Abstract: Aims/Background: Patients with liver cirrhosis and portal hypertension frequently exhibit a multitude of alterations of hormones and metabolism, but the relation of these alterations to liver function, degree of blood shunting, and hepatic encephalopathy remains unclear. Methods: Twenty-four patients were randomised to mesocaval interposition shunt (MIS) and 21 patients to repeated sclerotherapy (ST). Several peptide hormones, amino acids and lysosomal enzymes were monitored during a 4 year follow-up period. Results: Insulin and glucagon levels were elevated in the MIS group compared to pre-therapy levels, whereas the gastrin level was significantly higher in the ST group. Pancreatic polypeptide, somatostatin and vasoactive intestinal peptide levels were not affected by either treatment. The branched chain amino acids valine, leucine and isoleucine serum levels were all elevated after ST, and the arginine, proline and tyrosine levels were higher in the MIS group at follow-up. Other amino acids were not changed, neither were the lysosomal enzymes beta-hexosaminidase nor beta-glucoronidase during this long-term follow-up. Conclusion: MIS or repeated ST treatment only affected serum levels of hormones, amino acids and lysosomal enzymes to a limited extent. In this trial, the type of treatment had only a small influence on these parameters during long term follow-up.