A. Grieco

Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee.

We report the evidence-based Italian Association for the Study of Liver guidelines for the appropriate diagnosis and management of patients with nonalcoholic fatty liver disease in clinical practice and its related research agenda. The prevalence of nonalcoholic fatty liver disease varies according to age, gender and ethnicity. In the general population, the prevalence of nonalcoholic fatty liver disease is about 25% and the incidence is of two new cases/100 people/year. 2-3% of individuals in the general population will suffer from nonalcoholic steatohepatitis. Uncomplicated steatosis will usually follow a benign course. Individuals with nonalcoholic steatohepatitis, however, have a reduced life expectancy, mainly owing to vascular diseases and liver-related causes. Moreover, steatosis has deleterious effects on the natural history of HCV infection. Nonalcoholic fatty liver disease is usually diagnosed in asymptomatic patients prompted by the occasional discovery of increased liver enzymes and/or of ultrasonographic steatosis. Medical history, complete physical examination, etiologic screening of liver injury, liver biochemistry tests, serum lipids and insulin sensitivity tests should be performed in every patient. Occult alcohol abuse should be ruled out. Ultrasonography is the first-line imaging technique. Liver biopsy, the gold standard in diagnosis and prognosis of nonalcoholic fatty liver disease, is an invasive procedure and its results will not influence treatment in most cases but will provide prognostic information. Assessment of fibrosis by composite scores, specific laboratory parameters and transient elastography might reduce the number of nonalcoholic fatty liver disease patients requiring liver biopsy. Dieting and physical training reinforced by behavioural therapy are associated with improved nonalcoholic fatty liver disease. Diabetes and the metabolic syndrome should be ruled out at timed intervals in nonalcoholic fatty liver disease. Nonalcoholic steatohepatitis patients should undergo periodic evaluation of cardiovascular risk and of advancement of their liver disease; those with nonalcoholic steatohepatitis-cirrhosis should be evaluated for early diagnosis of hepatocellular carcinoma.

Low-dose lactose in drugs neither increases breath hydrogen excretion nor causes gastrointestinal symptoms

Background Despite the reported tolerance to a low dose of lactose, many lactose malabsorbers follow a rigorous lactose‐free diet also avoiding lactose‐containing drugs. Up to now, only a few case reports have described the onset of gastrointestinal symptoms in lactose malabsorbers following the ingestion of these drugs. It has been suggested that capsules/tablets contain no more than 400 mg of lactose.

Faecal calprotectin concentrations in untreated coeliac patients

Objective. Calprotectin is a granulocyte cytosolic protein that is considered to be a promising marker of subclinical inflammation. High faecal calprotectin concentrations (FCCs) have been found in several intestinal diseases, but no data are currently available on patients with coeliac disease. The purpose of this pilot study was to evaluate FCCs in untreated coeliac patients and to correlate them with clinical score and histological characteristics. Material and methods. Twenty-eight consecutive coeliac patients were recruited. Thirty healthy adult volunteers participated as the control group. FCCs were determined by ELISA. Clinical assessment was carried out in all patients. The histological severity of lesions and the infiltration of neutrophil polymorphs in the intestinal mucosa were also evaluated. Mean FCCs in patients and the control group were compared by means of the t-test for independent samples. In coeliac patients, differences in FCCs in subgroups identified by clinical score, lesion severity and neutrophil infiltration were evaluated by the Kruskal-Wallis non-parametric test. Results. FCCs in untreated coeliac patients were not significantly different from those in controls (p=0.163). Among coeliac patients, FCCs were not significantly different in relation to the level of clinical score, lesion severity or neutrophil infiltration (p=0.92, p=0.96 and p=0.74, respectively). Conclusions. This study shows, for the first time, that FCCs in untreated coeliac patients do not differ significantly from those in controls.

