Hepatitis: Rimola A

Miró JM, Torre-Cisnero J, Moreno A, Tuset M, Quereda C, Laguno M, Vidal E, Rivero A, Gonzalez J, Lumbreras C, Iribarren JA, Fortún J, Rimola A, Rafecas A, Barril G, Crespo M, Colom J, Vilardell J, Salvador JA, Polo R, Garrido G, Chamorro L, Miranda B. · AIDS Study Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). · Enferm Infecc Microbiol Clin. · Pubmed #15970168 links to  free full text

Abstract: Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at http://www.gesidaseimc.com.

Miro JM, Aguero F, Laguno M, Tuset M, Cervera C, Moreno A, Garcia-Valdecasas JC, Rimola A, Anonymous00329. · Infectious Diseases Service, Hospital Clinic - IDIBAPS, Villarroel, 08036 Barcelona, Spain. · J HIV Ther. · Pubmed #17589393 No free full text.

Abstract: The prognosis of HIV infection has dramatically improved in recent years with the introduction of combined antiretroviral therapy. Currently, liver disease is one of the most important causes of morbidity and mortality, even more so given the high rate of hepatitis C virus co-infection in countries where drug abuse has been an important HIV risk factor. Survival of HIV-co-infected patients with end-stage liver disease (ESLD) is poor and shorter than that of the non-HIV-infected population. One-year survival of HIV-infected patients with ESLD is only around 50-55%. HIV infection is no longer a contraindication to transplantation, which is becoming a standard therapy in most developed countries. The HIV criteria used to select HIV-infected patients for liver transplantation are quite similar in Europe and North America. Current criteria state that having had an opportunistic infection (e.g. tuberculosis, candidiasis, PCP) is not a strict exclusion criterion. However, patients must have a CD4 count above 100 cells/mm3 and a plasma HIV-1 RNA viral load that is suppressible with antiretroviral treatment. More than 200 orthotopic liver transplants (OLT) in HIV-infected patients have been published in recent years and the mid-term (3-year) survival was similar to that of HIV-negative patients. The main problems in the post-transplantation period are the pharmacokinetic and pharmacodynamic interactions between antiretroviral and immunosuppressive agents and the recurrence of HCV infection, which is the principal cause of post-transplantation mortality. There are controversial results regarding mid-term survival of HIV-HCV co-infected patients compared with HCV mono-infected patients. However, one study showed a trend of poorer 5-year survival of HIV-HCV co-infected patients. There is little experience with the treatment of recurrent HCV infection. Preliminary studies showed rates of sustained virological response ranging between 15% and 20% in HIV-HCV co-infected recipients. Liver transplantation in HIV-HBV co-infected patients had a good prognosis because HBV recurrence can be successfully prevented using immunoglobulins and anti-HBV drugs. Finally, this field is evolving continuously and the indications for liver transplantation or the management of HCV co-infection may change in the future as more evidence becomes available.

Miró JM, Laguno M, Moreno A, Rimola A, Anonymous00233. · Infectious Diseases Service, Hospital Clinic-IDIBAPS, Villarroel, 08036 Barcelona, Spain. · J Hepatol. · Pubmed #16352366 No free full text.

Abstract: Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

Miró JM, Montejo M, Rufí G, Bárcena R, Vargas V, Rimola A, Bañares R, Valdivieso A, Fabregat J, Vicente E, Margarit C, Moreno A, Miralles P, Aguirrebengoa K, Xiol FX, Fortún J, Pahissa A, Laguno M, Salcedo M, Cisneros JM, Quereda C, Tuset M, Castón JJ, Torre-Cisneros J, Anonymous00290. · Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15511394 links to  free full text

