Hepatitis: Forns X

Navasa M, Forns X. · No affiliation provided · Liver Transpl. · Pubmed #18756466 No free full text.

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García-Samaniego J, Forns X. · No affiliation provided · Hepatology. · Pubmed #17879358 No free full text.

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Carrión JA, Forns X. · No affiliation provided · Liver Transpl. · Pubmed #17192905 links to  free full text

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Navasa M, Forns X. · No affiliation provided · J Hepatol. · Pubmed #17161494 No free full text.

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Forns X. · No affiliation provided · Hepatology. · Pubmed #16317701 No free full text.

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Bruguera M, Forns X. · No affiliation provided · Enferm Infecc Microbiol Clin. · Pubmed #15482684 links to  free full text

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Martínez-Bauer E, Forns X. · Servicio de Hepatología. Institut de Malalties Digestives. Hospital Clínic. Barcelona. España. · Gastroenterol Hepatol. · Pubmed #12732104 No free full text.

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Castera L, Forns X, Alberti A. · Departments of Hepatology, Hospital Saint-André & Haut Lévêque, University Hospital of Bordeaux, Avenue Magellan, Pessac, France. · J Hepatol. · Pubmed #18334275 No free full text.

Abstract: Transient elastography (TE, FibroScan) is a novel non-invasive method that has been proposed for the assessment of hepatic fibrosis in patients with chronic liver diseases, by measuring liver stiffness. TE is a rapid and user-friendly technique that can be easily performed at the bedside or in the outpatient clinic with immediate results and good reproducibility. Limitations include failure in around 5% of cases, mainly in obese patients. So far, TE has been mostly validated in chronic hepatitis C, with diagnostic performance equivalent to that of serum markers for the diagnosis of significant fibrosis. Combining TE with serum markers increases diagnostic accuracy and as a result, liver biopsy could be avoided for initial assessment in most patients with chronic hepatitis C. This strategy warrants further evaluation in other aetiological types of chronic liver diseases. TE appears to be an excellent tool for early detection of cirrhosis and may have prognostic value in this setting. As TE has excellent patient acceptance it could be useful for monitoring fibrosis progression and regression in the individual case, but more data are awaited for this application. Guidelines are needed for the use of TE in clinical practice.

Bruguera M, Forns X. · Servicio de Hepatología, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, España. · Med Clin (Barc). · Pubmed #16828003 No free full text.

Abstract: Spain has a medium endemicity of hepatitic C infection among central Europe countries and Italy. Prevalence of anti-HCV varies among regions and it ranges from 1.6 to 2.6%, which means that there may be between 480,000 and 760,000 people infected with hepatitis C virus in Spain. The prevalence is very low in people under 20 years of age and it increases from age 30 years. Prisoners and drug addicts have the highest infectious rates, between 40 and 98%. Some populations of immigrants also have a high prevalence of HCV infection, especially people from Asia and sub-Saharan countries, whereas people from Latin America have rates lower than those in the autochtones population. Spanish people with chronic hepatitis C were mainly infected via blood transfusions, IV drug use, or during some medical and surgical hospitalization. The reduction in the use of IV drugs and the programs of needle sharing, as well as the eradication of post-transfusional hepatitis, have led to a progressive reduction in the incidence of new infections (from 6.8 per 100,000 in-habitants in 1997 to 2.3 in 2003). Preliminary data suggest that an important rate of new hepatitis C cases owe to nosocomial transmission. Transmission is almost exclusively vertical in children. In spite of a two-third reduction of incident cases of hepatitis C in Spain in last few years, it is foreseeable that the number of patients with advanced HCV liver disease attended in the health-care system will increase in forthcoming years. This is due to the fact that many, still undiagnosed patients will be likely recognized for the first time as a result of some complication of the disease. All efforts to increase the screening of hidden cases of hepatitis C in primary health-care centers, allowing a prompt treatment before an advanced stage, will have a beneficial impact both in economic and social terms.

Forns X, Costa J. · Liver Unit, Hospital Clinic, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain. · J Hepatol. · Pubmed #16343682 No free full text.

