Harald Hofer

Medical University of Vienna, Wien, Vienna, Austria

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Publications (113)919.59 Total impact

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    ABSTRACT: The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy. C-SALVAGE was an open-label study of grazoprevir 100 mg/elbasvir 50 mg QD with weight-based ribavirin BID for 12 weeks in cirrhotic and non-cirrhotic patients with chronic HCV genotype-1 infection who had not attained SVR after ⩾4 weeks of peginterferon and ribavirin plus either boceprevir, telaprevir, or simeprevir. Exclusion criteria included decompensated liver disease, hepatocellular carcinoma, and HIV or HBV co-infection. The primary efficacy outcome was SVR12 defined as a HCV RNA level below the assay limit of quantification 12 weeks after the end of treatment. Of the 79 patients treated with ⩾1 dose of study drug, 66 (84%) patients had a history of virologic failure on a regimen containing a NS3/4A protease inhibitor; 12 of the other 13 patients discontinued prior treatment because of adverse experiences. At entry, 34 (43.6%) of 78 evaluable patients harbored NS3 RAVs. SVR12 rates were 76/79 (96.2%) overall, including 28/30 (93.3%) patients with genotype 1a infection, 63/66 (95.5%) patients with prior virologic failure, 43/43 (100%) patients without baseline RAVs, 31/34 (91.2%) patients with baseline NS3 RAVs, 6/8 (75.0%) patients with baseline NS5A RAVs, 4/6 (66.7%) patients with both baseline NS3 and RAVs, and 32/34 (94.1%) cirrhotic patients. None of the 5 reported serious adverse events were considered drug-related. Grazoprevir/elbasvir plus ribavirin for 12 weeks provides a promising new treatment option for patients after failure of triple therapy containing an earlier-generation protease inhibitor. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 04/2015; DOI:10.1016/j.jhep.2015.04.009 · 10.40 Impact Factor
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    ABSTRACT: Interferon-based regimens with first generation protease-inhibitors have a limited efficacy and an unfavorable safety profile. Combination-therapies with two or more second generation direct acting antivirals (DAAs) plus/minus ribavirin revolutionized treatment-strategies in patients chronically infected with hepatitis C virus. In this rapidly evolving era patients in the transplant setting benefit from interferon-free treatment regimens. Scientific societies can barely keep up with this development, making it necessary to up-date the clinical guidelines by the American and European Associations for the Study of Liver Diseases (AASLD, EASL) within short periods. This review presents and discusses the currently available data of the use of IFN-free treatment in the setting of liver transplantation. However, costs, different reimbursement-strategies, and health-care options cannot be answered by guidelines and recommendations from scientific societies. Further investigator-initiated trials are needed to individualize treatment-concepts. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Transplant International 04/2015; DOI:10.1111/tri.12577 · 3.16 Impact Factor
  • Zeitschrift für Gastroenterologie 04/2015; 53(4):320-334. DOI:10.1055/s-0034-1399322 · 1.67 Impact Factor
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    ABSTRACT: Background & aim: The earliest characteristic alterations of the liver pathology in Wilson disease (WD) include steatosis which is sometimes indistinguishable from non-alcoholic fatty liver disease (NAFLD). Steatosis in WD may reflect copperinduced mitochondrial dysfunction. A genetic polymorphism in rs738409 in the patatin-like phospholipase domain-containing 3 gene (PNPLA3) is strongly associated with appearance of in NAFLD. This study evaluated the role of PNPLA3 and hepatic copper content for development of steatosis in patients with WD. Methods: Findings of liver biopsies obtained at diagnosis and the PNPLA3 genotype were analyzed in 98 Caucasian patients with WD (male: 52 [53.1%]; mean age: 27.6 [CI95%: 24.8-30.4, range: 5.8-61.5] years). Steatosis was graded as percentage of lipid containing hepatocytes by an expert hepatopathologist unaware of the results of genetic testing. Results: Moderate/severe steatosis (>33% of hepatocytes) was observed in 28 patients (pediatric: n=13/26 [50.0%], adult: n=15/72 [20.8%]; p=0.01). Forty-six patients (46.9%; pediatric: n=7, adult: n=39; p=0.022) had cirrhosis. Multivariate logistic regression identified PNPLA3 G allele (OR: 2.469, CI95%: 1.203-5.068; p=0.014) and pediatric age (OR: 4.348; 1.577-11.905; p=0.004) as independent variables associated with moderate/severe steatosis. In contrast, hepatic copper content did not impact on moderate/severe steatosis (OR: 1.000, CI95%: 1.000- 1.001; p=0.297). Conclusion: Steatosis is common in WD and the PNPLA3 G allele contributes to its pathogenesis. The roles of hepatic copper content and ATP7B mutations in steatosis development deserve further investigations.
