Guadalupe Costán

SOMATOSTATIN VERSUS SENGSTAKEN BALLOON TAMPONADE FOR PRIMARY HAEMOSTASIA OF BLEEDING ESOPHAGEAL VARICES : A RANDOMIZED PILOT STUDY

In this study we evaluate the efficacy of somatostatin (ST) versus balloon tamponade (BT) in controlling bleeding from esophageal varices. Forty-four consecutive patients with active variceal bleeding were randomly assigned to treatment with a continuous infusion of ST at 250 micrograms/h after an initial bolus of 50 micrograms (group A) or to treatment with BT (group B). Five cases were excluded from the final analysis because of methodological issues. Nineteen patients were allocated to group A and twenty to group B. No differences in age, sex, alcohol intake, severity of bleeding or liver failure were found between the groups. Initial haemostasia within the first 4 h of treatment was obtained in 14 (74%) of the patients receiving ST and in 12 (60%) of those receiving BT. Three patients in group A and two in group B had early rebleeding. Bleeding was controlled over a 24-h period or until elective sclerotherapy could be performed in 11 (58%) and 10 (50%) of the patients, in groups A and B, respectively. One BT-treated patient developed aspiration pneumonia. No complications were observed in patients treated with ST. No significant differences in initial haemostasia, definite control of bleeding or complications were found between the two groups. In this study, somatostatin infusion was found to be as effective as Sengstaken BT in controlling acute variceal bleeding until an elective session of endoscopic sclerotherapy could be performed. However, larger studies are still needed to confirm this theory.

Orthotopic liver transplantation after subacute liver failure induced by therapeutic doses of ibuprofen

1980;21:1098–100. 6. Prakash C, Lustman PJ, Freedland KE, Clouse RE. Tricyclic antidepressants for functional nausea and vomiting—clinical outcome in 37 patients. Dig Dis Sci 1998;43:1951–6. 7. Ricci DA, Saltzman MB, Meyer C, et al. Effect of metoclopramide in diabetic gastroparesis. J Clin Gastroenterol 1985; 7:25–32. 8. Talley NJ, Verlinden M, Jones M. Can symptoms discriminate among those with delayed or normal gastric emptying in dysmotility-like dyspepsia? Am J Gastroenterol 2001;96:1422–8. 9. Jian R, Ducrot F, Ruskone A, et al. Symptomatic, radionuclide and therapeutic assessment of chronic idiopathic dyspepsia. A double-blind, placebo-controlled evaluation of cisapride. Dig Dis Sci 1989;34:657–64. 10. Kellow JE, Cowan H, Shuter B, et al. Efficacy of cisapride therapy in functional dyspepsia. Aliment Pharmacol Ther 1995;9:153–60.

Role of NF-κB activation and nitric oxide expression during PGE1 protection against d-galactosamine-induced cell death in cultured rat hepatocytes

Abstract: Prostaglandin E1 (PGE1) reduces cell death in experimental and clinical liver dysfunction. Nitric oxide (NO) mediates PGE1 protection against d‐galactosamine (d‐GalN)‐induced cell death. Nuclear factor kappa‐B (NF‐κB) plays a protective role in different experimental models of cell death. We investigated if NF‐κB was responsible for inducible nitric oxide synthase (iNOS) expression and cytoprotection induced by PGE1 against d‐GalN cell death in cultured hepatocytes. Rat hepatocytes were isolated following the classical method of collagenase perfusion of liver. A kinetic study of cell death, NF‐κB activation, mRNA and protein iNOS expression, and NO production was carried in hepatocytes treated with d‐GalN (5 mM) in the presence or absence of PGE1 (1 μM) administered 2 h before the hepatotoxin. A proteasome inhibitor was used to evaluate the role of NF‐κB activation in our experimental conditions. PGE1 protection against d‐GalN‐induced cell death was associated with its capacity to rapidly enhance NF‐κB activation, mRNA and protein iNOS expression, and NO production in d‐GalN‐treated hepatocytes. The inhibition of NF‐κB activation abolished iNOS expression and cell protection by PGE1 in hepatocytes treated with the hepatotoxin. The present study shows that the cytoprotection by PGE1 against d‐GalN‐induced apoptosis was related to NF‐κB‐dependent iNOS expression.

Interleukin-6 is associated with liver lipid homeostasis but not with cell death in experimental hepatic steatosis

Hepatic steatosis is a risk factor for the progression of non-alcoholic fatty liver disease. The role of pro-inflammatory interleukin (IL)-6 in hepatic steatosis etiology is controversial. We investigated in vivo and in primary hepatocyte cultures whether IL-6 has a modulator role in liver and mitochondria lipid composition and cell death in a choline-deficient (CD) diet rat model of hepatic steatosis. Dietary choline deficiency increased triglycerides and cholesterol, and reduced phosphatidylcholine (PC), phosphatidylethanolamine (PE) and the membrane integrity marker PC:PE ratio in liver. Choline-deficient diet enhanced systemic IL-6, and IL-6 receptor expression and cell death vulnerability in hepatocytes. Derangement of the mitochondrial electron transport chain and of its phospholipid environment was found in CD rat liver mitochondria, which exhibited elevated concentrations of triglycerides, cardiolipin and PC and elevated PC:PE ratio. The cell treatment with IL-6, but not PC, eliminated much of the CD-promoted lipid imbalance in mitochondria but not tumor-necrosis factor (TNF)-α-induced cell death. However, PC supplementation prevented the TNF-α-induced DNA fragmentation, cytochrome-c release and caspase-3 activity in control and CD hepatocytes. In conclusion, IL-6 ameliorated the mitochondria lipid disturbance in hepatocytes isolated from steatotic animals. Furthermore, PC is identified as a new survival agent that reverses several TNFα-inducible responses that are likely to promote steatosis and necrosis.

