Lucia Cimino

Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects

BACKGROUND/AIMS Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. METHODS We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). RESULTS Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. CONCLUSIONS Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemial and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey

BACKGROUND Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

Diagnostic efficiency in discriminating liver malignancies from cirrhosis by serum gamma-glutamyltransferase isoforms

Total GGT and GGT complexed with low-density-lipoprotein plus very low-density lipoprotein (LDL + VLDL) have been evaluated in sera from 53 healthy subjects, 23 patients with chronic hepatitis, 87 with liver cirrhosis and 50 with liver tumors (primary and metastatic). A cut-off of 20 U/l of GGT complexed with LDL + VLDL results in a diagnostic sensitivity of 84% for liver tumor patients, and a diagnostic specificity of about 80% towards the two groups of patients affected by cirrhosis or chronic hepatitis. This test, because of its high diagnostic efficiency, is a useful addition to the battery of laboratory tests that serve to discriminate cirrhosis and chronic hepatitis from liver malignancies.

13C-Aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C

BACKGROUND & AIMS Although numerous non-invasive tests are currently available to explore liver function and disease activity in patients with HCV-related chronic diseases, none of these indicate the likelihood of disease progression in the individual patient. We aimed at assessing the prognostic ability of (13)C(2)-aminopyrine breath test ((13)C-ABT) in the prediction of liver fibrosis progression in patients with HCV chronic hepatitis who prospectively entered a long-term follow-up. METHODS Fifty patients with HCV-related chronic disease who underwent paired liver biopsy (at baseline and after a mean period of 86 months) were included in the study. (13)C-ABT was carried out at baseline and every 3 years. Histological progression was defined as increase of at least 2 fibrosis units according to Ishak score. RESULTS Fourteen patients progressed of at least 2 fibrosis units during the follow-up. These patients were more frequently infected with a HCV-1b genotype and had, at baseline, a significantly older age, higher BMI, AST levels, and AST to platelet ratio index (APRI). (13)C-ABT was altered in 57% of cases at baseline and in 100% of the cases at 3-year follow-up. In the univariate analysis, age (p=0.005), BMI (p=0.006), platelet count (p=0.03), AST (p=0.012) and ALT (p=0.04) levels, APRI (p=0.03), and baseline (13)C-ABT results (p<0.0001) were all independently associated with progression of liver fibrosis. By Coxs multiple regression analysis, the (13)C-ABT was the only covariate that significantly predicted liver fibrosis progression (HR 6.7; 95% CI 2.3-20.1; p<0.001). CONCLUSIONS (13)C-ABT accurately predicts the risk of disease progression in patients with HCV-related chronic hepatitis.

Per-rectal portal scintigraphy with technetium-99m pertechnetate for the early diagnosis of cirrhosis in patients with chronic hepatitis

We evaluated the role of per-rectal portal scintigraphy with 99m-technetium pertechnetate (99m-Tc test) for early diagnosis of cirrhosis. Forty patients with biochemical evidence of chronic liver disease were studied. Laparobiopsy documented chronic active hepatitis (CAH) without cirrhosis in 22 of the patients and CAH with cirrhosis (CAHc) in 18 patients. Clinical or laboratory findings could not differentiate between CAH and CAHc. Twelve healthy volunteers served as controls. The results, expressed as shunt index (SI), i.e., the ratio between heart radioactivity and the sum of heart and liver radioactivity in the first 30 s of observation, were: controls 5.66 +/- 1.66, CAH 15.27 +/- 2.83 and CAHc 24.88 +/- 3.95. A significant difference between the mean SI values in the three groups studied (F = 142.71, p less than 0.0001) was observed. At values less than 17, our test showed a predictivity of 100% for cirrhosis exclusion, while at values higher than 19 the predictive positive value for a diagnosis of cirrhosis was 100%. Invasive diagnostic procedures should be performed only in patients with SI values between 17-19.