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Drug-induced liver diseases (DILD) are clinico-pathologic patterns of liver injury caused by drugs or other foreign compounds. Steatohepatitis is a rare form of DILD, and drugs account for fewer than 2% of non-alcoholic steatohepatitis (NASH). Drugs known to be capable of inducing steatosis and steatohepatitis can be divided into three broad groups: those that cause steatosis and steatohepatitis independently (e.g., amiodarone, perhexiline maleate); drugs which can precipitate latent NASH (e.g., tamoxifen); drugs whic duce sporadic events of steatosis/steatohepatitis (e.g., carbamazepine). Clinical DILD syndromes include acute viral hepatitis-like injury, acute liver failure, cholestatic hepatitis,liver disease with signs of hypersensitivity, autoimmune hepatitis-like injury, acute venous-Outflow obstruction, chronic cholestasis, ciirrhosis, steatosis and steatohepatitis. The clinical picture is by no means dependent on the mechanism of injury (direct hepatotoxicity, idiosyncratic reactions, hypersensitivity reactions). Reliable diagnosis of drug-induced liver disease requires demonstration of close correlation between the patient history and clinical, laboratory, and histological data.

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.

Although liver transplantation has become standard therapy in the treatment of patients with liver failure, several problems should be considered in the management of these patients. Other approaches have been proposed, in particular cellular-based procedures. Isolated hepatocytes may be used instead of whole organ transplantation or integrated within the bioartificial devices, in order to replace the missing synthetic and metabolic liver functions. Moreover patient's own hepatocytes may be ex vivo genetically modified to provide the function of a mutant gene. However, new cell sources alternative to adult hepatocytes are actually under investigation, on the basis of recent advances in the field of liver repopulation. Xenogenic primary cells, human hepatoma cells, immortalized hepatocytes and stem cells have been testing in several experiments, even if up to now none of them represent a "gold-standard" for cell-based treatment of liver diseases. In the next future, it is possible that different clinical situations will require different therapeutic approaches, that will be finally defined from the concomitant advances in the development of artificial devices and liver cell biology.

The issue of whether or not liver function is compromised in the healthy elderly population remains unsolved.To investigate the putative age-related modifications of hepatic function using the 13C-methacetin breath test. Because endogenous CO2 production changes with age, motor activity and nutrition, a different form of processing the results was investigated.Twenty-nine elderly subjects (mean age, 79.8 +/- 7.9 years; female/male ratio, 17/12) and 28 adult subjects (mean age, 40.6 +/- 12.3 years; female/male ratio, 13/15) underwent 13C-methacetin breath test and trans-abdominal echosonography with Doppler pulsed wave analysis of the coeliac axis and portal vein.Although the 13CO2 peak occurred within 15-30 min in both elderly and adult subjects, it was significantly decreased in the former (30.66% +/- 9.2% vs. 38.33% +/- 6.05%; P0.001), as was the cumulative excretion (33.07% +/- 7.06% vs. 39.81% +/- 5.68%; P0.001). When correcting for the effects of CO2 excretion by age, the age-related modification of the cumulative dose became more evident (elderly group 30.15% +/- 6.46% vs. adult group 37.97% +/- 5.92%; P0.0001). The elderly group also showed an increase in the intra-hepatic resistance index using Doppler pulsed wave analysis, which inversely correlated with the results of the breath test.Hepatic function is not well preserved in healthy humans throughout life and may be due to an increase in vascular resistance.

Hepatitis C virus infection is associated with various extrahepatic manifestations such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis and porphyria cutanea tarda. The link between mixed cryoglobulinemia and hepatitis C virus infection is actually well known. Interferon alpha therapy decreases hepatitis C viremia and improves the clinical signs and biochemical abnormalities of cryoglobulinemia. The rare combination of hepatitis C and panarteritis nodosa has still not been confirmed. The sicca syndrome also seems to be associated with hepatitis C virus, but this is not the typical Sjogren's syndrome. It is not yet well established if hepatitis C virus plays a pathogenic role in the development of thyroid dysfunction and autoimmune thyroiditis. Probably interferon therapy may be implicated in the development in this and other extrahepatic manifestations of hepatitis C virus infection. Although an epidemiological association of hepatitis C with lichen planus, neuropathies and other diseases has been observed, the etiological role and the pathogenic involvement of the hepatitis C infection remains unclear. Extrahepatic clinical manifestations are frequently observed in hepatitis C virus patients and involve primarily the joints, muscles, and skin. The most frequent immunological abnormalities include mixed cryoglobulins, antinuclear antibodies, and anti-smooth muscle antibodies.