    Journal of Hepatology 02/2015; DOI:10.1016/j.jhep.2015.01.034 · 10.40 Impact Factor
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    ABSTRACT: Background Long-term outcome of chronic hepatitis C patients with successful viral eradication seems to be promising.AimTo evaluate mortality, incidence of hepatocellular carcinoma (HCC), liver failure and liver transplantation in sustained virological responders (SVR) and non-SVR patients with different stages of fibrosis.Methods Seven hundred and fourteen patients with a follow-up of 7.2 (1–21.1) years (age: 51.4 ± 12.0 years, 276 female, IFN-monotherapy: n = 19, IFN/RBV: n = 122, peg-IFN/RBV: n = 573, SVR: 551, non-SVR: 163) were studied. Two hundred and ten of 540 patients with a liver biopsy prior to treatment had advanced stages of fibrosis (Metavir F3/F4).ResultsForty-eight patients died during follow-up, 15 with SVR and 33 without (P < 0.001). Five- and 10-year mortality rates were 1.8% (10/551) and 2.7% (15/551) in the SVR group and 8.6% (14/163) and 19.1% (31/163) in the non-SVR patients (P < 0.001). In 29 patients, decompensation of liver disease [SVR: 9 (1.6%) vs. non-SVR: 20 (12.3%); P < 0.001] occurred and in 29 patients, HCC developed during follow-up [SVR: 10 (1.8%) vs. non-SVR: 19 (11.7%); P < 0.001]. Non-SVR was an independent predictor for developing (i) HCC [HR: 2.36 (95% CI: 1.07–5.23; P = 0.034], (ii) liver-related complications [HR: 2.62; (95% CI: 1.18–5.81; P = 0.018] and (iii) mortality (HR: 3.46; 95% CI: 1.91–6.29; P < 0.001). For patients with early stages of fibrosis (F0–F2), a survival benefit of SVR patients could not be demonstrated.Conclusions Successful anti-viral therapy decreases mortality, incidence of hepatocellular carcinoma and liver failure in patients with advanced fibrosis. However, hepatocellular carcinoma development or liver failure are not prevented completely, and further follow-up of patients is advisable.
    Alimentary Pharmacology & Therapeutics 01/2015; 41(6). DOI:10.1111/apt.13085 · 4.55 Impact Factor
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    ABSTRACT: The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:60-89. DOI:10.1111/jvh.12249 · 3.31 Impact Factor
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    ABSTRACT: Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:5-33. DOI:10.1111/jvh.12247 · 3.31 Impact Factor
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    ABSTRACT: The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:34-59. DOI:10.1111/jvh.12248 · 3.31 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S52. DOI:10.1016/S0168-8278(14)60127-6 · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S303-S304. DOI:10.1016/S0168-8278(14)60866-7 · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S438. DOI:10.1016/S0168-8278(14)61243-5 · 10.40 Impact Factor
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    ABSTRACT: Background Genetic factors can play an important role for treatment response and disease progression in chronic viral hepatitis.AimTo review the influence of host genetic factors on the clinical course as well as on treatment response in patients with viral hepatitis.Methods Review of the literature.ResultsA landmark genome-wide association study (GWAS) identified polymorphisms in the IL28B gene on chromosome 19 (19q13.13) associated with response to therapy with pegylated interferon-α (PEG-IFN) and ribavirin (RBV) and spontaneous viral clearance in acute hepatitis C. Furthermore, IL28B genotype is associated with changes of lipid metabolism and insulin resistance. A further GWAS demonstrated that ITPA genetic variants protect HCV genotype 1 patients from RBV-induced anaemia. Another polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) is associated with hepatic steatosis. Difficult-to-treat hepatitis C patients homozygous for GG had an up to five-fold lower chance of viral clearance on PEG/RBV than non-GG patients.In chronic hepatitis B patients treated with PEG-IFN several retrospective analyses of IL28B rs12980275 and rs12979860 genotypes yielded conflicting results which can be explained by the heterogeneity between the study populations. Some variants of the HLA-DP locus (HLA-DPA1 A allele and HLA-DPB1) protect against progression of chronic hepatitis B infection.Conclusions The determination of IL28B polymorphisms may be useful to individualise treatment options when using PEG/RBV based therapies for chronic hepatitis C infection. In contrast, so far identified genetic factors play only a minor role in chronic hepatitis B infection.
