Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver.

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.

The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease.

The Latin American Association for the Study of the Liver (Asociación Latinoamericana para el Estudio del Hígado; ALEH) represents liver professionals in Latin America with the mission of promoting liver health and quality patient care by advancing the science and practice of hepatology and contributing to the development of a regional health policy framework. Fatty liver disease associated with metabolic dysfunction is of specific concern in the ALEH region, where its prevalence is one of the highest globally, second only to the Middle East. A recent consensus from an international panel recommended a new definition of fatty liver disease associated with metabolic dysfunction, including a shift in name from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), and adoption of a set of positive criteria to diagnose the disease, independent of alcohol intake or other liver diseases. Given, the importance of this proposal, ALEH invited leading members of regional nations to come to a consensus on it from a local perspective. We reached a consensus to endorse the proposal that the disease should be renamed as MAFLD and that the disease should be diagnosed by the proposed simple and easily applicable criteria. We expect that this change in nosology will result in improvements in disease awareness and in advances in scientific, economic, public health, political, and regulatory aspects of the disease.

Sorafenib treatment by Child-Pugh score in Latin American patients with hepatocellular carcinoma.

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child-Pugh status. Results: Of 90 evaluable patients (37% Child-Pugh A, 46% Child-Pugh B and 3% Child-Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child-Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child-Pugh A (21% grade 3/4) and 46% with Child-Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child-Pugh A and B and is a treatment option for both groups.

Genetic diversity of hepatitis B virus and mutations associated to hepatocellular carcinoma in patients from Venezuela, with different stages of liver disease.

Globally, about 50% of liver cancer originates as a result of long term infection with hepatitis B virus (HBV), and some genotypes and mutations have been associated with an increased severity of infection. The aim of this study was to evaluate the genetic diversity of HBV in patients from Venezuela, with chronic infection, cirrhosis and hepatocellular carcinoma (HCC) and to compare the occurrence of mutations in all patient groups. Samples from patients with different pathologies of the liver, associated with HBV infection, were collected. The HBV S region was analyzed for genotype determination and, when available, the whole genome sequence was examined for mutations analysis. Genotype F was the most common genotype (87%). While the HBV subgenotype F3 was the most frequent genotype in the whole group of samples (44%), the subgenotype F2 predominated in HCC patients (56%). Mutations were more common in HCC and cirrhosis cases (p=0.01). The A1762T mutation was significantly associated with the advanced stage of liver disease (p=0.008). Additionally, mutations were more common in early stages of liver disease in HBV subgenotype F2-infected patients, and a significant association between this subgenotype and the emergence of T 1753C, A1762T, A1762T/G1764A (p=0.04) and C1773T (p=0.001) mutations in chronic patients was found, when compared to the HBV subgenotype F3. By comparing F2 with all other HBV subgenotypes, a positive association for the three basal core promoter (BCP) mutants (A1762T, A1762T/G1764A p=0.01, G1764A p=0.04) was found. These results suggest that the HBV subgenotype F2 might be associated to more severe forms of liver disease in comparison with the HBV subgenotype F3.

Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: The GIDEON study.

BACKGROUND & AIMS: GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) is a prospective, observational registry study evaluating the safety of sorafenib and treatment practices in hepatocellular carcinoma patients. This large global database allowed for assessment of the use and tolerability of sorafenib in patients with liver dysfunction. METHODS: Baseline characteristics and medical/treatment history were collected in patients for whom a decision to treat with sorafenib had been made. Adverse event, dosing, and outcomes data were collected during follow-up. RESULTS: In the overall safety population (n=3202), 1968 patients (61%) had Child-Pugh A status and 666 (21%) had Child-Pugh B. The majority of Child-Pugh A (72%) and Child-Pugh B (70%) patients received an initial sorafenib dose of 800mg, consistent with the label, and dose reduction rates were 40% and 29%, respectively. The type and incidence of adverse events were generally consistent across Child-Pugh subgroups. The incidence of drug-related adverse events leading to discontinuation was similar between Child-Pugh A and Child-Pugh B patients (17% and 21%). In the intent-to-treat population (n=3213), median overall survival (months [95% confidence interval]) was longer in Child-Pugh A patients (13.6 [12.8-14.7]) compared with Child-Pugh B patients (5.2 [4.6-6.3]). CONCLUSIONS: In clinical practice, the safety profile of sorafenib appeared to be consistent across Child-Pugh A and Child-Pugh B patients. Findings suggest sorafenib may be safely used in some Child-Pugh B patients and indicate the importance of careful patient evaluation when making treatment decisions. LAY SUMMARY: The GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) study is a large prospective registry of patients with liver cancer who were treated with sorafenib. The aims were to evaluate the safety and tolerability of sorafenib among those in which the liver was not functioning properly. The study showed that the safety profile of sorafenib was consistent across patients with preserved liver function and those in which the liver was not functioning properly, and therefore, suggesting that sorafenib may be a valid treatment for some patients with liver impairment.