Hepatic toxicity caused by propafenone is extremely rare. We here describe a case of acute cholestasis secondary to propafenone treatment in an elderly male with no history of preexistent liver disease. The clinical picture and time course of the symptoms seem to be compatible with a direct toxic reaction. Age-related delays in hepatic drug metabolism should explain the hazardous increase in the bioavailability of this drug. Despite the rarity of this complication, propafenone should be considered as a potential cause of drug-induced cholestasis in elderly patients. The literature on the hepatotoxicity of propafenone is also reviewed.

Antibiotic-associated diarrhoea can be attributed in part to imbalances in intestinal microflora. Therefore, probiotic preparations are used to prevent this diarrhoea. However, although several trials have been conducted, no conclusive evidence has been found of the efficacy of different preparations, e.g. Lactobacillus spp. and Saccharomyces spp.To conduct a meta-analysis of the data in the literature on the efficacy of probiotics in the prevention of antibiotic-associated diarrhoea.A literature search was performed of electronic databases, Abstract Books and single paper references. Data were also obtained from the authors. Only placebo-controlled studies were included in the search. The Mantel-Haenszel test was used to estimate the relative risk for single studies and an overall combined relative risk, each study being submitted to the Mantel-Haenszel test for homogeneity.Twenty-two studies matched the inclusion criteria. Only seven studies (881 patients) were homogeneous. The combined relative risk was 0.3966 (95% confidence interval, 0.27-0.57).The results suggest a strong benefit of probiotic administration on antibiotic-associated diarrhoea, but further data are needed. The evidence for beneficial effects is still not definitive. Published studies are flawed by the lack of a placebo design and by peculiar population features.

We report a case of Sweet's syndrome associated with monoclonal gammopathy of uncertain significance (MGUS) and positivity for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). A 65-year-old man patient came to our hospital complaining of remittent-intermittent fever, weight loss, associated with papules affecting all his body and without mucosal or ocular involvement. Histology of biopsy specimens of papules allowed the diagnosis of Sweet's syndrome. This is the first case of this rare syndrome associated both with MGUS and p-ANCA positivity. The monoclonal immunoglobulin, possibly directed to neutrophils like an antibody, may cause both their fragmentation and release of antigens responsible of p-ANCA appearance.

A 57-year-old man was admitted due to rapidly progressive renal failure and pulmonary edema. Chest X-ray showed a bilateral lung infiltrate, while a normal myocardial contractility was reported by echocardiography. Though initially ANCA were absent, a necrotizing vasculitis with polymorphonuclear leukocyte infiltrate was observed in a kidney biopsy specimen. Renal histology was compatible with microscopic polyangiitis because of necrotizing lesions located at small vessels and at glomeruli that were not crescentic. Corticosteroids and immunosuppressive treatment was played with significant clinical improvement. Six months later, the patient died of a gastrointestinal hemorrhage due to bowel perforation by vasculitic lesion. This time high p-ANCA positivity was detected and at renal histology crescentic glomeruli were observed.

BACKGROUND: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed. OBJECTIVE: To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection. DESIGN: Prospective blinded study. SETTING: Six clinical centers in the United States and Europe. PATIENTS: 84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms. MEASUREMENTS: At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy. RESULTS: Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%]). CONCLUSION: A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful

AIMS/HYPOTHESIS: The aim of the present study was to investigate the relationship between intramyocytic triglycerides levels, muscle TNF-alpha and GLUT4 expression and insulin resistance. METHODS: Insulin sensitivity was studied in 14 severely obese women (BMI>40 kg/m(2)), before and 6 months after low-dietary intake or bariatric malabsorptive surgery (bilio- pancreatic diversion, BPD), by the euglycaemic hyperinsulinaemic clamp technique, while the amount of intramyocytic triglycerides was chemically measured in needle muscle biopsies. Using reverse transcriptase-polymerase chain reaction analysis, the muscle mRNA expression of TNF-alpha and GLUT4 was also investigated. RESULTS: The weight loss after surgery was 25.98+/- 5.81 kg (P