Autoimmune Hepatitis with Acute Presentation: Clinical, Biochemical, and Histological Features of 126 Patients.

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease with a relevant inflammatory component and an unknown etiology. Evidence for clinical characteristics and risk factors in large cohorts of patients with acute AIH (AAIH) is lacking. We clinically characterized patients with AAIH, the prevalence of a combined adverse outcome (death or liver transplantation (LT)), and its risk factors. Methods: A retrospective study of adult patients diagnosed with AAIH at three centers (Santiago, Chile; 2000-2018) was conducted. Clinical and laboratory characteristics were obtained. A liver biopsy was performed for all patients. Descriptive statistics and logistic regression models were used. Results: A total of 126 patients were admitted; 77% were female, 33 (26.2%) had a severe presentation, and 14 (11.1%) had a fulminant presentation. Overall, 24 patients (19.0%) lacked typical autoantibodies, and 26.2% had immunoglobulin G levels in the normal range. The most frequent histological findings were plasma cells (86.5%), interface hepatitis (81.7%), and chronic hepatitis (81.0%). Rosettes were uncommon (35.6%). Advanced fibrosis was present in 27% of patients. Combined adverse outcomes occurred in 7.9% of cases, all fulminant with histological cholestasis. Alkaline phosphatase, bilirubin, and prothrombin less than 50% were independent risk factors for in-hospital death or LT (p value <0.05). Although corticosteroid treatment was associated with better outcomes (OR 0.095, p value = 0.013), more severe patients were less likely to receive this therapy. Discussion. In this large cohort of patients with AAIH, clinical characteristics differ from those reported in patients with chronic AIH. Fulminant hepatitis, histological cholestasis, alkaline phosphatase, bilirubin, and prothrombin were associated with death/LT.

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.

Liver transplantation in acute liver failure due to Hepatitis B. Two clinical cases.

Hepatitis B virus (HBV) related acute liver failure (ALF) is uncommon in our region, and there is limited HBV literature regarding the optimal management of these cases. In this article, we report two clinical cases of young men who have sex with men (MSM), both developed severe acute hepatitis caused by HBV, progressed to ALF and afterward required liver transplantation. Antiviral post-transplant treatment included entecavir without Hepatitis B Immunoglobulin (HBIG), and immunosuppression therapy with steroids, tacrolimus, and mycophenolate. Serologic follow-up showed early Hepatitis B surface Antigen (HBsAg) seroconversion, undetectable HBV viral load, and positive Anti-HBs titers. During later follow-up, Anti-HBs titers gradually fell (<10mUI/L after six months), with normal liver function. DISCUSSION: In cases of HBV-related ALF, the liver develops a robust immune response, leading to, an early undetectable viral load and seroconversion, with loss of HBsAg, and the appearance of Anti-HBs as a result of the inflammatory response. The management varies depending on whether this is a de novo acute infection or a reactivation of a previous chronic infection. In both cases, the use of antiviral therapy is recommended, with entecavir or tenofovir, among others, but the use of specific HBIG is supported only in ALF related to chronic HBV infection. The optimal length of the antiviral therapy after liver transplantation is still under discussion. CONCLUSION: These cases of HBV related ALF with an early HBsAg seroconversion demonstrates the relevance of requesting IgM antibody against hepatitis B core antigen (anti-HBc IgM) for the etiological study of ALF with negative HBsAg. Usage of HBIG does not seem essential during the post-transplantation period in these cases.

Hepatitis aguda por virus C: reporte de siete casos en centro de referencia en Chile

Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.

Síndrome de superposición autoinmune secuencial (hepatitis autoinmune/colangitis esclerosante primaria) y enfermedad inflamatoria intestinal: a propósito de tres casos clínicos / No disponible

La enfermedad inflamatoria intestinal (EII) se relaciona con distintas manifestaciones hepáticas como compromiso extraintestinal; la colangitis esclerosante primaria (CEP) es la más frecuente de ellas. Durante su evolución, pueden desarrollarse otras hepatopatías autoinmunes en lo que se conoce como síndrome de superposición (SS), entidad de menor asociación a EII que se presenta en forma concomitante o durante su evolución, lo cual se conoce como SS secuencial. Reportamos tres casos de SS secuencial en los cuales la hepatitis autoinmune es la primera manifestación, que tras 7-19 años de evolución desarrollaron una CEP y posteriormente una EII. Las manifestaciones extraintestinales hepáticas pueden preceder en varios años a la EII, por lo que es importante conocer esta asociación

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[Acute hepatitis C. Report of seven cases]. / Hepatitis aguda por virus C: reporte de siete casos en centro de referencia en Chile.

Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.

