RESUMO
Primary biliary cholangitis is a cholestatic, chronic autoimmune liver disease with a wide individual variation in disease progression. The diagnosis is predominantly based on chronic elevation of alkaline phosphatase and the presence of anti-mitochondrial antibodies or other specific antinuclear antibodies (i.e. anti-gp210 and anti-sp100). Even in early-stage disease, health-related quality of life can be severely impaired by symptoms such as pruritus, fatigue, and sicca syndrome and metabolic bone disease should be assessed and treated. The prognosis of the disease is, however, largely determined by the development of cirrhosis and its complications. Ursodeoxycholic acid is associated with an improved prognosis and should be initiated and continued in all patients. Clinical outcome is related to the biochemical response to ursodeoxycholic acid, but the prognosis of those with an incomplete response is still better than those who remain untreated. Obeticholic acid was recently approved as second-line treatment and bezafibrate may serve as an adequate off-label alternative, particularly in patients with pruritus. Preliminary data suggest an additive effect of triple therapy with ursodeoxycholic acid, obeticholic acid, and bezafibrate, whereas other promising drugs are being evaluated in clinical trials.
Assuntos
Doenças Autoimunes/diagnóstico , Colagogos e Coleréticos/uso terapêutico , Doença Hepática Terminal/terapia , Cirrose Hepática Biliar/diagnóstico , Transplante de Fígado , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/mortalidade , Doenças Autoimunes/terapia , Bezafibrato/uso terapêutico , Biomarcadores/sangue , Biomarcadores/metabolismo , Biópsia , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapêutico , Progressão da Doença , Quimioterapia Combinada/métodos , Técnicas de Imagem por Elasticidade , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/mortalidade , Fadiga/diagnóstico , Fadiga/imunologia , Fadiga/terapia , Feminino , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Fígado/diagnóstico por imagem , Fígado/enzimologia , Fígado/imunologia , Fígado/patologia , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/mortalidade , Cirrose Hepática Biliar/terapia , Testes de Função Hepática , Pessoa de Meia-Idade , Uso Off-Label , Prognóstico , Prurido/diagnóstico , Prurido/imunologia , Prurido/terapia , Qualidade de Vida , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/terapia , Taxa de Sobrevida , Resultado do Tratamento , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.