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ABSTRACT: Coinfection with GBV-C/HGV in patients with chronic hepatitis C (CHC) may influence clinical course and response rates of antiviral therapy. Aim of the study was to investigate the prevalence of GBV-C/HGV/HCV coinfection and its influence on outcome of interferon/ribavirin combination therapy. Three hundred and four patients with CHC [m/f = 211/93, age: 42 (18-65)] were investigated. HGV RNA detection was performed by polymerase chain reaction prior to and 6 months after the end of antiviral therapy. HGV/HCV coinfection could be identified in 37/304 (12.2%) patients with intravenous drug abuse as the most common source of infection (N = 21, (56.8%)). The predominant HCV genotype in coinfected individuals was HCV-3a (HCV-3a: 51.4%, HCV-1: 37.8%, HCV-4: 10.8%). HGV coinfection was more prevalent in patients infected with HCV-3 compared to HCV-1 or HCV-4 [19/45 (42.2%) vs. 14/185 (7.6%) vs. 4/52 (7.7%), P < 0.01]. Patients with HGV/HCV coinfection were younger [35 (18-56) vs. 43 (19-65), years; P < 0.01], and advanced fibrosis (F3-F4) was less frequent (22.2% vs. 42.9%, P < 0.05). A sustained virological response was achieved more frequently in HGV/HCV coinfected patients [26/37 (70.3%)] than in monoinfected patients [120/267 (44.9%), P < 0.01]. HGV RNA was undetectable in 65.7% of the coinfected patients at the end of follow-up. Intravenous drug abuse seems to be a major risk factor for HGV coinfection in patients with chronic hepatitis C. Coinfection with HGV does not worsen the clinical course of chronic hepatitis C or diminish response of HCV to antiviral therapy. Interferon/ribavirin combination therapy also clears HGV infection in a high proportion of cases.
Journal of Viral Hepatitis 07/2011; 18(7):513-7. · 4.09 Impact Factor
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Thomas Reiberger,
Karoline Rutter,
Arnulf Ferlitsch,
Berit Anna Payer, Harald Hofer,
Sandra Beinhardt,
Michael Kundi,
Peter Ferenci,
Alfred Gangl,
Michael Trauner,
Markus Peck-Radosavljevic
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ABSTRACT: There are limited data on the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV)-related cirrhosis, particularly on the impact of portal hypertension.
We assessed hepatovenous pressure gradient (HVPG), liver stiffness (transient elastography), and interleukin (IL)-28B polymorphisms (rs12979860) in 90 cirrhotic patients with HCV infection (82% genotype 1 or 4) before antiviral therapy with pegylated interferon and ribavirin. Efficacy and safety were evaluated.
Rates of sustained virologic response were significantly lower among patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mm Hg; n = 50) than among patients without CSPH (HVPG <10 mm Hg; n = 40): 14% vs 51% (P = .0007). Seventy-nine percent and 83% of patients with CSPH and without CSPH, respectively, received more than 80% of planned dose (P = .647). The predictive value of HVPG (area under the curve [AUC], 0.743) was greater than that of liver stiffness (AUC, 0.647) or of baseline HCV RNA levels (AUC, 0.620). The IL-28B polymorphism was not associated significantly with a sustained virologic response. Multivariate analysis revealed that HVPG (odds ratio [OR], 14.3; P = .009), baseline HCV RNA levels (OR, 5.3; P = .019), and HCV genotype (OR, 6.5; P = .046) were independent risk factors for treatment failure. A trend toward higher incidence of anemia and neutropenia was observed for patients with CSPH. The incidence and grade of thrombocytopenia were significantly higher among patients with than without CSPH (94% vs 75%; P = .006).
HVPG is an independent predictor of response to antiviral therapy, with better predictive value than liver stiffness, baseline HCV RNA levels, HCV genotype, or IL-28B polymorphism. The incidence and grade of thrombocytopenia during antiviral therapy are higher among patients with CSPH. In evaluating cirrhotic HCV patients for antiviral treatment, measurement of HVPG should be considered.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2011; 9(7):602-8.e1. · 5.64 Impact Factor
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ABSTRACT: Skills in gastrointestinal endoscopy mainly depend on experience and practice. Patients upon whom trainees perform their first endoscopic examinations are likely to suffer more discomfort and prolonged procedures. Training on endoscopy simulators may reduce the time required to reach competency in patient endoscopy.