Abstract: According to current estimates, there are 60,000 to 80,000 HIV and HCV coinfected individuals in Spain, and 5,000 to 10,000 HIV and HBV coinfected individuals. Among these patients, 10% to 15% have liver cirrhosis. Thus, end-stage liver disease is one of the major causes of death in our country. Liver transplantation is the only therapeutic option for these patients. Accumulated experience in North America and Europe in the last five years indicates that three-year survival in HIV-positive liver transplant recipients is similar to that of HIV-negative recipients. The selection criteria for HIV transplant candidates includes the following: no history of opportunistic infections, CD4 lymphocyte count higher than 100 cells/mm3, and HIV viral load suppressible with antiretroviral treatment. In Spain, where the majority of patients are former drug abusers, complete abstinence from heroin or cocaine use during two years is also required, with the possibility of the patient being in a methadone program. To date 26 hepatic transplants have been performed in the same number of patients, with only two deaths (7%) after a median follow-up of eight months (1-28). The main problems in the post-transplantation period in all the series has been recurrent HCV infection, which is the principle cause of post-transplantation mortality, and pharmacokinetic and pharmacodynamic interactions between the antiretroviral and immunosuppressive agents. There is little experience with pegylated interferon and ribavirin treatment in this population.

Sanchez Fueyo A, Rimola A, Bruguera M. · Unidad de Hepatología, Hospital Clínic i Provincial, Universidad de Barcelona. · Gastroenterol Hepatol. · Pubmed #10228325 No free full text.

This publication has no abstract.

Figueras J, Prieto M, Bernardos A, Rimola A, Suárez F, de Urbina JO, Cuervas-Mons V, Mata Mde L. · Hospital de Bellvitge, Barcelona, Spain. · Transpl Int. · Pubmed #16827681 No free full text.

Abstract: Steroid-free immunosuppressive regimens reduce corticosteroid-related side effects in liver transplant recipients although their efficacy is very variable. We evaluated the efficacy and safety of a steroid-free regimen in a 6-month, open-label, multicenter, pilot study, which involved 102 liver transplant patients treated with daclizumab (2 mg/kg within 6 h following transplant and 1 mg/kg on day 7), mycophenolate mofetil (MMF, 1 g b.i.d) and tacrolimus (trough levels of 5-15 ng/ml in the first month and 5-10 ng/ml thereafter). One intra-operative dose of methylprednisolone was administered. At 6 months, the acute rejection rate was 9.8%, and patient and graft survival rates were 96% and 95%, respectively. Acute rejection rates were similar for hepatitis C-positive patients (8.6%) and hepatitis C-negative patients (10.4%). Infections occurred in 22% of patients; most cases were considered mild or moderate. Post-transplantation hypertension and diabetes mellitus developed in 37% and 14% of patients, respectively, during the study period, but were markedly less frequent (8% and 6%, respectively) at 6 months. Hypercholesterolemia was observed in only 2% of patients. In conclusion, the steroid-free immunosuppressive regimen of daclizumab, MMF, and tacrolimus effectively prevents acute rejection after liver transplantation without decreasing safety.

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.

Neuhaus P, Clavien PA, Kittur D, Salizzoni M, Rimola A, Abeywickrama K, Ortmann E, Chodoff L, Hall M, Korn A, Nashan B, Anonymous00028. · Rudolf Virchow University, Berlin, Germany. · Liver Transpl. · Pubmed #11862589 links to  free full text

