Gabriele Budillon

Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies

This paper reviews the complications that arose after 68 276 percutaneous liver biopsies performed from 1973 to 1983. The complications are analyzed in relation to the underlying liver disease and to the type of needle used. Death was infrequent (9/100 000); it was always due to haemoperitoneum and occurred only in patients with malignant diseases or cirrhosis. Complications were less frequent in AVH (44/100 000) than in other liver diseases (from 125 to 278/100 000). Death, serious haemorrhagic complications, pneumothorax and biliary peritonitis were more frequent after biopsy with the Trucut needle than after biopsy with Menghinis needle (3/1000 against 1/1000). Sixty-one percent of complications were discovered within two hours of biopsy and 96% within one day. The data indicate a post biopsy observation period of at least 24 hours. The day-case procedure should be reserved for patients not presenting liver tumour or cirrhosis.

Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status, and oncogene expression in patients with chronic gastritis

BACKGROUND Helicobacter pylori, the main cause of chronic gastritis, is a class I gastric carcinogen. Chronic gastritis progresses to cancer through atrophy, metaplasia, and dysplasia. Precancerous phenotypic expression is generally associated with acquired genomic instability. AIM To evaluate the effect of H pylori infection and its eradication on gastric histology, cell proliferation, DNA status, and oncogene expression. METHODS/SUBJECTS Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patients withH pylori negative chronic gastritis, 53 withH pylori positive chronic gastritis, and 11 with gastric cancer. RESULTS All patients with chronic gastritis were in a hyperproliferative state related to mucosal inflammation, regardless of H pyloriinfection. Atrophy was present in three of 10 patients withH pylori negative chronic gastritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patients with atrophy and H pylori infection; eight of these also had c-Myc expression, associated in six cases with p53 expression. Fifty three patients withH pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastritis activity; atrophy previously detected in 21/45 disappeared in five, regressed from moderate to mild in nine, and remained unchanged in seven; complete metaplasia disappeared in 4/14, and markers of genomic instability disappeared where previously present. In the five patients in whomH pylori persisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged. CONCLUSIONS ChronicH pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gastritis; eradication ofH pylori infection can reverse inflammation and the related atrophy, metaplasia, and genomic instability.

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.

Prognostic value of the galactose test in predicting survival of patients with cirrhosis evaluated for liver transplantation: A prospective multicenter italian study

AIMS/METHODS The present study aimed to examine whether the galactose elimination capacity can be used to predict the survival of patients with advanced liver disease. We studied 194 patients with cirrhosis, belonging to Child class B and C, for 2 years each. RESULTS The overall probability of survival was 79% at 6 months, 72% at 1 year and 62% at 2 years. Variables significantly associated with the duration of survival, as assessed by univariate analysis, were the Child-Pugh score, presence of ascites, size of esophageal varices, prothrombin time, albumin, bilirubin, urea, creatinine, glucose and galactose elimination capacity. By a multivariable analysis, only Pugh score (p = 0.005), creatinine (p < 0.001), varices (p = 0.001) and galactose elimination capacity (p < 0.001) were independent predictors of mortality. The galactose elimination capacity was even more sensitive when the end-point was limited to deaths due to liver failure and hepatorenal syndrome. A new score obtained by summing the Pugh score with a score derived from galactose elimination capacity was quite simple and accurate for predicting survival. CONCLUSIONS The quantitative measurement of liver function as the galactose elimination capacity could be of use to identify patients with cirrhosis and probable short survival who might benefit most from urgent transplantation.

Gastroduodenal lesions and Helicobacter pylori infection in dyspeptic patients with and without chronic renal failure

Background.  Patients with chronic renal failure (CRF) often have dyspeptic symptoms and may develop peptic disease or digestive disorders leading to severe gastrointestinal complications. The primary aim of this study was to evaluate the prevalence of peptic lesions and Helicobacter pylori infection, and the severity of dyspeptic symptoms, in dyspeptic patients with and without CRF. Our secondary aim was to investigate whether uremic status may affect the diagnostic efficiency of the [13]C‐urea breath test ([13]C‐UBT).

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet

Background: Coeliac disease patients show a number of gastrointestinal motor abnormalities, including a decrease in lower oesophageal sphincter pressure. The prevalence of endoscopic oesophagitis in these subjects however is unknown. Aim: To evaluate whether untreated adult coeliac patients had an increased prevalence of reflux oesophagitis and, if so, to assess whether a gluten free diet exerted any beneficial effect on gastro-oesophageal reflux disease (GORD) symptoms. Patients and methods: We retrospectively studied 205 coeliac patients (females/males 153/52, median age 32 years) who underwent endoscopy for duodenal biopsy and 400 non-coeliac subjects (females/males 244/156, median age 37 years) referred for endoscopy for upper gastrointestinal symptoms. Each patient was given a questionnaire for evaluation of GORD symptoms prior to and 4–12 months after endoscopy. Coeliac patients were given a gluten free diet. Oesophagitis patients of both groups, following an eight week course of omeprazole, were re-evaluated for GORD symptoms at four month intervals up to one year. Significance of differences was assessed by Fisher’s exact test. Results: Oesophagitis was present in 39/205 (19%, 95% confidence interval (CI) 13.8–25.0%) coeliac patients and in 32/400 (8%, 95% CI 5.5–11.1%) dyspeptic subjects. At the one year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% CI 13–42.1%) coeliacs with oesophagitis and in 23/32 (71.8%, 95% CI 53.2–86.2%) non-coeliac subjects with oesophagitis. Conclusion: Coeliac patients have a high prevalence of reflux oesophagitis. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that coeliac disease may represent a risk factor for development of reflux oesophagitis.

