Impact of epidermal growth factor receptor and transforming growth factor-α on hepatitis C virus-induced hepatocarcinogenesis.

Epidermal growth factor receptor system plays a central hepato-protective and pro-regenerative role in liver. Transforming growth factor-α (TGF-α) is an important autocrine growth regulator of hepatocytes that plays a role in development of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC). This study was done on 40 core liver biopsies from patients with CHC, 20 liver specimens from HCC cases on top of CHC as well as five normal controls. All were immunohistochemically stained with epidermal growth factor receptor (EGFR) and TGF-α antibodies. Some selected HCC cases were submitted for FISH technique to detect EGFR gene alteration. By immunohistochemistry EGFR and TGF-α were overexpressed in HCC and cirrhotic cases compared to CHC cases without cirrhosis. Also, their expression was stronger in CHC cases with higher grades of activity and stages of fibrosis compared to lower ones. FISH positive results for EGFR were detected in 33.3% of the examined HCC cases. EGFR and TGF-α can be used as predictive markers for activity, fibrosis, and carcinogenesis in CHC patients. Overexpression of EGFR in HCC patients can be promising in selecting those who can get benefit from anti-EGFR target therapy.

The effect of portal vein branch plus heterochronous hepatic artery branch ligation on liver regeneration (experimental study).

The proliferative capacity of non-ligated liver lobes was designned experimental study on dogs in which portal vein and hepatic artery ligation was done either simultaneously or heterochronously. Dogs were divided into four groups: G I (control G); laparotomy was performed without vascular ligation, G II; dogs were subjected to ligation of the right lateral and median branches of portal vein alone, G III, dogs were subjected to hepatic artery branches ligation 48h after portal vein branches ligation. G IV, dogs were subjected to ligation of the same branches of the portal vein and hepatic artery simultaneously. Dogs from each group were subjected to a liver biopsy before and 24, 48, 72, & 168h (one week) after surgery. Standard serum liver functions were tested before ligation, 72 hs and one week after ligation. Hepatic regeneration in the non-ligated lobe was assessed through histo-pathological study, DNA quantitation of the hepatic nuclei by the computerized image analysis system and estimation of proliferation marker in hepatic tissue. In this study, the labeling index of the nuclear factor NF Kappa B (P105), a novel monoclonal antibody specific for P105 protein, was determined immunohistochemically. Results showed induction of the NK kappa B (P105) labeling index showed maximum levels G III. Quantitative determination of serum glutamic-oxalacetate transaminase (GOT) showed peak levels in G IV at 24h after surgery. Our finding for this index that heterochronous partial portal vein and hepatic artery ligation (i.e., G III) is effective, because this procedure leads to an increase in the compensatory hypertrophy of the non-ligated liver lobes that depends on the regenerative capacity of the lobes themselves. In contrast, in G IV (i.e., synchronous ligation of portal vein and hepatic artery branches) liver regeneration did not occur due to the severe systemic damage induced by infectious necrosis in the ligated lobe. The serial changes in liver function in G III indicate that the use of this technique may minimize dysfunction in the remaining hypertrophied liver lobes, similar to findings in G II. So, the PVBL plus heterochronous HABL procedure is safer and more effective than PVBL alone, or PVBL plus simultaneous HABL. A better knowledge of the events following such heterochronous ligation should improve the clinical outcome of hepatic resection for liver diseases.