Impact of the combined low dose prednisolone regimen on liver fibrosis in children with autoimmune hepatitis who responded to treatment

Autoimmune hepatitis [AIH] is a chronic liver disease characterized histologically by interface hepatitis. Hepatic fibrosis and cirrhosis can occur in many types of chronic liver injury including AIH. Recent studies have reported that hepatic fibrosis and cirrhosis may be reversible in some patients with AIH who respond to treatment. To assess the effects of treatment on fibrosis in liver biopsies of children with AIH who responded to the combined low dose prednisolone and azathioprine regimen. Twenty children with median age 8 +/- 3.5 yrs [9 girls, 11 boys], 18 AIH type I and two AIH type II, who were in clinical and biochemical remission for at least 6 months, and who had a diagnostic and a follow-up liver biopsy were included in this study. Different histological stains were used for assessing the grade of necroinflammatory activity [HAI] and for evaluating the stage of fibrosis according to Ishak scoring system. Morphometric analysis using LeicaQ500IS image analyzer was applied on Peri's stained liver sections to assess the percentage of liver fibrosis. Data revealed significant decrease in the median HAI from 8.85 to 3.6 [p=0.001]. The median fibrosis score showed significant reduction from 3.9 to 2.4 [p=0.001] and the median fibrosis percentage decreased from 28.7 to 12.8 [p=0.001]. These data provide evidence for regression of fibrosis in AIH in children who responded to the combined low dose immunosuppressive prednisolone and azothioprine regimen. Fibrosis control is associated with regression of necroinflammatory activity, which is the main treatment component in AIH

Biochemical markers of fibrogenesis in pediatric chronic liver diseases

Objectives: Non-invasive diagnosis of hepatic fibrosis has become the focus, especially in the surveillance of treatment and in screening hepatic fibrosis. To investigate the clinical usefulness of fibrogenesis markers in evaluating liver fibrosis, we determined serum levels of TGF-beta1, collagen IV, and laminin., and their relationships with frequently used liver function tests, and findings of liver ultrasonography and liver biopsy were investigated

Methods: 50 patients with chronic liver diseases were enrolled from the National Liver Institute, Menoufiya University. Serum markers of fibrosis, liver function indices [for the patients and 30 controls], and ultrasonography for all patients were performed and compared with histologic fibrotic changes

Results: Serum levels of TGF-beta1, collagen IV. and laminin were significantly higher in patients than those in control [P<0.000]. The levels of serum fibrosis markers were not correlated with fibrotic scores [P>0.05], but laminin was positively correlated to histologic activity index. There were no significant changes in the level of serum fibrosis markers related to ultrasonographic findings. Their levels were also not correlated to ALT or AST. The cut-off values, specificity and sensitivity were determined for all markers, among which collagen IV was the marker with the highest sensitivity and specificity

Conclusion: Serum level of TGF-beta1, collagen IV, and laminin can be used as indices for the diagnosis of hepatic fibrosis. Among them, collagen IV is more sensitive. Biochemical markers of fibrogenesis might be useful in regular monitoring of disease development and treatment effectiveness and should be inseparable part of progression assessment in all chronic hepatopathies

Serum aspartate aminotransferase isoenzymes in cholestatic infants and children

Serum aspartate aminotranferase enzyme [AST] and its isoenzymes; the cytosolic [c-AST] and mitochondrial [m-AST] are usually increased in different liver diseases. The aim of this work is to determine the level of AST isoenzymes in infants with cholestasis and to assess the value of such determination in differentiating intrahepatic from extrahepatic causes and also in predicting disease severity. This study included 50 patients suffering from neonatal cholestasis, admitted to National Liver Institute, Menoufiya University. They were: 26 patients with extrahepatic biliary atresia [EHBA]; 13 patients with idiopathic neonatel hepatitis [INH]; 3 patients with paucity of interlobular bile ducts [PILBD]; 3 patients with alpha-one-antitrypsin deficiency [alpha 1-ATD]; 2 patients with septicemia; 1 patient with choledochal cyst; 1 pataient with Niemann Pick disease and 1 patient with primary sclerosing cholangitis [PSC]. Ten normal healthy infants of matched age and sex served as a control group. All patients were subjected to full history taking, thorough clinical examination and appropriate investigations. Aspartate aminoransferase enzyme and its isoenzymes were measured in all groups and it was found that: all patient groups had significantly elevated total AST levels in comparison to the normal controls, the total AST level was significantly higher in patients with INH as compared to those with EHBA, the c-AST level in all patient groups was significantly higher than that in normal controls, all patient groups had significantly elevated m-AST levels in comparison to the normal controls, the m-AST level was significantly higher in patients with INH as compared to those with EHBA, in the subgroups of both EHBA and INH, the c-AST was preferentially elevated in subgroup a [fair outcome, Child class B] while the m-AST was preferentially elevated in subgroup b [poor outcome, Child class C], the m-AST/total AST ratio showed a statistically significant difference between EHBA and INH on one hand and between INH and alpha -1ATD on the other hand. In comparative analysis of m-AST/total AST ratio among various patient groups, we found that there was a high statistically significant difference between EHBA and INH [P<0.01] and according to the cut-off point of this ratio, we found that any homeostatic infant having a ratio more than 0.359 is most probably diagnosed as an intrahepatic cholestasis, while any ratio less than 0.359 is most probably diagnosed as an extrahepatic cholestasis. c-AST level is increased in all groups of cholestatic disorders in which there is mild damage of hepatocyte plasma membrane [cases of fair outcome], while the m-AST level is highly increased in severe hepatocellular injury which cause mitochondrial damage [cases of poor outcome]. Also, we conclude that a cut-off point of 0.359 of the m-AST total AST ratio is useful in differentiating between intra-hepatic and extrahepatic cholestasis

