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Xavier Forns

Publications and source records attributed to Xavier Forns.

34 records · Page 2Linked to original sources
PubMed2004

Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation.

BACKGROUND: Hepatitis C recurrence after liver transplantation is often associated with accelerated graft fibrosis and progression to cirrhosis. Because drugs blocking the action of angiotensin-II can reduce fibrosis in different human and experimental models, we assessed the possible beneficial effect of these drugs on graft fibrosis in hepatitis C recurrence after liver transplantation. METHODS: We retrospectively reviewed the charts of 128 liver-transplant recipients with hepatitis C recurrence. Twenty-seven patients (group I) received angiotensin converting enzyme inhibitors or angiotensin-II receptor antagonists as antihypertensive treatment, and 101 patients (group II) did not receive these drugs. RESULTS: No significant differences were found between groups I and II in demographic, clinical, and laboratory data. In contrast, cirrhosis in the graft was less frequently observed in group I than in group II during postransplant follow-up: 15% versus 35% (P=0.035), respectively, with a probability of cirrhosis of 9% versus 32% at 5 years after transplantation and 35% versus 70% at 10 years (P=0.0049). Furthermore, the fibrosis stage (scored from 0-4) in the liver biopsy obtained at the end of follow-up was significantly lower in group I than in group II (median [and range]: 1 [0-4] vs. 2 [0-4]; P=0.038), and the fibrosis progression index (increase of fibrosis stage per year) was also lower in group I than in group II (0.21 [0-0.45] vs. 0.52 [0-2.58]; P=0.006). CONCLUSION: The administration of angiotensin-blocking agents may be beneficial to reduce the development of graft fibrosis in hepatitis C recurrence after liver transplantation.

Adolescent↗
PubMed2004

[Use of complementary and alternative medicine in patients with chronic hepatitis C].

BACKGROUND AND OBJECTIVE: Complementary and alternative medicines (CAM) have achieved a great development in western countries. However, their use among patients simultaneously treated by the mainstream medicine is largely unknown. Our goal was to assess how many patients with chronic hepatitis C treated in a tertiary hospital use or have used CAM. PATIENTS AND METHOD: Analysis of the answers of 319 patients to a self-administered questionnaire. RESULTS: 113 (37%) patients had used or were using CAM, 63 (20%) because of chronic hepatitis and 50 (17%) for other reasons. Women, those with higher education, divorced and widows were those who more frequently used CAM. More than half of patients felt some subjective improvement, yet none of them normalized their serum transaminase activities. CONCLUSIONS: CAM are used by a high proportion of patients who are simultaneously attended by 'official' physicians. The perceived efficacy of these practices is high but no changes in the hepatic disease could be seen in any of the patients who answered the questionnaire.

Complementary Therapies↗
PubMed2004

Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation.

Preliminary reports suggested that hepatitis C virus (HCV) infection has a more aggressive course following living donor liver transplantation (LDLT) compared to cadaveric liver transplantation (CLT). The aim of this prospective study was to establish if HCV disease recurrence differs between LDLT and CLT. A cohort of 116 consecutive HCV-infected patients undergoing 117 LTs in a single center from March 2000 to August 2003 were followed-up, including systematic liver biopsies. Severe recurrence (SR) was defined as biopsy-proven cirrhosis and/or the occurrence of clinical decompensation. After a median follow-up of 22 months (2.6-44 months), 26 (22%) patients developed SR (decompensation in 12), involving 17 (18%) of 95 patients undergoing CLT and 9 (41%) of 22 undergoing LDLT. The 2-year probability of presenting SR was significantly higher in LDLT compared to CLT (45% vs. 22%, P = .019). By univariate analysis LDLT (P = .019) and an ALT higher than 80 IU/L 3 months after LT (P = .022) were predictors of SR. In 93 patients from whom a liver biopsy was available 3 months after LT, a lobular necroinflammatory score >1 (P < .01), LDLT (P < .01), and biliary complications (P = .046) were associated with SR. However, the only variables independently associated with SR were LDLT (odds ratio [OR], = 2.8; 95% CI,1.19-6.6; P = .024) and a lobular necroinflammatory score > 1 (OR, 3.1; 95% CI, 1.2-8; P = .013). In conclusion, HCV recurrence is more severe in LDLT compared to CLT. Although our results were based on a single-center experience, they should be considered in the decision-making process of transplant programs, since severe HCV recurrence may ultimately compromise graft and patient survival.

