RESUMEN
BACKGROUND & AIMS: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. METHODS: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. RESULTS: During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p <0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p <0.001). CONCLUSIONS: In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. IMPACT AND IMPLICATIONS: Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/tratamiento farmacológico , Estudios de Cohortes , Estudios Retrospectivos , Estudios Transversales , Antivirales/uso terapéutico , Factores de Riesgo , Europa (Continente) , Fibrosis , África del Sur del Sahara/epidemiología , Virus de la Hepatitis B/genéticaRESUMEN
PURPOSE: This study aims to investigate the antiviral effect of polyethylene glycol (PEG)-interferon α-2a and PEG-interferon α-2b treatment on hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) at the 48th week of treatment and the 24th and 48th week after withdrawal, in order to provide guidance on the antiviral treatment of HBeAg-positive CHB patients. MATERIAL AND METHODS: Antiviral treatment was performed on 155 HBeAg-positive CHB patients. Among these patients, 66 patients received PEG-interferon α-2a treatment and 89 patients received PEG-interferon α-2b treatment; and these treatments were administered by subcutaneous injection, once per week, which lasted for 48 weeks. Other antiviral and hepatoprotective drugs were not used during the treatment. RESULTS: At the 48th week of treatment, ALT recovery rate, HBsAg seroconversion rate, HBeAg seroconversion rate and HBV DNA titers dropped below 200 IU/mL rate were 69.7%, 6.1%, 27.3% and 50.0%, respectively, in the PEG-interferon α-2a group; and were 70.8%, 6.7%, 33.7% and 62.9%, respectively, in the PEG-interferon α-2b group. At the 24th and 48th week of follow-up after withdrawal, HBsAg seroconversion rate in these two groups did not change; and HBeAg seroconversion rate further increased. Furthermore, HBV DNA revealed a low recurrence rate. The difference between these two groups was not significantly significant. CONCLUSIONS: PEG-interferon α-2a and PEG-interferon α-2b are effective antiviral drugs for the treatment of HbeAgpositive CHB, which has a HBsAg seroconversion rate of more than 5%. Furthermore, this sustained response effect was maintained at the 24th and 48th week of follow-up after withdrawal.
Asunto(s)
Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Antivirales/efectos adversos , Biomarcadores/sangre , ADN Viral/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Recurrencia , Estudios Retrospectivos , Seroconversión , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
Alagille syndrome is a multisystem disorder with an autosomic dominant pattern of inheritance that affects the liver, heart, eyes, kidneys, skeletal system and presents characteristic facial features. Mutations of the JAG1 gene have been identified in 20-89% of the patients with Alagille syndrome, this gene encodes for a ligand that activates the Notch signaling pathway. In the present study we analyzed 9 Mexican patients with Alagille syndrome who presented the clinical criteria for the classical presentation of the disease. By using the denaturing high performance liquid chromatography mutation analysis we were able to identify different mutations in 7 of the patients (77.77%), importantly, we found 5 novel mutations in JAG1 gene. The allelic frequency distribution of 13 polymorphisms in Mexican population is also reported. The overall results demonstrated an expanding mutational spectrum of JAG1 gene in the Mexican population.