Abstract: Basiliximab, a high-affinity chimeric monoclonal antibody, is effective in reducing acute rejection episodes in renal allograft recipients. We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients. Adult recipients of a primary cadaveric liver transplant were randomized to treatment, stratified by hepatitis C virus (HCV) seropositivity. Patients were administered 40 mg of basiliximab (n = 188) or placebo (n = 193) as two 20-mg bolus injections days 0 and 4, plus cyclosporine and steroids. Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point, including death or graft loss, and were assessed at 6 and 12 months and by HCV cohort. Because of differential efficacy responses between HCV-positive and HCV-negative cohorts, an additional analysis incorporating HCV recurrence as a component of treatment failure, termed problem-free transplant, was introduced. Safety and tolerability were monitored over the 12 months of the study. All 381 patients were assessable, and no meaningful differences in background characteristics were apparent between treatment groups. Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1% in the basiliximab group versus 43.5% in the placebo group. For death, graft loss, or first biopsy-confirmed acute rejection, rates were 44.1% versus 52.8%, respectively. The reduction in rejection episodes was concentrated in the HCV-negative cohort (14.5% relative to placebo; P =.034), with a much smaller difference (2.9%) in the HCV-positive cohort. For HCV-positive patients, problem-free transplant was shown at 12 months in 26.6% of the basiliximab group versus 11.6% in the placebo group (P =.020) and for all patients at 12 months in 39.7% of the basiliximab group versus 30.1% in the placebo group (P =.035). The incidence of infection and other adverse events was similar across the two treatment groups. There were 56 deaths (25 deaths, basiliximab group; 31 deaths, placebo group) over the 12-month study. The intravenous bolus injection was well tolerated. Immunoprophylaxis with 40 mg of basiliximab, in combination with cyclosporine and steroids, reduces the incidence of acute rejection episodes with no clinically relevant safety or tolerability concerns. The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant, incorporating recurrence as a component of treatment failure.

Cirera I, Mas A, Salmerón JM, Jiménez DF, Sanjosé A, Navasa M, Rimola A, Roca M, Grande L, Garcia-Valdecasas JC, Rodés J. · Liver Unit and Digestive Surgery, Institut de Malalties Digestives, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain. · Transplant Proc. · Pubmed #11406246 No free full text.

This publication has no abstract.

Cisneros L, Londoño MC, Blasco C, Bataller R, Miquel R, Bruguera M, Ginès P, Rimola A. · Liver Unit, Centro de Investigación Biomédica en Red de Enfermedades hepaticos y digestivas, Barcelona, Spain. · Liver Transpl. · Pubmed #17600343 links to  free full text

Abstract: The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.

Blasco A, Forns X, Carrión JA, García-Pagán JC, Gilabert R, Rimola A, Miquel R, Bruguera M, García-Valdecasas JC, Bosch J, Navasa M. · Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. · Hepatology. · Pubmed #16496308 No free full text.

Abstract: Liver biopsy is essential in the follow-up of HCV-infected liver transplant recipients. The aim of this study was to prospectively compare percutaneous (PLB) versus transjugular liver biopsy (TLB) in the assessment of liver damage. We also explored the diagnostic value of hepatic venous pressure gradient (HVPG) to identify patients at risk of severe HCV disease recurrence after liver transplantation (LT). One hundred sixteen paired PLB and TLB (with HVPG measurement) were performed 3 or 12 months after LT in 80 patients. Concordance for necroinflammation and fibrosis was fair or good, particularly 1 year after LT (kappa > or = 0.6). At this point, a significant positive association was seen between the median HVPG and the fibrosis stage (2.5 mm Hg for F0; 5 mm Hg for F1, 6 mm Hg for F2, and 11.5 mm Hg for F3; Kruscal-Wallis < 0.001). Despite this strong association, portal hypertension (HVPG > or = 6 mm Hg) was detected in 1 (5%) of 22, 4 (16%) of 25, and 6 (60%) of 10 patients with fibrosis stages 0, 1, and 2, respectively. After a median follow-up of 38 months, clinical decompensation occurred in 15 (19%) of 80 patients. Although the presence of significant fibrosis (F2-F3) 1 year after transplantation was good to predict clinical decompensation (AUC: 0.80), an HVPG of 6 mm Hg or greater was extremely accurate at identifying patients at risk of disease progression (AUC: 0.96). In conclusion, HVPG determination is a valuable tool for follow-up in patients with HCV recurrence after LT.

Massaguer A, Forns X, Costa J, Feliu A, García-Retortillo M, Navasa M, Rimola A, García-Valdecasas JC, Sánchez-Tapias JM. · Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. · Transplantation. · Pubmed #15912117 No free full text.

