Progression of liver fibrosis in HIV/hepatitis C virus-coinfected individuals on antiretroviral therapy with early stages of liver fibrosis at baseline.

OBJECTIVES: The aim of the study was to assess the progression of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients with no or mild-to-moderate fibrosis (stages F0-F2). METHODS: Liver fibrosis was reassessed by transient elastometry (TE) between January 2009 and November 2011 in HIV/HCV-coinfected patients with stage F0-F2 fibrosis in a liver biopsy performed between January 1997 and December 2007. Patients with liver stiffness at the end of follow-up < 7.1 kPa were defined as nonprogressors, and those with values ≥ 9.5 kPa or who died from liver disease were defined as progressors. Cirrhosis was defined as a cut-off of 14.6 kPa. The follow-up period was the time between liver biopsy and TE. Cox regression models adjusted for age, gender and liver fibrosis stage at baseline were applied. RESULTS: The median follow-up time was 7.8 years [interquartile range (IQR) 5.5-10 years]. The study population comprised 162 patients [115 (71%) nonprogressors and 47 (29%) progressors; 19 patients (11.7%) had cirrhosis]. The median time from the diagnosis of HCV infection to the end of follow-up was 20 years (IQR 16.3-23.1 years). Three progressors died from liver disease (1.8%). The variables associated with a lower risk of progression were age ≤ 38 years (hazard ratio (HR) 0.32; 95% confidence interval (CI) 0.16-0.62; P = 0.001], having received interferon (HR 2.18; 95% CI 1.14-4.15; P = 0.017), being hepatitis B virus surface antigen (HBsAg) negative (HR 0.20; 95% CI 0.04-0.92; P = 0.039), and baseline F0-F1 (HR 0.43; 95% CI 0.28-0.86; P = 0.017). CONCLUSIONS: A high proportion of patients with stage F0-F2 fibrosis progress to advanced liver fibrosis. Advanced liver fibrosis must be included in the list of diseases associated with aging. Our results support the recommendation to offer HCV antiviral therapy to HIV/HCV-coinfected patients at early stages of liver fibrosis.

Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis.

BACKGROUND & AIMS: Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. METHODS: All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. RESULTS: Nine patients (mean age 67 years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. CONCLUSIONS: Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities.

A prospective study of T- and B-lymphocyte subpopulations, CD81 expression levels on B cells and regulatory CD4(+) CD25(+) CD127(low/-) FoxP3(+) T cells in patients with chronic HCV infection during pegylated interferon-alpha2a plus ribavirin treatment.

Resolution of hepatitis C virus (HCV) infection requires a complex interplay between innate and adaptative immune responses. The role of lymphocyte subpopulations during combined antiviral treatment remains to be defined. This study was conducted to assess the effect of pegylated interferon-alpha2a (pegIFN-α2a) and ribavirin treatment on peripheral blood lymphocytes, mainly on CD81 expression on B cells and CD4(+) CD25(+) CD127(low/-) FoxP3(+) regulatory T cells (Tregs) in patients with chronic HCV infection. Thirty-five patients with chronic HCV infection who started pegIFN-α2a and ribavirin treatment were enrolled. Peripheral blood mononuclear cells (PBMC) were obtained at baseline before treatment (BT), mid-treatment (MT), the end of treatment (ET) and 24weeks post-treatment (PT). During combined antiviral treatment, a significant decrease in the percentage of CD3(+) , CD8(+) , CD3(+) gamma/delta (γδ)(+) , CD19(+) lymphocyte subpopulations and Tregs was observed. There was also a significant increase in the percentage of the CD4(+) lymphocyte subpopulation and in CD81 expression levels on CD19(+) B cells when BT was compared with ET (all P<0.05). Seventeen patients were nonresponders (NR) and 18 had a sustained virological response (SVR). At baseline, NR patients had higher CD81 expression levels on CD19(+) B cells (P=0.017) and a higher Tregs percentage (P=0.025) than SVR patients. Our results suggest that immunomodulation fluctuates during antiviral treatment and that percentage CD81 expression levels on B cells and Tregs might be useful as an immunological prognostic factor for pegIFN-α2a and ribavirin treatment response in chronic HCV infection.

Gene expression profiles for the human pancreas and purified islets in type 1 diabetes: new findings at clinical onset and in long-standing diabetes.

