Aspectos morfológicos de la enfermedad hepática inducida por drogas / Morphological Issues of Drug Induced Liver Disease

La enfermedad hepática inducida por drogas es un fenómeno multifacético y su espectro morfológico es muy variado imitando cualquier patrón de daño hepático, tanto en pacientes expuestos en forma aguda o crónica, en aquellos susceptibles en forma idiosincrática a una dosis terapéutica o por toxicidad intrínseca, a su vez puede estar afectada por otros factores como son los genéticos, la edad o el sexo, el estado nutricional, la exposición a otros fármacos o la existencia de una enfermedad de base; puede ser la única manifestación clínica del efecto adverso de una droga o estar acompañado de manifestaciones sistémicas o de otros órganos, e incluso puede llegar a ser fatal (1). Su incidencia no está bien definida, algunos estudios afirman que la incidencia global es variable encontrándose entre 1-15 x 100.000 personas/año, en USA ocurren 20 nuevos casos x 100.000 habitantes/año. Se han descrito como causantes de lesión hepática más de 900 drogas, productos herbales, homeopáticos, suplementos dietéticos o toxinas, sean productos naturales o de la industria farmacéutica, utilizados o no en dosis terapéuticas, que son las responsables de aproximadamente 15% de consultas y hospitalizaciones por ictericia, hepatitis aguda o crónica; en la población adulta, por encima de los 50 años, llega a 40% de todos los casos de hepatitis. Es también la causante de 11-50% de casos de falla hepática aguda. Los datos publicados indican que los antibióticos son responsables entre un 27-46% de los casos, seguidos por medicamentos para enfermedades del sistema nervioso central entre 13-17%, antiinflamatorios y analgésicos de 5-17% y los productos herbales 9%. Nuevos biomarcadores y el uso de microRNA se están estudiando y serán prometedores en un futuro cercano para identificar pacientes que puedan presentar hepatotoxicidad inducida por medicamentos. Son tantos los tipos de lesión hepática atribuidos a estos agentes que solo podremos dar algunos ejemplos en este artículo, basados en los patrones de daño hepático y enfatizando la importancia de una adecuada y profunda correlación clínica (2, 3).

Drug-induced liver disease is a multifaceted phenomenon which has a varied morphological spectrum that mimics other patterns of liver damage both in cases of acute drug exposure and in cases of chronic exposure to drugs. Those patients who are idiosyncratically susceptible at the therapeutic dose or to intrinsic toxicity may also be affected by other factors including genetic factors, age, sex, nutritional status, exposure to other drugs and the existence of an underlying disease. The only clinical manifestation of the disease may be the adverse effect of a drug, but it can also be accompanied by systemic manifestations and manifestations in other organs, and it can even be fatal (1). The incidence of drug-induced liver disease is not well defined, but some studies claim that its overall annual incidence varies between 1/100,000 people and 15/100,000 people. In the United States, twenty new cases per 100,000 inhabitants occur every year. More than 900 natural and pharmaceutical drugs, herbal medicines, homeopathic products, dietary supplements and toxins have been reported to cause liver damage. This can occur whether or not they are used at normal therapeutic doses. These cases are responsible for about 15% of consultations and hospitalizations for jaundice, acute hepatitis, and chronic hepatitis in adults above the age of 50, and in up to 40% of all cases of hepatitis. Drug-induced liver disease also accounts for 11% to 50% of all cases of acute liver failure. Published data indicate that antibiotics are responsible for between 27% and 46% of cases, that drugs for diseases of the central nervous system are responsible for between 13% and 17%, anti-inflammatory and analgesic agents are responsible for between 5% and 17%, and herbal products are responsible for 9%. New biomarkers and the use of microRNA are being studied and may become promising alternatives in the near future for identifying patients susceptible to drug-induced hepatotoxicity. There are so many types of liver damage attributed to these agents that only give some examples can be provided in this article. These examples have been chosen on the basis ofn the patterns of liver damage with emphasis on the importance of proper and thorough clinical correlation (2, 3).

Hepatopatología para gastroenterólogos y hepatólogos. Tercera parte: patología de la enfermedad hepática necroinflamatoria crónica / Hepatology for Gastroenterologists and Hematologists. Part Three: pathology of chronic necroinflammatory liver disease

En la interpretación de una biopsia hepática, las enfermedades necroinfl amatorias hepáticas están entre laspatologías halladas más a menudo, y en el estudio histopatológico es habitual enfrentarse a varias preguntasal respecto: ¿Qué es? ¿Qué tan grave es la enfermedad? ¿Qué es lo que el clínico espera? Se buscará eneste artículo dar respuesta a tales preguntas.