Residents in internal medicine without experience of endoscopy were randomized to a group who trained on a simulator before conventional training (group S) or one that received conventional training only (group C) before starting upper gastrointestinal endoscopy in patients. After endoscopy, discomfort and pain were evaluated by patients, who were blind to the beginners' training status. Results in terms of time, technique (intubation, pyloric passage, J-maneuver), and diagnosis of pathological entities were evaluated by experts.
From 2003 to 2007, 28 residents were enrolled. Comparing group S with group C in their first ten endoscopic examinations in patients, time taken to reach the duodenum (239 seconds (range 50 - 620) vs. 310 seconds (110 - 720; P < 0.0001) and technical accuracy ( P < 0.02) were significantly better in group S. Diagnostic accuracy did not differ between the groups. Fourteen residents (7 simulator-trained, 7 not simulator-trained) continued endoscopy training. After 60 endoscopic examinations, investigation time was still shorter in group S. Technical and diagnostic accuracy improved during on-patient training in both groups; here differences between groups were no longer observable. There were no significant differences in discomfort and pain scores between the groups after 10 and after 60 endoscopies. Discomfort and pain were higher than for endoscopy performed by experts.
This randomized controlled trial shows that virtual simulator training significantly affects technical accuracy in the early and mid-term stages of endoscopic training. It helps reduce the time needed to reach technical competency, but clinically the effect is limited. Simulator training could be useful in an endoscopy training curriculum but cannot replace on-patient training.
Endoscopy 10/2010; 42(12):1049-56. · 5.21 Impact Factor
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ABSTRACT: Efficacy and safety of antiviral combination therapy in patients with Crohn's disease (CD) and chronic hepatitis C (CHC) is presently not established and consequently CHC is rarely treated in CD patients.
To analyse the efficacy and tolerability of antiviral interferon/ribavirin therapy in patients with CHC and CD.
Eleven HCV-infected CD patients received either 3 x 1.5 microg/kg/week interferon-alpha-2b or 180 microg/week peginterferon-alpha-2a (PEGASYS; Roche, Basel, Switzerland) as monotherapy (n = 1) or in combination with 800-1200 mg/day ribavirin (COPEGUS; Roche) (n = 10) for 24-54 weeks according to HCV-genotype and initial response respectively. Eight patients were under CD-specific therapy.
Five (46%) patients (HCV-1: a = 3; HCV-2: n = 0; HCV-3: n = 1; unknown: n = 1) achieved a sustained virological response, three (27%) patients relapsed, three (27%) were nonresponders (all GT 1b). At baseline, the Harvey--Bradshaw Index was 0 (0-8) [median (range)], increased on antiviral therapy to 4 (1-15) (P = 0.005) and decreased to baseline level 0 (0-6) after 6-month follow-up.
This preliminary experience demonstrates that treatment of CHC in patients with CD is comparable to the treatment of CHC in those without CD. However, gastrointestinal symptoms may be temporarily exacerbated and haemopoietic growth factors may be required.
Alimentary Pharmacology & Therapeutics 10/2008; 28(6):742-8. · 3.77 Impact Factor
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ABSTRACT: Antiviral treatment results in a sustained virologic response (SVR) in 50-75% of patients with chronic hepatitis C. Long-term follow up studies have observed ongoing SVR in the overwhelming majority of them. Thus chronic hepatitis C is considered 'cured' if an SVR is achieved. Consequently, it is expected that in sustained virologic responders long-term complications of hepatatic C virus (HCV) related chronic liver disease including hepatocellular carcinoma are eliminated or have a decreased incidence. We report on five patients (three from Austria, two from USA) who developed hepatocellular carcinoma during follow up (3-6 years) after achieving SVR. During follow up and at diagnosis all were HCV-RNA neg. None of the patients had other liver diseases. One patient presented with bilateral adrenal metastasis, the remaining four with large hepatic tumours. Three patients were noncirrhotic at the start of treatment at the time of tumour diagnosis. Successful antiviral treatment in HCV patients does not prevent development of hepatocellular carcinoma even in non-cirrhotic livers. Long-term follow up of patients with SVR is mandatory and should include surveillance for hepatocellular carcinoma.
