RESUMO
The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased among the general population and chronic hepatitis B (CHB) patients worldwide. Although fatty liver disease is a well-known risk factor for adverse liver outcomes like cirrhosis and hepatocellular carcinoma, its interactions with the hepatitis B virus (HBV) and clinical impacts seem complex. The presence of hepatic steatosis may suppress HBV viral activity, potentially leading to attenuated liver injury. In contrast, the associated co-morbidities like diabetes mellitus or obesity may increase the risk of developing adverse liver outcomes. These findings implicate that components of MAFLD may have diverse effects on the clinical manifestations of CHB. To this end, a clinical strategy is proposed for managing patients with concurrent CHB and MAFLD. This review article discusses the updated evidence regarding disease prevalence, interactions between steatosis and HBV, clinical impacts, and management strategies, aiming at optimizing holistic health care in the CHB population.
Assuntos
Hepatite B Crônica , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores de Risco , Cirrose Hepática/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologiaAssuntos
Gastroenterologia/organização & administração , Hepatopatia Gordurosa não Alcoólica , Guias de Prática Clínica como Assunto , Adolescente , Ásia , Cirurgia Bariátrica , Carcinoma Hepatocelular/etiologia , Ácido Quenodesoxicólico/administração & dosagem , Ácido Quenodesoxicólico/análogos & derivados , Criança , Dieta , Exercício Físico , Ácidos Graxos Ômega-3/administração & dosagem , Humanos , Neoplasias Hepáticas/etiologia , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/complicações , Obesidade/cirurgia , Ilhas do Pacífico , Risco , Revisões Sistemáticas como Assunto , Tiazolidinedionas/administração & dosagem , Vitamina E/administração & dosagemRESUMO
This study aimed to investigate the role of src-homology protein tyrosine phosphatase-1 (SHP-1)-signal transducer and activator of transcription 3 (STAT3) pathway in liver fibrogenesis and the anti-fibrotic effect of SHP-1 agonist. The antifibrotic activity of SC-43, a sorafenib derivative with an enhanced SHP-1 activity, was evaluated in two fibrosis mouse models by carbon tetrachloride induction and bile duct ligation. Rat, human, and primary mouse hepatic stellate cells (HSCs) were used for mechanistic investigations. The results showed that SHP-1 protein primarily localized in fibrotic areas of human and mouse livers. SC-43 treatment reduced the activated HSCs and thus effectively prevented and regressed liver fibrosis in both fibrosis mouse models and improved mouse survival. In vitro studies revealed that SC-43 promoted HSC apoptosis, increased the SHP-1 activity and inhibited phospho-STAT3. The enhanced SHP-1 activity in HSCs significantly inhibited HSC proliferation, whereas SHP-1 inhibition rescued SC-43-induced HSC apoptosis. Furthermore, SC-43 interacted with the N-SH2 domain of SHP-1 to enhance the activity of SHP-1 as its antifibrotic mechanism. In conclusion, the SHP-1-STAT3 pathway is crucial in fibrogenesis. SC-43 significantly ameliorates liver fibrosis through SHP-1 upregulation. A SHP-1-targeted antifibrotic therapy may represent a druggable strategy for antifibrotic drug discovery.