Abstract: Virological assessment of HCV infection relies on a series of assays that are essential for diagnostic purposes and to adopt therapeutic decisions. Diagnostic assays can be classified in three groups: assays that are designed to detect specific antibodies to HCV; techniques that detect and quantify viral load; and tests aimed at determining the infecting HCV type. In general, the use of these assays is similar in HCV infected patients as in those co-infected with HCV and HIV. Co-infected patients, however, have some inherent characteristics (deficient immune status, high HCV-RNA concentrations, particular genotype distribution, low response to antiviral therapy) that make the interpretation of such assays slightly different. Regarding assays to detect antibodies to HCV, last generation tests have a similar sensitivity in mono-infected and co-infected individuals. HCV-RNA testing might be helpful in anti-HCV negative individuals with clinical or analytical suspicion of liver disease. Genotype determination in patients co-infected with HCV and HIV should be performed by methods relying on sequence analysis, since serotyping assays have shown a lower sensitivity in co-infected cohorts. HCV-RNA concentration is a strong predictor of response to therapy. Due to the higher viral load of co-infected patients compared to HCV mono-infected individuals, those assays with a wide dynamic range seem more appropriate to monitor viral load during treatment.

Laguno M, Sánchez-Tapias JM, Murillas J, Forns X, Blanco JL, Martínez E, Larrousse M, León A, Loncá M, Milinkovic A, Miró JM, García F, Gatell JM, Mallolas J. · Servicio de Enfermedades Infecciosas, Hospital Clínic-Universitari de Barcelona-IDIBAPS, Universitat de Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15701331 links to  free full text

Abstract: The chronic infection by the hepatits C virus represents a serious sanitary problem affecting 1-3% of the world-wide population. It is transmitted by sexual route, vertical route and mainly after blood exposure by percutanea route. While HIV shares similar routes of transmission, the co-infection HCV-HIV is very frequent and the chronic hepatopathy and complications associated with its clinical course are an important cause of morbi-mortality in this population. The gold standard of the treatment for the HCV, has been the interferon and later the combination therapy of interferon plus ribavirine. Currently, the combination of ribavirine and a new pegilated formulation of the interferon has become the standard in the treatment reaching rates of sustained viral response around 40-80%.

Garcia-Retortillo M, Forns X. · Liver Unit, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain. · J Hepatol. · Pubmed #15246200 No free full text.

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Ramos-Casals M, García-Carrasco M, López-Medrano F, Trejo O, Forns X, López-Guillermo A, Muñoz C, Ingelmo M, Font J. · Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, School of Medicine, University of Barcelona, Spain. · Medicine (Baltimore). · Pubmed #12640185 No free full text.

Abstract: To determine the clinical characteristics and outcome of patients with chronic hepatitis C virus (HCV) infection presenting severe autoimmune cytopenia unrelated to interferon alpha therapy, we analyzed characteristics and outcomes of 35 patients with HCV (16 from our departments and 19 from the literature). We considered active autoimmune hemolytic anemia (AHA) as a decrease of at least 2 g/dL in hemoglobin levels, an increase of at least 0.6 mg/dL in the serum unconjugated bilirubin level, a reticulocyte count >5%, and a positive direct Coombs test. Severe neutropenia was defined as a neutrophil count <0.5 x 10(9)/L, and severe thrombocytopenia as a platelet count <30 x 10(9)/L. We identified the following cytopenias: AHA (17 cases), severe thrombocytopenia (16 cases), aplastic anemia (2 cases), severe neutropenia (1 case), refractory sideroblastic anemia (1 case), and pure red cell aplasia (1 case). Three patients simultaneously presented 2 types of severe cytopenias. Twenty-seven patients (77%) were female and 8 (23%) male, with a mean age at diagnosis of cytopenia of 51.7 years (range, 18-84 yr). Immunologic markers were detected in 19 (68%) of 28 patients, the most frequent being hypocomplementemia in 16 (57%), cryoglobulins in 15 (54%), antinuclear antibodies in 12 (43%), and rheumatoid factor in 5 (18%). Other associated processes were autoimmune diseases in 14 (50%) of 28 and human immunodeficiency virus (HIV) coinfection in 3 (9%) of 32. We found clinical and immunologic differences between HCV patients with AHA and those with severe thrombocytopenia. Patients with HCV-related AHA showed a higher prevalence of associated autoimmune diseases (71%), cryoglobulins (67%), and cirrhosis (59%). All had a good response to corticosteroids, but a poor prognosis (47% mortality). In contrast, patients with HCV-related severe thrombocytopenia had a lower prevalence of associated autoimmune diseases (11%), a poorer response to corticosteroids (55%), and lower mortality (6%), with HIV/HBV coinfections in some patients. The 35 cases presented demonstrate that different types of immune-mediated cytopenias may be severe and clinically significant in patients with HCV infection. Hemolytic anemia and severe thrombocytopenia were the most frequent cytopenias observed. Most patients responded well to corticosteroids, although a higher rate of mortality was observed in those with liver cirrhosis.