Journal of Viral Hepatitis 09/2008; 15(9):659-65. · 4.09 Impact Factor
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ABSTRACT: The characteristic histological feature of autoimmune hepatitis (AIH) is interface hepatitis with predominant portal lymphoplasmacytic necroinflammatory infiltration. Centrilobular necrosis (CN), reminiscent of toxic or circulatory liver injury, has been reported in AIH. The aim of this study was to assess the frequency of CN in patients with AIH and its correlation with laboratory and clinical data.
Liver biopsies were obtained from 114 patients (90 women, 24 men, mean (SD) age 45.4 (19.4) years) with AIH and were evaluated under code by a single pathologist according to the modified Knodell score.
CN was found in 20 (17.5%) patients with virtually unaffected portal areas in four cases. Patients with AIH with CN had a higher total hepatic activity index (median (range) 11 (6 to 15) v 5 (2 to 10)) and presented less frequently with cirrhosis (10% v 38%). Patients with CN had a higher frequency of acute onset (87% v 32%), higher bilirubin (median (range) 12.0 (0.43 to 40.0) v 1.9 (0.36 to 46)) and higher ALT levels (median (range) 25.6 (2.7 to 63.9) v 7.2 (0.7 to 62.6)), than did patients with AIH without centrizonal injury.
CN with sparing of the portal areas represents a rare histological pattern in AIH. CN is associated with an acute clinical presentation and might reflect an early lesion preceding portal involvement. Recognition of this particular histological appearance enables early diagnosis of AIH and a timely initiation of immunosuppressive therapy.
Journal of Clinical Pathology 04/2006; 59(3):246-9. · 2.31 Impact Factor
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ABSTRACT: Combination anti-viral therapy achieves a sustained virological response (defined as HCV-RNA negativity 6 months after the end of therapy) of 56% of patients with chronic hepatitis C. Little is known about long-term durability of HCV-RNA negativity in patient treated with pegylated interferon.
To evaluate the durability of virologic response in patients with sustained virological response to anti-viral therapy treated at our centre.
A total of 187 sustained virological responses (50% genotype 1, 42% genotype 2 or 3 and 8% genotype 4; 20% with cirrhosis) with a follow-up of >12 months post-therapy were studied. Twelve patients received monotherapy with interferon-alpha2a or -2b. One hundred and seventy-five received combination therapy with ribavirin and standard interferon-alpha (n = 73) or pegylated interferon-alpha2a or 2b (n = 102). Qualitative serum HCV-RNA was tested by COBAS AMPLICOR HCV test, v2.0.
Median follow-up time was 29 months (range 12-172). Recurrence of HCV infection was not observed in any of the 187 sustained virological responders. Alanine aminotransferase values were normal in 90% and two patients showed minimal elevation of alpha-fetoprotein levels.
No recurrence of HCV infection was seen in any patient. Thus, long-term prognosis in chronic hepatitis C patients with a sustained virological response to therapy with pegylated interferon +/- ribavirin is promising, but long-term studies need to continue.
Alimentary Pharmacology & Therapeutics 02/2006; 23(4):507-11. · 3.77 Impact Factor
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ABSTRACT: Immune response to viral infection is an important determinant of liver injury in chronic hepatitis C (CHC). Experimental and clinical data suggest a protective role of interleukin-10 (IL-10) in hepatic fibrogenesis. The significance of two SNPs of the interleukin-10 receptor 1 (IL-10R1), S138G (SNP3) and G330R (SNP4) was investigated on (i) susceptibility to CHC, (ii) progression of hepatic fibrosis and (iii) response to interferon/ribavirin therapy. DNA and liver biopsies were obtained from 212 patients with HCV (hepatitis C virus)-genotype-1 infection. The allele frequencies were 0.17 for SNP3 and 0.33 for SNP4, both of which were indifferent from healthy controls (0.17 and 0.32, respectively). Stage 1 liver fibrosis was found in 22 cases (10.4%), stage 2 in 108 (50.9%), stage 3 in 27 (12.8%), and stage 4 (cirrhosis) in 55 (25.9%). An association was found between the SNP4 allele and the presence of cirrhosis (P=0.01). Homozygous SNP4 individual variants segregated within the cirrhosis group (P=0.03). We found neither an association with SNP3 nor with the necroinflammatory disease activity (as measured by ALT levels) nor with the response to antiviral therapy. Our work implies that IL-10R1 SNP4 is a recessively inherited risk factor for hepatic cirrhosis in HCV genotype-1 infection.
