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Background and Aim: Refractory ascites in liver-cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritional-support could improve outcomes in cirrhotic patients. Methods: Cirrhotic patients undergoing serial large-volume paracentesis for refractory-ascites were enrolled and randomized into three groups. Group A received post-paracentesis intravenous nutritional-support in addition to a balanced oral diet and a late-evening protein snack, group B received the same oral nutritional-protocol as the first group but without parenteral support, and group C (the control group) received a low-sodium or sodium-free diet. Clinical, anthropometric and laboratory nutritional parameters and biochemical tests of liver and renal function were reported for 12 months of follow-up. Results: We enrolled 120 patients, who were randomized into three groups of equal size. Patients on the nutritional-protocol showed better preservation of clinical, anthropometric and laboratory nutritional parameters that were associated with decreased deterioration of liver function compared with patients on the low-sodium or sodium-free diet (group C). Groups A and B had lower morbidity and mortality rates than the control group (C). Mortality rates were significantly better in patients who were treated with parenteral-nutritional-support than for the other two groups. In patients who were on the nutritional-protocol, there was a reduction in the requirement of taps for the treatment of refractory ascites. Conclusions: Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites.

We aimed to validate the non-invasive criteria for the characterization of portal vein thrombosis (PVT) in patients with cirrhosis and hepatocellular carcinoma (HCC). In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non-invasive diagnosis of HCC, as a criterion for characterizing macroscopic PVT (EASL/AASLD extension criteria).

BACKGROUND: Nonalcoholic fatty liver disease describes a set of conditions that range from fatty liver to nonalcoholic steatohepatitis (NASH), and is considered the hepatic manifestation of metabolic syndrome. Obesity and insulin resistance are strongly associated with systemic markers of inflammation. OBJECTIVE: Focusing on this aspect, we have attempted to find a noninvasive method that could likely assess the presence of NASH and help to decide the liver biopsy performance. METHODS: Using histology as a gold standard to diagnose nonalcoholic fatty liver disease, we consecutively studied 43 patients with NASH and 40 with fatty liver, comparing their data with those of 48 healthy control participants. The outcomes evaluated were ultrasonographic spleen longitudinal diameter coupled with the splenic artery resistive index, serum IL-6 and vascular endothelial growth factor concentrations. RESULTS: The NASH group had higher spleen longitudinal diameter values (P=0.0001) as well as significantly higher IL-6 and vascular endothelial growth factor concentrations than the other groups (P=0.0001). The optimal cut-off value for spleen longitudinal diameter that best discriminated NASH from fatty liver patients was 116 mm (specificity 95% and sensitivity 88%); the sensitivity and specificity of this parameter was better than both IL-6 and vascular endothelial growth factor in the same setting (area under the receiver operating characteristic curve 0.920 vs. 0.817 and 0.678). Splenic artery resistive index was similar between patients with NASH and those with fatty liver, but differed when compared with controls, P=0.0001. CONCLUSIONS: IL-6 was highly specific in confirming the absence of NASH at normal values. In our series, normal values of spleen longitudinal diameter and IL-6 were strongly associated with fatty liver.

Factors responsible for the progression of primary biliary cirrhosis (PBC) are still poorly understood. In the present study, we investigated the associations between the stage of PBC and the immune reaction triggered by oxidative stress; the presence of obesity, steatosis,steatohepatitis; and other toxic, metabolic, or steatogenic factors.We studied clinical, laboratory, and histological data for 274 untreated patients with serum antimitochondrial antibody (AMA)-positive PBC. Circulating IgG against human serum albumin adducted with malondialdeyde, the major product of lipid peroxidation, was measured in these patients and in a group of 98 sex-, age and body mass index (BMI)-matched controls.Steatosis was present in 40.5% of all patients. Steatohepatitis was present in 14.9% of all patients. There was a significant association between the frequencies of steatosis and steatohepatitis and the worsening of PBC. Circulating IgG against lipid peroxidation products was significantly higher in the PBC patients than in the controls. Titers of lipid peroxidation-related antibodies were significantly increased in patients with steatosis and inpatients at more advanced stages. Bivariate analysis revealed a significant association between indirect evidence of oxidative stress, steatosis, steatohepatitis, age, BMI, frequency of diabetes, alcohol intake, iron grade after Perl's stain, and PBC stage. Logistic regression analysis confirmed that the titers of antibodies against lipid peroxidation products (odds ratio 4.5, p.001, 95% confidence interval 3.9–14.4), the presence of steatosis (odds ratio 4.1, 95% confidence interval 2.5–15.4, p.001), higher BMI (odds ratio 3.9, p.021, 95%confidence interval 1.4–9.5), and alcohol intake (males ≥ 30 g/day, females ≥ 20 g/day, odds ratio 4.5,95% confidence interval 1.3–19.8, p.029) were independently associated with more advanced stages of the disease.The immune reactions triggered by oxidative stress, steatosis, obesity, and alcohol intake are independent predictors of PBC stage progression.