Abstract: BACKGROUND: In the liver transplantation (LTx) setting, there are several situations where measurement of hepatitis C virus (HCV)-RNA concentration may provide relevant information. However, HCV-RNA quantification is expensive and not routinely available in all laboratories. An assay to quantify total HCV core antigen in serum has been recently developed. The aim of this study was to compare the performance of HCV-RNA and HCV core antigen determination in a cohort of 116 HCV-infected patients who underwent LTx. METHODS: HCV-RNA and HCV core antigen concentrations were determined in serum samples (n=435) obtained before LTx and at weeks 4, 12, and 48 after LTx. RESULTS: There was an excellent correlation between HCV-RNA and HCV core antigen levels (r=0.802 P<0.001), with an equivalence of 9,900 IU/mL of HCV-RNA per pg/mL of HCV core antigen. The determination of core antigen was linear in samples containing between 20,000 and 2,500,000 IU/mL of HCV-RNA and highly reproducible (mean coefficient of variation, 15%). Overall, HCV core antigen tested positive in 378 (92%) of 410 samples with detectable HCV-RNA (>600 IU/mL); the percentage increased to 98% in samples taken later than 4 weeks after LTx. In fact, almost all samples (369 of 375 [98.4%]) with HCV-RNA levels higher than 20,000 IU/mL were positive for HCV core antigen, whereas 56 of 57 samples with undetectable core antigen had HCV-RNA levels below 50,000 IU/mL. CONCLUSIONS: The performance of total HCV core antigen immunoassay is appropriate for monitoring viral load in HCV-infected patients undergoing LTx and might be considered a useful alternative to HCV-RNA testing.

Sala M, Fuster J, Llovet JM, Navasa M, Solé M, Varela M, Pons F, Rimola A, García-Valdecasas JC, Brú C, Bruix J, Anonymous00345. · Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Catalonia, Spain. · Liver Transpl. · Pubmed #15376311 links to  free full text

Abstract: Surgical resection and liver transplantation offer a 5-year survival greater than 70% in patients with hepatocellular carcinoma, but the high recurrence rate impairs long-term outcome after resection. Pathological data such as vascular invasion and detection of additional nodules predict recurrence and divide patients into high and low risk profile. Based on this, we proposed salvage liver transplant to resected patients in whom pathology evidenced high recurrence risk even in the absence of proven residual disease. From January 1995 to August 2003 we have evaluated 1,638 patients. Resection was indicated in 77 patients, but only 17 (22%) (all cirrhotics, 14 hepatitis C virus+) were optimal candidates for both resection and transplantation. Of them, 8 exhibited a high risk profile at pathology and were offered transplantation. Among the 8 high risk patients, 7 presented recurrence, compared with only 2 of the 9 at low risk (P = .012). Two of the high risk patients refused transplant and developed multifocal disease during follow-up. The other 6 were enlisted and all but 1 had tumor foci in the explant. Only 1 presented extrahepatic dissemination early after transplant and died 4 months later. The others are free of disease after a median follow-up of 45 months. Two recurrences were detected in low risk patients, 1 of them being transplanted 18 months after surgery. These data in a small series of patients confirm that pathological parameters identify patients at higher risk of recurrence, which allow them to be listed for liver transplantation without proven malignant disease. In conclusion, this policy is clinically effective and could further improve the outcome of resected patients.

Rimola A, Londoño MC, Guevara G, Bruguera M, Navasa M, Forns X, García-Retortillo M, García-Valdecasas JC, Rodes J. · Liver Unit, Hospital Clinic, IDIBAPS, Villaroal 170, 08036 Barcelona, Spain. · Transplantation. · Pubmed #15371669 No free full text.

Abstract: 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.

