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AIM To demonstrate the non-inferiority (15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate (TDF) vs the combination of lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic response in patients with chronic hepatitis B (CHB) and prior failure with LAM. METHODS This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed. RESULTS Forty-six patients were evaluated [median age: 55.4 years (30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA (HBV-DNA) remained undetectable, all patients remained HBeAg negative, and hepatitis B surface antigen (HBsAg) positive. Alanine aminotransferase (ALT) values at the end of the study were similar in the 2 groups (25.1 ± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects (AEs) (53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively (P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment (€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001). CONCLUSION TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs.

Eltrombopag is an oral thrombopoietin-receptor agonist. This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing an elective invasive procedure.We randomly assigned 292 patients with chronic liver disease of diverse causes and platelet counts of less than 50,000 per cubic millimeter to receive eltrombopag, at a dose of 75 mg daily, or placebo for 14 days before a planned elective invasive procedure that was performed within 5 days after the last dose. The primary end point was the avoidance of a platelet transfusion before, during, and up to 7 days after the procedure. A key secondary end point was the occurrence of bleeding (World Health Organization [WHO] grade 2 or higher) during this period.A platelet transfusion was avoided in 104 of 145 patients who received eltrombopag (72%) and in 28 of 147 who received placebo (19%) (P0.001). No significant difference between the eltrombopag and placebo groups was observed in bleeding episodes of WHO grade 2 or higher, which were reported in 17% and 23% of patients, respectively. Thrombotic events of the portal venous system were observed in 6 patients who received eltrombopag, as compared with 1 who received placebo, resulting in the early termination of the study. The incidence and severity of other adverse events were similar in the eltrombopag and placebo groups.Eltrombopag reduced the need for platelet transfusions in patients with chronic liver disease who were undergoing elective invasive procedures, but it was associated with an increased incidence of portal-vein thrombosis, as compared with placebo. (Funded by GlaxoSmithKline; ELEVATE ClinicalTrials.gov number, NCT00678587.).

Objective: the aim of our study was to examine, in a prospective way, whether any nutritional parameter could predict outcomes after liver transplantation. Material and subjects: a nutritional assessment was performed in 31 consecutive patients six months prior to undergoing orthotopic liver transplantation (OLT) at a single center (Hospital U. Río Hortega) and after six months of OLT (December 2002-June 2004). The nutritional evaluation included Subjective Global Assessment (SGA), Mini Nutritional Assessment test (MNA), anthropometry, laboratory tests, and three-day diet diary completed. The body composition analysis was performed by tetrapolar body electrical bioimpedance and skin folds in a standard way. Results: our patients had an average age of 56.2 ± 8.11 years; weight was 72.9 ± 15.3 kg, and body mass index was 26.6 ± 4.1. The anthropometric evaluation showed the following data: tricipital skin fold 12.2 ± 6.1 mm, mid-arm circumference 24.5 ± 4.1 cm, fat-free mass 54.5 ± 10.9 kg, fat mass 18.4 ± 6.5 mm, and body water 41.4 ± 9.1 kg. After six months from liver transplantation, these parameters remained unchanged. Energy intake, as corrected by weight, was similar pre- and post-liver transplantation (28.1 ± 6 kcal/kg vs. 27.5 ± 5.8 kcal/kg: ns). Albumin, prealbumin and transferrin improved after 6 months from transplantation. Length of stay in hospital was 22.4 ± 14.9 days, and length of stay in ICU was 0.7 ± 1.7 days. The nutritional status (SGA and MNA tests) of patients did not influence length of stay in either hospital or ICU. No intercurrent events (infections: urinary tract infection, pneumonia, and peritonitis) were recorded during the 6-month study period. Two patients died after liver transplantation (6.5%), and 3 patients had acute rejection (9.6%). Patients with malnutrition (SGA and MNA tests classification) showed no differences in rejection and mortality. Conclusions: our liver transplantation population had normal nutritional status and dietary intake. Nutritional parameters showed no association with outcomes after liver transplantation. Liver transplantation improved serum protein levels and did not modify weight or dietary intake. Further studies are needed to clarify the role of liver transplantation on nutritional status and of nutritional status on liver transplantation outcomes, considering different populations of patients. Objetivo: el objetivo de nuestro estudio fue examinar de una manera prospectiva si la situación nutricional y la ingesta dietética pueden influir en los resultados del postrasplante hepático. Material y pacientes: se realizó una valoración nutricional basal y a los 6 meses en 31 pacientes consecutivos que fueron sometidos a trasplante hepático ortotópico (THO), en el Hospital U. Río Hortega. La evaluación nutricional incluyó el test de valoración subjetiva global (VSG), el test mininutritional assessment (MNA), antropometría convencional, analítica sérica y una encuesta nutricional de 3 días. Resultados: los pacientes tuvieron una edad media de 56,2 ± 8,11 años, peso (72,9 ± 15,3 kg) e índice de masa corporal de (26,6 ± 4,1). La valoración antropométrica mostró los siguientes datos: pliegue tricipital 12,2 ± 6,1 mm, circunferencia muscular del brazo 24,5 ± 4,1 cm, masa libre de grasa 54,5 ± 10,9 kg, masa grasa 18,4 ± 6,5 mm y agua corporal 41,4 ± 9,1 kg. Tras seis meses del trasplante estos parámetros permanecieron inalterados. La ingesta calórica fue similar en el pre- y post-trasplante (28.1 ± 6 vs. 27,5 ± 5,8 kcal/kg: ns). Los niveles séricos de albúmina, prealbúmina y transferrina mejoraron a los 6 meses. La estancia media hospitalaria fue de 22,4 ± 14,9 días y la estancia en cuidados intensivos de 0,7 ± 1,7 días. EL estado nutricional determinado por los tests VSG y MNA no influyó en las estancias. Dos pacientes fallecieron tras el trasplante hepático (6,5%) y 3 tuvieron rechazo agudo (9,6%). El estado nutricional determinado por los test VSG y MNA tampoco influyó en estos dos parámetros. Conclusiones: nuestra población pretrasplante presenta una buena situación nutricional e ingesta dietética. Los parámetros nutricionales no mostraron ninguna relación con parámetros clínicos post-trasplante. El trasplante hepático mejoró el nivel de las proteínas séricas. Son necesarios nuevos estudios con diferentes poblaciones de pacientes con hepatopatía para evaluar la relación entre la situación nutricional y las variables clínicas postrasplante.