Acute liver failure in a patient with multiple sclerosis treated with interferon-β

Sir Acute liver failure (ALF) is a rare but frequently fatal disorder, defined by the onset of coagulopathy and encephalopathy within 1 26 weeks of presentation, without underlying liver disease [1]. The mortality rate reaches 60 90%, depending on the grade of encephalopathy, and urgent liver transplantation is recommended when criteria are fulfilled (King’s College and Clichy criteria). We report an uncommon case of ALF requiring liver transplant occurring five years after starting interferon-b treatment in a patient with multiple sclerosis (MS). A 39-year-old woman with jaundice and malaise was admitted to our unit. She had relapsing MS, diagnosed 10 years earlier and had been receiving interferon-b (Betaferon, Schering) for five years at a dose of 25 mcg subcutaneously every two days, without any serious adverse event so far. There was no history of alcohol or paracetamol abuse, and without concomitant medications during the last five years. At admission her mental status was normal, without signs of encephalopathy or fever. The liver function tests at presentation were as follows: AST 1609 U/L, ALT 1082 U/L, GGT 175 U/L, ALP 176 U/L, total bilirubin 10.4 mg/dL, prothrombin activity 26% and factor V 26%. The values of other parameters such as glucose, BUN, creatinin, sodium, potassium, amylase, total protein, albumin, ceruloplasmin, copper, a-1-antitrypsin and a-fetoprotein were normal. All serum viral markers of HCV, HBV, HAV and systemic viruses (CMV, Herpes, Epstein-Barr) were negative. Autoimmune profile demonstrated positivity for ANA and SMA antibodies with a titre of 1:1260 and 1:160, respectively. Abdominal ultrasound examination showed normal liver size and no features of portal hypertension. The administration of interferon-b was discontinued, and the patient started on steroid treatment (methyl prednisolone 1 mg/kg weight i.v.). After 10 days, liver function tests improved partially (AST 101 UI/L, ALT 214 UI/L, bilirubin 15.4 mg/dL, prothrombin activity 23.7%, factor V 23.6%), but abdominal ultrasound showed presence of ascites and hepatic atrophy. At day 13 after admission the patient developed decreased level of consciousness and asterixis. Liver transplant was performed 24 h later, and the explant showed massive hepatic necrosis without specific aetiological features. The outcome of the patient was satisfactory and she was discharged 20 days after OLT with normal graft function. An association between MS and other autoimmune disorders has already been reported (thyroiditis, myasthenia gravis and rheumatoid arthritis). Some authors have suggested that the prevalence of AIH in MS patients is nearly 10 times higher than in the general population through similar B-cellmediated mechanisms [2]. The treatment of AIH includes steroids and azathioprine. On the other hand, interferon-b is considered as the gold standard treatment for MS, but abnormal liver function tests are reported in up to 36% of patients, based on postmarketing studies [3]. Several cases of AIH [4,5] or acute liver injury requiring liver transplantation [6] have been recorded in patients with MS treated with interferon-b. Although interferon-b treatment is safe and generally well tolerated, patients should be frequently monitored in order to detect eventual deterioration of liver function.

Factores pronósticos de complicaciones postoperatorias en el trasplante hepático

OBJECTIVES the postoperative evolution of patients submitted to orthotopic liver transplant (OLT) is frequently associated with the appearance of different types of complications such as renal failure, graft rejection, infections, and neurological disorders. These complications are the most significant causes of early morbidity and mortality in patients undergoing OLT. The purpose of the present study was the identification of factors related to the different postoperative complications after OLT. EXPERIMENTAL DESIGN a prospective study was carried out. PATIENTS seventy-eight variables were analyzed in 32 consecutive patients undergoing OLT. The factors independently associated with the appearance of postoperative complications were identified using a stepwise logistic regression analysis. RESULTS the multivariate analysis showed that malondialdehyde and creatinine pretransplant serum levels were associated with the development of renal dysfunction. The pretransplant levels of haemoglobin and the units of platelets administered during surgery were prognostic factors of infections. Acute graft rejection was predicted by ?-glutamyl transpeptidase and total bilirubin serum levels. The pretransplant sodium and glutaredoxin levels in serum were associated with neurological complications. CONCLUSIONS we propose these markers for the identification of high-risk patients allowing an early surveillance and/or treatment to improve morbidity and survival in patients submitted to OLT.