HBx M130K and V131I (T-A) mutations in HBV genotype F during a follow-up study in chronic carriers.

BACKGROUND: Around 400 million people worldwide are chronically infected with Hepatitis B virus (HBV). An estimated 10% of these chronic patients develop progressive liver damage including cirrhosis and Hepatocellular Carcinoma (HCC). The HBx gene encodes a protein of 154 amino acids which is a transactivator and has been associated with HBV pathogenesis. A change in the amino acid sequences at positions 130 and 131 in the HBV-X protein (M130K and V131I) produced by T-A point mutations at the nucleic acids level has been associated with severe liver damage and HCC in patients from China and Africa. Further, such changes have been proposed as a prognostic marker for progressive liver damage and HCC. The purpose of this study was to determine if T-A mutations are present in HBV chronic carriers with genotype F (the major genotype in Costa Rica) and further, if these mutations are associated with HBV disease progression in Costa Rica HBV patients from 1972 to 1985. RESULTS: Serum samples from 50 HBV positive individuals were amplified and directly sequenced, 48 belonged to genotype F, 1 from genotype D and another was classified as D or E. T-A mutations were absent in 17 acute patients who recovered, but was present in 12 of 29 chronic carrier samples (42.8%), in one sample the T-A mutations were detected as early as 29 days after clinical onset of disease. In 17 carriers with available liver biopsies, T-A mutations were found in 8 sera of 13 (61.5%) classified as moderate or severe, and none in 4 biopsies with mild liver damage. However, it was not possible to demonstrate a statistical association between the presence of T-A mutations and moderate/severe liver damage, using a Fischer exact test, 1 tail, p = 0.05. In 4 patients HCC was diagnosed, and 2 of them presented the T-A mutations in their sera. CONCLUSION: T-A mutations were found in HBV genotype F in chronic carriers but not in patients who recovered from acute infection. These mutations could be developing early during infection although the possibility of infection with the mutant virus could not be excluded. More studies are necessary to establish if the T-A mutation can be used as a prognostic marker for severity of liver disease in patients infected with HBV.

Enfermedad de Wilson fulminante en Costa Rica: Estudio clinico patologico de 7 casos / Fulminant Wilson's disease in Costa Rica: pathological clinical study of 7 cases

En los últimos 18 añno (entre 1972-1989), alrededor de 150 casos de enfermedad de Wilson se han diagnosticado en Costa Rica (6/100.000 habitantes). En el Hospital San Juan de Dios se han estudiado alrededor de 120 casos durante este período, de los cuales 7 han muerto con un cuadro de insuficiencia hepática aguda, anemia hemolítica, encefalopatía, sangrado digestivo e insuficiencia renal. En cuatro de estos casos se realizaron estudios histopatológicos postmorten, con microscopía de alta resolución, revelando extensa necrosis submasiva del hígado, con severa colestasis y necrosis lítica y acidófila con regeneración irregulary nodular y especialmente esteatosis microvacuolar, diferente a la observada en otras formas de hepatitis fulminante. Con los hallazgos clínicos, de laboratorio e histopatológicos, concluimos que la enfermedad de Wilson fulminante es una entidad clínica-patológica bien definida, de fatal evolución sin respuesta al tratamiento, incluído la iniciación sin respuesta al tratamiento, incluíndo la iniciación temprana de penicilamina e esteroides