Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study.

BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).

Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20-30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

Alcohol-related liver disease: Clinical practice guidelines by the Latin American Association for the Study of the Liver (ALEH).

Alcohol-related liver disease (ALD) is a major cause of advanced chronic liver disease in Latin-America, although data on prevalence is limited. Public health policies aimed at reducing the alarming prevalence of alcohol use disorder in Latin-America should be implemented. ALD comprises a clinical-pathological spectrum that ranges from steatosis, steatohepatitis to advanced forms such as alcoholic hepatitis (AH), cirrhosis and hepatocellular carcinoma. Besides genetic factors, the amount of alcohol consumption is the most important risk factor for the development of ALD. Continuous consumption of more than 3 standard drinks per day in men and more than 2 drinks per day in women increases the risk of developing liver disease. The pathogenesis of ALD is only partially understood and recent translational studies have identified novel therapeutic targets. Early forms of ALD are often missed and most clinical attention is focused on AH, which is defined as an abrupt onset of jaundice and liver-related complications. In patients with potential confounding factors, a transjugular biopsy is recommended. The standard therapy for AH (i.e. prednisolone) has not evolved in the last decades yet promising new therapies (i.e. G-CSF, N-acetylcysteine) have been recently proposed. In both patients with early and severe ALD, prolonged abstinence is the most efficient therapeutic measure to decrease long-term morbidity and mortality. A multidisciplinary team including alcohol addiction specialists is recommended to manage patients with ALD. Liver transplantation should be considered in the management of patients with end-stage ALD that do not recover despite abstinence. In selected cases, increasing number of centers are proposing early transplantation for patients with severe AH not responding to medical therapy.

Current controversies in cholangiocarcinoma.

Cholangiocarcinoma represents 10% of primary liver malignancies and accounts for less than 3% of all gastrointestinal malignant tumors, with an enormous geographical variation. This neoplasia can arise from the biliary tract epithelium or hepatic progenitor cells. Depending on the anatomic localization, it is classified into three subtypes: intrahepatic, perihilar and distal. This fact is one of the main difficulties, because there are many studies that indistinctly include the results in the management of these different types of cholangiocarcinoma, without differentiating its location and even including gallbladder cancer. There are many controversial points in epidemiology, liver transplantation as a treatment, limitations of different results by group and type of treatment, histological testing and chemotherapy. This is a narrative review about topics in cholangiocarcinoma. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Advances in Genomic Data and Biomarkers: Revolutionizing NSCLC Diagnosis and Treatment.

Non-small cell lung cancer (NSCLC) is a significant public health concern with high mortality rates. Recent advancements in genomic data, bioinformatics tools, and the utilization of biomarkers have improved the possibilities for early diagnosis, effective treatment, and follow-up in NSCLC. Biomarkers play a crucial role in precision medicine by providing measurable indicators of disease characteristics, enabling tailored treatment strategies. The integration of big data and artificial intelligence (AI) further enhances the potential for personalized medicine through advanced biomarker analysis. However, challenges remain in the impact of new biomarkers on mortality and treatment efficacy due to limited evidence. Data analysis, interpretation, and the adoption of precision medicine approaches in clinical practice pose additional challenges and emphasize the integration of biomarkers with advanced technologies such as genomic data analysis and artificial intelligence (AI), which enhance the potential of precision medicine in NSCLC. Despite these obstacles, the integration of biomarkers into precision medicine has shown promising results in NSCLC, improving patient outcomes and enabling targeted therapies. Continued research and advancements in biomarker discovery, utilization, and evidence generation are necessary to overcome these challenges and further enhance the efficacy of precision medicine. Addressing these obstacles will contribute to the continued improvement of patient outcomes in non-small cell lung cancer.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis.

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

Molecular characterization of hepatitis c virus in multi-transfused Colombian patients.

