Intrahepatic and extrahepatic clinical manifestations and treatment progress for hepatitis type E / 中华肝脏病杂志

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

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.

Prediction of fibrosis progression in chronic viral hepatitis

Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

Diagnóstico e tratamento de hepatites virais: revisão atual / Diagnosis and treatment of viral hepatitis: an updating

As hepatites virais, principalmente as causadas pelos vírus A, B e C, são muito prevalentes no mundo inteiro. As formas crônicas das hepatites B e C são as mais comuns no nosso meio e acarretam importantes conseqüências, tanto sociais quanto econômicas . Sendo assim, é importante que o clínico, independente de sua área, saiba diagnosticar e encaminhar pacientes infectados. Este artigo tem como objetivo revisar os algoritmos diagnósticos das hepatites e expor os tratamentos atualmente preconizados para as formas crônicas destas afecções (hepatites B e C).

Effect of antiviral therapy on hematological parameters in patients with chronic hepatitis

To find out the effect of antiviral therapy on hematological parameters in patients of chronic hepatitis. Interventional descriptive study. Military hospital [MH] Rawalpindi Pakistan from May to Oct 2004. 31 patients admitted to M.H Rawalpindi for treatment of chronic hepatitis were studied. Their hematological parameters including Total Leucocyte count [TLC], Haemoglobin [Hb] and Platelet count [Plt] were recorded before starting antiviral therapy and then at 3 monthly intervals. All the patients were given Inj Alpha-Interferon [INF] and Tab Ribavirin as antiviral therapy. Data was collected over a period of 6 months. Descriptive statistics were applied to the recorded data using SPSS ver-10.0 for analysis. 31 patients with mean age +/- SD 38.58 +/- 8.85 years [range 16-49 years] were studied. There was mean hemoglobin [Hb] fall of 0.87g/dl at 3 months and 2g/dl at 6 months of antiviral therapy. Mean Total leukocyte count [TLC] fall of 1.30x10[9]/L at 3 months and 1.87x109/L was noted at 6 months. Similar downward trend was noted in Platelet [Plt] values with mean fall of 23.19x10[9]/mm[3] and 28.29/ mm[3] at 3 and 6 months of antiviral therapy respectively. 10% of the cases developed clinically significant anemia as evidenced by hemoglobin 11g/dl after 6 months of antiviral therapy. Clinically significant leucopenia [< 2.5x10[9]/l] was noted in 7% of the cases. This fall was noted only in first three months of treatment. There is significant decrimental response of hematological parameters to antiviral therapy

Hepatitis crónica activa en un caso de hipertiroidismo severo / Active chronic hepatitis in a severe hyperthiroidism case

Se describe una adolescente que sufría de hipertiroidismo severo de larga evolución, con pobre respuesta a medicamentos antitiroideos y dos episodios de ictericia previos, que ingresó con un hipertiroidismo clínicamente activo a pesar de estar recibiendo propiltiouracilo, ictericia intensa y hepatomegalia. El estudio y manejo de su hepatitis fue complejo, dado que las posibilidades de disfunción hepática en el contexto de un hipertiroidismo, podrían obedecer a toxicidad por drogas, insuficiencia cardíaca, hipertiroidismo por sí mismo o hepatitis autoinmune. Se manejó con suspensión del propiltiouracilo, régimen hipercalórico, propanolol y dos dosis de I131, con lo cual se logró controlar el hipertiroidismo. El estudio de laboratorio e histopatológico fue compatible con hepatitis crónica activa que se manejó con corticoides orales, coincidiendo con lo cual la paciente está asintomática, si bien la biopsia hepática muestra aún signos de actividad

Comparison of low dose and high dose interferon alpha in chronic hepatitis C

40 patients with chronic hepatitis [proven by liver biopsy and by raised ALT and other liver enzymes 1.5 times the normal value] are enrolled in the study. They are divided randomly into 2 groups. Group I comprised 20 patients [14 males and 6 females]. They were given Interferon alpha 6 million units. Group II comprised 20 patients [15 males and 5 females], they were given Interferon alpha 3 million units. The liver enzymes were estimated every month for the period of one year. Only the first and the last samples were included in the study. Before treatment, all patients have positive HCV ab and HCV RNA. Results showed that liver enzymes respond significantly in group I [P <0.0001] than in group II. The degree of normalization of enzymes was higher in group I [60%] if compared with group II [35%]. In conclusion, these finding suggested that high dose interferon-alpha [6 MU] given for one year is more effective that low dose [3 MU] to reduce liver enzymes, for normalization in more percentage of patients, and in reducing the viremia in patients with chronic hepatitis C. In the same time, it has high incidence of side effects on the bone marrow

