Serological markers of autoimmunity in children with hepatitis A: relation to acute and fulminant presentation.

OBJECTIVES: Hepatitis A virus (HAV) infection tends to be a self-limiting disease without serious sequelae, but fulminant hepatitis, with a high mortality, develops in 0.1-0.2% of the cases. Sometimes, HAV infection precipitates autoimmune hepatitis (AIH). We aimed to assess the frequency and clinical significance of serologic markers of autoimmunity during hepatitis A infection with an acute or fulminant presentation compared with those in AIH. METHODS: The study included 126 children: 46 with HAV infection (33 with acute and 13 with fulminant presentation), 53 with AIH, and 27 healthy controls. In all, we measured autoantibodies titer (antinuclear antibody, antismooth muscle antibody, and liver kidney microsomal antibody-1) and serum gammaglobulins. RESULTS: Autoantibodies were detected in the majority of HAV (63.1%) and AIH (79.2%) groups, but in none of the controls. Gammaglobulins were significantly higher in the HAV group (1.93±0.57 g/dl) than in the controls (1.32±0.29 g/dl), but lower than that in the AIH group (2.93±1.2 g/dl) (P<0.0001 for all). In the HAV group, gammaglobulins were significantly higher in those with fulminant (2.21±0.46 g/dl) than in those with acute presentation (1.82±0.57 g/dl) (P=0.019), but comparable with that in AIH (P=0.095). Gammaglobulins correlated significantly with disease severity in both HAV and AIH groups. CONCLUSION: Hypergammaglobulinemia and a high occurrence of autoantibodies are encountered in HAV infection. This may support the immunological basis of its pathogenesis. Moreover, the higher gammaglobulins in fulminant HAV, with an insignificant difference from that in AIH, suggest that a more aggressive immunological reaction is related to this presentation.

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.