Liver disease due to hepatitis C virus (HCV) is an increasingly frequent indication for liver transplantation. We performed a clinical and virological study of 20 HCV-infected liver transplant recipients to correlate virological markers with histological recurrence of disease.In ninety-four patients who were given transplants for end-stage cirrhosis, IgG and IgM antibodies to HCV and IgM to HCV tested by ELISA; all samples were further examined in a four-antigen recombinant immunoblot assay (2-RIBA). HCV viremia was measured by the conventional nested PCR, HCV genotype was determined by PCR amplification using type-specific primers. We have analyzed de novo infection by HCV, HCV recurrence and the influence of genotype in these recurrence.Nineteen of 20 antibody-positive patients (95%) had HCV RNA before transplantation. All 19 patients who were viremic before transplantation had persistent infection after LT. HCV genotype 1b was the predominant type before and after LT (75%). Ten of the 20 (50%) patients developed histological findings of chronic hepatitis (CH) in liver allografts. HCV recurrent liver disease after LT was not related with HCV genotype. Of 4 deaths after transplant in hepatitis C group, only one was related to recurrent disease. We have not found de novo hepatitis C.Our results indicate the general persistence of hepatitis C virus infection and the excellent short-term prognosis after liver transplantation. Chronic hepatitis by HCV in liver transplant was not related with HCV genotype.

The prevalence of HBV and HCV infections in patients with hepatocellular carcinoma may be related to variations in the geographic area of study. For this reason, we have analized the relative prevalence of HBV and HCV infections in 94 patients with hepatocellular carcinoma from Cantabria (North of Spain).We have studied 94 patients with hepatocellular carcinoma from January 1988 to December 1993. Commercially available radioimmunoassay or ELISA were used for detection of HBsAg, anti-HBs and anti-HBc. The HBV DNA was analized by PCR. The HCV infection was assayed by ELISA-2 and RT-PCR.The HBV infection was detected in 27 patients: 19 patients were HBsAg positive and 8 patients HBsAg negative, anti-HBc positive, DNA HBV positive by PCR. The HCV infection was found in 57 patients. Forty patients were infected with both viruses. Of the remain twenty-four, forty were alcoholics. We found in 61 patients more than one etiological factor. Hepatoma was the first manifestation of liver disease in 24 cases and these were more frequently in HCV than in those with HBV infection. Moreover, the first group were older and have lower alcohol intake.1) In Cantabria, Spain, the majority of cases of hepatocellular carcinoma are related to HBV, HCV and alcohol. 2) Analysis of DNA HBV and RNA HCV by PCR allows the diagnosis of cryptic infections by both viruses, especially in the cases of HBV and HCV coinfection. 3) Hepatoma is the first manifestation of liver disease in a high percentage of cases.