HCV genotyping, a predictor to response to interferon alpha therapy in patients with chronic hepatitis C

The aim of this study was to find out a correlation between HCV genotype and the response to treatment with interferon [IFN] alpha in patients with chronic hepatitis due to virus C infection. 20 patients [14 males and 6 females] with chronic hepatitis proven by liver biopsy and raised ALT level 1.5 the normal value were enrolled in the study. All the patients were given IFN 6 million units 3 times per week for 6 months. Genotyping was done for all patients by RFLP technique. Results has shown that 10 patients have genotype 4 and 9 patients have genotype 1 and one patient has genotype 3. Patients were divided into group I [with genotype 4] [8 males and 2 females] and group II [with genotype I] [6 males and 3 females]. Serum ALT level decreased significantly after 6-month treatment in group I [P <0.001], while in group II SGPT is the only enzyme which showed significant decline. In conclusion, these findings suggested that genotype 4 is the most prevailing genotype in Egypt than the other genotypes, and that patients with genotype 4 have better response to treatment with interferon than genotype I. So, genotyping can be a good indicator to predict response to treatment with interferon

Reacción en cadena de la polimerasa "on-stage" y "nested": comparación de dos métodos para detectar el ARN del virus C en pacientes con hepatitis crónica C tratados con alfa interferón / One-stage and nested polymerase chain reaction: comparison of two methods to detect virus C RNA in patients with chronic hepatitis C treated with alfa interferon

El ARN del virus (HCV RNA) se detecta con la técnica de la reacción en cadena de la polimerasa (PCR), utilizándose dos variantes: la PCR "one-stage" y la PCR "nested". Comparamos ambas variantes en 40 muestras de suero de pacientes con hepatitis crónica C, 20 obtenidas antes del tratamiento con interferón alfa recombinante y 20 al concluir el mismo. El HCV RNA se detectó en 16 (80 ciento por ciento) de las muestras post-tratamiento, con iguales resultados positivos y negativos en ambas variantes. En 7 casos estudiamos las muestras pre y post-tratamiento de los mismos pacientes. Las muestras de los 7 pacientes fueron positivas por PCR "one-stage" y PCR "nested" al comenzar el tratamiento y de sólo 4 al concluirlo (1 con respuesta completa inmediata y 3 no respondedores). Tres pacientes se negativizaron con respuesta completa inmediata. Nuestro estudio muestra una correlación absoluta entre la PCR "one-stage" y la PCR "nested", sin que ésta se modifique por las posibles variaciones de la viremia provocadas por el interferón

Hepatites crônicas de estágio recente: resultados com o tratamento de imunossupressäo / Cronic hepatitis of recent stage: results with the immunossupression treatment

A hepatite viral possibilita a evoluçäo para a cronicidade em 5 a 10% dos casos, sendo que, desses, um terço à metade poderá chegar ao quadro final de cirrose hepática. Com o objetivo de interferir nessa evoluçäo, os autores estudaram 16 doentes portadores de hepatite tipo B, com permanencia do quadro clínico e laboratorial por tempo aproximado de 6 meses. Os mesmos foram divididos em 2 grupos iguais, sendo que um deles recebeu como tratamento imunossupressor (prednisolona e azotioprina) em dosagems pré-estabelecidas, permanecendo o outro grupo sem terapêutica. Através de exames laboratoriais e biópsias de fígado avaliam os resultados após 6 meses de estudo, concluindo que os doentes tratados apresentaram melhores resultados do que aqueles näo tratados, concluindo a açäo benéfica das drogas utilizadas

Hepatites cronicas na infancia: analise clinica, bioquimica, morfologica e evolutiva / Hepatitis chronics in the childhood: analysis clinical, biochemical, morpholical and evolutional

