Comparison on the Efficacy and Safety of Biphenyl Dimethyl Dicarboxylate and Ursodeoxycholic Acid in Patients with Abnormal Alanine Aminotransferase: Multicenter, Double-blinded, Randomized, Active-controlled Clinical Trial / 대한소화기학회지

BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events. RESULTS: A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period. CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.

Hepatitis alcohólica severa no respondedor a a glucocorticoides: reporte de un caso / Alcoholic hepatitis not responding to corticosteroids: a case report

INTRODUCCIÓN: La hepatitis alcohólica corresponde a un daño inflamatorio agudo sobre un hígado progresivamente dañado por la ingesta excesiva y prolongada de alcohol. Puede presentar ictericia, manifestaciones de alcoholismo crónico e insuficiencia hepática progresiva. PRESENTACIÓN DEL CASO: Varón de 60años con antecedentes de daño hepático crónico secundario a alcoholismo activo, que presentó cuadro de dos semanas de ictericia progresiva, prurito y bradipsiquia, asociado a leucocitosis, hiperbilirrubinemia, y elevación discreta de transaminasas, con predominio de GOT sobre GPT. Hemocultivos, urocultivo y serologías para virus hepatotropos fueron negativos. La ecografía abdominal mostró signos de hepatopatía crónica, sin dilatación de vía biliar. Con una función discriminante de Maddrey de 106 puntos se inició pentoxifilina, evolucionando tórpidamente. Se agregó prednisona durante siete días; se obtiene una puntuación de Lille de 0,99 (no respondedor), suspendiendo los corticoides. Progresó la insuficiencia hepática, con posterior insuficiencia renal aguda, acidosis metabólica, trastornos hidroelectrolíticos y fallecimiento al mes de evolución. DISCUSIÓN: La hepatitis alcohólica posee alta mortalidad. Existen múltiples escalas pronósticas. Los corticoides están indicados en casos severos, sin embargo hasta un 40 por ciento se catalogan como no respondedores. Se requieren nuevos tratamientos para mejorar la supervivencia de estos pacientes.

INTRODUCTION: Alcoholic hepatitis constitutes an acute inflammatory episode due to prolonged alcohol abuse on a previously damaged liver. Clinical features include jaundice, signs of chronic alcoholism and progressive liver failure. CASE REPORT: A 60-yearold male with a history of cirrhosis due to ongoing excessive intake of alcohol presented a two week history of progressive jaundice, pruritus, and bradypsychia. Laboratory tests showed leukocytosis, hyperbilirubinemia and a mild elevation of liver enzymes (GOT over GPT). Blood and urine cultures as well as serological markers for viral hepatitis were negative. Abdominal ultrasound showed signs of chronic liver disease, with no bile duct dilatation. A modified Maddrey’s discriminant function of 106 was determinant on starting therapy with pentoxifyline. However, patient’s status deteriorated. Prednisone was added to the treatment but seven days later, the patient was categorized as a non-responder (Lille score of 0.99), so the glucocorticoids were suspended. The patient’s liver failure progressed, after which renal failure, metabolic acidosis and electrolytic abnormalities developed; that led to his death after one month from admission. DISCUSSION: Alcoholic hepatitis requires prompt diagnosis and treatment, due to its high death rate. There are various prognostic scales available, one of which is the modified Maddrey’s discriminant function. The fundamental therapeutic measure is the use of intravenous glucocorticoids; yet up to 40 percent of patients qualify as non-responders.

Effect of lecithin with vitamin-B complex and tocopheryl acetate on long-term effect of ethanol induced immunomodulatory activities.