Garcia-Retortillo M, Forns X, Llovet JM, Navasa M, Feliu A, Massaguer A, Bruguera M, Fuster J, Garcia-Valdecasas JC, Rimola A. · Liver Unit, Hospital Clinic, Institut de Malalties Digestives, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. · Hepatology. · Pubmed #15349910 No free full text.

Abstract: 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.

Rimola A, Sánchez-Fueyo A. · Liver Unit, Hospital Clínic, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain. · J Hepatol. · Pubmed #15030998 No free full text.

This publication has no abstract.

García-Valdecasas JC, Fuster J, Charco R, Bombuy E, Fondevila C, Navasa M, Rodríguez-Laiz G, Ferrer J, Amador MA, Llovet JM, Forns X, Rimola A. · Sección de Cirugía Hepática y Trasplante, Institut de Malalties Digestives, Hospital Clínic, Universidad de Barcelona, Barcelona, España. · Gastroenterol Hepatol. · Pubmed #14642237 No free full text.

Abstract: INTRODUCTION: In the last 2-3 years, adult living donor liver transplantation (ALDLT) has been developed on an international scale, multiplying the number of procedures performed. Despite this, analysis of the results is still incomplete. The aim of the present study was to perform a descriptive analysis of the results after the first 3 years of the initiation of the program. MATERIAL AND METHODS: During this period, 30 ALDLT were performed. In all procedures, right lobe grafts were used. The mean age of donors and recipients was 31.8 and 52.7 years, respectively. The main indication for liver transplantation was liver cirrhosis due to hepatitis C virus (70%) and 38% of recipients were stage C in the Child-Pugh classification. A total of 46.7% of recipients had hepatocellular carcinoma. RESULTS: Donors: The mean volume of the remnant liver was 632 cc (40.5% of the previous hepatic mass). Ten donors (33%) presented complications. The most frequent complication was biliary fistula (20%) and three patients required reintervention. The mean length of hospital stay among donors was 11.7 days. Recipients: The mean weight of the graft was 775 g, with a mean difference between graft weight and that of the recipient of 1.11. Fifteen recipients (50%) presented biliary leaks and nine of these (30%) required reintervention. There were no graft losses for technical reasons. Four patients died. With a median follow-up of 14 months, actuarial survival at 18 months was 92.9%. CONCLUSION: ALDLT is an effective method for reducing the number of patients on the waiting list. The probability of survival is similar to that of cadaveric transplantation. Biliary complications in the recipient constitute a problem, the long-term repercussions of which remain to be resolved.

Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, Navasa M, Rimola A, Rodes J. · Liver Unit, Institut de Malalties Digestives, Hospital Clinic, University of Barcelona, Villaroel 170, Barcelona 08036, Catalonia, Spain. · Hepatology. · Pubmed #11870384 No free full text.

Abstract: 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.

Sánchez-Fueyo A, Restrepo JC, Quintó L, Bruguera M, Grande L, Sánchez-Tapias JM, Rodés J, Rimola A. · Liver Unit, Hospital Clínic, University of Barcelona, Villarroel 170, Barcelona 08036, Spain. · Transplantation. · Pubmed #11792978 No free full text.

Abstract: BACKGROUND: The impact of hepatitis C virus (HCV) infection recurrence after orthotopic liver transplantation (OLT) on graft viability is still not accurately defined. Our study aims to evaluate the magnitude and rate of progression of HCV-induced liver damage after OLT in a single institution cohort of 122 HCV-infected recipients. METHODS: All patients transplanted at our institution between 1988 and 1996 with positive serum HCV antibodies before OLT, minimum postoperative survival of 6 months, and without hepatitis B virus coinfection or severe non-HCV-related graft complications were retrospectively included in the study. RESULTS: HCV infection recurrence was almost universal, and genotype 1b was observed in 87% of the cases. After a median histological follow-up of 43 months (range: 7-96), evidences of HCV-induced histological damage were found in 94% of the cases. The actuarial rates of severe graft damage (including cirrhosis, fibrosing cholestatic hepatitis, and submassive liver necrosis) were 15%, 33%, and 44% at 3, 5, and 7 years, respectively, and among these patients, 52% developed decompensated liver disease during the follow-up and 36% lost their grafts. The biochemical severity at the onset of the recurrent hepatitis and the development of cholestasis or cytomegalovirus disease were independent predictors of severe HCV-related graft damage. No differences were found in graft and patient survival when positive-HCV OLT recipients were compared with a coetaneous cohort of 215 non-HCV OLT recipients. CONCLUSIONS: HCV infection recurrence leads to severe liver damage and subsequently to clinical decompensation in a significant proportion of OLT recipients. Some clinical and biochemical characteristics can predict the severity of HCV-induced graft damage.