Forns X, Sánchez Tapias JM, Parés A, Llovet JM, Bruix J, Rodés J. · Liver Unit, Hospital Clínic, Institut d'Investigaciones Biomédiques August Pi i Sunyer, University of Barcelona, Spain. · Best Pract Res Clin Gastroenterol. · Pubmed #12473301 No free full text.

Abstract: It is very difficult to predict new developments in hepatology so we have decided to analyse the most important issues related to three clinical conditions in hepatology. The first is chronic hepatitis. Here, we discuss the relevance of occult forms of hepatitis B virus infection in the development of cryptogenic liver disease and hepatocellular carcinoma. In addition, the role of genotyping in hepatitis B is analysed, indicating that patients with genotype A have a better prognosis than those with genotype D. The treatment of hepatitis B virus infection is also reviewed, and it has been suggested that research should be directed towards the development of new anti-viral agents to suppress virus replication. The natural history of hepatitis C virus infection is considered, emphasizing the need to know the progression of fibrosis in these patients. The chapter also suggests that treatment of hepatitis C virus infection with pegilated interferon and ribavirin is currently relatively effective. New therapeutic strategies will be required in the future, the most important challenge being the development of a hepatitis C virus vaccine. The second section is on chronic cholestasis. The role of anti-mitochondrial antibodies in primary biliary cirrhosis is considered. The possible infectious agents implicated as potential triggers of primary biliary cirrhosis are also discussed, suggesting that several infections may play a role in the pathogenesis of this condition. Other aetiopathogenic factors, for example organic compounds, drugs and chemicals, are indicated. It is possible that, in the near future, the precise sequence and molecular basis by which infectious agents or xenobiotics may initiate the cascade of the autoimmune response will be defined. One of the most important challenges in primary sclerosing cholangitis concerns the mechanisms that may induce the development of this disease. Up until now, genetic factors have been suggested, recent data reporting a clear-cut association between primary sclerosing cholangitis and the tumour necrosis factor-alpha(2) allele. The third part of this chapter includes recent progress achieved in hepatocellular carcinoma, discussing developments in the knowledge of hepatocellular carcinogenesis. Hepatocellular carcinomas appear so far to be genetically heterogeneous neoplasms, and this heterogeneity may correlate with the variety of aetiological factors involved. The risk factors and primary, secondary and tertiary prevention of the condition are also analysed. Finally, the development of new therapeutic strategies for hepatocellular carcinoma is evaluated by evidence-based studies.

Forns X, Bukh J, Purcell RH. · Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Villaroel 170, Barcelona 08036, Spain. · J Hepatol. · Pubmed #12399239 No free full text.

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García-Retortillo M, Forns X. · Unidad de Hepatología, Institut de Malalties Digestives (IMD), Hospital Clínic e IDIBAPS, Universitat de Barcelona, España. · Gastroenterol Hepatol. · Pubmed #12361535 No free full text.

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Forns X. · Servicio de Hepatología. Institut de Malaties Digestives. Hospital Clínic. Barcelona. Spain. · Gastroenterol Hepatol. · Pubmed #11985814 No free full text.

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Bukh J, Forns X, Emerson SU, Purcell RH. · Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Md 20892-0740, USA. · Intervirology. · Pubmed #11509874 No free full text.