Genetic diversity of hepatitis B virus and mutations associated to hepatocellular carcinoma in patients from Venezuela, with different stages of liver disease / Diversidad genética del virus de la hepatitis B y mutaciones asociadas con carcinoma hepatocelular en pacientes de Venezuela, con diferentes estados de la enfermedad del hígado

Globally, about 50% of liver cancer originates as a result of long term infection with hepatitis B virus (HBV), and some genotypes and mutations have been associated with an increased severity of infection. The aim of this study was to evaluate the genetic diversity of HBV in patients from Venezuela, with chronic infection, cirrhosis and hepatocellular carcinoma (HCC) and to compare the occurrence of mutations in all patient groups. Samples from patients with different pathologies of the liver, associated with HBV infection, were collected. The HBV S region was analyzed for genotype determination and, when available, the whole genome sequence was examined for mutations analysis. Genotype F was the most common genotype (87%). While the HBV subgenotype F3 was the most frequent genotype in the whole group of samples (44%), the subgenotype F2 predominated in HCC patients (56%). Mutations were more common in HCC and cirrhosis cases (p=0.01). The A1762T mutation was significantly associated with the advanced stage of liver disease (p=0.008). Additionally, mutations were more common in early stages of liver disease in HBV subgenotype F2- infected patients, and a significant association between this subgenotype and the emergence of T1753C, A1762T, A1762T/G1764A (p=0.04) and C1773T (p=0.001) mutations in chronic patients was found, when compared to the HBV subgenotype F3. By comparing F2 with all other HBV subgenotypes, a positive association for the three basal core promoter (BCP) mutants (A1762T, A1762T/G1764A p=0.01, G1764A p=0.04) was found. These results suggest that the HBV subgenotype F2 might be associated to more severe forms of liver disease in comparison with the HBV subgenotype F3.

Mundialmente, alrededor del 50% del cáncer de hígado se origina como consecuencia de la infección a largo plazo con el virus de la hepatitis B (VHB), y algunos genotipos y mutaciones han sido asociados con severidad incrementada de la infección. El objetivo de este estudio fue evaluar la diversidad genética del VHB en pacientes de Venezuela con infección crónica, cirrosis y carcinoma hepatocelular (CHC) y comparar la ocurrencia de mutaciones en los tres grupos de pacientes. Se reunieron muestras de pacientes con diferentes patologías de la enfermedad del hígado asociada a la infección por VHB. La región S del VHB fue analizada para la determinación del genotipo y cuando estuvo disponible, la secuencia del genoma completo fue examinada para análisis de mutaciones. El genotipo F de VHB fue el más frecuente (87%). Mientras que el F3 fue el subgenotipo más encontrado en el grupo completo de muestras (44%), el F2 fue predominante en pacientes con CHC (56%). Las mutaciones fueron más comunes en casos de pacientes con cirrosis y CHC (p=0,01). La mutación A1762T estuvo asociada significativamente con estado avanzado de la enfermedad del hígado (p=0,008). Adicionalmente, las mutaciones fueron más comunes en estados tempranos de la enfermedad del hígado en pacientes infectados con el subgenotipo F2, encontrándose una asociación significativa entre este subgenotipo y la ocurrencia de las mutaciones T1753C, A1762T, A1762T/ G1764A (p=0,04) y C1773T (p=0,001) en pacientes crónicos, en comparación con el subgenotipo F3. Por otro lado, al comparar F2 con los demás subgenotipos de VHB, se encontró una asociación positiva para las tres mutantes del promotor basal de la cápside (PBC) (A1762T, A1762T/G1764A p=0,01, G1764A p=0,04). Estos resultados sugieren que el subgenotipo F2 de VHB puede estar asociado a formas más severas de la enfermedad del hígado en comparación al subgenotipo F3.

