Evaluation of some liver fibrosis markers in chronic liver diseases

Liver fibrosis is a dynamic bi-directional process involving phases of progression and regression. Its diagnosis is dependent on histopathological examination of biopsy specimens. The aim of this study was to evaluate some non invasive serum markers of liver fibrosis and to correlate them with liver biopsy. Fifty patients with chronic liver diseases matched with 10 age and sex healthy blood donors were included in the study. For both groups; estimation of serum matrix metalloproteinase 9[MMP-9], tissue inhibitor of metalloproteinase 1[TIMP-1] by ELISA technique and haptoglobin by RID, scoring of the age-platelet index [API], AST to platelet ratio index[APRI],and prothrombin time [PT] were done. For the patients, histopathological examination of liver biopsy specimens for assessment of necroinflammatory grade [A] and fibrosis stage [F] applying the METAVIR scoring system. API showed a significant positive correlation with both fibrosis and necroinflammatory activity, by using ROC curve for discrimination of significant fibrosis [F>/= 2] and moderate to severe necroinflammatory activity [A>/= 2], the AUROCs were 0.88 +/- 0.09 and 0.69 +/- 0.16 respectively. In case of Platelet count the AUROC was 0.80 +/- 0.12 for the diagnosis of established cirrhosis [F4]. PT showed a significant positive correlation with fibrosis progression, and it was a sensitive predictor of significant fibrosis and the AUROCs, for [F >/= 2] and [F4] were 0.67 +/- 0.15 and 0.76 +/- 0.15 respectively. While APRI showed a significant positive correlation with both fibrosis stage and necroinflammatory grade and the AUROCs were 0.68 +/- 0.15 and 0.69 +/- 0.15, for [F >/= 2] and [F4] respectively .The mean serum level of MMP-9 was significantly higher in patients than controls [P < 0.05] and showed a significant negative correlation with fibrosis stage [P < 0.05]. By using ROC curve to assess MMP-9 for discrimination of significant fibrosis [F>/= 2] and cirrhosis [F4], the AUROCs were 0.67 +/- 0.17 and 0.69 +/- 0.18 respectively, while for [A>/= 2], it was0.75 +/- 0.16. The mean value of serum TIMP-1 was significantly higher in patients than controls [P < 0.05], with significant positive correlation with necroinflammatory grade[P < 0.05]. The AUROCs for [F>/= 2] and [F4] were 0.58 +/- 0.2 and 0.53 +/- 0.19 respectively, while for [A>/= 2], it was 0.67 +/- 0.17. Haptoglobin showed a significant negative correlation with fibrosis progression[r=-0.4, P < 0.05] and AUROC for [F>/= 2] and [F4] were 0.75 +/- 0.17 and 0.78 +/- 0.15 respectively. MMP-9 was a fair marker of fibrosis as well as inflammatory activity, and TIMP-1 was a sensitive and to a lesser extent specific marker of advanced liver disease, discriminating inflammatory activity rather than fibrosis stage. On the other hand API was the best marker that can discriminate significant fibrosis, while platelet count for diagnosis of cirrhosis. Among the assessed serum markers, haptoglobin, API and PT were the most sensitive predictors of significant fibrosis, while haptoglobin and API were the most sensitive predictors of cirrhosis. Finally, these serum assays, although promising, are still in need of being refined with further prospective studies

Is there a role for islet cell antibodies [ICA] in hepatitis C virus-diabetes mellitus mysterious link?

There is an increasing evidence of strong association between hepatitis C virus [HCV] and diabetes mellitus particularly, non-insulin dependent diabetes mellitus [NIDDM], the cause of which is still obscure. Autoantibodies of different types have been screened in-patients with HCV. The presence of islet cell antibodies was conducted to clarify the possible role of ICA in this association and to find any correlation between ICA and other autoantibodies. We studied 48 patients with HCV as diagnosed by RIBA II and PCR. Patients were divided into group I [NIDDM group] and group II [Non diabetic group]. Group I comprised 14 males and 10 females with a mean age of 39,75 +/- 6 years, group II comprised 16 males and 8 females with a mean age of 39.60 +/- 5.8 years. Non of the patients received antiviral therapy. They were tested for: Blood glucose, liver functions [ALT, AST, Alkaline Phosphatase, Albumin and Prothrombin time]. The following non organ-specific autoantibodies were screened: Anti-mitochondrial antibodies [AMA], anti-smooth muscle antibodies [ASMA], and antinuclear antibodies [ANA]. Islet cell antibodies [ICA] were screened in their sera by indirect immunoflurescence test [Inova Lite, Research kit]. The results of the study showed relatively increased prevalence of ICA in group I [33.3%] than in group II [12.5%], but the difference was statistically non significant [P > 0.05], In group I A MA, ASMA and ANA were positive in 8.3%, 41.6% and 20.8% respectively, while in group II they were positive in 8.3%, 37.5%. and 16.7% respectively, with no statistical significant difference between both groups. ICA correlated significantly with ASMA in both groups and with ANA only in group II. No correlation was detected between ICA and AMA. Neither ICA nor other studied auto-antibodies did correlate to any of the studied liver functions, in group I, ICA did not correlate to either patient's age, sex or family history of diabetes. In [1] The HCV-Diabetes Mellitus Link deserves careful evaluation, [2] ICA alone could not explain the relatively high incidence of diabetes mellitus in HCV patients, [3] ICA might be present in the sera of HCV patients as a part of immune disturbances present in the disease. [4] There is a significant correlation between ICA and ASMA, [4] HCV might trigger an autoimmune phenomena that persist even after cessation of the disease activity, [5] other possible mechanisms for HCV-diabetes mellitus link might be: iron overload, metabolic effect, receptor and /or post-receptor effect, viral pancreatitis or HLA association