Type 1 diabetes (T1D) is caused by the selective destruction of the insulin-producing beta cells of the pancreas by an autoimmune response. Due to ethical and practical difficulties, the features of the destructive process are known from a small number of observations, and transcriptomic data are remarkably missing. Here we report whole genome transcript analysis validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and correlated with immunohistological observations for four T1D pancreases (collected 5 days, 9 months, 8 and 10 years after diagnosis) and for purified islets from two of them. Collectively, the expression profile of immune response and inflammatory genes confirmed the current views on the immunopathogenesis of diabetes and showed similarities with other autoimmune diseases; for example, an interferon signature was detected. The data also supported the concept that the autoimmune process is maintained and balanced partially by regeneration and regulatory pathway activation, e.g. non-classical class I human leucocyte antigen and leucocyte immunoglobulin-like receptor, subfamily B1 (LILRB1). Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms.

Dendritic cells pulsed with antigen-specific apoptotic bodies prevent experimental type 1 diabetes.

Dendritic cells (DCs) are powerful antigen-presenting cells capable of maintaining peripheral tolerance. The possibility to generate tolerogenic DCs opens new therapeutic approaches in the prevention or remission of autoimmunity. There is currently no treatment inducing long-term tolerance and remission in type 1 diabetes (T1D), a disease caused by autoimmunity towards beta cells. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow islet regeneration. Apoptotic cells--a source of autoantigens--are cleared rapidly by macrophages and DCs through an immunologically silent process that contributes to maintaining tolerance. Our aims were to prevent T1D and to evaluate the re-establishment of peripheral tolerance using autologous DCs pulsed in vitro with apoptotic bodies from beta cells. Immature DCs derived from bone marrow of non-obese diabetic (NOD) mice were obtained and pulsed with antigen-specific apoptotic bodies from the beta cell line NIT-1. Those DCs that phagocytosed apoptotic cells diminished the expression of co-stimulatory molecules CD40 and CD86 and reduced secretion of proinflammatory cytokines. Moreover, these cells were resistant to increase the expression of co-stimulatory molecules after lipopolysaccharide activation. The administration of these cells to NOD transgenic mice expressing interferon-beta in their insulin-producing cells, a model of accelerated autoimmune diabetes, decreased diabetes incidence significantly and correlated positively with insulitis reduction. DCs pulsed with apoptotic cells that express disease-associated antigens constitutes a promising strategy to prevent T1D.

Endoscopist experience as a risk factor for colonoscopic complications.

AIM: We aimed to determine the incidence of colonic perforation (CP) following colonoscopy and postpolypectomy bleeding (PPB) in a teaching hospital, assessing the influence of endoscopist experience as a risk factor. METHOD: All colonoscopies performed between 1995 and 2008 were reviewed. Demographic data, endoscopic procedure information, incidence of CP and PPB, and endoscopist experience were recorded. RESULTS: In the 14-year period, 25,214 endoscopic colonic procedures were performed, and 3991 patients underwent polypectomy. The overall CP risk was 0.51/1000 procedures; and PPB 14.7/1000. The relative risk (RR) ratio of complications was 2.8/1000 procedures. The RR rate was highest for endoscopists performing less than 591 procedures per year (4.0/1000 [95% CI, 3.7-4.3] vs 2.9/1000 [95% CI, 2.6-3.2]), P < 0.001). CONCLUSION: The complication rate after colonoscopy was comparable to that previously reported. Colonoscopy carried out by a low-volume endoscopist was independently associated with bleeding and perforation.

Natural killer cells are required for accelerated type 1 diabetes driven by interferon-beta.

The destruction of beta cells by the islet infiltrating lymphocytes causes type 1 diabetes. Transgenic mice models expressing interferon (IFN)-beta in beta cells, in the non-obese diabetic (NOD) strain and in a diabetes-free, major histocompatibility complex-matched, homologous strain, the non-obese resistant (NOR) mice, developed accelerated type 1 diabetes after 3 weeks of age. Our aim was to determine if natural killer (NK) cells could affect the acceleration of the disease. We determined the amount of NK cells in the pancreas, spleen and lymph nodes from NOD rat insulin promoter (RIP)-IFN-beta mice. Pancreatic cytokines were assessed by quantitative real-time polymerase chain reaction and protein arrays. To confirm the relevance of NK cells in the acceleration of autoimmune diabetes this subset was depleted with anti-asialo GM1 antibodies. An increase of intrapancreatic NK cells characterized the accelerated onset of diabetes both in NOD and NOR RIP-IFN-beta transgenic models. Cytokines involved in NK function and migration were found to be hyperexpressed in the pancreas from accelerated diabetic mice. Interestingly, the depletion of NK cells in vivo abolished completely the acceleration of diabetes. NK cells connect innate to adaptive immunity and might play a role in autoimmunity. We report here that NK cells are required critically in the pancreas for accelerated diabetes. This model links inflammation to acceleration of beta cell-specific autoimmunity mediated by NK cells.

