treatment was 48 weeks for all 3 groups, with a 6 month follow-up period. 336 patients were enrolled in the study and included in the intention-to-treat analysis; 78 never started treatment (35 in group A, 28 in group B and 15 in group C): 101 in group A, 98 in group B and 59 in group C. Results: Demographic data, PCR results and reasons for early withdrawal have been statistically analysed. At baseline, the 3 groups did not show any statistical difference regarding age, gender, race, genotypes and METAVIIR score. At week 24 on treatment, HCV ribonucleic acid RNA was undetectable in 87% in group A, in 79% in group B and in 69% in group C. At the end of treatment, 73% 74% and 58% respectively, had a negative PCR result. At week 24 of follow-up, these results were 71%, 64% and 48%, respectively. When comparing the efficacy of the daily interferon (+ ribavirin) and the PEG-interferon (+ ribavirin) regimen, no statistical difference was found (p = 0.32). In group A, 38%, SCOPUS: ar.j, info:eu-repo/semantics/published

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

Significant advances in the management of chronic hepatitis B (CHB) have been made over the past decade. During this period we have witnessed improvements in survival as well as reduction of disease progression in CHB patients due to the introduction of effective antiviral therapy. The need for effective antiviral therapy is underscored by the results of the REVEAL-HBV study in which 3653 hepatitis B virus (HBV) carriers were followed over 12 year period. This study demonstrated that a persistently elevated serum HBV DNA level was the most important risk factor for the development of hepatocellular carcinoma (HCC). The ultimate goal of antiviral therapy for CHB patients should include halting the progression to cirrhosis and its life threatening complications and in preventing/reducing the development of HCC. An earlier study of 651 CHB patients with cirrhosis or advanced fibrosis from countries in Asia also demonstrated that treatment with lamivudine (LVD) not only delayed disease progression but also reduced the development of HCC. These landmark studies reaffirm the need for active antiviral therapy for CHB. Current treatment options for patients with CHB include interferon and nucleos(t)ide analogues. As we gain experience with these agents, it has become increasingly clear that long-term therapy benefits patients with CHB.