Sánchez-Fueyo A, Giménez-Barcons M, Puig-Basagoiti F, Rimola A, Sánchez-Tapias JM, Sáiz JC, Rodés J. · Liver Unit, Institut Clínic de Malalties Digestives, Hospital Clínic, IDIBAPS, University of Barcelona, Spain. · J Med Virol. · Pubmed #11536232 No free full text.

Abstract: Recurrence of hepatitis C virus (HCV) infection after liver transplantation is almost universal and usually leads to chronic hepatitis with different degrees of severity. The pathogenic mechanisms underlying the variable outcome of HCV infection recurrence are not well defined, but recent data suggest that the dynamics of HCV quasispecies may be involved. HCV quasispecies evolution was traced by longitudinal single strand conformation polymorphism, direct sequencing, and cloning analyses of pre- and post-transplant HCV-1b isolates from patients with histologically severe (seven cases) or mild or moderate (nine cases) HCV infection recurrence. Differences between the two groups of patients that concerned the level of viremia or the degree of HCV quasispecies complexity and diversity were not observed at any of the three time points analyzed. However, emergence of nucleotide and amino acid changes during the 12 months follow-up was significantly more frequent in patients with mild or moderate than in those with severe HCV infection recurrence. The ratio of non-synonymous to synonymous nucleotide substitutions 12 months after transplantation was also greater in the former, suggesting that the HVR1 of HCV is under stronger selective pressure in these subjects. These findings suggest that the degree of amino acid diversification in the HVR1 of HCV, which probably reflects the strength of immune pressure on HCV, is inversely related to the histological severity of HCV infection recurrence.

García-Valdecasas JC, Fuster J, Grande L, Fondevila C, Rimola A, Navasa M, Cirera I, Bombuy E, Visa J. · Unidad de Cirugía Hepática y Trasplante Hepático. IMD. Hospital Clínico. Universidad de Barcelona. · Gastroenterol Hepatol. · Pubmed #11459562 No free full text.

Abstract: AIM: To analyze the preliminary results of the implementation of a living donor liver transplantation program. PATIENTS AND METHOD: Between March and September 2000 we performed 7 living donor liver transplantations using the right hepatic lobe. The donors were 5 men and 2 women with a mean age of 39.3 11.5 years. Three donors were genetically related (daughter, mother, son). The mean relative liver volume transplanted was 58.8 2.5%. The mean age of the recipients was 50.4 16.5 years. Six patients presented hepatitis C virus-induced cirrhosis and one presented familial amyloidotic polyneuropathy. RESULTS: Three complications occurred in the donors: 1 slight infection and 2 biliary fistulae. Graft function was adequate in all recipients and there were three acute rejections. Four biliary leakages occurred of which two required reoperation. None of the patients developed vascular thrombosis. Two recipients died, 53 and 72 days after the operation, with a correctly functioning graft. CONCLUSION: Living donor liver transplantation constitutes a necessary complement to the current cadaveric donor program to increase the number of patients who can benefit from this treatment, which may represent 10% of the activity of our center. The technical complexity of this procedure is much greater than that of cadaveric transplantation. The right hepatic lobe provides sufficient hepatic mass for most adult recipients.