Regional differences in sorafenib-treated patients with hepatocellular carcinoma: GIDEON observational study.

BACKGROUND & AIMS: Treatment approaches for hepatocellular carcinoma (HCC) vary across countries, but these differences and their potential impact on outcomes have not been comprehensively assessed. Data from the multinational GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) registry evaluated differences in patient characteristics, practice patterns and outcomes in HCC across geographical regions in patients who received sorafenib. METHODS: GIDEON is a non-randomised, observational registry study conducted in 39 countries across five global regions. HCC patients in whom a decision to treat with sorafenib was made in clinical practice and according to local practices were included. RESULTS: 3202 patients were evaluable for safety analysis: Asia-Pacific (n = 928), Japan (n = 508), Europe (n = 1113), USA (n = 563) and Latin America (n = 90). Patients in Japan had earlier-stage disease at initial diagnosis compared with patients in other regions (Barcelona Clinic Liver Cancer stage A; 43.7% vs 9.1-24.3%). Use of locoregional therapies before sorafenib, including transarterial chemoembolisation, was more common in Japan (84.4%) and Asia-Pacific (67.2%) compared with the USA (49.4%) and Europe (43.5%). Treatment patterns with respect to sorafenib also differed, with a shorter duration of treatment reported in the USA and Asia-Pacific. Time from initial diagnosis to death was longer in Japan compared with other regions (median, 79.6 months vs 14.8-25.0 months). CONCLUSIONS: Data from GIDEON highlight regional variations in the management of HCC and patient outcomes. Greater standardisation of management may help optimise outcomes for HCC patients.

TACE Treatment in Patients with Sorafenib-treated Unresectable Hepatocellular Carcinoma in Clinical Practice: Final Analysis of GIDEON.

PURPOSE: To evaluate transarterial chemoembolization (TACE) use prior to and concomitantly with sorafenib in patients with unresectable hepatocellular carcinoma (HCC) across different global regions. MATERIALS AND METHODS: GIDEON is an observational registry study of more than 3000 HCC patients. Patients with histologically, cytologically, or radiographically diagnosed HCC, and for whom a decision had been made to treat with sorafenib, were eligible. Patients were enrolled into the registry from 39 countries beginning in January 2009, with the last patient follow-up in April 2012. Detailed data on treatment history, treatment patterns, adverse events, and outcomes were collected. All treatment decisions were at the discretion of the treating physicians. Documented approval from local ethics committees was obtained, and all patients provided signed informed consent. Descriptive statistics, including minimum, median, and maximum, were calculated for metric data, and frequency tables for categorical data. Kaplan-Meier estimates with 95% confidence intervals were calculated for survival end points. RESULTS: A total of 3202 patients were eligible for safety analysis, of whom 2631 (82.2%) were male. Median age was 62 years (range, 15-98 years). A total of 1511 (47.2%) patients underwent TACE prior to sorafenib; 325 (10.1%) underwent TACE concomitantly. TACE prior to sorafenib was more common in Japan and Asia-Pacific compared with all other regions (362 [71.3%] and 560 [60.3%] vs 12-209 [13.3%-37.1%]). Adverse events were reported in 2732 (85.3%) patients overall, with no notable differences in the incidence of adverse events, regardless of TACE treatment history. Overall survival was 12.7 months in prior-TACE patients, 9.2 months in non-prior-TACE patients, 21.6 months in concomitant-TACE patients, and 9.7 months in non-concomitant-TACE patients. CONCLUSION: Global variation exists in TACE use in sorafenib-treated HCC patients. The combination of TACE with sorafenib appears to be a well-tolerated and viable therapeutic approach.

Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

Trends and projections of hepatitis C virus epidemiology in Latin America.

BACKGROUND AND AIM: The purpose of the present investigation is to provide an analysis of previous works on the epidemiology of the hepatitis C virus (HCV) infection from six countries throughout Latin America, to forecast the future HCV prevalence trends in Argentina, Brazil, Mexico and Puerto Rico, and to outline deficiencies in available data, highlighting the need for further research. METHODS: Data references were identified through indexed journals and non-indexed sources. Overall, 1080 articles were reviewed and 150 were selected based on their relevance to this work. When multiple data sources were available for a key assumption, a systematic process using multi-objective decision analysis (MODA) was used to select the most appropriate sources. When data were missing, analogues were used. Data from other countries with similar risk factors and/or population compositions were used as a proxy to help predict the future trends in prevalence. RESULTS: The review indicates that the dominant genotype is type 1. HCV prevalence in the analysed countries ranges from 1 to 2.3%. The Latin American countries have been very proactive in screening their blood supplies, thus minimizing the risk of transmission through transfusion. This suggests that other risk factors are set to play a major role in continued new infections. The number of diagnosed and treated patients is low, thereby increasing the burden of complications such as liver cirrhosis or hepatocellular carcinoma. The HCV prevalence, according to our modelling is steady or increasing and the number of infected individuals will increase. CONCLUSIONS: The results herein reported should provide a foundation for informed planning efforts to tackle hepatitis.

Treatment of intermediate/advanced hepatocellular carcinoma in the clinic: how can outcomes be improved?

Hepatocellular carcinoma (HCC) is a complex condition associated with a poor prognosis. Treatment outcomes are affected by multiple variables, including liver function, performance status of the patient, and tumor stage, making a multidisciplinary approach to treatment essential for optimal patient management. Only ∼30% of patients are eligible for curative therapies (surgery or ablation); palliative treatments include transcatheter arterial chemoembolization (TACE) and sorafenib. Treatment choice is guided by staging systems and treatment guidelines, although numerous systems exist and treatment guidelines vary by region. The current standard of care for patients unsuitable for potentially curative therapy is locoregional therapy with TACE. This treatment is associated with survival benefits, but there is no consensus regarding the optimum treatment/retreatment strategy. For patients with more advanced disease or who have failed locoregional therapy, sorafenib is the standard of care. Sorafenib is a targeted agent with proven survival benefits as monotherapy in these patients, and ongoing studies will clarify its role in combination with other agents and in patients with impaired liver function. Although other novel agents and therapeutic approaches are emerging, such as radioembolization and various targeted agents, further suitably designed randomized clinical trials (RCTs) comparing these agents with the standard of care are needed. In addition to RCTs, the collection of real-life data will also be important to allow physicians to make fully informed treatment decisions. The Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study is a global, noninterventional study of patients with unresectable HCC receiving sorafenib. The aim of that study is to compile a large robust database to evaluate local, regional, and global factors influencing the management of patients with HCC. It is hoped that findings from the GIDEON study along with phase III RCT data will lead to better outcomes for patients with intermediate-advanced HCC.

Genotype F prevails in Venezuelan urban patients with chronic hepatitis B.

Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H). Genotypes A, D and F have been identified in some South American countries, but in Venezuela studies have been more restricted to aboriginal communities where genotype F is predominant. The aim of the present study was to identify the prevalence of HBV genotypes among native HBsAg carriers in Venezuelan urban areas. In addition, we correlated the predominant HBV genotype with epidemiological, serological and virological features of the infection. Non-Venezuelan migrant patients were excluded from this study. Serum samples from 90 patients (21 children and 69 adults) with chronic hepatitis B (CHB) were analyzed. Seventy-four patients had CHB e-antigen positive and 16 CHB e-antigen negative. HBV DNA serum levels of the whole group ranged from 4.1 to 8.8 log10 IU/mL. Patients with CHB e-antigen positive showed significantly higher viral loads (P = 0.0001) than the group with CHB e-antigen negative. Eighty-eight patients (97.8%) exhibited HBV genotype F while two non-related patients (2.2%) were infected with A + F genotypes. Genotype F is the main circulating HBV strain among HBsAg carriers from Venezuelan urban areas. This genotype is associated mostly with CHB eantigen positive and high rate of transmission. Progression to cirrhosis and hepatocellular carcinoma could be major clinical events of this patient population independently of age at acquisition or transmission route.

