Role of fibrogenic markers in chronic hepatitis C and associated hepatocellular carcinoma.

Detection and follow up of fibrogenesis in chronic hepatitis C (CHC) is mandatory for early treatment and risk stratification. The current study included 120 patients with CHC, of whom 30 had liver cirrhosis (LC) and 30 had hepatocellular carcinoma (HCC). 15 wedge liver biopsies, taken during laparoscopic cholecystectomy, were included as normal controls. Cases were subjected to laboratory investigations, serologic markers for viral hepatitis and assessment of circulating levels of hyaluronic acid (HA) and platelet-derived growth factor (PDGF). Immunohistochemical expression of connective tissue growth factor (CTGF), PDGF and transforming growth factor-ß1 (TGF-ß1) was also carried out. A significant increase (p < 0.01) in serum HA was noticed in CHC, LC and HCC compared to controls. Although, a significant decrease in serum PDGF was detected in CHC and LC compared to controls, HCC values were comparable. A significant up-regulation of CTGF was detected in CHC, LC and HCC (p < 0.01) in contrast to its limited mild expression in normal livers. Intense PDGF positive staining was noticed in CHC, LC and HCC compared to scattered faint expression in controls. The significant expression and marked intensity of PDGF staining matched the progress to tumorigenesis. A positive TGF-ß1 immunostaining was also noticed in CHC, LC and HCC. An intense and extensive cytoplasmic expression of TGF-ß1 was encountered in patients with LC revealing that CTGF, PDGF and TGF-ß1 act synergistically in LC. Data revealed that HA and CTGF may be implicated as important diagnostic parameters for assessment of hepatic fibrosis and PDGF for monitoring malignant transformation in CHC.

Effect of splenectomy on liver regeneration and function following partial hepatectomy: experimental study.

The presence of enough remaining functioning liver parenchyma to avoid life-threatening post-operative liver failure is a major prerequisite for hepatic resection in patients with hepato-biliary carcinoma. There are clinical reports which confirm the beneficial clinical effects of splenectomy on integrity of the residual liver following liver resection for hepatocellular carcinoma in cirrhotic patients with hypersplenism and portal hypertension. This experimental study was designed on hamsters to evaluate the proliferative capacity and function of the remaining liver lobes; in which splenectomy was done simultaneously with partial hepatectomy compared with those in which splenectomy was not done. Forty hamsters were divided into two groups: GI; in which partial hepatectomy was performed without splenectomy and the GII; in which animals were subjected to partial hepatectomy with prior splenectomy. Animals from each group were subjected to liver biopsy from the remaining lobes 48, 72 hours and one week after surgery. Also, serum alanine aminotransferase (ALT) and total bilirubin were tested before, 48, 72 hours and one week after hepatectomy. Hepatic regeneration in the remaining lobes was assessed through histo-pathological study, DNA ploidy of the hepatic nuclei using computerized image analysis system and determining of the labeling index of the nuclear factor NF Kappa B (P105), a novel monoclonal antibody specific for P105 protein by immunohistochemistry. In GII: induction of NK kappa B (P105) labeling index showed maximum expression depending on the regenerative capacity of the remaining liver lobes. In contrast, in GI; liver regeneration was slow. Also, changes in liver function of GII indicated that splenectomy prior hepatecotomy may minimize dysfunction in the remaining hypertrophied liver lobes.