BACKGROUND: Hepatitis C virus (HCV) infects 170 million persons worldwide and is a public health problem. Considering that HCV is principally transmitted by exposure to infected blood, multi-transfused patients constitute one of the most important risk groups in developing countries. To explore the dynamics of this infection in Colombia, we performed a study to determine the genotypes of HCV in a cohort of multi-transfused patients. RESULTS: The serum samples from patients positive for anti-HCV were evaluated for HCV RNA by nested-PCR of the 5'untranslated region (5'UTR). Viral genotype was determined by RFLP and/or automated sequencing. HCV subtype 1b was found in eight cases (66.7%) and subtype 1a in two cases (16.7%); seven isolates of subtype 1b were obtained from patients who had received the first transfusion before 1986. Either genotypes 2b (8.3%) or 3a (8.3%) were found in the remaining positive specimens. CONCLUSIONS: This is the first HCV genotyping study developed in multi-transfused patients in Colombia where HCV subtype 1b was the most prevalent. The mutation G235A in the 5'UTR of three isolates generated an additional restriction site and an RFLP pattern different from those previously described for genotype 1.

[Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in adults: report of three cases]. / Síndrome de superposición de hepatitis autoinmune y colangitis esclerosante primaria en adultos: reporte de tres casos.

Overlap syndromes are cases of liver diseases that share clinical, serological, histological and radiological criteria of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). No definitions have been fully established and therefore there is no solid evidence on the diagnosis and treatment. This article presents the cases of three adult patients with overlapping features of AIH and PSC. Orthotopic liver transplantation was considered the best therapeutic alternative due to advanced disease progression in one patient, while medical treatment was provided in the remaining two patients.

Genetic diversity of hepatitis C virus and resistance associated substitutions to direct-acting antiviral treatment in Colombia.

Hepatitis C virus (HCV) infection is one of the leading risk factors for end-stage liver disease development worldwide. This RNA virus displays high genetic diversity with 8 genotypes and 96 subgenotypes with heterogeneous geographical distribution around the world. In this study, we carried out an active case finding of individuals with a history of transfusion events before 1996 in three cities in Colombia. Then, the characterization of the HCV genotypes, subgenotypes, and resistance associate substitutions (RAS) was performed in samples positives for antibodies anti-HCV + from this study population. In addition, samples from PWID and patients with end-stage liver disease submitted to liver transplantation were included in the phylogenetic and RAS analysis. The 5'UTR, NS5A, and NS5B regions of the HCV genome were amplified in serum or liver explants samples. After the edition, assembly, and alignment of the sequences, genotyping through phylogenetic analysis was performed using IQTREE V2.0.5 based on the maximum likelihood approach. The identification of RAS was carried out by alignments based on the reference sequence (GenBank NC_004102). Two hundred sixty individuals with blood transfusion events before 1996 were recruited. The seroprevalence of antibodies anti-HCV was 2.69% in this population. The HCV genotypes 1, 2, and 4 and subgenotypes 1a, 1b, 2a, 4a and 4d were characterized in samples of the study populations. Three RAS (Q30R, C316N, and Y93H) were identified in samples obtained from 2 individuals who received blood transfusion before 1996 and without previous antiviral treatment and 6 samples obtained from patients with end-stage liver disease. Among the 20 samples analyzed, the HCV genotype 1, subgenotype 1b, was the most frequent (60%). We report the first characterization of HCV subgenotypes 4a and 4d and the first RAS identification in patients in Colombia.

The establishment of public health policies and the burden of non-alcoholic fatty liver disease in the Americas.

Non-alcoholic fatty liver disease (NAFLD) affects 20-25% of the general population and is associated with morbidity, increased mortality, and elevated health-care costs. Most NAFLD risk factors are modifiable and, therefore, potentially amenable to being reduced by public health policies. To date, there is no information about NAFLD-related public health policies in the Americas. In this study, we analysed data from 17 American countries and found that none have established national public health policies to decrease NAFLD-related burden. There is notable heterogeneity in the existence of public health policies to prevent NAFLD-related conditions. The most common public health policies were related to diabetes (15 [88%] countries), hypertension (14 [82%] countries), cardiovascular diseases (14 [82%] countries), obesity (nine [53%] countries), and dyslipidaemia (six [35%] of countries). Only seven (41%) countries had a registry of the burden of NAFLD, and efforts to raise awareness in the Americas were scarce. The implementation of public health policies are urgently needed in the Americas to decrease the burden of NAFLD.