Recurrent Acute Hepatitis Associated with Use of Cetirizine

OBJECTIVE To describe a case of recurrent acute hepatitis related to the use of cetirizine, a selective histamine1-receptor antagonist approved for the treatment of common allergic diseases. CASE SUMMARY A 26-year-old man was hospitalized with a week-long history of weakness, nausea, anorexia, and hyperchromic urine, which had developed after 6 days of therapy with oral cetirizine 10 mg/day for allergic rhinitis. Admission laboratory testing revealed evidence of acute hepatitis and seropositivity for liver–kidney microsome antibodies. Liver biopsy findings of diffuse portal tract and lobular inflammation with a prominent eosinophilic infiltrate were consistent with drug-related hepatitis. The patient was discharged after one week of treatment with tocopherol and glutathione. Three months after discharge, transaminase levels were normal. At 6 months, seropositivity for liver–kidney microsome antibodies was still present, but considerably less intense. The patient had suffered 2 previous episodes of “acute hepatitis of unknown origin,” and both had occurred after cetirizine use. DISCUSSION Use of the Naranjo probability scale indicated cetirizine as the probable cause of acute hepatitis, and the positivity for liver–kidney microsome antibodies is suggestive of an autoimmune mechanism for liver damage. As of September 13, 2004, ours is the fourth reported case of acute hepatitis associated with cetirizine and the second in which liver–kidney microsome antibodies have been documented. CONCLUSIONS Although cetirizine is considered to have low potential for severe hepatic toxicity, the possibility that it can provoke autoimmune-mediated hepatotoxicity should be considered.

Intrafamilial transmission of hepatitis C virus in Italy: a systematic review

Background Hepatitis C virus (HCV) transmission is mainly due to parenteral exposure; however, in absence of such risk factor, there are reports of intrafamilial spread of HCV and observational studies suggest an increased risk for households of infected subjects. The aim of our study was to systematically review and meta-analyse studies about HCV prevalence among households of HCV patients in Italy. Methods PubMed and Embase were searched to identify Italian studies about HCV intrafamilial transmission. Keywords used were: ‘HCV’, ‘Hepatitis C’, ‘intrafamilial’, ‘family’ and ‘Italy’. Selected studies were reviewed to assess the quality and meta-analysed using StatsDirect software. Results 25 studies were selected. The pooled overall prevalence was 9% (95% CI 7.1% to 11.1%). The highest pooled prevalence was found among sexual partners of index cases: 14.7% (95% CI 10.7% to 19.2%) globally and 9.9% (95% CI 3.6% to 18.8%) and 17.6% (95% CI 12.1% to 24%) in northern and central-southern regions, respectively. The meta-analysis of high-quality studies yielded the lowest HCV prevalence. Conclusion To be a HCV patient household is a risk factor for HCV and counselling for these households should be provided.

Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms

BACKGROUND Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease. METHODS Cross-sectional, case-control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication. RESULTS The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16-4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24-5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12-3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76-6.36). CONCLUSION Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms.

P817 EARLY MENOPAUSAL STATUS IS ASSOCIATED WITH THE SEVERITY OF LIVER FIBROSIS IN ITALIAN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Methods: In 651 consecutive NAFLD patients (244 from Sicily, and 407 from Northern Italy), we assessed clinical, biochemical and histological features (Kleiner score). As controls, we evaluated 168 patients without clinical or histological evidence of steatosis. PNPLA3 rs738409 C>G and MERTK rs4374383 A>G SNPs were also assessed. Results: MERTK A>G SNP distribution was similar in cases compared to controls (p = 0.99). In the entire cohort, MERTK AA genotype (OR 0.25, 95%CI 0.10–0.58, p = 0.001) was independently associated with severe steatosis together with PNPLA3 GG status (OR 2.18, 95%CI 1.32–3.59, p = 0.002). In the high-risk group of PNPLA3 GG patients, severe steatosis was observed in none patients with MERTK AA (0/11) compared to 39% (33/84) with MERTK GG/GA genotype (p =0.01). The presence of fibrosis >F1 was independently linked to MERTK AA genotype in Sicilian cohort only (OR 0.28; 95%CI 0.11–0.69, p = 0.006), but not in the Northern Italy and in the entire cohorts. However, when excluding subjects with BMI > 40kg/m from the entire cohort F2–F4 fibrosis was observed in 19.2% patients with MERTK AA compared to 30.3% with MERTK GG/GA (p =0.04), being this data confirmed at multivariate analysis (OR 0.44; 95%CI 0.21–0.89, p = 0.02). Conclusions: MERTK AA genotype is protective against severe steatosis in patients with NAFLD, especially in those at high risk because of PNPLA3 GG genotype, while its effect on liver fibrosis needs to be further investigate.