Necroinfl ammatory liver diseases are one of the most frequently encountered pathologies when interpreting a liver biopsy. In a histopathological study, we faced several questions including: What is it? How severe is the illness? And what does the clinician expect? This article attempts to answer these questions.

Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters.

Background and Aims: Hepatic steatosis (HS) is highly prevalent in chronic hepatitis C and is an important variable predicting progression of histological injury, insulin resistance, and reduced response to antiviral therapy. There are limited data on HS in patients with chronic hepatitis B (CHB). This is relevant since response to current antiviral therapies for CHB is rather limited. We investigated the spectrum and predictors of HS in CHB patients. Materials and Methods: Liver biopsies of consecutive patients of chronic Hepatitis B Virus (HBV) infection were studied and were categorized as: Group I - hepatosteatosis (>5%) and Group II - no steatosis (£5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. Results: Of the 350 patients, 118 (33.7%) liver biopsies showed steatosis (Group I); 65 (55.1%) had mild (6 to <25%) and 53 (44.9%) had moderate to severe steatosis (325%). Patients in group I, compared with group II, were older (35.5 ± 10.5 vs 27.9 ± 14.0 years, P < 0.01), predominantly male (M: F, 10.8: 1 vs 4.8: 1, P = 0.035), obese (75.0% vs 23.4%, P < 0.01), with higher body mass index (25.2 ± 4.8 vs 20.4 ± 3.5, P < 0.01), with higher triglycerides (138.8 ± 62.1 vs 88.0 ± 27.9, P = 0.02), with higher cholesterol (171.9 ± 43.5 vs 139.3 ± 37.6, P = 0.017), and with higher serum insulin (13.1 ± 9.1 vs 9.1 ± 6.0, P < .027) levels. HBV DNA level was significantly lower in group I than group II; however, HBV genotype did not influence HS. By multivariate regression analysis, only high serum triglyceride level was independent parameter associated with HS. Conclusions: Steatosis is seen in one-third cases with HBV-related chronic liver disease and is associated with host metabolic factors, especially serum triglyceride levels, whereas HBV DNA level negatively correlated with HS.

Factors associated with liver stiffness in chronic liver disease / 대한간학회지

BACKGROUND/AIMS: Transient elastography is a new noninvasive tool for measuring liver stiffness that accurately predicts significant fibrosis and cirrhosis. However, several studies have indicated that liver stiffness can be significantly influenced by major changes in aminotransferase in patients with chronic viral hepatitis. The aim of this study was to determine the factors influencing liver stiffness in patients with chronic liver disease. METHODS: We studied 158 patients with chronic liver disease who underwent transient elastography and liver biopsy sampling. Histologic findings on fibrosis and necroinflammatory activity in the biopsy specimens were evaluated according to the Korean Society of Pathologists Scoring System. Routine biochemical tests were performed according to standard methods. RESULTS: Liver stiffness was strongly correlated with liver fibrosis stage (Spearman coefficient=0.636, P<0.001), lobular activity (Spearman coefficient=0.359, P<0.001), and portoperiportal activity grade (Spearman coefficient=0.448, P<0.001). Liver stiffness was significantly associated with serum levels of total bilirubin (P=0.025), direct bilirubin (P=0.049), gamma-glutamyl transpeptidase (P=0.014), platelet count (P=0.004), albumin (P<0.001), and international normalized ratio (P<0.001). Multivariate analysis showed that fibrosis stage (B 3.50, P=0.009) and lobular activity grade (B 3.25, P=0.047) were independently associated with liver stiffness. CONCLUSIONS: Liver stiffness as measured by transient elastography is associated with the grade of necroinflammatory activity and the stage of fibrosis, irrespective of serum ALT levels.

Associations of Expressions of HBcAg and HBsAg with the Histologic Activity of Liver Disease and Viral Replication

BACKGROUND/AIMS: Subcellular localization of hepatitis B virus (HBV) core antigen (HBcAg) and HBV surface antigen (HBsAg) is known to be related to the activity of liver disease and the level of HBV replication. The aim of this study was to determine the correlation between histologic activity, viral replication, and the intracellular distributions of HBcAg and HBsAg. METHODS: We enrolled 670 patients with chronic hepatitis B who underwent liver biopsy at Bundang CHA hospital between 1997 to 2007. The data from medical records were reviewed retrospectively. RESULTS: The stage of fibrosis was higher (3.31+/-1.34 vs. 2.43+/-1.39, mean+/-SD, p0.05). CONCLUSIONS: These observations suggest that the histologic activity of hepatitis is higher and viral replication is lower in cHBcAg positive patients than in those with nHBcAg.