Changes Of Albumin Binding Function In Patients With Liver Injury And Liver Resection

Backgroud:Viral hepatitis in some countries, especially Asian countries, has an incidence rate that is 8% or higher. It is recognized as an important contributive factor for cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease (NAFLD) is becoming a common chronic disease in both developed and developing countries with increasing incidence. Non-alcoholic steatohepatitis (NASH) may also cause cirrhosis and eventually lead to hepatocyte carcinoma. This makes early diagnosis, assessment and timely treatment of this disease very important. However, currently there is no indicator that can evaluate actual liver lesion for early stages of viral hepatitis, non-alcoholic fatty liver disease (NAFLD) and cirrhosis. Aim of this study was to investigate if albumin metal ion and fatty acid binding function could better reflect liver function in these liver diseases.Methods:An observational study was performed on 193 patients with cirrhosis (n= 133), early NAFLD (n = 23), viral hepatitis (n = 37), and 60 healthy volunteers as controls. Cirrhosis patients were separated according to Child-Pugh score into A, B, and C subgroup. Albumin metal ion binding capacity (Ischemia-modified albumin transformed, IMAT=1-IMA) and fatty acid binding capacity (Total binding sites, TBS) were detected.Results:No differences were observed in albumin levels among the healthy control, NAFLD, and Hepatitis patients (P=0.36). However, the albumin levels of cirrhotic patients were significantly lower than those of the non-cirrhotic patients (P<0.001). Furthermore, the albumin levels continued to decrease as the liver lost more function. IMA assay reflected the serum albumin that had lost metal ion binding ability, IMAT indicated the tested albumin had higher metal ion binding capacity. However, both IMAT and TBS were significantly decreased in patients with NAFLD and early hepatitis compared with Control group (both P<0.001). In hepatitis group, they declined prior to changes of liver enzymes. IMAT was significantly higher in cirrhosis Child A group than hepatitis patients (0.51±0.13 vs 0.41±0.12, P=0.005), and decreased in Child B and C patients. No difference of TBS was observed between Child A and Hepatitis patients (P=0.31). Both IMAT/Albumin and TBS/Albumin decreased significantly in Hepatitis and NAFLD group patients (P<0.01), but obviously increased in Child A and Child B cirrhosis patients (P<0.05). We further divided the viral hepatitis patients into 3 subgroups according to the amount of viral genome presented in serum. Analysis of IMAT and TBS among these three subgroups showed that the ion-binding and fatty acid-binding activities were both affected, but had different changes among these patients.Conclusions:This is the first study to discover changes of albumin metal ion and fatty acid binding capacities prior to conventional biomarkers for liver damage in early stage of liver diseases. They may become potential earliest sensitive indicators for liver function evaluation, which could have positive impacts on evaluation and treatment of early stage liver diseases.Background:Assessing liver function in patients undergoing liver resection is crucial. As albumin concentration is regarded as an important marker of liver function, serum albumin concentration rather than its binding function is usually determined. Albumin concentration, however, is not an accurate determinant of albumin binding activity, as circulating albumin may have lost its binding function. Recent researches have disclosed that albumin binding function is very important, which decreases when liver injury. The effect of liver resection on it has not been determined. This study investigated effects of hepatectomy on albumin binding function in patients with and without cirrhosis.Methods:Patients who underwent liver surgery from January 2014 to March 2015 at the Department of Liver Surgery, Peking Union Medical College Hospital, were eligible. The study included 42 cirrhotic patients who underwent liver resection for hepatocellular carcinoma, and 17 non-cirrhotic patients who underwent resection for hepatic cavernous hemangioma. The control group included 50 healthy volunteers. Peripheral venous blood was drawn from all patients undergoing surgery on preoperative day 1 and on post-operative days (POD) 1,3, and 7. Albumin metal ion binding capacity was assayed as ischemia-modified albumin transformed (IMAT), and albumin fatty acid binding strength was also tested.Results:Tumor size was significantly smaller in the cirrhotic than in the non-cirrhotic group (5.94±3.46 cm vs 10.88±5.64 cm, P=0.00). Patients in the cirrhotic group who underwent resection of several liver segments or hemihepatectomy received infusions of 20 g/day commercial albumin for 3-5 days. Albumin infusions were not administered to patients in the cirrhotic group who underwent resection of a single liver segment or to patients in the non-cirrhotic group. Preoperative IMAT was significantly higher in healthy volunteers than in cirrhotic patients (P=0.02), but not than in non-cirrhotic patients (P=0.79). Following surgery, a prolonged and sharp reduction in IMAT was observed in cirrhotic patients; whereas, in non-cirrhotic patients, the decreased IMAT rose sooner and faster. IMAT in both operated groups rose to preoperative concentrations 7 days after surgery. In the cirrhotic group, only minor IMAT/Albumin fluctuations occurred after surgery (P=0.23), whereas in the non-cirrhotic group, IMAT began to increase after surgery and peaked on post-operative day 7 (P=0.00). The ratio of high-affinity to low-affinity fatty acid binding sites in both operated groups decreased for the first 3 days after hepatectomy, but increased to preoperative concentration by day 7. This ratio was higher in non-cirrhotic than in cirrhotic patients at all time points.Conclusions:This study is the first to show that albumin binding function decreases following liver resection in patients with and without cirrhosis, especially the former. Binding capacity is a better indicator of liver damage than albumin concentration, with the results less affected by albumin infusion. Albumin binding capacity may be an important indicator of liver function.