    Alimentary Pharmacology & Therapeutics 03/2014; DOI:10.1111/apt.12717 · 4.55 Impact Factor
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    Journal of Hepatology 01/2014; DOI:10.1016/j.jhep.2013.12.028 · 10.40 Impact Factor
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    ABSTRACT: Chronic inflammatory bile duct diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) result in progressive fibrosis of the biliary tract and ultimately cirrhosis of the liver. Since the etiology and pathogenesis of these fibrosing cholangiopathies are still poorly understood, therapeutic options are rather limited at present. Ursodeoxycholic acid (UDCA) is the paradigm therapeutic bile acid and established standard treatment for PBC, but its role for medical therapy of PSC is still under debate. Promising novel bile acid-based therapeutic options include 24-norursodeoxycholic acid, a side chain-shortened C23 homologue of UDCA, and bile acid receptor/farnesoid X receptor agonists (e.g. obeticholic acid) which currently undergo clinical development for fibrosing cholangiopathies such as PBC and PSC. Other nuclear receptors such as vitamin D receptor and fatty acid-activated peroxisome proliferator-activated receptors are also of considerable interest. This review article is a summary of an overview talk given at Falk Symposium 191 on Advances in Pathogenesis and Treatment of Liver Diseases held in London, October 3-4, 2013, and summarizes the recent progress with novel therapeutic bile acids and bile acid derivatives as novel therapies for fibrosing cholangiopathies such as PBC and PSC. © 2014 S. Karger AG, Basel.
    Digestive Diseases 01/2014; 32(5):631-6. DOI:10.1159/000360517 · 1.83 Impact Factor
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    ABSTRACT: The IL28B genotype in rs12979860 predicts success of peginterferon/ribavirin (PEG/RBV) therapy in patients with chronic hepatitis C (CHC). Recently, a dinucleotide frame shift variant in ss469415590 (TT or ΔG) was described, which generates the novel interferon lambda 4 protein (IFNL4). IFNL4 ss469415590 (ΔG) allele carriers have an impaired clearance of HCV infection and response to IFN-α therapy. In this study, we compared the role of IFNL4 polymorphism with the two commonly used IL28B SNPs rs12979860 and rs8099917 on response to PEG/RBV in patients with CHC. To compare the role of IFNL4 polymorphism with the two commonly used IL28B SNPs rs12979860 and rs8099917 on response to PEG/RBV in patients with CHC. A total of 754 PEG/RBV patients treated (male/female = 484/270; Caucasians: 98.8%; mean age: 42.8 [CI 95%: 42.0-43.6] y; genotype (GT)1: n = 435, GT2: n = 23, GT3: n = 185, GT4: n = 114) were investigated. Liver fibrosis was assessed by liver biopsy in 456 patients. Single nucleotide polymorphisms (SNPs) in ss469415590, rs12979860 and rs8099917 were analysed by RT-PCR system. Of the patients, 12.9% (n = 97) had the ss469415590 ΔG/ΔG genotype (IFNL4), 51.3% (n = 387) were heterozygous (TT/ΔG) and 35.8% (n = 270) had TT/TT. IFNL4 polymorphism was independently associated with SVR in GT1 (OR: 2.539, CI 95%: 1.629-3.021, P < 0.001) and GT4 (OR: 12.573, CI 95%: 3.427-46.133, P < 0.001), but not in GT3 (OR: 1.514, CI 95%: 0.933-2.458, P = 0.093). IFNL4 correlated strongly with rs12979860 (ρ = 0.988, P < 0.001), but only moderately with rs8099917 (ρ = 0.598, P < 0.001). These findings underscore the role of IFNL4 for treatment response in patients with CHC genotypes 1 and 4. However, due to its strong correlation with rs12979860 in IL28B, there is no benefit in additional testing for IFNL4 for treatment prediction in Caucasian patients. By contrast, IFNL4 improves prediction of response to interferon-based therapies, if SNP rs8099917 is used.