Adult↗
PubMed2004

Evolution of hepatitis C virus quasispecies immediately following liver transplantation.

Liver cirrhosis caused by chronic hepatitis C virus (HCV) infection is the main indication for liver transplantation (LT). There is little information on HCV genetic evolution following transplantation. The aim of this study was to carefully assess early evolution of HCV quasispecies in a cohort of 18 liver transplant recipients followed prospectively. Quasispecies analysis was performed by sequence analysis of the hypervariable region 1 (HVR1) before transplantation and at day 4 and week 4 following LT. A predominant variant was present in 12 (67%) of the 18 patients before transplantation and the same variant was propagated and remained predominant after LT in 6 (50%) of these patients. In the remaining individuals, there were major changes in the quasispecies composition, mostly occurring during the first days after LT. There was a progressive decrease in the nonsynonymous (dN)/synonymous (dS) ratios from baseline (1.2) to day 4 (.6) (P = .08) and to week 4 after LT (.3) (P = .015). Similarly, genetic distance (GD) declined from baseline (.1) to day 4 (.03) (P = .07) and to week 4 (.04) (P = .04). We did not find any differences in HCV genetic evolution between patients with mild (n = 10) or severe (n = 8) disease recurrence. In conclusion, during the first days following transplantation, HCV quasispecies becomes more homogenous, even after major changes in its composition. Importantly, these changes persist and even increase during the 1st month after transplantation. The "bottleneck" effect caused by the implantation of a new graft and the lack of selective pressure due to the strong immunosuppression most likely explain this particular pattern of genetic evolution.

Adult↗
PubMed2004

Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients.

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.

Antiviral Agents↗
PubMed2003

Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation.

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.

Adult↗
PubMed2003

Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases.

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.

Adolescent↗
PubMed2002

DNA-based vaccination against hepatitis C virus (HCV): effect of expressing different forms of HCV E2 protein and use of CpG-optimized vectors in mice.

DNA-based immunization may be of prophylactic and therapeutic value for hepatitis C virus (HCV) infection. In efforts to improve the immunogenicity of a plasmid expressing the second envelope protein (E2) of HCV, we evaluated in mice the role of the antigen localization and demonstrated that membrane-bound and secreted forms induced higher titers of E2-specific antibodies, as well as earlier and higher seroconversion rates, than the intracellular form, but all three forms induced strong CTL. We also investigated whether E2-specific antibody responses could be enhanced by CpG optimization of the plasmid backbone and showed that removal of neutralizing CpG dinucleotides did not have a significant effect but addition of 64 immunostimulatory CpG motifs significantly enhanced anti-E2 titers. These results may have implications for the design and development of HCV DNA vaccines.

Animals↗
PubMed2002

Expected developments in hepatology.

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.

Antiviral Agents↗
PubMed2002

Hepatitis C virus kinetics during and immediately after liver transplantation.

The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope -0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope -0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT.

Adult↗
PubMed2002

Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model.

Liver biopsy is required for staging hepatic fibrosis in patients with chronic hepatitis C, but it is an expensive procedure with occasional complications and poor patient acceptance. This cohort study was designed to assess the accuracy of a noninvasive method aimed to discriminate between patients with and without significant liver fibrosis (stages 2-4 versus 0-1). Clinically relevant variables were analyzed in a cohort of 476 consecutive untreated patients (estimation group, 351 patients; validation group, 125 patients) with chronic hepatitis C who underwent a liver biopsy. Multivariate analysis identified age, gamma glutamyl transpeptidase (GGT), cholesterol, platelet count, and prothrombin time as independent predictors of fibrosis. We constructed a model and a score system combining age, GGT, cholesterol, and platelet count that proved useful to identify patients without significant hepatic fibrosis. The area under the ROC curve was 0.86 for the estimation group and 0.81 for the validation group. Using the best cutoff score (less than 4.2), presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (negative predictive value of 96%) in 125 (36%) of 351 patients. Similarly, it could be excluded with the same certainty in 49 (39%) of the 125 patients of the validation group. Only 2 patients with liver fibrosis stage 2 were incorrectly classified. In conclusion, a combination of easily accessible variables accurately predicts the absence of significant fibrosis and might render liver biopsy unnecessary in more than one third of patients with chronic hepatitis C.

Adult↗