RESUMEN
BACKGROUND: Fibrosis-4 index (FIB-4) is a surrogate marker for hepatic fibrosis in hepatitis B virus (HBV) carriers. AIM: To investigate whether FIB-4 index stratifies the risks of adverse liver events. METHODS: A total of 2075 treatment-naïve, noncirrhotic the patients with chronic HBV infection were included. Most of them (82.1%) were HBeAg-negative patients and their baseline FIB-4 levels were explored to stratify the risks of cirrhosis, cirrhosis-related complications and liver-related mortality. RESULTS: During a mean follow-up period of 15.47 years, we found a higher baseline FIB-4 index was associated with increased incidence rates of cirrhosis in addition to the common host and viral factors. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with increased risks of cirrhosis, cirrhosis-related complications and liver-related mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76-8.05), 6.88, (3.68-12.86) and 7.79, (4.54-13.37) respectively. Within the first 3 years of follow-up, FIB-4 remained stable and its kinetics were consistently associated with the develoopment of adverse liver events. Furthermore, FIB-4 index of 1.29 was able to stratify all the risks of adverse liver events even in HBeAg-negative patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000 IU/mL and ALT <40 U/L). Only 1 patient with FIB-4 index <1.29 developed cirrhosis but not other events within 15 years of follow-up. CONCLUSIONS: In noncirrhotic patients with chronic HBV infection, a higher FIB-4 index was associated with increased risks of adverse liver events. FIB-4 index <1.29 is useful for the prediction of the lowest risks of disease progression.
Asunto(s)
Virus de la Hepatitis B , Hepatitis B Crónica/sangre , Hepatitis B Crónica/mortalidad , Cirrosis Hepática/sangre , Cirrosis Hepática/mortalidad , Adulto , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
BACKGROUND: Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. METHODS: We explored the association between viral genomic factors and HBsAg loss in 2121HBeAg-negative patients. HBV pre-core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/mL (N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers. RESULTS: The cumulative lifetime (age 28-75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg-negative patients. We found that genotype C, but not pre-core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4-2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re-included HBeAg-positive, cirrhotic and treatment-experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers. CONCLUSION: Genotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers.
Asunto(s)
Portador Sano/virología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B/sangre , Adulto , Anciano , Estudios de Cohortes , ADN Viral/genética , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Incidencia , Masculino , Persona de Mediana EdadAsunto(s)
Cromosomas Humanos X/genética , Proteínas del Ojo/genética , Ligamiento Genético/genética , Trastornos de la Audición/diagnóstico , Mutación , Infecciones del Sistema Respiratorio/genética , Retinitis Pigmentosa/diagnóstico , Adolescente , Anciano , Secuencia de Aminoácidos , Niño , Proteínas del Ojo/inmunología , Femenino , Trastornos de la Audición/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Recurrencia , Retinitis Pigmentosa/genética , SíndromeRESUMEN
Resistin, the peptide specifically secreted from adipocytes, is a hormone antagonistic to insulin action and, thus, may serve as a link between human obesity due to adiposity and insulin resistance associated with type 2 diabetes. To test this hypothesis, we studied the gene expression of resistin in adipocytes isolated from rats fed with a fructose diet which induced insulin resistance. Compared to the control rats (C) on a normal chow diet, the fructose-fed rats (F) developed hyperinsulinemia, glucose intolerance, hypertriglyceridemia and hypertension, a profile reminiscent of the syndrome X of patients with non-insulin-dependent diabetes mellitus (NIDDM). The F rats had significantly elevated plasma free fatty acids (FFA), enlarged epididymal fat pads, and increased adipocyte size compared with the C rats. We examined the glucose transport and the relative quantity of resistin mRNA produced in the adipocytes of these two groups of rats. Compared to the C rats, the F rats had a clearly reduced insulin-stimulated glucose transport. The gene expression of resistin and other adipocyte peptides was measured on the mRNA by semiquantitative RT-PCR; the validity of this technique was established in advance with a rat-fasting and then refeeding experiment. The F rats showed a decreased expression of the resistin gene, whereas gene expression of leptin and angiotensinogen in contrast increased. Free fatty acids were found to suppress the expression of resistin gene in normal rat adipocytes. These results demonstrate that an insulin-resistant instance in the fructose diet rat model exists with the decreased gene expression of resistin.