[Liver injury induced by "natural remedies": an analysis of cases submitted to the Spanish Liver Toxicity Registry]. / Hepatotoxicidad secundaria a "productos naturales": análisis de los casos notificados al Reigstro Español de Hepatotoxicidad.

BACKGROUND: toxic liver damage associated with the use of natural remedies is a growing health problem. OBJECTIVES: to analyze the demographics, and clinical and epidemiological characteristics of patients developing liver injury related to these remedies. PATIENTS AND METHODS: all DILI cases associated with the use of herbal remedies (HR) or dietary supplements (DS) submitted to the Spanish Registry were analyzed. Type of liver damage, severity, and outcome were specifically evaluated. RESULTS: thirteen cases out of 521 DILI cases (2%) submitted to the Spanish Liver Toxicity Registry between 1994 and 2006 were related to HR/DS, which ranked as the 10th therapeutic group with a greater number of cases and above pain killers, anxiolytics, and antipsychotic drugs. Nine patients (69%) were female (mean age 45 years). Nine cases (69%) had jaundice at presentation. The predominating type of liver damage was hepatocellular (12; 92%), and 31% of cases exhibited the common features of hypersensitivity. Camellia sinensis (3, 23%) was the main causative herb, followed by Rhamnus purshianus and isoflavones (Fitosoja(R), Biosoja(R)) (2 cases each, 15%). Three cases (23%) were rechallenged with the offending product. CONCLUSIONS: the incidence of hepatic damage related to HR/DS is not so rare, the most common profile of affected patients being a woman with acute hepatocellular hepatitis. Low suspicion regarding the putative role of herbs in hepatotoxicity makes diagnosis more difficult, and probably increases the incidence of inadvertent rechallenge in these patients.

Treatment of chronic he1patitis C genotype 1 with peginterferon-alpha2a (40 kDa) plus ribavirin under routine clinical practice in Spain: early prediction of sustained virological response rate.

BACKGROUND: Sustained virological response rates of up to 52% have been obtained with peginterferon alpha2a (40 kDa) plus ribavirin in patients suffering from chronic hepatitis C genotype 1 in randomized-controlled trials. AIM: To assess early virological response and its clinical utility in predicting an sustained virological response in patients suffering from chronic hepatitis C genotype 1 in routine clinical practice in Spain. METHODS: Treatment-naïve patients received pegylated interferon alpha2a (40 kDa) 180 microg/week plus ribavirin 1000/1200 mg/day for 48 weeks, and were followed for a further 24 weeks. Overall, 475 patients received at least one dose of medication and were included in the efficacy population. RESULTS: The overall sustained virological response rate was 48%. Of those with week 12 virological data, 83% had an early virological response. The negative predictive value of an early virological response was 93%. CONCLUSION: If sustained virological response is the goal, a treatment-decision based on a 12-week evaluation during routine clinical practice is feasible.

Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO).

BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis. AIM: To evaluate in the phase III, open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis. METHODS: Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed. RESULTS: Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91-100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients. CONCLUSIONS: Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807].

[Atypical presentation of distant metastases from hepatocarcinoma]. / Presentación atípica de metástasis a distancia de hepatocarcinoma.

Hepatocarcinoma (HCC) is the most frequent primary malignant hepatic tumour. These tumours usually develop in cirrhotic liver; for this reason, periodic screening using alphafetoprotein determination and abdominal ultrasonography is considered in cirrhotic patients with preserved hepatocellular function. This strategy allows early detection of HCC, increasing the proportion of curable tumours. The most frequent metastasic dissemination is portal vein neoplasic thrombosis, being unusual the occurrence of spread metastases in other organs. We present 3 cases of atypical HCC metastasis with non specific clinical manifestations which initial diagnosis was wrong. Because of a longer survival of these patients in recent years, spread metastasis might be considered in patients with known HCC and non specific symptoms.

[Gasometric alterations in hospitalized cirrhotic patients]. / Alteraciones gasométricas en pacientes cirróticos hospitalizados.