Hepatic hemodynamic changes during acute viral hepatitis in children: Assessment by color Doppler Sonography

To study the pattern of hemodynamic changes in both portal vein [PV] and hepatic artery [HA] through the different stages of acute viral hepatitis in children and to determine any sonographic correlation with the prognosis or with other studied paprameters including clinical features and liver function tests, we performed color Doppler sonography [after full clinical examination and laboratory investigation] with point spectral analysis in 50 children suffered from acute viral hepatitis for four consequtive weeks and compared the results with those in 20 normal controls. The portal vein diameter and velocity showed no significant changes either during different stages of acute hepatitis or with the control group while during the acute phase, the peak-systolic [PSV] and end-diastolic [EDV] velocity of the hepatic artery were significantly larger than those in normal arteries [P < 0.01]. During the recovery phase, these indexes of the hepatic artery decreased significantly to the control levels [P < 0.01]. The resistive indexes [RI] related to vascular resistance in the hepatic artery during the acute phase were significantly less than those in normal arteries [P < 0.01], and they increased significantly to the control levels during the recovery phase [P < 0.01]. No significant correlation was found between these indexes of the hepatic artery and the parameters of liver function tests. However, the interval between the acute phase and the recovery phase did significantly correlate negatively with the peak-systolic velocity of the hepatic artery in the acute phase [r=-0.341, P < 0.05] and correlate highly significant with the end-diastolic velocity [r=- 0.837, P < 0. 01]. We conclude that Doppler sonography is useful for imaging hepatic hemodynamic changes in patients with acute viral hepatitis. We found that significant changes occur only in hepatic artery while no changes occurred in the portal vein. Also measurement of hepatic arterial flow during acute phase may be a convenental and reliable of determining the prognosis of patients with viral hepatitis where the increased hepatic arterial blood flow during the acute phase may provide a marker for earlier recovery from hepatitis-induced damage and may be considered as a good marker for the prognosis

Fas antigen in serum and liver tissue of patients with chronic hepatitis C

Fas [APO-1/CD95], a member of the tumor necrosis factor receptor Family, can mediate apoptosis when engaged by its ligand or by anti-Fas antibody. Fas is upregulated on the surface of hepatocytes in patients with a variety of liver pathologies, including hepatitis, alcoholic cirrhosis, and acute liver failure. Moreover, expression of Fas ligand is substantially upregulated, in areas of lymphocytic infiltration, in liver diseases, suggesting Fas/FasL interactions may mediate liver damage in humans. The purpose of this study was to evaluate the relationship of serum soluble Fas [sFas] levels and hepatic Fas antigen expression with the degree of hepatic inflammatory activity in patients with chronic hepatitis C infection. The effect of concomitant schistosomiasis, as an endemic liver disease in Egypt, on serum and liver Fas expression was also studied. Serum sFas levels were measured by enzyme-linked immunosorbant assay in 69 chronic hepatitis C patients; 16 of them were under 18 years and compared with those in normal volunteers, and patients with chronic HBV infection. The results of serum tests were compared with ALT levels. HCV-RNA titer, histological inflammatory activity, and Fas expression in liver biopsies. The effect of combined HCV infection and schistosomal infestation on serum sFas and tissue Fas expression was also studied. Serum sFas and tissue Fas expression were then evaluated with each components of histological inflammatory activity scoring system [modified Knodell's HAI]. Serum sFas levels in chronic hepatitis C patients were significantly higher than those in normal volunteers [p<0.001]. They showed no difference from those in patients with chronic HBV infection [p>0.05]. Hepatic schistosomiasis didn't affect serum sFas levels or tissue expression of Fas antigen in chronic hepatitis C patients. Histologically, serum sFas levels showed strong correlation with tissue Fas expression [p<0.001] and with the degree of hepatic inflammatory activity [p<0.01]. Likewise, tissue Fas expression correlated with the degree of histological inflammatory activity [p<0.05]. Moreover, positive correlation was found between serum sFas and tissue Fas expression and the degree of interface hepatitis [piecemeal necrosis] in chronic hepatitis C patients with mild [p<0.01] and moderate and severe activity [p<0.05]. However, no correlation was observed between serum sFas and serum ALT levels. Also, no correlation was observed between HCV-RNA titer and sFas levels or tissue Fas expression. Our findings suggest that serum sFas levels may reflect the expression of Fas antigen on hepatocytes and the severity of liver inflammation in chronic hepatitis C and may be used as a serological indicator of histological inflammatory activity. They also support the concept that immune-mediated apoptosis may play a crucial role in the pathogenesis of chronic hepatitis C. Hepatic schistosomiasis seems to have no impact on serum sFas levels or hepatic tissue Fas expression