Temporal histopathological changes in biliary atresia: A perspective for rapid fibrosis progression.

INTRODUCTION AND OBJECTIVES: Biliary atresia (BA) is characterized by rapid progression of fibrosis with no definite causes. Histopathological findings have been extensively described, but very few studies have assessed temporal changes in BA. Understanding these short-term changes and their relationship with fibrosis progression could have an impact on ameliorating rapid fibrogenesis. We aimed to study the relationship between temporal histopathological changes and fibrosis progression in BA within a short time interval. PATIENTS AND METHODS: Forty-nine infants with BA who underwent Kasai portoenterostomy, a diagnostic liver biopsy, and an intraoperative liver biopsy were recruited. Histopathological characteristics of the two biopsies were examined. Temporal histopathological changes were assessed by comparing the two types of biopsies. Correlation of temporal changes in fibrosis with age, interval between biopsies, laboratory profiles, and temporal histopathological changes were studied. RESULTS: In the univariate analysis, bile ductular proliferation (BDP), portal infiltrate, giant cells, hepatocellular swelling, and fibrosis showed significant temporal changes within a short interval (5-31 days). BDP and fibrosis showed the most frequent increase in their grades (32/49 and 31/49 cases, respectively). In the multivariate analysis, BDP was the only independent pathological feature showing a significant temporal increase (p = 0.021, 95% confidence interval: 1.249-16.017). Fibrosis progression was correlated with temporal changes in BDP (r = 0.456, p = 0.001), but not with age (p = 0.283) or the interval between the biopsies (p = 0.309). CONCLUSIONS: Fibrosis in BA progresses rapidly and is significantly correlated with BDP. Assessment of targeting BDP as an adjuvant medical therapy is recommended.

Serum cystatin C correlates negatively with viral load in treatment-naïve children with chronic hepatitis C.

OBJECTIVES: Hepatitis C virus (HCV) infection is a serious health problem that causes chronic infection in up to 85% of cases. HCV nonstructural (NS) cysteine protease, NS2/3, is required for viral replication in vivo. Cystatin C is a naturally occurring cysteine protease inhibitor in human cells. We aimed to investigate the relation between serum levels of cystatin C and HCV viremia in treatment-naïve children with chronic hepatitis C. METHODS: Serum cystatin C levels were measured in 27 children with chronic hepatitis C and determined their relation with liver functions, histopathological parameters, and hepatitis C viral load. Serum cystatin C was compared with that of 25 age- and sex-matched healthy controls. RESULTS: Cystatin C was significantly higher in patients than in controls (1.4 ±â€Š0.47 vs 0.99 ±â€Š0.49; P = 0.006), and in those with low viremia than in those with moderate viremia (1.55 ±â€Š0.41 vs 0.99 ±â€Š0.43; P = 0.013). Cystatin C was not correlated with histopathological findings in liver biopsy (P > 0.05 for all). In addition, there was no significant difference of cystatin C levels in patients with normal versus those with elevated transaminases (P > 0.05). Of importance, cystatin C correlated negatively with viral load (P < 0.0001). CONCLUSIONS: Cystatin C levels correlated negatively with HCV viremia. This finding may reflect an inhibitory effect of cystatin C on HCV replication through inhibiting its NS2/3 and tempting for further studies for cystatin C as a possible adjuvant therapy for HCV infection.