BACKGROUND AND OBJECTIVES: Gas exchange alterations have been described in cirrhotic patients; but by the moment, a few prospective studies have focused in them. The aim of this study was to describe the frequency and severity of gasometric alterations in hospitalized cirrhotic patients, a their correlation with hepatocellular disfunction. PATIENTS AND METHODS: 50 consecutive cirrhotic patients (41 males) admitted for liver decompensation (ascites, liver encephalopathy, alcoholic hepatitis and upper gastrointestinal bleeding) without acute or chronic cardiopulmonary disfunction were included in the study. Patients were classified according with Child-Pugh score (A, n = 13; B, n = 21; C, n = 16). Severe alcoholic hepatitis (SAH) was confirmed in 7 patients. Arterial gasometry was performed in all patients before discharge. Contrast echocardiography was performed in any case of suspicion of hepatopulmonary syndrome (HPS). RESULTS: Light hypoxemia was observed (80.9 mmHg), without differences with Child-Pugh. Hypocapnia was significantly more evident in Child C than in A and B (31.2 +/- 3.1 vs. 38.1 +/- 4.3 y 36.3 +/- 5 mmHg; p < 0,05), respectively. Cirrhotic patients with SAH showed a significantly higher hypocapnia by comparison with others (31.2 +/- 3.1 vs. a 36.3+/-5 mmHg; p < 0.05). In multivariate analysis, independent prognostic variables for hypocapnica were plasmatic levels of protrombin time, albumin and sodium. HPS was confirmed in 8 patients (16%). CONCLUSIONS: The most prevalent gas exchange abnormality in cirrhosis was the alteration of alveolar-arterial oxygen tension gradient, directly correlated with hepatocellur disfunction. Hypocapnia could be a compensatory mechanism or the result of the activation of central respiratory centres by non-depurated substances by the liver.

Diaphragmatic pressures: transvenous vs. direct phrenic nerve stimulation.

Diaphragmatic force, determined by stimulating the phrenic nerve while simultaneously measuring the pressures in a closed respiratory system, was assessed in five anesthetized dogs over a 5-h period to evaluate the inherent variability of this technique. Transdiaphragmatic pressure (Pdi) was measured at functional residual capacity during stimulation (120 Hz, 0.2-ms duration) of one phrenic nerve by either direct phrenic nerve stimulation (DPNS) or transvenous phrenic nerve stimulation (TPNS). An analysis of variance showed no significant (P greater than 0.50) change during the 5-h period. There was a significant correlation (r = 0.94, P less than 0.001) between Pdi obtained by TPNS and that obtained by DPNS. It is concluded that either DPNS or TPNS can be used to evaluate diaphragmatic strength over a 5-h period and that TPNS can be used in lieu of DPNS.

Impact of portacaval anastomosis on plasma fatty acid profile in cirrhosis: a randomized 24-month follow-up study.

BACKGROUND: Portacaval anastomosis has an hypolipemic effect in familial hypercholesterolemia and in healthy animals. In cirrhosis, it raises serum cholesterol, but there is no information on its effect upon plasma fatty acids. However, indirect data suggest that portacaval shunting might contribute to the polyunsaturated fatty acid deficit of these patients. We assessed the effect of portacaval anastomosis on plasma fatty acid profile in cirrhosis. METHODS: Forty-four Child-Pugh class A/B bleeding cirrhotics were randomized to be treated with portacaval anastomosis (n = 20) or nonsurgical therapy (n = 24). Fatty acid profile in plasma total lipids, alcohol intake, anthropometry, Child-Pugh score, serum cholesterol, triglycerides, and antioxidant micronutrients were assessed before and 3, 6, 12, 18, and 24 months after surgery or the start of nonsurgical therapy. Time course of plasma fatty acids was assessed using unbalanced repeated measures models with the above mentioned variables acting as covariates. RESULTS: No changes in the time course of percent plasma saturated, monounsaturated, and essential fatty acids were found between groups. Percent long-chain omega-6 and omega-3 polyunsaturated fatty acids decreased during follow-up in shunted patients compared with controls (p = .007 and p < .0005). However, this was not due to a true decrease in polyunsaturated fatty acid levels but to greater increases in saturated and monounsaturated fatty acid concentrations in shunted patients compared with control patients (p = .047 and p = .006). CONCLUSIONS: Portacaval anastomosis does not worsen plasma polyunsaturated fatty acid deficiency in cirrhosis. However, by increasing saturated and monounsaturated fatty acids, it further decreases plasma lipid unsaturation.

Plasma polyunsaturated fatty acids in liver cirrhosis with or without chronic hepatic encephalopathy: a preliminary study.