O estudo baseia-se na caracterizacao da Hepatite Cronica (HC) na infancia, quanto as manifestacoes clinicas presentes na ocasiao do diag nostico, aspectos evolutivos clinico, bioquimico e morfologico, bem como a resposta a terapeutica no grupo de criancas portadoras de Hepatite Cronica Ativa (HCA). Foi realizada a analise de 38 pacientes, de ambos os sexos, com idades compreendidas entre 3 meses e 16 anos e 7 meses, por ocasiao do diagnostico, os quais foram acompanhados por periodo de tempo que variou de 28 dias a 14 anos e 2 meses. O diagnostico de Hepatite Cronica Persistente (HCP) foi estabelecido em21 pacientes e HCA em l7. As manifestacoes clinicas iniciais foram heterogeneas e nao houve correlcao entre as mesmas e a gravidade da evolucao em ambos os gru-pos. Ictericia associada a hepato e/ou esplenomegalia foi o achado mais frequen-temente associado a ambas formas de hepatite cronica. A HCP caracterizou-se pe- la melhoria espontanea dos parametros clinicos, bioquimicos e morfologicos, sen-do que em 5 pacientes foi demonstrada a normalizacao dos parametros e foram con-siderados curados. Nos portadores HCA a terapeutica corticosteroide induziu a m lhoria daqueles parametros, 7 pacientes apresentaram recidiva da atividade da doenca e 11 deles evoluiram com cirrose; nestes casos a associacao de azatioprina a prednisona mostrou-se eficaz quanto ao controle da atividade da HCA. So foi possivel determinar a etiologia do processo em 34% dos casos.

Tratamiento de la hepatitis crónica activa tipo B con interferón leucocitario humano

Se administró interferon leucocitario humano a 62 pacientes con hepatitis crónica activa tipo B, durante un período de seis meses a una dosis total de 400 millones U.I. Se siguieron mensualmente durante un periodo de un año, repitiéndose la biopsia hepática. Las cifras de alanino-amino-transferasa se normalizaron en el 67.7 por ciento de los pacientes y se logró la seroconversión antígeno-anticuerpo o en el 59 por ciento. El antígeno no fue detectable al final del tratamiento en solo cuatro pacientes. La histología hepática mostro una normalización en 17 pacientes y una mejoría en casi la mitad de los mismos. Solo 3 pacientes evolucionaron hacia una cirrosis hepática. Los mejores resultados se apreciaron en sujetos jóvenes y en aquellos que no habían recibido previamente terapia inmunosupresora

Tratamiento de la hepatitis crónica viral / Treatment of chronic viral hepatitis

Gracias a los actuales conocimientos sobre la patogénesis de la hepatitis crónica viral y a la contemporánea disponibilidad de un amplio espectro de fármacos capaces de modular el sistema inmunitario y de interferir en la replicación viral, es hoy posible plantear una estrategia terapéutica más eficaz con respecto al esquema empírico y desilusionante del pasado. Se destaca la importancia del diagnóstico etiológico de la infección viral y del daño hepático para la elección del tratamiento más apropiado para cada uno de los pacientes, considerando los factores que favorecen o desfavorecen una buena respuesta terapéutica. Entre los fármacos disponibles el Interferon ha demostrado la mayor eficacia, pero su empleo es limitado a un grupo particular de pacientes. Tratamientos combinados han dado resultados interesantes en este último tiempo en pacientes refractarios al Interferon Alfa

Resultados y factores de pronóstico en el tratamiento de las hepatitis crónicas activas con prednisona y azathioprina / Results and factors of prognosis in the treatment of chronic active hepatitis with prednisone and azathioprine

Cincuenta y dos pacientes con hepatitis crónica activa (H.C.A.) fueron tratados con la asociación de prednisona-azathioprina. El 73% de los pacientes curaron. La curación se observó en el 94% de los enfermos que no presentaban puenteo necrótico previo al tratamiento, en cambio fue sólo del 43% en los que lo tenían. Las H.C.A. No A- No B curaron en el 81% mientras que las H.C.A. B + lo hicieron sólo en el 66%. El 100% de las H.C.A. No A- No B que curaron lo hicieron en un intervalo de tratamiento no mayor de 3 años, mientras que sólo el 40% de las H.C.A. B + que curaron, lo consiguieron en dicho período. El otro 60% de las B + curaron entre los 3 y los 12 años de tratamiento. En la H.C.A. B + el sexo masculino curó en el 75% mientras que el femenino lo hizó sólo en el 33%. El 7.6% de los pacientes evolucionaron a una cirrosis activa. Todos eran positivos. La mortalidad fue del 3.8% y se observó únicamente en las B +. Como conclusión se debe destacar que la presencia de puentes necróticos, el virus B y el sexo femenino fueron factores de peor pronóstico en la respuesta de la H.C.A. al tratamiento combinado prednisona-azathiprina