Experiencia clínica con Telbivudina en Hepatitis crónica B en Venezuela

De acuerdo a consensos científicos a nivel internacional el objetivo primordial en el tratamiento de la hepatitis crónica B (HCB) es actualmete lograr la supresión de la replicación viral de manera potente y en el menor tiempo posible. A continuación presentamos la experiencia clínica acumulada en Venezuela empleando el análogo nucleosido telbivudina en pacientes con HCB. Se analizaron 29 portadores con HCB, promedio de edad 44±17 años, con una proporción 2/1 sexo masculino/sexo femenino, 23 con HCB antígeno e positivo y 6 con HCB antígeno e negativo. Las variables escogidas de evaluación fueron la viremia (ADN VHB), el valor de ALT y la tolerancia al tratamiento. Durante un período promedio de tratamiento de 7,3 meses cada paciente recibió 600 mg diarios de telbivudina. 86,2% de ellos disminuyó significativamente la carga circulante de ADN VHB de 7,3±1,2 log10 copias/mL a 1,9±1,0 log10 copias/mL (p= 0,0001). Adicionalmente, se demostró disminución significativa de los valores de ALT, de un promedio de 4,3 veces a una media de 1,4 veces el límite superior normal (p=0,01). Exceptuando un paciente con elevación importante de creatin-quinasa y otro que se quejó de sensación de acidez, la tolerancia reportada fue muy buena. Es concluyente que la telbivudina indujo supresión de la carga viral en forma potente y temprana tanto en pacientes con HCB antígeno e positivo como antígeno e negativo, mejoró los valores de ALT y fue bien tolerada la dosis por la mayoría. La reducción de la carga viral a niveles incluso indetectables durante el primer año de tratamiento, debería contribuir a prevenir la emergencia temprana de cepas del VHB resistentes a esta droga antiviral.

According to international scientific consensus, the fundamental goal in the treatment of chronic hepatitis B (CHB) is currently to achieve suppression of the viral replication in a very potent way at the shortest possible time. It follows our clinical experience accomplished in Venezuela by using the nucleoside analog telbivudine in patients with CHB. We studied twenty-nine carriers with CHB, mean age of 44±17 years old, male/female ratio 2/1, 23 of them with e antigen positive CHB and the remaining 6 with e antigen negative CHB. We selected the viral load (HBV DNA), the ALT value and the treatment tolerance as the parameters to be assessed. During an average treatment period of 7,3 months each patient received 600 mg daily of telbivudine. 86.2% of them showed significant decreased of the circulating HBV DNA load, from 7.3±1.2 log10 copies/mL to 1.9±1.0 log10 copies/mL (p= 0.0001). In addition, a significant decrease of ALT values from a mean of 4.3 fold to 1.4 fold (p=0.01) was also demonstrated. The group of patients showed very good tolerance of the doses, except one who presented increased creatine kinase value and another one who complained from peptic symptoms. It is conclusive that Telbivudine induced early and potent viral suppression, either in e antigen positive or e antigen negative CHB, improved the ALT values and was very well-tolerated by the majority. The viral load reduction, even undetectable during the first year of treatment, should contribute to prevent the early emergency of resistant strains to this antiviral drug.

