The Effect of Somatostatin on Mediators of Liver Inflammation and Fibrosis in Viral Cirrhosis

Background. Somatostatin and its synthetic analog octreotide are suppressive hormones that have been used in the treatment of variceal bleeding or bleeding from portal hypertensive gastropathy. They are also used in the treatment of some cancers, including hepatocellular carcinoma (HCC). Experimental evidence reported that they have potentially useful effects on liver inflammation and fibrosis, acting on Kupffer cells (KCs) and hepatic stellate cells (HSCs). However, clinical data is missing. Therefore, the effect of somatostatin and octreotide was studied on several fibrosis mediators in patients with compensated cirrhosis. Patients and Methods. Fifty-eight patients with HCV-related compensated cirrhosis treated with either somatostatin or octreotide for bleeding from portal gastropathy were compared with twenty-nine healthy controls matched for age and sex. Serum levels of three metalloproteases (MMP1, MMP2 and MMP9) and their inhibitors, TIMP1 and TIMP2, were measured. Additional fibrosis and inflammation mediators—such as nitric oxide (NO), TNFα, soluble ICAM-1, and the CC chemokines RANTES (CCL5) and MIP1a (CCL3)—were also measured. Results. Serum levels of MMP1, MMP2, MMP9 and TIMP1 were significantly decreased in cirrhosis (p < 0.01). TIMP2 levels were increased (p < 0.01). RANTES levels were also significantly decreased (p < 0.01), but NO, TNFα, MIP1a and sICAM-1 were significantly increased (p < 0.01). Administration of somatostatin had no effect on MMP2 or MMP9 but significantly decreased all other mediators. Octreotide had similar but milder effects, but it had no effects on MIP1a and sICAM-1 were demonstrated. Conclusions. Somatostatin and octreotide modulate factors implicated in the progression of fibrosis in the short term. Whether they could be used in the long term as treatment for liver diseases with progressive fibrosis or in cases with intense inflammatory reactions, such as alcoholic hepatitis, requires further investigation.