Acute liver failure due to white phosphorus ingestion.

BACKGROUND: White phosphorus is chemical compound available in military ammunition as well as in explosive powder of recreational use. This latter form is commonly found in Latin America and Asia as a main ingredient of gunpowder used to make street firecrackers. Small firecrackers may be ingested accidentally or used as a toxic agent in suicidal attempts which may cause of acute liver failure and death; however the clinical features, incidence and outcome are poorly described in the literature. METHODS: We describe three cases of white phosphorus intoxication with acute liver failure secondary to the consumption of firecrackers. In two cases, ingestion occurred secondary to suicidal attempts and in one, ingestion occurred by accident. In one case, liver injury improved with supportive care, in the other, the patient required liver transplantation and the third case had a fatal outcome. CONCLUSIONS: Clinicians providing care of patients with acute hepatitis of unclear etiology should be aware that the ingestion of firecrackers containing white phosphorus might cause acute liver failure that may require liver transplantation.

Polymorphisms in alcohol dehydrogenase (ADH1) and cytochrome p450 2E1 (CYP2E1) genes in patients with cirrhosis and/or hepatocellular carcinoma / Polimorfismos en los genes de la enzima alcohol deshidrogenasa (ADH1) y la citocromo P450 2E1 (CYP2E1) en pacientes con cirrosis y carcinoma hepatocelular

Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.

Introducción. Uno de los principales factores de riesgo del carcinoma hepatocelular es el consumo crónico de alcohol. En estudios en diferentes poblaciones, se sugiere que las variantes genéticas de las enzimas que participan en el metabolismo del alcohol, como la alcohol deshidrogenasa (ADH) y la citocromo P450 (CYP2E1), estarían asociadas con riesgo de enfermedades hepáticas terminales.Objetivo. Identificar y caracterizar las variantes alélicas de los genes ADH1B, ADH1C y CYP2E1 en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular.Materiales y métodos. Se incluyeron muestras de pacientes atendidos entre el 2005 y el 2007, y entre el 2014 y el 2016, en la unidad de hepatología de un hospital de Medellín. La genotipificación de las muestras se hizo mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) con análisis de los polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Los resultados se compararon con los de dos grupos de control y con lo reportado en la base de datos del 1000 Genomes Project.Resultados. Se recolectaron 97 muestras de pacientes con diagnóstico de cirrosis y carcinoma hepatocelular. Los dos factores de riesgo más frecuentes fueron el consumo crónico de alcohol (18,6 %) y las colangiopatías (17,5 %). Los genotipos más frecuentes en la población de estudio fueron el ADH1B*1/1 (82 %), el ADH1C*1/1 (59 %) y el CYP2E1*C/C (84 %).Conclusiones. En este primer estudio de los polimorfismos en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular, los genotipos más frecuentes fueron el ADH1B*1/1, el ADH1C*1/1 y el CYP2E1*C/C. No se observaron diferencias estadísticamente significativas en la frecuencia de los genotipos entre los casos y los controles. Se requieren estudios adicionales en población colombiana para evaluar el riesgo de la enfermedad hepática terminal por consumo crónico de alcohol y laasociación con los polimorfismos.

Serious liver disease induced by infliximab.

Infliximab, a chimeric monoclonal antibody that binds the tumor necrosis factor alpha (TNFalpha), is used in the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Previous cases of significant secondary liver disease associated with infliximab treatment have been reported in patients with RA, CD, and psoriatic arthritis. Two additional patients with RA who developed a serious liver disease associated with infliximab treatment are reported here. A 39-year old RA patient was admitted with cholestatic liver disease after 8 months of treatment with infliximab. She had no history of hepatic diseases, exposure to hepatotoxic or illicit drugs, or alcohol abuse. A liver biopsy showed severe ductal proliferation with collapse and enucleation of the hepatocytes. Despite aggressive treatment with oral prednisolone, she developed hepatic failure. On the 45th day, a liver transplant was performed. The second patient, a 54-year old RA patient, was diagnosed with autoimmune hepatitis after 12 infliximab infusions. She fulfilled autoimmune hepatitis type 1 criteria. A liver biopsy disclosed an altered lobulillar structure with chronic inflammation and the formation of collagen bands. She was treated with prednisolone and azatioprine and a complete recovery was noted 1 month later. These cases should alert rheumatologists to the possibility of new adverse reactions (liver injury) associated with the use of TNFalpha blockers in an autoimmune setting.