Correlación entre el diámetro de la vena porta, recuento plaquetario y tiempo de protrombina en el diagnóstico de várices esofágicas en pacientes con enfermedad hepática crónica del Hospital de Lídice durante el período Enero 2002- Marzo 2007

Estudios recientes han reportado alternativas diagnósticas no invasivas para Várices Esofágicas (VE), identificando factores pronósticos como: bajo recuento plaquetario, esplenomegalia, diámetro de la vena porta aumentado, disminución de la actividad de protrombina (PT) y una clasificación avanzada de Child-Pugh. Objetivo: determinar la relación entre diámetro de vena porta, recuento plaquetario y PT como valores predictivos negativos para la presencia de VE. Metodología: Se realizó un estudio retrospectivo de pacientes con enfermedad hepática crónica y diagnóstico endoscópico de várices esofágicas (VE), correlacionándolos con diámetro de la vena porta, recuento plaquetario y tiempo de protrombina (PT), en el Servicio de Gastroenterología del Hospital "Jesús Yerena" de Lídice; enero 2002 marzo 2007. Resultados: El diámetro de la vena porta osciló entre 8,00 y 20,00mm, recuento plaquetario entre 44,000 y 650,000 por mm y el diferencial de PT se encontró entre 0,00 y 12,30 segundos. El diagnóstico endoscópico de VE mas frecuente fue el grado II con un 58,00%, relacionado con una media de diámetro de vena porta de 12,21mm, recuento plaquetario de 151,18mm y PT de 1,36 segundos. Discusión: Se encontró una relación directamente proporcional entre el diámetro de vena porta y grado de VE, e inversamente proporcional con respecto al recuento plaquetario y PT.

Recent studies have reported non invasive diagnostic alternatives for Esophageal Varices (EV), identifying prognostic factors such as: low platelet count, enlarged spleen, augmented portal vein diameter, diminished prothrombin activity level (PT), and an advanced Child-Pugh classification. Objectives: to determine the relationship between portal vein diameter, platelet count and PT as negative predictors for the presence of EV. Methods: A retrospective study was carried out among patients with chronic hepatic disease and endoscopic diagnosis of EV, correlating portal vein diameter, platelet count and PT, at the Gastroenterology Service, Hospital of Lídice; between January 2002 and March 2007. Results: The diameter of the portal vein ranged from 8, 00 to 20, 00 mm; the platelet count between 44,000 and 650,000 mm and the difference between the PT varied from 0, 00 secs and 12, 30 secs. The most frequent endoscopic diagnosis of EV was grade II (58%), related with a mean portal vein diameter of 12, 21 mm, platelet count of 151,18mm and PT of 1, 36 secs. Discussion: we found a direct proportional relationship between portal vein diameter and the grade of EV, and an inversely proportional relationship with platelet count and PT.

Correlación entre el diámetro de la vena porta, recuento plaquetario y tiempo de protrombina en el diagnóstico de várices esofágicas en pacientes con enfermedad hepática crónica del Hospital de Lídice durante el período Enero 2002- Marzo 2007

Estudios recientes han reportado alternativas diagnósticas no invasivas para Várices Esofágicas (VE), identificando factores pronósticos como: bajo recuento plaquetario, esplenomegalia, diámetro de la vena porta aumentado, disminución de la actividad de protrombina (PT) y una clasificación avanzada de Child-Pugh. Objetivo: determinar la relación entre diámetro de vena porta, recuento plaquetario y PT como valores predictivos negativos para la presencia de VE. Metodología: Se realizó un estudio retrospectivo de pacientes con enfermedad hepática crónica y diagnóstico endoscópico de várices esofágicas (VE), correlacionándolos con diámetro de la vena porta, recuento plaquetario y tiempo de protrombina (PT), en el Servicio de Gastroenterología del Hospital "Jesús Yerena" de Lídice; enero 2002 marzo 2007. Resultados: El diámetro de la vena porta osciló entre 8,00 y 20,00mm, recuento plaquetario entre 44,000 y 650,000 por mm? y el diferencial de PT se encontró entre 0,00 y 12,30 segundos. El diagnóstico endoscópico de VE mas frecuente fue el grado II con un 58,00%, relacionado con una media de diámetro de vena porta de 12,21mm, recuento plaquetario de 151,18mm? y PT de 1,36 segundos. Discusión: Se encontró una relación directamente proporcional entre el diámetro de vena porta y grado de VE, e inversamente proporcional con respecto al recuento plaquetario y PT.