    Alimentary Pharmacology & Therapeutics 11/2013; 39(1). DOI:10.1111/apt.12547 · 4.55 Impact Factor
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    ABSTRACT: Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in well-characterized Austrian cohort of patients with Wilson disease. We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry. The mean observation-period was 14.8±11.4 y (range, 0.5 y-52 y) resulting in 3116 patient-y. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at pre-symptomatic stages. Patients with hepatic presentation were diagnosed younger (21.2±12.0 y) than patients with neurologic disease (28.8±12.0; P<.001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required liver transplantation and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 y (92%) than healthy Austrians (97%), adjusted for age and sex (P=.03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P=.013) and need for liver transplantation (odds ratio, 07; 95% confidence interval, 0.016-0.307; P<.001). Only 84% of patients with cirrhosis survived 20 y after diagnosis (compared with healthy Austrians, P=.008). Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases risk of death and liver disease. Early diagnosis, at a pre-cirrhotic stage, might increase survival times and reduce the need for liver transplantation.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2013; 12(4). DOI:10.1016/j.cgh.2013.09.025 · 6.53 Impact Factor
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    ABSTRACT: IL28B-polymorphisms, jaundice, decline in HCV-RNA, IP-10 and gender have been proposed to be indicative for spontaneous clearance of acute hepatitis C virus infection. Aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development to viral persistence and need for early antiviral treatment. 136 patients (male:74;35±15years) were analyzed. From variables predictive for spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cutoffs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cutoffs were: (I)presence of IL28B-C/C (P=0.027), (II)age (P=0.031;cutoff:35years), (III)peak-bilirubin (P=0.018;cutoff:6mg/dl), (IV)HCV-RNA-decline within 4 weeks (P<0.001;cutoff:>2.5log), (V)serum IP-10 (P=0.003;cutoff:546pg/ml), (VI)presence of CD4(+)Th1-cells (P=0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA-decline of ⩾1log(10) but <2.5log(10) 1 point, a decline of ⩾2.5log(10) to 2 points. Three scores were evaluated (Score1:I-IV; Score2:I-V; Score3:I-VI). A cutoff of ⩾3 points out of 5 in Score1 (AUROC:0.82; DeLong95%CI:0.76-0.93) predicted spontaneous clearance with a sensitivity of 71% (95%CI:0.53-0.86) and specificity of 87% (95%CI:0.73-0.95). PPV and NPV were 79% and 82%. Corresponding findings for Score2 including IP-10 (AUROC:0.93; DeLong95%CI:0.86-0.93) at a cutoff ⩾4 were: sensitivity 81%, specificity 95% (PPV:100%;NPV:77%). A cutoff of ⩾5 in Score3 (AUROC:0.98; DeLong95%CI:0.95-1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV:100%;NPV:88%). The scores enable a reliable discrimination between AHC-patients with high potential for spontaneous clearance from candidates for early therapeutic intervention due to marginal chance of spontaneous resolution.
    Journal of Hepatology 07/2013; DOI:10.1016/j.jhep.2013.06.028 · 10.40 Impact Factor
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    ABSTRACT: Single nucleotide polymorphisms (SNP's) in the inosine triphosphate pyrophosphatase (ITPA) gene protect patients from ribavirin induced anemia. To investigate other possible protective cofactors gender differences were analyzed in patients with HCV genotype 1. Hemoglobin levels at baseline (Hb0) and the decline after 4 weeks of treatment (HbΔ4) were analyzed in 308 chronic hepatitis C patients participating in 5 Austrian trials (n=308, age 43.9±11.1, male:185, female:123, BMI 25.3±3.9, no cirrhosis: n=259, liver cirrhosis: n= 49. All patients were treated with 180 mcg peginterferon-alpha 2a and ribavirin [1000-1200mg/d; females: mean (95%CI) 15.8 mg/kg (15.4 - 16.2); males 14.3 (14.1 - 14.5);p<0.001]. The SNP's rs6051702, rs1127354, rs7270101 and IL28B rs12979860 were analyzed by the StepOnePlus Real time PCR System. 188 were major alleles homozygotes; 95 (30.8%) carried the minor allele (C) of rs6051702, 47 (15.3%) of rs1127354 (A) and 69 (22.4%) of rs7270101 (C). The overall Hb0 was 14.8 g/dl (14.6-14.9) [mean (95%CI); females 13.7 (13.5-13.9); males 15.5; 15.3-15.6;p<0.001]). The overall HbΔ4 was greater in major allele homozygotes [2.8 g/dl (2.6-3.0)] than in minor allele carriers [1.6 (1.4-1.9);p<0.001]. Irrespective of the ITPA genotypes HbΔ4 was smaller in female [2.0 (1.7-2.2)] than in male patients [2.6 (2.4-2.8);p<0.001] and among females in premenopausal [1.5 (1.3-1.8)] than in postmenopausal patients [2.7 (2.3-3.1);p<0.001]. Irrespective of the protective effect of ITPA mutations premenopausal females less likely develop ribavirin induced anemia.