Few published studies have examined the results obtained from repeat liver biopsies in obese patients with nonalcoholic fatty liver disease (NAFLD). The progressive form of this disease may be largely limited to a subgroup of NAFLD patients with nonalcoholic steatohepatitis (NASH). The presence of intralobular fibronectin (Fn) and other variables was investigated in relation to subsequent fibrosis progression.In this prospective study, 271 obese patients admitted to the hospital with NAFLD and abnormal liver enzymes were scheduled to undergo a repeat liver biopsy at least 5 years after the initial biopsy. After excluding cirrhotic patients, basal biopsy specimens obtained from patients who underwent a second liver biopsy were stained with antibodies against Fn. The progression of fibrosis in the follow-up sample was correlated with the amount of Fn and other clinicopathological variables.We obtained a second liver biopsy from 149 patients after a median time of 6.4 years. Of these, 132 showed suitable Fn staining for semi-quantitative assessments. In all, 44 out of 83 patients (53%) with basal NASH showed fibrosis progression by at least one stage in the second liver biopsy. The amount of Fn (odds ratio=14.1; P0.001), a diagnosis of hypertension (odds ratio=4.8; P=0.028), and homeostasis model assessment parameter of insulin resistance (HOMA-IR) scores (8, odds ratio=1.9; P=0.004) were independent predictive factors of worsening fibrosis.A semi-quantitative assessment of the amount of parenchymal Fn present at an early stage in obese patients with NASH is valuable for predicting the progression of fibrosis. Similarly, lobular Fn deposition may be a sensitive and early indicator of active fibrogenetic processes in the liver. Hypertension and higher HOMA-IR scores are other clinical independent risk factors that predict the progression of fibrosis.

To clarify which method has accuracy: 2nd generation contrast-enhanced ultrasound or biopsy of portal vein thrombus in the differential diagnosis of portal vein thrombosis.One hundred and eighty-six patients with hepatocellular carcinoma and portal vein thrombosis underwent in blinded fashion a 2nd generation contrast-enhanced ultrasound and biopsy of portal vein thrombus; both results were examined on the basis of the follow-up of patients compared to reference-standard.One hundred and eight patients completed the study. Benign thrombosis on 2nd generation contrast-enhanced ultrasound was characterised by progressive hypoenhancing of the thrombus; in malignant portal vein thrombosis there was a precocious homogeneous enhancement of the thrombus. On follow-up there were 50 of 108 patients with benign thrombosis: all were correctly diagnosed by both methods. There were 58 of 108 patients with malignant thrombosis: amongst these, 52 were correctly diagnosed by both methods, the remainder did not present malignant cells on portal vein thrombus biopsy and showed on 2nd generation contrast-enhanced ultrasound an inhomogeneous enhancement pattern. A new biopsy during the follow-up, guided to the area of thrombus that showed up on 2nd generation contrast-enhanced ultrasound, demonstrated an enhancing pattern indicating malignant cells.In patients with hepatocellular carcinoma complicated by portal vein thrombosis, 2nd generation contrast-enhanced ultrasound of portal vein thrombus is very useful in assessing the benign or malignant nature of the thrombus. Puncture biopsy of thrombus is usually accurate but presents some sampling errors, so, when pathological results are required, 2nd generation contrast-enhanced ultrasound could guide the sampling needle to the correct area of the thrombus.

Background/Aims Liver iron deposits are frequent in patients with non-alcoholic steato-hepatitis (NAFLD), but their role is not well defined. To investigate the effect of liver iron excess on the prevalence of hepatocellular carcinoma (HCC) in patients with NASH-related cirrhosis. Methods Hepatic iron was measured retrospectively with a semiquantitative method in liver biopsies of 153 patients with NASH-related cirrhosis: 51 with HCC and 102 controls without HCC, matched for age, sex and stage of liver disease. The corrected total iron score (0–60) was the sum of three scores: the hepatocytic iron score (0–36), sinusoidal iron score (0–12), and portal iron score (0–12), multiplied by 3/3, 2/3, or 1/3 depending on the localisation of the iron in the nodules. Results Conditional logistic regression analysis showed that iron deposits (corrected total iron score>0) were more frequent in HCC patients than in controls. The median corrected total iron score was significantly higher in HCC patients than in controls. The liver iron overload was sinusoidal. Conclusions Iron deposition in the liver was more frequent in patients with NASH-related cirrhosis with HCC than in HCC-free controls. Liver iron overload may be associated with development of HCC in patients with NASH-related cirrhosis.

A S L D A b st ra ct s levels were significantly decreased in UDCA group compared to control group. Microarray analysis revealed that gene expression of glutathione S-transferase (GST) ismarkedly increased in UDCA group compared to control group. Since Nrf2-activated genes such as glutamatecysteine ligase, catalytic subunit (Gclc), heme oxygenase 1 (HO-1) exert antioxidant effects, we next investigated mRNA expression levels of these genes by quantitative real-time PCR. Quantitative real-time PCR revealed the elevated expression of both Gclc and HO-1 in UDCA group. Conclusion : UDCA administration blocks progression of liver inflammation in NASH by inducing Nrf2-regulated antioxidant gene expression and reducing serum ROS levels.