Genes and Immunity 06/2005; 6(3):242-7. · 3.87 Impact Factor
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ABSTRACT: Even with pegylated (PEG) interferons (IFN), therapy of chronic hepatitis C (genotype 1) remains unsatisfactory. The initial viral response to IFN identifies patients infected with IFN resistant viruses not responding to standard IFN/ribavirin therapy. The impact of primary IFN unresponsiveness for PEG-IFN-alpha-2a/ribavirin therapy is unknown. Viral load was measured in 22 chronic hepatitis C (genotype 1) patients before and 24 h after 9 MU IFN-alpha-2a (days 0 and 1), and before and during weekly 180 microg PEG-IFN-alpha-2a (days 7, 8, 11, 14 and 21) administration. Thereafter, ribavirin (800 mg/d) was added for 6 months. Virological responders continued treatment for a further 6 months. Twenty-eight patients treated with standard IFN/ribavirin therapy in a previous study using an analogous protocol served as historic controls. After 6 months 15 (68.2%) patients were (HCV-RNA) negative, eight of whom (36.4%) had a sustained response. The decrease in viral load 24 h after 9 MU IFN-alpha-2a was greater in virological responders (1.05 log [0.25-1.67]) than in nonresponders (NR) (0.34 [0.14-0.65]; P=0.003). In contrast, viral decline was not different between responders and NRs during the first 2 weeks on PEG-IFN-alpha-2a. All patients with an initial decline > 1.4 log became sustained responders. Five of 12 patients with a log change < 0.8 became end of treatment responders, two had a sustained response. Antiviral response to PEG-IFN-alpha-2a is different to that on standard IFN. In spite of a lower initial response PEG-IFN-alpha-2a/ribavirin combination therapy may overcome predicted IFN unresponsiveness.
Journal of Viral Hepatitis 01/2003; 10(1):37-42. · 4.09 Impact Factor
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P Ferenci,
H Brunner,
K Nachbaur,
C Datz,
M Gschwantler, H Hofer,
R Stauber,
F Hackl,
W Jessner,
M Rosenbeiger,
P Munda-Steindl,
K Hegenbarth,
A Gangl,
W Vogel
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ABSTRACT: The initial clearance of hepatitis C virus (HCV) during interferon-alfa therapy is dose-dependent. Therefore, higher initial interferon doses (induction therapy) may improve treatment results. This concept was tested in a prospective, randomized controlled trial. Previously untreated patients with chronic hepatitis C were randomized to receive 3 different interferon doses during the first 14 weeks of therapy (Group A, n = 130: 10 MU IntronA [AESCA-Schering Plough, Traiskirchen, Austria]/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; Group B, n = 124: 5 MU/day for 14 weeks; Group C, n = 119; 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. Throughout the whole study all patients received 1 to 1.2 g ribavirin/day. On treatment, no differences in viral clearance rates were observed. Sustained response rates were also not different among the groups (A: 48.5%, B and C: 41.3%, intent to treat). When data were analyzed according to genotypes, sustained response was almost twice as high in patients with genotype 1 receiving high-dose interferon induction therapy (A: 44.2%, B: 28.6%, C: 27%, P <.05). In contrast, results were not different in genotype 3a patients (A: 61.3%, B: 75.9%, C: 56.3%; P >.1). These data indicate that high-dose interferon induction therapy may improve the outcome of interferon/ribavirin combination therapy in genotype 1 patients.
Hepatology 12/2001; 34(5):1006-11. · 11.66 Impact Factor
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ABSTRACT: Only 30% of patients with chronic hepatitis C virus genotype 1 (HCV-1) infection achieve a sustained virological response to interferon and ribavirin combination therapy. We prospectively assessed decline in viral load 24 h after one dose of interferon alfa as a predictor of non-response to 6 months of treatment with interferon and ribavirin. Interferon sensitivity was measured before initiation of combination therapy. We measured viral load in 29 consecutive patients, who had not previously been treated with interferon and who were chronically infected with HCV-1 within 24 h after one dose of 5 MU or 10 MU interferon alfa-2b, and 14 days of daily 5 MU interferon alfa-2b. A 24 h viral load decline by less than 70% of baseline after 5 MU interferon was the best pretreatment measure to identify non-responders (specificity 100%, n=10, 95% CI 74-100], sensitivity 83% [15/18], 59-96]).
The Lancet 11/2001; 358(9289):1241-2. · 38.28 Impact Factor
