Alberto Premoli

Adipokines in NASH: Postprandial lipid metabolism as a link between adiponectin and liver disease†

Circulating levels of four adipokines (adiponectin, TNF‐α, leptin, and resistin) and the postprandial lipid and adiponectin responses to an oral fat load were assessed in 25 non‐obese, non‐diabetic patients with biopsy‐proven nonalcoholic steatohepatitis (NASH) and correlated with metabolic indices and liver histology. Circulating adiponectin was lower in NASH compared with controls (5,476 ± 344 vs. 11,548 ± 836 ng/mL; P = .00001) and on multiple regression analysis correlated negatively with liver steatosis, necroinflammation (OR = 5.0; P = .009), and fibrosis (OR = 8.0; P = .003).The magnitude of postprandial lipemia was significantly higher in NASH than in controls and was related to fasting adiponectin (β = −0.78; P = .00003). Controls showed a significant increase in serum adiponectin in response to the fat load, whereas patients with NASH showed a slight decrease. Postprandial free fatty acids response correlated inversely with adiponectin response in both groups and independently predicted the severity of liver steatosis in NASH (β = 0.51; P = .031). In conclusion, hypoadiponectinemia is present before overt diabetes and obesity appear and correlates with the severity of liver histology in NASH. Impaired postprandial lipid metabolism may be an additional mechanism linking hypoadiponectinemia and NASH and posing a higher cardiovascular risk to these subjects. The mechanism(s) underlying these differences are unknown, but the type of dietary fat seems to play a role. These findings may have important pathogenetic and therapeutic implications in both liver and metabolic disease. (HEPATOLOGY 2005.)

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study

Background  Many reports of autoimmune hepatitis (AIH) were written in the ‘pre‐Hepatitis C era’ and data on the natural history are still incomplete.

Plasma Adiponectin Levels in Primary Biliary Cirrhosis: A Novel Perspective for Link Between Hypercholesterolemia and Protection Against Atherosclerosis

INTRODUCTION:Hypercholesterolemia is a common finding in primary biliary cirrhosis (PBC), but the risk of cardiovascular events in PBC patients is not increased in respect to the general population. High serum adiponectin levels appear to play a protective role in the development of either metabolic syndrome or cardiovascular disease.AIM:To investigate factors potentially preventing atherosclerosis in PBC patients.METHODS:Circulating levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha (TNF-α) were measured in 137 consecutive PBC patients (125 women, 12 men; mean age 61.6 ± 12.3 yr), 137 sex- and age-matched healthy controls, and 30 female patients with nonalcoholic steatohepatitis (NASH) and associated metabolic syndrome.RESULTS:The body mass index (BMI) was comparable in the three groups, whereas total cholesterol was significantly higher in both PBC and NASH cases than in controls (221.6 ± 50.5 mg/dL in PBC vs 221.7 ± 39.7 mg/dL in NASH vs 209.8 ± 39.2 mg/dL in controls, P < 0.05). Serum concentrations of adiponectin, resistin, and leptin were significantly higher in PBC patients than in either NASH cases or controls (P < 0.05). Among the PBC patients, only adiponectin correlated positively with histological progression of the disease (P= 0.001) and negatively with BMI (P= 0.01). Logistic regression analysis revealed that adiponectin correlated independently with age, BMI, Mayo score, and gamma-glutamyl transpeptidase.CONCLUSIONS:The high adiponectin concentrations observed in PBC patients should be regarded as a possible protective factor against atherogenesis. The search for further protective factors should be encouraged.

Type 1 autoimmune hepatitis and adipokines: new markers for activity and disease progression?

PurposeCytokines may play an important role as inflammatory factors in liver diseases. There is some evidence suggesting a link between adiponectin–biliary function and liver disease. The aim of this study was to clarify the behavior of adipokines in autoimmune hepatitis type 1.MethodsWe assessed the circulating levels of adiponectin, tumor necrosis factor-α, resistin and leptin in 42 patients with autoimmune hepatitis, comparing them with 42 healthy subjects who were matched for age and sex and with 31 patients with nonalcoholic steatohepatitis (NASH), evaluating the associations with markers of cytolysis, cholestasis, and histological severity.ResultsAdiponectin and TNF-α values were higher in patients compared to controls. The patients showed significantly higher Homeostasis Model Assessment values, suggesting an increased insulin resistance and serum levels of adiponectin positively correlated with γ-glutamyltranspeptidase and alkaline phosphatase values after a simple regression analysis. Serum levels of resistin positively correlated with elevated aminotransferases and bilirubin values, and serum levels of TNF-α positively correlated with elevated alanine-aminotransferase and resistin values. The concentration of adiponectin increased significantly with staging of the disease. Patients with NASH showed lower levels of adiponectin and higher levels of resistin than AIH patients and controls.ConclusionsPatients with AIH showed significantly higher adiponectin concentrations than controls despite their higher HOMA-IR values. The significant correlation between adiponectin levels and serological features of cholestasis suggested an association with biliary function. Our results indicate that adiponectin may be a possible marker for disease progression in AIH.