Abstract: Persistent infection with hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. Therefore, the development of vaccines to prevent HCV infection, or at least to prevent progression to chronicity, is a major goal. Potential HCV vaccine candidates include recombinant proteins, recombinant viruses, DNA constructs, synthetic peptides and virus-like particles. Various vaccine candidates have been shown to generate humoral and cellular immune responses in animals, primarily in mice. However, the efficacy of most vaccine candidates in protecting against HCV has not been tested because the chimpanzee, the only animal other than humans that is susceptible to HCV, is not readily available, requires special facilities, and is very expensive. The course of infection in chimpanzees is similar in its diversity to that in humans and detailed studies in this model are beginning to define the immune responses that can terminate HCV infection. Of relevance for vaccine evaluation was the titration in chimpanzees of different HCV variants to provide well-characterized challenge pools. In addition, monoclonal virus pools generated from chimpanzees infected with cloned viruses make it possible now to examine immunity to HCV without the confounding factor of antigenic diversity of the challenge virus (quasispecies). The vaccine trials performed in chimpanzees to date all have tested the efficacy of immunizations with various forms of the envelope proteins of HCV.

Forns X, Bukh J. · Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. · Clin Liver Dis. · Pubmed #11291246 No free full text.

Abstract: Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. HCV is a positive-strand genotype RNA virus with extensive genetic heterogeneity; HCV isolates define 6 major genotypes, and HCV circulates within an infected individual as a number of closely related but distinct species, termed a quasispecies. This article reviews characteristic aspects of HCV molecular biology and their implications for treatment and vaccine development.

Forns X, Purcell RH, Bukh J. · Hepatitis Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · Trends Microbiol. · Pubmed #10498948 No free full text.

Abstract: Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. This RNA virus circulates as a quasispecies and its genetic heterogeneity has been implicated in the lack of protective immunity against HCV and in its persistence following infection. HCV might escape from immune surveillance by developing mutations in proteins that are subject to immune pressure.

Herrmann E, Zeuzem S, Sarrazin C, Hinrichsen H, Benhamou Y, Manns MP, Reiser M, Reesink H, Calleja JL, Forns X, Steinmann GG, Nehmiz G. · Medizinische Klinik und Poliklinik, Innere Medizin II, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. · Antivir Ther. · Pubmed #16759054 No free full text.

Abstract: We analysed viral kinetics from a 2-day treatment with BILN 2061, a serine protease inhibitor of hepatitis C virus, in patients chronically infected with genotype 1 hepatitis C virus. The efficiency (E), describing inhibition of viral production, was above 99.45% in all patients with minor or moderate fibrosis receiving doses of 200mg and 500 mg twice daily and larger than in previous studies for interferon-based treatments. However, epsilon was slightly smaller in patients with cirrhosis given 200mg and markedly smaller in patients given 25 mg. Estimates of viral clearance and infected-cell loss support conclusions on these rates and on treatment mechanisms from previous studies on interferon-alpha-based treatments.

Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens RE, Calleja JL, Forns X, Erhardt A, Crönlein J, Chaves RL, Yong CL, Nehmiz G, Steinmann GG. · Medizinische Universitätsklinik, Kiel, Germany. · Gastroenterology. · Pubmed #15521004 No free full text.

Abstract: BACKGROUND AND AIMS: Novel, potent, and well-tolerated hepatitis C virus (HCV) drugs are needed. BILN 2061 is a potent and specific inhibitor of HCV serine protease in vitro. Preclinical toxicology data and studies in healthy volunteers supported the administration of BILN 2061 to patients with HCV infection. METHODS: The antiviral efficacy, pharmacokinetics, and tolerability of 25, 200, and 500 mg BILN 2061 twice daily given as monotherapy for 2 days in 31 patients infected with chronic genotype 1 HCV infection and with minimal liver fibrosis (Ishak score of 0-2) were assessed in a placebo-controlled, double-blind pilot study. In 2 subsequent placebo-controlled studies of similar design, 200 mg BILN 2061 twice daily was administered for 2 days to 10 patients with advanced liver fibrosis (Ishak score of 3 or 4) and to 10 patients with compensated cirrhosis (Ishak score of 5 or 6). RESULTS: Viral RNA reductions of 2-3 log 10 copies/mL were achieved in most of the patients. There was a trend toward a higher number of patients receiving 500 mg BILN 2061 achieving a viral RNA reduction > or =3 log(10) copies/mL as compared with patients receiving 25 mg BILN 2061. Advanced fibrosis or compensated cirrhosis did not affect the antiviral efficacy of BILN 2061. BILN 2061 was well tolerated in all studies. CONCLUSIONS: BILN 2061 is a well-tolerated and very active compound that reduced serum viral RNA concentrations after 2 days of treatment in patients infected with genotype 1 HCV independent of the degree of fibrosis. Nevertheless, further clinical trials are on hold pending resolution of animal toxicity issues.