Disminución de la seroprevalencia del virus de la hepatitis A en Santiago de Chile, comparación de una década / Decrease in seroprevalence of hepatitis A virus in Santiago, Chile: A decade-long comparison

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Manifestaciones gastrointestinales y hepatobiliares en pacientes con inmunodeficiencia común variable: a propósito de 3 casos clínicos / Gastrointestinal and hepatobiliary manifestations in patients with common variable immunodeficiency: In relation to three clinical cases

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[Interferon Lambda 4 RS12979860 C>T polymorphism is not associated with liver fibrosis in patients with hepatitis C]. / El polimorfismo rs12979860 C>T en el gen Interferón lambda 4 no está asociado a riesgo de fibrosis hepática en pacientes chilenos con hepatitis crónica por virus C.

BACKGROUND: Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. AIM: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. MATERIAL AND METHODS: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR. Fibrosis present in liver biopsies was assessed using the METAVIR score, comparing patients with either no fibrosis, mild fibrosis, or intermediate fibrosis (F0+F1+F2, n = 96), with patients with severe fibrosis or cirrhosis (F3+F4, n = 54). RESULTS: In F0-F2 patients the distribution of rs12979860 genotypes was 22 CC, 57 CT and 17 TT, whereas in patients F3-F4 the distribution was 10, 29 and 15, respectively. No association between IFNL4 rs12979860 genotype and risk of fibrosis was observed in uni or multivariate analyses. CONCLUSIONS: IFNL4 rs12979860 C>T polymorphism is not associated with risk of liver fibrosis in this group of patients with CHC.

[Hepatitis E virus seroprevalence in blood donors in a university hospital in Chile]. / Seroprevalencia de virus hepatitis E en donantes de sangre en un hospital universitario en Chile.

In Chile, there are few studies about seroprevalence of IgG antibodies against hepatitis E virus (HEV) in blood banks, between 4 and 8%. The development of new techniques with greater sensitivity and specificity, account for an increase in the seroprevalence of HEV in various countries, the current status in Chile being unknown. In the present study, we determined the seroprevalence of anti-HEV IgG in blood donors of the Clinical Hospital University of Chile, with last generation ELISA techniques. Out of a total of 186 samples, collected in 2014, 56 (30.1%) were positive, without gender differences, but with a significant increase with age (p < 0.001). These results show an increase in the seroprevalence of HEV in blood donors performed with immunoassays of greater sensitivity.

Seroprevalencia de virus hepatitis E en donantes de sangre en un hospital universitario en Chile / Hepatitis E virus seroprevalence in blood donors in a university hospital in Chile

Resumen En Chile, existen escasos estudios de seroprevalencia de anticuerpos IgG anti virus hepatitis E (VHE) en bancos de sangre, entre 4 y 8%. El desarrollo de nuevas técnicas con mayor sensibilidad y especificidad, dan cuenta de un aumento de la seroprevalencia de VHE en diversos países, siendo desconocido el estado actual en Chile. En el presente estudio, determinamos la seroprevalencia de IgG anti VHE en donantes de sangre del Hospital Clínico Universidad de Chile, con técnicas de ELISA de última generación. De un total de 186 muestras, recolectadas el año 2014, 56 (30,1%) resultaron positivas, sin diferencias de género, pero con un incremento significativo con la edad (p < 0,001). Estos resultados muestran un aumento en la seroprevalencia de VHE en donantes de sangre realizados con inmunoensayos de mayor sensibilidad.

In Chile, there are few studies about seroprevalence of IgG antibodies against hepatitis E virus (HEV) in blood banks, between 4 and 8%. The development of new techniques with greater sensitivity and specificity, account for an increase in the seroprevalence of HEV in various countries, the current status in Chile being unknown. In the present study, we determined the seroprevalence of anti-HEV IgG in blood donors of the Clinical Hospital University of Chile, with last generation ELISA techniques. Out of a total of 186 samples, collected in 2014, 56 (30.1%) were positive, without gender differences, but with a significant increase with age (p < 0.001). These results show an increase in the seroprevalence of HEV in blood donors performed with immunoassays of greater sensitivity.

El polimorfismo rs12979860 C> T en el gen Interferón lambda 4 no está asociado a riesgo de fibrosis hepática en pacientes chilenos con hepatitis crónica por virus C / Interferon Lambda 4 RS12979860 C> T polymorphism is not associated with liver fibrosis in patients with hepatitis C

Background. Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. Aim: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. Material and Methods: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR. Fibrosis present in liver biopsies was assessed using the METAVIR score, comparing patients with either no fibrosis, mild fibrosis, or intermediate fibrosis (F0+F1+F2, n = 96), with patients with severe fibrosis or cirrhosis (F3+F4, n = 54). Results: In F0-F2 patients the distribution of rs12979860 genotypes was 22 CC, 57 CT and 17 TT, whereas in patients F3-F4 the distribution was 10, 29 and 15, respectively. No association between IFNL4 rs12979860 genotype and risk of fibrosis was observed in uni or multivariate analyses. Conclusions: IFNL4 rs12979860 C>T polymorphism is not associated with risk of liver fibrosis in this group of patients with CHC.

IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study.

BACKGROUND AND PURPOSE: Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. METHODS: A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records. RESULTS: 2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection. CONCLUSION: This large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East.