Investigation of intestine and liver function in cirrhosis using combined sugar oral loads

Active and passive intestinal absorption and the efficiency of hepatic galactose clearance were studied in 12 patients with liver cirrhosis and 8 healthy control subjects using differential absorption techniques in which paired sugar markers were ingested simultaneously. Such differential absorption procedures overcome the effects of variation in gastric emptying, intestinal transit, distribution space and renal clearance which could invalidate tests incorporating a single marker only. In the cirrhotic group, active absorption of D-xylose (D-xyl) compared with that of 3-O-methyl-D-glucose (3-OMG), indicated by the ratio of D-xyl/3-OMG concentration in plasma, showed no reduction in respect to the control group. The passive intestinal permeability to lactulose (lac) compared with that of L-rhamnose (rham), indicated by urinary lac/rham excretion ratio, was not raised. These findings indicate no dysfunction of small intestinal mucosa in cirrhotic patients in spite of the clinical evidence of portal hypertension. Urinary galactose (gal) excretion after oral load was 10 times higher in the cirrhotic group (P less than 0.001). The gal/3-OMG excretion ratio correlated well with galactose elimination capacity as assessed by an intravenous method. Estimation of plasma D-xyl/3-OMG concentration and both urinary lac/rham and gal/3-OMG excretion ratios after appropriate oral loads provided a convenient and simultaneous evaluation of intestinal absorption, permeability and hepatic galactose elimination.

The Metabolism of Nicotinamide in Human Liver Cirrhosis: A Study on N-Methylnicotinamide and 2-Pyridone-5-Carboxamide Production

OBJECTIVES:Nicotinamide methylation followed by urinary excretion of N-methylnicotinamide increases in cirrhotic patients, despite the derangement of the overall methylation processes in liver disease. The rise in N-methylnicotinamide could depend, at least in part, on a reduced transformation of this molecule into 2-pyridone-5-carboxamide. The aim of this study was to investigate this hypothesis.METHODS:Serum and urinary levels (mean ± SEM) of N-methylnicotinamide and urinary excretion of 2-pyridone-5-carboxamide were measured in 10 healthy controls and 10 patients with liver cirrhosis in basal conditions and after a nicotinamide oral load (1.5 mg/kg body weight).RESULTS:N-methylnicotinamide serum levels increased significantly (p < 0.01) in cirrhotic patients compared to controls, both as basal values (0.43 ± 0.07 nmol/ml; 0.15 ± 0.01) and as area under the curve 5 h after a nicotinamide load (cirrhotics: 562.4 ± 50.5 nmol/ml · min; controls: 314.4 ± 23.8). Twenty-four-hour urinary excretion of N-methylnicotinamide and 2-pyridone-5-carboxamide was also significantly (p < 0.05) increased in cirrhotic patients versus controls, both in basal conditions (N-methylnicotinamide: 82.0 ± 8.4 μmol, 48.8 ± 4.8; 2-pyridone-5-carboxamide: 129.3 ± 23.0, 64.6 ± 9.8) and after a nicotinamide oral load (N-methylnicotinamide: 290.1 ± 23.1, 180.8 ± 7.4; 2-pyridone-5-carboxamide: 694.7 ± 32.5, 391.0 ± 21.9). Moreover, 24 h N-methylnicotinamide/2-pyridone-5-carboxamide ratio was similar in patients and controls (basal: 0.78 ± 0.39, 0.90 ± 0.51; load: 0.42 ± 0.11, 0.48 ± 0.16).CONCLUSIONS:In cirrhotic patients nicotinamide methylation is increased, as shown by the rise in urinary N-methylnicotinamide and 2-pyridone-5-carboxamide that is concurrent and proportional (constant 24-h metabolite ratio). The hyperfunction of this methylating pathway might play a protective role against the toxic effect of intracellular accumulation of nicotinamide deriving from the catabolic state of cirrhosis.

Effects of carbonated water on functional dyspepsia and constipation

Objective The effects of carbonated beverages on the gastrointestinal tract have been poorly investigated. Therefore, this study aims to assess the effect of carbonated water intake in patients with functional dyspepsia and constipation. Methods Twenty-one patients with dyspepsia and secondary constipation were randomized into two groups in a double-blind fashion. One group (10 subjects) drank carbonated water and the other (11 subjects) tap water for almost 15 days. Patients were evaluated for dyspepsia and constipation scores, and underwent a satiety test by a liquid meal, radionuclide gastric emptying, sonographic gallbladder emptying and colonic transit time, using radio-opaque markers. Results The dyspepsia score was significantly reduced with carbonated water (before = 7.9 ± 2.8 vs after = 5.4 ± 1.7;P < 0.05) and remained unmodified after tap water (9.7 ± 5.3 vs 9.9 ± 4.0). The constipation score also decreased significantly (P < 0.05) after carbonated water (16.0 ± 3.9 vs 12.1 ± 4.4;P < 0.05) and was not significantly different with tap water (14.7 ± 5.1 vs 13.7 ± 4.7). Satiety was significantly reduced with carbonated water (before = 447 ± 146 kcal vs after = 590 ± 245;P < 0.01). Gallbladder emptying (delta percent contraction) was significantly improved only with carbonated water (39.9 ± 16.1%vs 53.6 ± 16.7%;P < 0.01). Conclusion In patients complaining of functional dyspepsia and constipation, carbonated water decreases satiety and improves dyspepsia, constipation and gallbladder emptying.

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias.

Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes.