Results of hepatitis C virus treatment in patients on hemodialysis: data from published meta-analyses in 2008.

Reports on the outcome of treatment for hepatitis C virus (HCV) infection in dialysis patients are limited by small patient series, nonrandomized study designs, and few case-control studies. We reviewed 2 meta-analyses (Meta-1 and Meta-2) published in 2008, which analyzed sustained viral responses (SVR), adverse effects, and reasons for discontinuing treatment. Meta-1 analyzed the results obtained in 645 patients and Meta-2 the results in 459 patients (19 studies were duplicated). The overall SVR was 40%; the SVR in genotype 1 was 33%, with pegylated interferon providing few additional benefits over conventional interferon. Adverse events were reported in <50% of cases compiled in the meta-analyses. A high percentage of anemia was documented, although the use of erythropoietin, intravenous iron administration, or transfusions was not generally reported. A typical flu-like syndrome occurred in 41% of patients, requiring withdrawal of antiviral treatment in 11%. Severe adverse events were divided into the following groups: hormonal (thyroid): bone pain; cytopenia; gastrointestinal; immunological (prior graft rejection); central nervous system; cardiovascular; and infectious problems. The authors of the meta-analyses pointed out bias in the selection of candidates for treatment, limitations related to the number and type of adverse effects and their clinical evaluation, and in the cases of discontinuation of treatment or loss to follow-up. Additional studies reporting individual patient data are needed because the paucity of controlled studies limits generalization of the results to the population of dialysis patients.

Preliminary results of treatment with pegylated interferon alpha 2A for chronic hepatitis C virus in kidney transplant candidates on hemodialysis.

INTRODUCTION: At present, there is little published information on the outcome of treatment with pegylated interferon (Peg-IF alpha 2a) in hepatitis C virus (HCV)-infected hemodialysis patients awaiting renal transplantation. The objective of this study was to assess the efficacy and tolerance of Peg-IF alpha 2a in this population. PATIENTS AND METHODS: Twelve noncirrhotic HCV-infected patients (10 men, 50 +/- 8 years of age, genotype 1b 84%), were prescribed Peg-IF alpha 2a, at 135 microg/wk for 48 weeks. Liver biopsy was performed in 11 of 12 cases. RESULTS: Six patients completed 48 weeks of treatment, with one end of treatment response (ETR), two sustained viral responses (SVRs), and three HCV relapses. Treatment was shorter in the six remaining patients: two cases 24 weeks (one due to medical reasons with relapse, one due to nonresponse), one patient chose to discontinue at 14 weeks (with relapse), one patient died of stroke at 10 weeks, and in two additional patients interferon was withdrawn at 18 weeks because of severe anemia (SVR) and at 26 weeks due to prolonged fever (relapse). Other secondary treatment-related events included anemia (requiring transfusion in two patients and major erythropoietin administration in six), and fever in four patients. CONCLUSIONS: Peg-IF had limited efficacy in this group, with ETR in 83%, SVR in only 25%, and recurrence in 50%. Tolerance was moderate, with 4/12 (33%) discontinuing treatment due to adverse events, personal decision, or death. Large randomized controlled studies are needed to determine the role of Peg-IF treatment in this population.

Validation of the Spanish version of the liver disease quality of life instrument among candidates for liver transplant.

OBJECTIVE: To validate a Spanish version of the Liver Disease Quality of Life Questionnaire (LDQOL 1.0) among patients awaiting hepatic transplantation. METHODS: This observational, cross-sectional study was performed between May 2002 and June 2006. We included ambulatory or hospitalized patients aged 18 or over with chronic liver disease awaiting transplantation. Patients completed the LDQOL 1.0. The feasibility of the LDQOL for clinical use was tested by examining the administration time and values for the questionnaire's 12 disease-specific scales. Reliability was tested by examining the internal consistency of the scales (Cronbach's alpha). Known group validity was tested by examining the questionnaire's ability to discriminate between patients with hepatocellular (HCC), liver cirrhosis (CH), hepatitis C virus infection, and alcohol-induced CH. RESULTS: A total of 200 patients were included in the analysis. Their mean age (SD) was 52.6 (9.8) years; 73% of the sample were men. The most common indication for liver transplant was HCC (34%). The mean (SD) time to complete the LDQOL 1.0 was 35 minutes (21 minutes). Over 20% of patients scored at the ceiling (maximum possible score) on seven of the 12 disease-specific scales. Floor effects were less marked. All dimensions had Cronbach alpha coefficients over 0.60. The lowest value (0.64) was found in the sexual problems (women) dimension. Patients with HCC had significantly higher scores on several scales, including symptoms of liver disease (P = .000), effects of liver disease (P = .000), concentration (P = .002), memory (P = .015), quality of social interaction (P = .030), sleep (P = .000), loneliness (P = .043), and stigma (P = .028). Statistically significant differences were found between HCC patients and alcohol-induced CH patients in only two dimensions. CONCLUSIONS: Among pretransplant patients, the Spanish version of the LDQOL 1.0 showed substantial ceiling effects and the length of administration makes its application in clinical practice difficult. This preliminary analysis showed good internal consistency for the disease-specific scales and acceptable known group validity.

Impact of cyclosporine on the development of immunosuppressive therapy in liver transplantation.

Over the last 20 years, immunosuppression protocols in liver transplant patients have been based on calcineurin inhibitors, such as cyclosporine (CsA). Currently, there are three outstanding clinical issues related to the use of CsA in the liver transplant setting that merit further attention: (1) dose adjustment according to 2-hour postdose (instead of trough) concentrations to improve efficacy and safety, (2) possible synergistic effect between CsA and antiviral treatments for recurrent posttransplant hepatitis C infection, and (3) preliminary results showing favorable outcomes after liver transplantation in HIV-positive patients receiving antiviral therapy.

[Transcultural adaptation of the Liver Disease Quality of Life instrument (LDQOL 1.0) for its use in the Spanish population]. / Adaptación transcultural del cuestionario específico de calidad de vida para hepatopatías crónicas (LDQOL 1.0) para su uso en la población española.

Instruments of health-related quality of life (HRQOL) help us to interpret the results of treatments and health interventions. In Spain there is no HRQOL instrument specifically designed for use in patients with liver disease or to measure the effect of interventions such as liver transplantation. The Liver Disease Quality of Life (LDQOL 1.0) questionnaire is an American instrument developed for use in these patients. The aim of this study was to produce an appropriate version of this questionnaire for use in Spain. Cultural adaptation was performed in 3 phases: a) modification for use in Spain of a Hispanic version of this questionnaire supplied by the original authors; b) back-translation to English of a new version of the questionnaire and comparison with the original version in English, and c) a pilot test in a small sample of patients. In the first phase consisting of revision of the Hispanic version, the changes were mainly linguistic due to cultural and idiomatic differences. The validated Spanish version of the SF-36 was directly incorporated and items that could be of interest to local investigators were added. Few changes were made in the second phase of the process: changes involved an item on the appearance of feces and another item on taking naps. In the final phase, various changes suggested by the patients were introduced. Before applying the new version of the LDQOL 1.0 in clinical studies in Spain, its psychometric properties (its reliability, validity and sensitivity to change) must be verified in a subsequent validation study.

[Domino or sequential liver transplantation. Is it a feasible technique?]. / El trasplante hepático dominó o secuencial, es una técnica factible?

BACKGROUND: In domino liver transplantation (LT), the explanted liver of a patient with familial amyloidotic polyneuropathy (FAP) is donated to another patient. PATIENTS AND METHOD: Between February 1999 and March 2001 we performed 131 LT with 121 cadaveric donors in our unit. Ten domino LTs were performed. RESULTS: Patients with FAP were younger (37 years) than recipients of the second LT (64 years). The evolution of patients undergoing transplantation for FAP was excellent and all are currently alive and without complications. Among recipients of the second LT, one patient died in the postoperative period. A further two patients died from tumoral recurrence and hepatitis C virus recurrence 18 months and 9 months after transplantation, respectively. The remaining patients have shown no symptoms of FAP during the follow-up. CONCLUSION: The results of this study show that domino LT is technically feasible. The technique increases the number of grafts without apparent risk either to the recipient with FAP or to the recipient of the latter's explanted liver.

Efficacy of interferon for chronic hepatitis C virus-related hepatitis in kidney transplant candidates on hemodialysis: results after transplantation.

OBJECTIVES: Interferon-alpha (IFN) may have undesirable effects on a functioning graft. The aim of this study was to evaluate IFN treatment in kidney transplant candidates during the hemodialysis period as well as the results after transplantation. METHODS: A total of 29 noncirrhotic hemodialysis patients with chronic hepatitis C virus (HCV) infection (based on long-term rise in ALT, HCV serology, HCV RNA by polymerase chain reaction methods, and histological evidence) were included. Tolerability to IFN treatment, pre- and posttransplantation therapeutic results, and long-term outcome were recorded. IFN regimen consisted of 3 million units (MU) times per week after hemodialysis sessions for 6 months, followed by 1.5 MU after each hemodialysis session for an additional 6 months. All patients gave informed consent for participation. RESULTS: IFN therapy was fairly well tolerated. Adverse effects due to IFN toxicity, renal disease, or causes related to the immunological properties of IFN were observed in 24% of patients. At the end of treatment, ALT had normalized in 23/28 patients (82.1%), and HCV RNA had cleared in 23/28 patients (82.1%). During follow-up, HCV RNA was persistently negative in 18 patients (64%, including transplant recipients). A total of 14 patients (nine HCV RNA-negative) received a kidney transplant. Mean follow-up after the procedure was 41 +/- 28 months. In all, 12 patients had a functioning graft, one had acute vascular rejection, and one died of carcinoma. All transplanted patients maintained normal ALT levels, and eight remained HCV RNA-negative. CONCLUSIONS: Treatment results in our study population were better than those observed in the general population. The long-term response achieved, which was maintained after transplantation, supports the use of IFN for HCV hepatitis in kidney transplant candidates under hemodialysis.

[Analysis of 500 liver transplantations at Bellvitge Hospital, Spain]. / Análisis de 500 trasplantes hepáticos en el Hospital de Bellvitge.

BACKGROUND: We present the experience of the liver transplantation program at the Hospital of Bellvitge with 500 transplantations performed during 15 years, to describe changes in liver transplantation observed throughout the time and to analyze the long term results. PATIENTS AND METHOD: Five groups each one including 100 consecutive transplantations are studied. RESULTS: The main indications were hepatocellular carcinoma (23%), alcoholic cirrhosis (22.8%), and post-hepatitis C cirrhosis (18.8%). Sixty-five retransplantations were performed in 59 patients (13%), being the more frequent indications arterial thrombosis (13 patients) and primary nonfunction of graft (10 patients). In 10 patients a hepatorenal transplantation was performed. In group I, the most frequent donor cause of death was cranial traumatism (80%), while in group V it was the vascular pathology (52%). There were other significative differences between these groups of patients (I vs V): patients with stage 2 or 3 from UNOS status (45 vs 19%), blood use (29.6 [26] vs 4.6 [5.3] PRBC), ICU stay (13 [13] vs 7.4 [11] days), hospital stay (40 [52] vs 23.7 [17] days), rejection rate (46 vs 20%) and primary graft nonfunction (9 vs 3%). However, the infection rates (48 vs 54.5%) and biliary tract complications (26 vs 20%) have not shown statistically significant differences. Actuarial one and 5-year survival are 83 and 70% respectively. CONCLUSIONS: An important and progressive improvement of liver transplantation results has been observed. However, de novo tumours, hepatitis C virus recurrence and chronic rejection can limit long term results.