The alcoholic liver disease usually causes overall immunological alterations which might be attributed to hepatic disease, to ethanol action, and/or to malnourishment. In the present study, efficacy of lecithin with vitamin-B complex to treat ethanol induced immunomodulatory activity was compared with the effect of lecithin alone and tocopheryl acetate (vitamin E). Ethanol (1.6 g/kg body wt/day for 12 weeks) exposure increased thiobarbituric acid reactive substance (TBARS) level, while decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) content in whole blood hemolysate of 8-10 week-old male BALB/c mice (weighing 20-30 g). The activities of transaminase (AST and ALT) enzymes, interleukin (IL)-10 and gamma interferon (IFN-gamma) elevated, while IL-2 and IL-4 reduced in mice serum due to ethanol exposure. These suggested that oxidative stress and immunomodulatory activities were interdependent and associated with ethanol induced liver damage. Lecithin treatment significantly reduced AST (32.44%), ALT (32.09%), IL-10 (25.63%) activities and TBARS content (12.76%) compared to ethanol treated group. However, lecithin with vitamin-B complex treatment, significantly reduced AST (62.83%); ALT (61.96%); IL-10 (35.88%); IFN-gamma (22.55%) activities and TBARS content (31.58%), while significantly elevated GSH content (36.49%) and SOD activity (61.21%). Tocopheryl acetate treatment significantly reduced AST (62.83%); ALT (61.54%); IL-10 (36.35%): IFN-gamma (23.28%) activities and TBARS content (35.84%). while significantly elevated GSH content (28.76%) and SOD activity (62.42%) compared to ethanol treated group. These findings persuasively argued that lecithin with vitamin-B complex was a new promising therapeutic approach in controlling ethanol induced immunomodulatory activities involving liver damage processes. Prevention of oxidative stress with correction of nutritional deficiency caused alteration in the ethanol-induced immunomodulatory activities and associated liver diseases.

Uso bem-sucedido do corticóide na hepatite alcoólica grave / Sucessful use of steroids in severe alcoholic hepatitis

Abuso e dependência alcoólica são os mais sérios problemas médicos do mundo industrializado. Cerca de 10% a 35% dos alcoólatras cursam com hepatite crônica ativa, síndrome inflamatória que traduz necrose hepática em diferentes graus de intensidade, dependentes da quantidade de álcool ingerido diariamente ao longo dos anos. Alguns revelam-se pouco sintomáticos ou assintomáticos. Forma mais grave da doença expressa-se pelo aparecimento de icterícia, ascite, sinais de coagulopatia e até encefalopatia. Esses doentes cursam ainda com dor em hipocôndrio direito, hepatomegalia, febre e leucocitose. A mortalidade nesse caso é alta, todos evoluindo com neutrofilia, metabolismo alterado dos carboidratos, lipídeos e minerais. Nesses casos graves, a literatura mundial preconiza, dentre outras terapias, o uso de corticóides com o objetivode suprimir a inflamação tecidual, diminuir a formação de colágeno, bloquear os mecanismos de perpetuação imunológica da doença, melhorar o apetite e estimular a síntese de albumina. Este artigo tem por objetivo apresentar um caso de hepatite alcoólica aguda grave que evoluiu com sucesso após o tratamento com corticóide e revisar esse tema tão atual e problemático em nosso país.

Efecto terapéutico de la silimarina en las hepatopatías agudas de etiología viral y alcohólica / Therapeutic effect of silymarin on acute hepatic diseases of viral and alcoholic etiology

Con el fin de estudiar el efecto y tolerancia terapéutica de silimarina en hepatopatías agudas de origen viral y alcohólico, se estudiaron 30 pacientes a los que se les administró el medicamento en grageas durante 30 días a razón de 140 mg, tres veces al día. Los pacientes fueron divididos en dos grupos. El grupo I fue compuesto por 15 pacientes con diagnóstico clínico, bioquímico y serológico de hepatitis viral. Doce pacientes fueron varones y tres mujeres, con edad de 18 a 38 años, edad media 25.5 ñ 5.81. El grupo II incluyó 15 pacientes con diagnóstico clínico, bioquímico e histológico de hepatitis alcohólica, 13 varones y dos mujeres con edad de 32 a 67 años, edad media 48.8 ñ 8.93. Cada semana fue valorada la eficacia y tolerancia al fármaco tomando como referencia da evolución clínica y exámenes de laboratorio practicados, los cuales fueron: pruebas funcionales hepáticas completas, biometría hepática, química sanguínea y examen general de orina. Los resultados demonstraron que silimarina fue bien tolerada en ambos grupos. En cuanto a la eficacia, los pacientes del grupo I presentaron respuesta terapéutica excelente en 40%, buena en 20%, regular en 6.67% y nula en 33.33%. En el grupo II la respuesta fue excelente en 33.33%m buena en 13.33%, regular en 40% y nula 13.33%. Silimarina fue útil en ambos grupos de pacientes, con respuesta eficaz clínica y bioquímica de 86.67% en el grupo II y de 66.67% en el grupo I