Recent studies have reported non invasive diagnostic alternatives for Esophageal Varices (EV), identifying prognostic factors such as: low platelet count, enlarged spleen, augmented portal vein diameter, diminished prothrombin activity level (PT), and an advanced Child-Pugh classification. Objectives: to determine the relationship between portal vein diameter, platelet count and PT as negative predictors for the presence of EV. Methods: A retrospective study was carried out among patients with chronic hepatic disease and endoscopic diagnosis of EV, correlating portal vein diameter, platelet count and PT, at the Gastroenterology Service, Hospital of Lídice; between January 2002 and March 2007. Results: The diameter of the portal vein ranged from 8, 00 to 20, 00 mm; the platelet count between 44,000 and 650,000 mm? and the difference between the PT varied from 0, 00 secs and 12, 30 secs. The most frequent endoscopic diagnosis of EV was grade II (58%), related with a mean portal vein diameter of 12, 21 mm, platelet count of 151,18mm? and PT of 1, 36 secs. Discussion: we found a direct proportional relationship between portal vein diameter and the grade of EV, and an inversely proportional relationship with platelet count and PT.

ación del child-pugh y sodio sérico en pacientes con diagnóstico de cirrosis hepática en el servicio de gastroenterología Dr. Alí Rivas. Hospital Jesús Yerena, Lídice: Años 2002-2006

La clasificación de Child-Pugh mide la severidad de la enfermedad hepática crónica en pacientes con cirrosis hepática. El nivel de sodio (Na) sérico en estos pacientes disminuye a medida que progresa la enfermedad hepática. Objetivo: determinar la relación de la severidad de la enfermedad hepática crónica medida con la escala de Child-Pugh, con el nivel de sodio sérico. Metodología: se realizó un estudio retrospectivo descriptivo, analizando las historias clínicas de los pacientes evaluados en las consultas externas y hospitalizados en el servicio de Gastroenterología del Hospital "Jesús Yerena" de Lídice entre los años 2002 y 2006. Se calculó el puntaje de Child-Pugh a cada paciente, y luego se relacionó con los valores séricos de Na. Resultados: se hallaron 12 pacientes (24,49%) en la categoría Child- Pugh A, 21 (42,86%) clase B, y 16 (32,65%) clase C. Se encontró una relación inversa en cuanto al nivel sérico de Na y el puntaje de Child-Pugh. Conclusión: La severidad de la enfermedad hepática crónica, medida por la escala Child-Pugh, es inversamente proporcional con en nivel de Na sérico de estos paciente.

The Child-Pugh classification assesses the severity of chronic hepatic disease in patients with hepatic cirrhosis. Serum sodium level in these patients decreases along with the severity of the hepatic disease. Objective: to determine the relationship between the severity of chronic hepatic disease, measured with the Child-Pugh scale, and serum sodium levels. Methods: we made a retrospective descriptive study, analyzing the clinical history of outpatients and hospitalized patients of the Gastroenterology Service of "Jesús Yerena Hospital of Lidice" between 2002 and 2006. We calculated the Child-Pugh scale of each patient, and then correlated it to serum sodium levels. Results: we found 12 patients (24, 49%) in the Child- Pugh A category, 21 (42, 86%) in the class B category, and 16 (32, 65%) in the class C category. They all had an inverse relationship with serum sodium levels. Conclusion: the severity of chronic hepatic disease, measured in the Child-Pugh scale, is inversely proportional to the serum sodium level in these patients.

Genetic contribution of major histocompatibility complex class II region to type 1 autoimmune hepatitis susceptibility in Venezuela.