Forns X, García-Retortillo M, Serrano T, Feliu A, Suarez F, de la Mata M, García-Valdecasas JC, Navasa M, Rimola A, Rodés J. · Liver Unit, Hospital Clínic, Institut de Malalties Digestives, IDIBAPS, Escala 7, 3 pis., Villarroel 170, Barcelona 08036, Spain. · J Hepatol. · Pubmed #12927925 No free full text.

Abstract: BACKGROUND/AIMS: After liver transplantation (LT) infection of the graft with the hepatitis C virus (HCV) is almost universal and chronic hepatitis and cirrhosis develop in a significant proportion of patients. One of the possible strategies to prevent HCV infection recurrence is to eradicate HCV before LT. METHODS: We evaluated the efficacy and safety of antiviral therapy to prevent HCV recurrence in 30 HCV-cirrhotic patients awaiting LT. At the time of inclusion 15 patients were Child-Pugh A and 15 Child-Pugh B/C. The infecting genotype was 1b in 25 patients. Treatment with interferon alpha-2b 3 MU/day and ribavirin 800 mg/day was initiated when the expected time for LT was less than 4 months and continued until LT. The median duration of treatment was 12 weeks. RESULTS: Nine patients (30%) achieved a virological response and 21 did not respond to therapy. In nine (43%) of the 21 non-responders viral load decreased > or =2 log10 during treatment. A viral load decrease > or = 2 log10 at week 4 of treatment was the strongest predictor of virological response. All nine virological responders have already undergone LT; six patients remain free of infection after a median follow-up of 46 weeks and HCV infection recurred in three patients after LT. In one of these patients HCV-RNA was still detectable in the explanted liver. Side effects were frequent and dose reduction was necessary in 19 (63%) of the 30 patients; no patient died while on therapy. CONCLUSIONS: Our data support the utilization of antiviral therapy in HCV-infected patients awaiting LT as one of the strategies to prevent hepatitis C recurrence after transplantation.

Forns X. · Unidad de Hepatología. Institut de Malalties Digestives. Hospital Clínic de Barcelona. · Med Clin (Barc). · Pubmed #11222177 No free full text.

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Guilera M, Forns X, Torras X, Enríquez J, Coll S, Solà R, Morillas R, Planas R, Ampurdanès S, Soler M, Costa J, Sáiz JC, Sánchez-Tapias JM, Rodés J. · Institut de Malalties Digestives, Hospital Clinic, IDIBAPS, Universitat de Barcelona, Spain. · J Hepatol. · Pubmed #10905597 No free full text.

Abstract: BACKGROUND/AIMS: Alpha interferon administration is quite disappointing as a single therapy in chronic hepatitis C. A brief course of corticosteroid therapy might increase the effectiveness of subsequent alpha interferon administration, but data on this issue are controversial. METHODS: One hundred and fifty-six consecutive patients with chronic hepatitis C were randomly assigned to be treated blind with tapering doses of oral prednisolone or placebo for 4 weeks. Two weeks after cessation of therapy, patients received alpha interferon (3 MU t.i.w.) for 48 weeks and were followed for 24 additional weeks. Response was defined by the presence of normal alanine aminotransferase (ALT) and negative HCV-RNA in serum. RESULTS: ALT activity decreased during prednisolone administration and rebounded upon withdrawal in 38% of the patients treated with this drug. Significant changes in serum bilirubin were not observed. HCV-RNA serum concentration tended to increase during prednisolone administration and to decrease upon withdrawal. ALT and HCV-RNA did not change during administration of placebo. At the end of interferon administration, 33% of patients treated with prednisolone and 25% of those treated with placebo presented biochemical and virological response. At the end of post-treatment follow-up, response was maintained in 12% and 13% of patients treated with prednisolone or placebo respectively. Response was not related to ALT or HCV-RNA changes observed during the pre-interferon phase of the study. No adverse events related to prednisolone administration were observed. CONCLUSIONS: Prednisolone administration and withdrawal induced a rebound in ALT activity and a decrease in HCV-RNA serum concentration in about one third of the patients with chronic hepatitis C. However, these changes did not enhance the effectiveness of subsequent alpha interferon therapy.