Segovia R, Sánchez-Fueyo A, Rimola A, Grande L, Bruguera M, Costa J, Soguero C, Uriz J. · Liver Unit, Hospital Clinic, Institut D'Investigacions Biomèdiques August Pi y Sunyer (IDIBAPS), University of Barcelona, Villaroel 170, Barcelona 08036, Spain. · Liver Transpl. · Pubmed #11172393 links to  free full text

Abstract: De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is commonly believed to be a relatively benign condition, in contrast to post-OLT infection recurrence, considered a very aggressive complication. We reviewed the charts of 569 non-HBV-related OLTs performed at our institution and identified 19 patients (3%) with de novo HBV infection (appearance of hepatitis B surface antigen [HBsAg] after OLT). After a median follow-up of 25 months beyond the detection of HBsAg, 12 patients (63%) had developed serious HBV-related graft damage (cirrhosis in 6 patients, bridging chronic hepatitis in 4 patients, and fulminant hepatitis in 2 patients); 7 patients (37%) had lost their grafts; and 4 patients (21%) had died. All graft losses and deaths were related to de novo HBV infection. Similar rates of severe graft damage (62%), graft loss (38%), and death (33%) related to HBV infection were found in a concomitant series of 21 patients with recurrent HBV infection after OLT. Responses to antiviral therapy (interferon or lamivudine) were also similar in the 2 groups of patients. In 12 patients with de novo HBV infection, evidence of past HBV infection (positive serum antibody to hepatitis B core antigen and/or serum or liver tissue HBV DNA) were detected in the donor (7 patients) or recipient (5 patients). No differences were observed in the clinical course after stratification according to the attributed origin of de novo HBV infection. We conclude that de novo HBV infection after OLT is associated with high rates of morbidity and mortality, similar to those described for post-OLT HBV infection recurrence.

Sánchez-Fueyo A, Rimola A, Grande L, Costa J, Mas A, Navasa M, Cirera I, Sánchez-Tapias JM, Rodés J. · Institut Clinic de Malalties Digestives, Hospital Clínic Barcelona, University of Barcelona, Barcelona, Spain. · Hepatology. · Pubmed #10655276 No free full text.

Abstract: It is widely agreed that hepatitis B virus immunoglobulin (HBIG) should be administered for at least 12 months to patients transplanted for hepatitis B virus (HBV)-related diseases to prevent HBV recurrence. No data are available, however, on how long this treatment should be used, and most centers currently administer HBIG on a life-long basis. Herein, we report the results of a new prophylactic strategy aiming at the discontinuation of HBIG treatment and consisting of the administration of double dose recombinant HBV vaccine (0, 1-, and 6-month schedule) to liver transplant recipients fulfilling the following criteria: (1) liver transplantation for conditions related to nonreplicative HBV infection (hepatitis B surface antigen [HBsAg] positive, hepatitis B e antigen [HBeAg] negative, and HBV DNA negative); (2) at least 18 months of HBIG administration; and (3) no HBV infection recurrence, normal or slightly altered liver graft function, and low-grade immunosuppression at the time of vaccination. Seventeen patients received HBV vaccination and 14 of them (82%) developed protective serum titers of anti-HBs (>10 IU/L). Six patients seroconverted after a first course of vaccination, whereas 8 patients required a second course (3 additional doses of vaccine). Responding patients were followed for a median of 14 months (range, 3-50) after seroconversion. During this period no HBV recurrence occurred and in only 2 patients a decrease of anti-HBs titers below 10 UI/L was observed. Our data suggest that in selected liver transplant recipients, posttransplantation HBV vaccination may be a useful and cost-effective strategy in the prophylaxis of HBV recurrence, allowing the discontinuation of life-long HBIG treatment.

Sanchez-Fueyo A, Martinez-Bauer E, Rimola A. · No affiliation provided · Hepatology. · Pubmed #12085376 No free full text.

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