Impacto medioambiental y socioeconómico en la salud generado por la minería artesanal del oro en Colombia

Introducción: Este artículo de revisión sistemática describe el impacto medioambiental y socioeconómico en salud generado por la minería artesanal del oro en Colombia. Para el estudio se tuvieron en cuenta artículos publicados entre 2010 y 2019. El objetivo de esta revisión bibliográfica fue describir el impacto medioambiental y socioeconómico en la salud generado por la minería artesanal del oro en Colombia. Materiales y métodos: Trabajo construido mediante revisión sistemática, usando los siguientes descriptores: minería, sector informal, riesgo a la salud, condiciones de salud. Para esta búsqueda se utilizaron las bases de datos Scopus, Web of Science, ProQuest, Publindex, así como la normatividad colombiana. Resultados: Se desarrollan las categorías ambientales, socioeconómico y salud. En la categoría ambiental se detalla información sobre sostenibilidad ambiental, manejo de vertimientos, pruebas fisicoquímicas y control gubernamental; En la categoría socioeconómica se describen los dilemas entre minería y medio ambiente, el dilema entre pequeña minería o artesanal y minería a gran escala o industrializada, y el conflicto social y económico. En la categoría salud se analizan las afectaciones y la percepción de la población sobre los daños en la salud, la protección laboral, la innovación social y las oportunidades de cambio para una producción más limpia y saludable. Conclusiones: Los estudios realizados se concentran principalmente en el departamento de Antioquia evidenciando la necesidad de realizar investigaciones en otras zonas del país. A pesar de que en Colombia existe legislación minera, se requiere que el gobierno establezca medidas efectivas de control, capacite y socialice a los mineros sobre métodos adecuados de procesamiento del oro, garantizado el desarrollo ambiental, social y protección laboral.

Introduction: This systematic review article describes the environmental and socioeconomic impact on health generated by handmade gold mining in Colombia. For this study articles published between 2010 and 2019 were considered. The objective of this bibliographic review is to describe the environmental and socioeconomic impact on health generated by gold mining in Colombia. Materials and methods: Work constructed through systematic review, using the following descriptors: mining, informal sector, health risk, health conditions. For this search, Scopus, Web of Science, ProQuest, Publindex databases were used, as well as Colombian regulations. Results: The environmental, socioeconomic, and health categories were developed. In the environmental category, information on environmental sustainability, management of discharges, physicochemical tests, and government control is detailed. In the socioeconomic category, the dilemmas between mining and the environment are described, the dilemma between small or artisanal mining and large-scale or industrialized mining, and the social and economic conflict. In the third category, health, the effects and perception of the population regarding health damage, labor protection, social innovation, and opportunities for change for cleaner and healthier production are analyzed. Conclusions: The studies carried out are mainly concentrated in the department of Antioquia, showing the need to carry out research in other areas of the country. Although there is mining legislation in Colombia, the government is required to establish effective control measures, train, and socialize the miners on adequate gold processing methods, guaranteeing the environmental and social development and protection of its miners.

Orthotopic liver transplantation in an adult with situs inversus: an easy way to fit the liver.