    Journal of Hepatology 07/2013; DOI:10.1016/j.jhep.2013.06.030 · 10.40 Impact Factor
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    ABSTRACT: In chronic hepatitis C (CHC), steatosis is associated with fibrosis and impaired response to antiviral therapy. Recently, a polymorphism of single nucleotide polymorphism SNP rs2645424 of farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified in NAFLD/NASH as a possible causal link to steatosis and fibrosis progression. SNP rs738409 in the adiponutrin gene (PNPLA3) is a well described factor for steatosis. This study evaluated the relation of these SNPs on steatosis, fibrosis and treatment response in CHC. The SNPs rs738409478 and rs2645424 were determined by real-time PCR in 478 patients with CHC (m/f: 314/164; mean age: 44.9 ± 10.7; GT1: 387, GT4: 91) who completed treatment with peg-IFN-α-2a/ribavirin. All had a pretreatment liver biopsy. Steatosis and fibrosis were graded by board-certified pathologists according to Brunt and METAVIR respectively. The distribution of FDFT1 rs2645424 was GG: 186 (38.9%), AG: 222 (46.4%) and AA: 70 (14.6%) and of the rs738409 PNPLA3 allele: CC: 269 (56.3%), CG: 177 (37.0%) and GG: 32 (6.7%). Overall, FDTF1 polymorphism was not linked to the extent of steatosis or fibrosis. However, in patients without steatosis the AA genotype was associated with advanced fibrosis [AA: 8/20 (40.0%), AG: 6/70 (8.5%), GG: 9/57 (16.1%), P = 0.003]. In contrast, the minor PNPLA3 allele was associated with both steatosis and advanced fibrosis (P < 0.001). Both SNPs did not influence treatment response. The minor allele in FDFT1 was associated with advanced fibrosis in the non-steatotic but not in the steatotic subgroup. This may reflect different metabolic pathways in fibrosis progression for steatotic and non-steatotic patients with CHC.
    Liver international: official journal of the International Association for the Study of the Liver 06/2013; 34(3). DOI:10.1111/liv.12269 · 4.41 Impact Factor
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    ABSTRACT: BACKGROUND: The introduction of direct-acting anti-virals has increased sustained virological response (SVR) rates in chronic hepatitis C genotype 1 infection. At present, data on long-term durability of viral eradication after successful triple therapy are lacking. AIM: To evaluate the long-term durability of viral eradication in patients treated with triple therapy, including direct-acting anti-virals. METHODS: Patients who participated in randomised, controlled trials or an extended access programme of treatment with peginterferon-α2a/ribavirin in combination with a direct-acting anti-viral (telaprevir, danoprevir, faldaprevir, simeprevir, mericitabine, balapiravir) were followed after achieving SVR. The median follow-up after the patients was 21 (range: 7-64) months. RESULTS: One hundred and three patients with chronic hepatitis C genotype 1 infection [f/m: 34/69; GT-1b: 67 GT-1a: 34, GT-4: 2; mean age: 47.6 years (45.5-49.7; 95% CI)] achieving a SVR triple therapy were followed. Two cases of late relapses (2/103, 1.9%; 95% CI: 0.24-6.8) were observed. One patient was cirrhotic, both carried the genotype 1b and completed the prescribed treatment. The relapses occurred 8 and 12 months after cessation of anti-viral treatment. Cloning sequencing revealed identical sequence in both patients. Resistance analysis revealed no presence of viral resistance. CONCLUSION: Like the SVR after peginterferon-α2/ribavirin combination treatment, HCV eradication after triple therapy remains durable after long-term follow-up.
    Alimentary Pharmacology & Therapeutics 05/2013; 38(2). DOI:10.1111/apt.12350 · 4.55 Impact Factor

Publication Stats

2k Citations
919.59 Total Impact Points

Institutions

  • 2002–2015
    • Medical University of Vienna
      Wien, Vienna, Austria
  • 2000–2015
    • University of Vienna
      • • Department of Internal Medicine IV, Gastroenterology and Hepatology
      • • Division of Gastroenterology and Hepatology
      Wien, Vienna, Austria
  • 2013
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • Elisabethinen Hospital
      Linz, Upper Austria, Austria
  • 2006
    • Allgemeines Krankenhaus Linz
      Linz, Upper Austria, Austria
  • 2003
    • Semmelweis University
      Budapeŝto, Budapest, Hungary