Helicobacter pylori seroprevalence in patients with autoimmune hepatitis.

Autoimmune hepatitis is characterized by a continuing hepatocyte necrosis that usually progresses to liver cirrhosis. Autoimmunity is also a feature of chronic infection by Helicobacter pylori, a gram-negative bacterium involved in the pathogenesis of peptic ulcer and upper gastrointestinal bleeding, with both events frequently occurring in patients with chronic liver disease. A newly described pathogenetic mechanism for chronic hepatitis and hepatocellular carcinoma in the mouse is linked to Helicobacter spp. infection. A high prevalence of H. pylori infection was demonstrated in patients with viral-related cirrhosis but never studied in cases of autoimmune hepatitis. In a case-control study, we examined 31 consecutive patients (25 women and 6 men, age range 20–66, mean age 46 ± 4.3 years) suffering from autoimmune hepatitis and 62 sex- and age-matched blood donors (50 women, 12 men, age range 20–65, mean age 46 ± 5.4 years) resident in the same area. Antibodies to H. pylori were present in 20 of 31 (64.5%) autoimmune patients compared to 33 of 62 (53.2%) controls (P = 0.3, odds ratio 1.60, 95% CI 0.60–4.28). The difference was not statistically significant either in female or male patients. In conclusion, the prevalence of H. pylori infection in patients and controls was similar in our study of patients with chronic autoimmune hepatitis.

Male sexual disturbances in liver diseases: what do we know?

The alterations of sexual function known as the erectile dysfunction are quite frequent among patients affected by liver diseases and they tend to increase in advanced liver failure. This process is directly linked to cirrhosis or its treatments, such as liver transplantation, or to certain drugs (e.g. beta-blockers). Independent of cirrhosis, other factors may cause sexual problems in these patients. Alcohol itself seems to worsen sexual function in the absence of cirrhosis. Viral hepatitis has an uncertain influence on male gonadic function and even antiviral therapy itself can worsen some seminal and hormonal parameters, although it is reversible. Quality of life may be greatly decreased in cases of cirrhosis where these alterations are present, so it is important to value and care for them, if possible. This review investigates the major male sexual disturbances in liver diseases of various origins.

Overlap Syndromes of Autoimmune Hepatitis: An Open Question

The headword “overlap syndromes” of liver diseases includes the coexistence of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. These syndromes often represent a diagnostic and therapeutic challenge for hepatologists; it remains unclear whether these overlap syndromes form distinct entities or they are only variants of the major autoimmune liver diseases. The most frequent reported association occurs between autoimmune hepatitis and primary biliary cirrhosis, whereas the overlap between autoimmune hepatitis and primary sclerosing cholangitis is less frequent, typically at young age and often attendant with an inflammatory bowel disease. The choice therapy is based on ursodeoxycholic acid and immunosuppressive drugs, used at the same time or consecutively, according to the course of disease. The diagnostic scores for autoimmune hepatitis can help for diagnosis, even though their definitive soundness is lacking.

REVIEW: Overlap Syndromes of Autoimmune Hepatitis: What Is Known So Far

The pattern of some autoimmune hepatitis can be difficult to classify, sometimes due to the overlap of these with primary biliary cirrhosis, primary sclerosing cholangitis and chronic viral hepatitis. The etiology of these variant forms remains unclear. The distinction among the overlap syndromes poses different problems both of prognosis and therapeutic approach. Presently, the utility of the scoring system devised and revised by the International Autoimmune Hepatitis Group regarding these cases is under discussion. Histological examination seems to be an important tool, but often the result does not help in defining a correct diagnosis. To date, the overlap syndromes can be classified at an intermediate level between cholestatic forms of autoimmune hepatitis or hepatic forms of cholestatic syndromes, but it cannot be excluded that the syndromes represent independent disorders.