Situs inversus (SI) is a rare congenital disorder with a complete mirror image of thoracic and abdominal organs. In adults with SI and decompensated cirrhosis experience with liver transplantation is limited. Orthotopic liver transplantation (OLT) in an adult with cirrhosis using a technique where the recipient liver was placed using a 90-degree rotation of the graft was previously reported by Klintmalm et al, however no other reports using this technique have been described. We report a case of a 41 year-old man with situs inversus and decompensated cirrhosis who successfully underwent OLT using this technique. The donor liver was rotated 90-degrees towards the left and easily fitted into the recipients'fossa with the left lobe pointing toward the left lower quadrant. The patient had an uneventful recovery and has been followed for 21 months without any complications. This technique has the advantage of preventing compromise of the size of the donor liver, permits an easy reconstruction of vascular and biliary tree and in this case was associated with an excellent outcome.

Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis.

BACKGROUND: Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype. METHODS: A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses. RESULTS: Nine (22.5%) cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs. CONCLUSIONS: This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia.

Hepatitis C virus seroprevalence in multi-transfused patients in Colombia.

BACKGROUND: Hepatitis C Virus (HCV) infection is a public health problem worldwide, with particular relevance in multi-transfused patients given that HCV is principally transmitted by exposure to infected blood. STUDY DESIGN: Between February and September 2003 a cross-sectional study was carried out in four hospital centres in Bogotá and Medellin, Colombia, to determine the risk factors for HCV infection in 500 multi-transfused patients. RESULTS: The study population was distributed in five groups: haemophilia, haemodyalsis, acute bleeding, ontological illnesses and sickle cell disease or thalassemia. Serum samples from patients were tested for HCV antibodies (Asxym, Abbott). An overall prevalence (9.0%; 95% confidence interval (CI): 6.4-11.6) (45/500) of HCV infection was found. Anti-HCV antibodies were detected in 32.2% of patients with haemophilia, 6.1% of patients undergoing haemodialysis, 7.1% of patients with sickle cell disease or thalassemia, 2.6% of patients with acute bleeding and 3.4% of patients with ontological or hematological diseases. The main risk factors associated with infection by HCV were: to be hemophilic (odds ratio, OR = 18.03; 95% Cl: 3.96-114.17), having received transfusions before 1995 (OR = 12.27; 95% Cl: 5.57-27.69), and having received more than 48 units of blood components (OR = 6.08; 95% CI: 3.06-12.1). In the multivariate analysis, only the year of transfusions (before 1995) remained significantly associated with risk of infection by HCV. CONCLUSIONS: The data show a 3-fold reduction in the infection risk between 1993 and 1995, when the serological screening for HCV in blood donors was being introduced. A reduction greater than 90% was achieved by 1995 when the screening coverage reached 99%.

Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft.

BACKGROUND: The impact of hepatitis C virus (HCV) infection recurrence after orthotopic liver transplantation (OLT) on graft viability is still not accurately defined. Our study aims to evaluate the magnitude and rate of progression of HCV-induced liver damage after OLT in a single institution cohort of 122 HCV-infected recipients. METHODS: All patients transplanted at our institution between 1988 and 1996 with positive serum HCV antibodies before OLT, minimum postoperative survival of 6 months, and without hepatitis B virus coinfection or severe non-HCV-related graft complications were retrospectively included in the study. RESULTS: HCV infection recurrence was almost universal, and genotype 1b was observed in 87% of the cases. After a median histological follow-up of 43 months (range: 7-96), evidences of HCV-induced histological damage were found in 94% of the cases. The actuarial rates of severe graft damage (including cirrhosis, fibrosing cholestatic hepatitis, and submassive liver necrosis) were 15%, 33%, and 44% at 3, 5, and 7 years, respectively, and among these patients, 52% developed decompensated liver disease during the follow-up and 36% lost their grafts. The biochemical severity at the onset of the recurrent hepatitis and the development of cholestasis or cytomegalovirus disease were independent predictors of severe HCV-related graft damage. No differences were found in graft and patient survival when positive-HCV OLT recipients were compared with a coetaneous cohort of 215 non-HCV OLT recipients. CONCLUSIONS: HCV infection recurrence leads to severe liver damage and subsequently to clinical decompensation in a significant proportion of OLT recipients. Some clinical and biochemical characteristics can predict the severity of HCV-induced graft damage.