Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett\u27s esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations

Treatment and Prognosis of Hepatitis B Virus Concomitant with Alcoholism

Hepatitis B virus (HBV) infection is a global disease worldwide. The Asia-Pacific region has a high prevalence of viral hepatitis, and Taiwan is a region of high prevalence of chronic hepatitis B (CHB) with increasing alcoholic liver disease. We have investigated the prognosis and treatment of patients with concomitant hepatitis B virus (HBV) infection and alcoholism. The 10-year cumulative incidence of hepatocellular carcinoma (HCC) is much higher in patients with concomitant alcoholism and HBV infection than in those with alcoholism or HBV infection alone. Treatment with antiviral therapy and abstinence may be started in patients with decompensated cirrhosis and compensated cirrhosis with high HBV DNA. In pre-cirrhotic cases, treatment with antiviral therapy and abstinence may be started in patients with persistently elevated ALT levels and high HBV DNA, and significant fibrosis with minimal elevated or normal ALT levels and mild high HBV DNA. Treatment with antiviral therapy and abstinence reduces the incidence of HCC in patients with concomitant HBV infection and alcoholism. In conclusion, patients with concomitant HBV infection and alcoholism have high incidence of cirrhosis, HCC, and mortality. Treatment with antiviral therapy and abstinence may be started to reduce the incidence of cirrhosis, HCC, and mortality in these patients

Alcoholic Liver Disease in the Asian–Pacific Region with High Prevalence of Chronic Viral Hepatitis

The hospitalized cases and mortality from alcoholic liver disease (ALD) are increasing in Taiwan and worldwide. Meanwhile, the Asia–Pacific region also has a high prevalence of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC). The Taiwanese have the highest percentage of aldehyde dehydrogenase 2 (ALDH2) deficiency and the lowest amount of alcohol consumption. Based on the histological changes, ALD is clinically classified as steatosis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatitis on cirrhosis. Patients with overt alcoholic hepatitis often develop marked hepatomegaly, audible hepatic arterial bruit, mild leukocytosis, and mild fever. Patients having alcoholic cirrhosis had much more serious complications and mortality. It is clinically important to identify hepatic fibrosis and cirrhosis earlier for early management. Active assessments for esophageal varices and ascites may help the diagnosis of cirrhosis. Sonography is helpful for exanimating features of cirrhosis including portal hypertension, ascites, increased hepatic portal flow, and collaterals. Synergistic damage of viral hepatitis on ALD patients lead to rapid progression to cirrhosis and HCC. Distinct from the Western population, 30% of Taiwanese alcoholics had concomitant chronic HBV regardless of the different histologic categories. Patient groups with combined alcoholics and HBV had fewer platelet counts and much more cirrhosis with Ishak Stage 5–6 fibrosis. The annual incidences of HCC were significantly higher in alcoholic cirrhotic patients having concomitant HBV infection than those with only HBV infection or alcoholism alone. Antiviral nucleotide and nucleoside analogs therapy reduces the prevalence of HCC to a similar level to those ALD patients without active HBV

Metabolic Signature of Hepatic Fibrosis: From Individual Pathways to Systems Biology

Hepatic fibrosis is a major cause of morbidity and mortality worldwide, as it ultimately leads to cirrhosis, which is estimated to affect up to 2% of the global population. Hepatic fibrosis is confirmed by liver biopsy, and the erroneous nature of this technique necessitates the search for noninvasive alternatives. However, current biomarker algorithms for hepatic fibrosis have many limitations. Given that the liver is the largest organ and a major metabolic hub in the body, probing the metabolic signature of hepatic fibrosis holds promise for the discovery of new markers and therapeutic targets. Regarding individual metabolic pathways, accumulating evidence shows that hepatic fibrosis leads to alterations in carbohydrate metabolism, as aerobic glycolysis is aggravated in activated hepatic stellate cells (HSCs) and the whole fibrotic liver; in amino acid metabolism, as Fischer’s ratio (branched-chain amino acids/aromatic amino acids) decreases in patients with hepatic fibrosis; and in lipid metabolism, as HSCs lose vitamin A-containing lipid droplets during transdifferentiation, and cirrhotic patients have decreased serum lipids. The current review also summarizes recent findings of metabolic alterations relevant to hepatic fibrosis based on systems biology approaches, including transcriptomics, proteomics, and metabolomics in vitro, in animal models and in humans

Role of Zinc in Subclinical Hepatic Encephalopathy: Comparison with Somatosensory-Evoked Potentials

Background and Aim: The purpose of the present paper was to determine the role of zinc in subclinical portosystemic encephalopathy (SPSE). Methods: The serum zinc levels were studied for 10 cirrhotic patients who did not suffer SPSE and for 10 patients who did, and the results compared with those deriving from 10 healthy volunteers. The nutritional evaluation included serum prealbumin, albumin, and transferrin levels, body mass index (BMI), mid-arm muscle circumference (MAMC), and tricep skin-fold ( TSF). The occurrence of SPSE was defined as a situation when the N20-N 65 interpeak latencies of median nerve-stimulated somatosensory-evoked potentials (SEP) exceeded 2.5 SD of the control mean value. Results: Cirrhotic patients suffering SPSE (57.5 +/- 10.5 mug/dL) had lower serum zinc levels than those not experiencing SPSE (69.5 +/- 16.6 mug/dL, P = 0. 03 ) and controls (77.7 +/- 6.8 mug/dL, P < 0.001). Four of the non-SPSE and nine SPSE patients had zinc levels less than the lower normal limit. Cirrhotic patients suffering SPSE had lower levels of albumin (2.8 +/- 0.4 g/dL vs 3.8 +/- 0.4 g/dL, P < 0.001), prealbumin (9.0 +/- 4.3 mg/dL vs 14 .3 +/- 6.0 mg/dL, P = 0.02), and transferrin (158 +/- 56 g/L vs 218 +/- 50 g/L, P = 0.01), but a greater total bilirubin level (1.2 +/- 1.5 mg/dL vs 0.9 +/- 0.4 mg/dL, P = 0.005) than those not suffering SPSE. The serum zinc levels correlated with N20-N65 interpeak latencies (P = 0.03), serum albumin (P = 0.006), prealbumin (P < 0.001), and total bilirubin (P = 0.02 ) levels. Conclusions: The data show that zinc deficiency is common in cases of non-alcoholic cirrhosis with SPSE. The early assessment of malnutrition and zinc deficiency are important. (C) 2004 Blackwell Publishing Asia Pty Ltd