Fatty acid levels (from C14:0 to C22:6n3) in plasma lipid fractions were prospectively studied in 11 cirrhotic patients with chronic hepatic encephalopathy and compared with those in 23 cirrhotic patients without chronic hepatic encephalopathy with similar age, sex distribution, and liver and nutritional status, and in 11 age- and sex-matched, healthy subjects. Plasma lipid fractions were separated by thin-layer chromatography and fatty acids were identified by capillary column gas-liquid chromatography. Total n6 polyunsaturated fatty acid plasma levels were lower in cirrhotic patients--with and without chronic hepatic encephalopathy--than in control subjects. In addition, arachidonic acid levels, both in total lipids and fractions, were lower in patients with than in those without chronic encephalopathy. On the other hand, a selective decrease of plasma docosahexaenoic acid (a major component of neuronal membranes) was observed in those patients with chronic encephalopathy as compared with both control and cirrhotic subjects without chronic encephalopathy. These findings may be due to various mechanisms. Differences in long-chain polyunsaturated fatty acid content in fish- and meat-restricted diets partly may account for these findings. However, it could be speculated that polyunsaturated fatty acid biosynthesis may be reduced further in patients with chronic hepatic encephalopathy because of either a decrease in portal essential fatty acid extraction in the postabsorptive phase due to portal-systemic shunting or to the effect of protein-restricted diets. Furthermore, the finding of low plasma docosahexaenoic acid in these patients raises the possibility that this deficiency might be an additional pathogenic factor in chronic hepatic encephalopathy.

Occult liver involvement by polyarteritis nodosa.

The diagnosis of panarteritis nodosa is usually difficult because of the variability of clinical manifestations. Herein is presented a case of occult liver involvement by polyarteritis nodosa. Several biopsies were performed but the diagnosis was made with the contribution of a hepatic arteriography.

Dualism and uniformism in sleep.

The phenomenological evidence for distinguishing between REM and NREM sleep is overwhelming. However, this difference has only been found thanks to electrophysiological analytical methods, and is practically non existent in phenotypic terms, i.e., observable with the naked eye. It is well accepted that the selective pressure determining evolutionary changes can only work upon phenotypic differences. Hence, it follows that the differences between REM and NREM could not have been selected through evolution and this implies that, in functional terms, both states could be equivalent.

[Pseudotumorous hyperplasia of the caudate lobe of the liver in a patient with Alagille syndrome]. / Hiperplasia seudotumoral del lóbulo caudado del hígado en una paciente con síndrome de Alagille.

The Alagille's syndrome consists in hypoplasia of the intrahepatic biliary ducts associated to congenital abnormalities of different organs. It is usually diagnosed in infancy due to cholestasis with good prognosis. The case of a 31-year old women who presented prominent chin, micrognathia, flattening of the nasal bone, infundibular stenosis of the pulmonary artery and cholestasis is reported. Ultrasonography demonstrated a lesion in the space of the hepatic caudate lobe with punction showing sinusoidal dilatation and infiltration of some portal spaces by lymphocytes, eosinophils and neutrophils. Samples of liver tissue obtained during laparotomy showed an absence of intrahepatic biliary ducts in the right and left lobes and preservation of those of the caudate lobe, which was also increased in size with a pseudotumoral appearance. The patients was asymptomatic with slight anicteric cholestasis at 16 months of diagnosis. The rarity of these forms of Alagille's syndrome with areas free of hypoplasia of the intrahepatic biliary ducts are of note.

[Prophylactic sclerosis of esophageal varices. Results of a controlled prospective study]. / Esclerosis profiláctica de varices esofágicas. Resultados de un estudio prospectivo controlado.

BACKGROUND: Endoscopic sclerosis of esophageal varices is effective both to treat active hemorrhage and to prevent recurrences. By contrast, its usefulness for the prophylaxis of the first episode of hemorrhage is not well established, the available data being contradictory. METHODS: Overall 46 patients with cirrhosis and esophageal varices of type B or higher, without previous upper gastrointestinal hemorrhage, were randomized to be treated with prophylactic sclerosis or not (n = 22 and 24, respectively). Both groups were comparable in age, sex, etiology of cirrhosis (mainly alcoholic), Child's degree of hepatic failure, coagulation studies, laboratory data and endoscopic findings. RESULTS: In a mean follow up of 16 months, the patients treated with sclerosis had a higher frequency of hemorrhage from gastroesophageal varices (27%) than those in the control group (8%) (n.s.). However, this difference reached significance (p = 0.02) when only patients from Child's classes A and B were considered (31% in the sclerosis group vs 5% in the control group). The mortality rate was similar in both groups, with a probability of one year survival of 80 and 76% in the sclerosis and control groups, respectively. CONCLUSIONS: The results indicate that prophylactic sclerotherapy does not improve short-term survival or reduce the risk of a first hemorrhage due to gastroesophageal varices of type B or higher in hepatic cirrhosis. It may even facilitate the development of this severe complication in Child's A and B class patients.