AIMS: Autoimmune hepatitis (AIH) is a progressive liver disease characterized by the presence of circulating autoantibodies, hypergammaglobulinaemia and a favourable response to immunosuppressive treatment. Although the pathogenesis of type 1 AIH is unknown, disease susceptibility is partially determined by genes linked to the class II region of the major histocompatibility complex. Type 1 AIH has been associated with DRB1*03, DRB1*04 and DRB3 alleles in European and North American Caucasians, with DRB1*0405 in Japanese, with DRB1*0404 in Mexican, and with DRB1*1301 in Argentinean populations. METHODS: To analyse the molecular basis of these associations in Venezuela (mestizo population), we examined the frequency of human leucocyte antigens (HLA)-A -B -C, HLA-DQ and HLA-DR genes by low- and high-resolution oligonucleotide typing in a population of 41 type 1 AIH patients and 111 ethnic- and aged-matched healthy subjects. RESULTS: The frequencies of both DRB1(*)1301 (P<0.0001) and DRB1*0301 (P<0.005) were significantly higher in patients than in controls. In addition, patients showed a strong association with the DRB3 allele (P<0.01). In contrast, the DQB1*04 allele was significantly decreased in the patient group (P<0.01). The frequencies of haplotypes A*01-B*08-DQB1*02-DRB1*03-DRB3, DQB1*05-DRB1*1301, DQB1*06-DRB1*1301 and A*02-DRB1*1301, B*45-DRB3 were significantly increased in type 1 AIH patients compared with the controls (P<0.01). CONCLUSIONS: In conclusion, our data indicate that type 1 AIH predisposition in a Venezuelan mestizo population of different ethnic backgrounds is associated with DRB1*1301 and DRB1*0301 alleles. In addition, our findings suggest that protection against disease might be conferred by the DQB1*04 allele, with distinct ethnic differences from other populations.

Eficacia del mofetil micofenolato en el tratamiento de la hepatitis autoinmune en pacientes resistentes o intolerantes a tratamiento convencional

Evaluar la eficacia del Mofetil Micofenolato (MMF) como opción terapéutica en pacientes con Hepatitis Autoinmune (HAI), que no responden o no toleran la prednisona y/o azatioprina. Pacientes y métodos: se evaluaron 6 pacientes con diagnóstico de HAI tipo 1, entre 36 a 61 años, quienes fueron tratados inicialmente con Azatioprina sola o combinada con esteroides sin respuesta bioquímica, o con intolerancia a estos medicamentos. Se administró 1 g B.I.D a todos los pacientes, 2 pacientes recibieron sólo MMF y 4 pacientes recibieron esteroides a dosis mínimas y MMF. Se evaluó el efecto del MMF en el valor de las enzimas hepáticas (AST y ALT), de la bilirrubina y en la concentración de inmunoglobulina G (IgG), los cuales se determinaron después del inicio del MMF cada 3 a 6 meses. Los pacientes fueron evaluados durante 27-19 meses. Resultados: los valores de AST, ALT mejoraron de 3 a 26 veces en los 6 pacientes y se normalizaron en 3 pacientes; la bilirrubina y la concentración de IgG disminuyeron de 1 a 5 veces su valor en los 6 pacientes. Conclusiones: el MMF en HAI, solo o en combinación con esteroides resulta eficaz para el control de la inflamación hepática demostrado por la mejoría de los parámetros bioquímicos y disminución de IgG, por lo que puede ser una alternativa para el tratamiento de pacientes seleccionados con HAI.

To assess the value of mycophenolate mofetil (MMF) as a therapeutic option in patients with autoimmune hepatitis (AIH), who did not respond or not tolerate prednisone and/or azathioprine. Patients and methods: Six patients with AIH were studied; age range between 36 and 61 years old, were evaluated. Initial treatment in all patients was azathioprine alone or combined with prednisone who did not demonstrate biochemical response or patients who could not tolerate this former treatment. All patients received MMF 2 g/day, 2 patients received MMF alone and 4 patients received minimal doses of steroids and MMF. Endpoints were normalization or improvement in liver function tests and immunoglobulin G (IgG) concentration. Patients were followed-up after they started treatment with MMF every 3 months during 27 μ19 months. Results: AST and ALT levels improved in 6 patients 3 to 26 times their value, and normalized in 3 patients; bilirrubin and IgG were in the normal range after treatment in all patients. Conclusions: MMF in AIH was effective and well tolerated and all patients showed improvement in liver function test (AST, ALT, and TB) and normalization of IgG. MMF seems to be an alternative treatment in selected patients with AIH.