Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C.

OBJECTIVES: Antiviral treatment in chronic hepatitis C (CHC) involves ribavirin, a hemolytic agent. We planned a prospective study to evaluate whether drug-induced iron perturbation is clinically relevant as it relates to therapeutic outcome. METHODS: Iron variables were sequentially assessed in 206 CHC patients undergoing antiviral therapy and were correlated with pretreatment iron status and histology, hemolysis, and therapeutic outcome. RESULTS: At week 1 of therapy, serum iron (SI), transferrin saturation (TS), and serum ferritin (SF) increased markedly in all patients. All iron parameters correlated with hemolysis up to week 4; this correlation was lost for SF at later time points. SF rise during treatment was inversely related to baseline SF and iron deposits in hepatic mesenchymal/Kupffer cells. Both baseline SF and mesenchymal iron significantly correlated with fibrosis at multivariate analysis (P=0.015 and 0.008, respectively). Interestingly, baseline SF, despite good specificity (89%), had low sensitivity in predicting siderosis (25%). During therapy, SI, TS, and hemolysis parameters did not correlate with sustained virological response (SVR), whereas SF rise became an independent predictor of therapeutic response: a 2.5-fold increase of SF at week 12 associated with higher likelihood of SVR (odds ratio 1.91, P=0.032). Accordingly, lack of mesenchymal iron deposits at the baseline biopsy correlated with SVR (odds ratio 3.02, P=0.043). CONCLUSIONS: In CHC, SF is a useful marker for assessing disease duration and progression before starting treatment and for predicting therapeutic response while on therapy. SF rise during antiviral therapy is largely independent of hemolysis and likely indicates activation of macrophages in response to antivirals.

Intermittent gastric outlet obstruction due to a gallstone migrated through a cholecysto-gastric fistula: a new variant of "Bouveret's syndrome".

Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus.In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.

Endozepines in recurrent stupor.

Stupor is a condition from which the subject can be aroused only by vigorous stimuli. Most patients with stupor have a diffuse organic cerebral dysfunction. Rarely stupor is recurrent and no specific causes can be found. Patients with idiopathic recurrent stupor were awakened by i.v. administration of an antagonist (flumazenil) of the benzodiazepine recognition site located in the GABA(A) receptor. Since no exogenous benzodiazepines were detected in plasma and cerebrospinal fluid by high performance liquid chromatography, an excess of endogenous benzodiazepine-like compounds (endozepines) was proposed as the cause of stupor. The existence of endozepines, their widespread distribution in the CNS and their involvement in hepatic encephalopathy are established. However, the origin of these compounds, how biosynthesis occurs and the mechanisms and causes through which they alter brain functions are poorly understood. The fact that a number of synthetic benzodiazepines are difficult to detect using conventional techniques and the discovery that some cases of recurrent stupor were caused by fraudulent administration of lorazepam question whether the concept of endozepine recurrent stupor can be sustained. This review summarizes the state of endozepine physiology and pharmacology and the clinical syndromes attributed to their involvement. A diagnostic work-up to define endozepine-induced recurrent stupor is suggested.

Type III intestinal metaplasia, Helicobacter pylori infection and gastric carcinoma risk index in an Italian series of 1750 patients.

BACKGROUND/AIMS: To evaluate the utility of 2 biopsies of antrum and gastric body on routine endoscopy for the assessment of type III intestinal metaplasia (IM-3) and Helicobacter pylori (Hp), 1750 patients (pts) (895 males; 855 females) were considered from June'98 to June'00. METHODOLOGY: Specimens were graded 0 to 3 for atrophy, IM-3 and Hp. 610 pts treated previously with antibiotics or not eligible for biopsy were excluded from initial 2360 pts. RESULTS: IM-3 was found in 118 pts (6.7%), 100 pts (5.7%) only in the antrum. 10 of 355 pts (2.8%) with normal endoscopy and 47 of 702 (6.6%) with non-erosive endoscopic gastritis resulted IM-3 positive in the antrum. 709 pts (40.5%) were positive for Hp in antrum and/or corpus. The presence of Hp and IM-3 in the antrum was not correlated (p=0.99; Spearman test). A positive correlation (p=0.000) between duodenal ulcer and Hp was found when antral Hp positivity was taken into account. The gastric carcinoma risk index (GCRI) was found in 358 pts (20.4%); in this group 131 pts (36.6%) were Hp positive, 81 pts (22.65%) had IM-3 only in the antrum, 184 pts (51.4%) had atrophy. CONCLUSIONS: The incidence of IM-3 is low (6.7%) in routine endoscopy. Normal endoscopy doesn't exclude the presence of IM-3. Biopsy is necessary to discover IM-3 in the antrum in 5.3% of pts with normal or aspecific endoscopic gastritis. Application of the GCRI might be useful for identifying a group of patients carrying a higher risk for gastric carcinoma.

[Bile peritonitis: a case report and a review of literature about post-cholecystectomy damages]. / Peritonite biliare in cirrosi epatica post-alcolica. Descrizione di un caso e revisione della letteratura sui danni post-colecistectomia.

A laparoscopic cholecystectomy in cirrhosis was complicated by bile ascites and evolved in bile peritonitis. Starting from the differential diagnosis problem between ascitic decompensation and bile-peritonitis caused by a biliary tree damage, we reviewed the literature about post-cholecystectomy damages suggesting a flow chart about this topic.

Effect of Helicobacter pylori eradication on bulbitis and duodenal gastric metaplasia.

BACKGROUND/AIMS: Duodenal gastric metaplasia seems to be linked to infection by Helicobacter pylori, to the extent of acid secretion and to bulbitis. An investigation was made of the relationship between bulbitis and duodenal gastric metaplasia, or whether bulbitis can arise along with duodenal gastric metaplasia after Helicobacter pylori eradication in an average of six years. METHODOLOGY: We compared 22 patients with duodenal ulcers [male/female 16/6; (mean age+/-SD) 55+/-12 years] Helicobacter pylori-negative after eradication, with 23 Helicobacter pylori-positive patients free from active duodenal ulcers [male/female 17/6; (mean age+/-SD) 59+/-12 years]. RESULTS: The bulbitis score was found to be lower in the Helicobacter pylori-negative than in the Helicobacter pylori-positive group (p=0.02). The duodenal gastric metaplasia score in the Helicobacter pylori-negative was higher than in the Helicobacter pylori-positive group (p=0.001). We failed to find any relationship between the presence of bulbitis and duodenal gastric metaplasia. We found a non-significant inverse correlation between the presence of duodenal gastric metaplasia and chronic body gastritis (p=0.07). CONCLUSIONS: Bulbitis and duodenal gastric metaplasia may depend on different causal factors not related to Helicobacter pylori infection. The extension of duodenal gastric metaplasia with time following recovery from peptic ulcer disease may represent a mucosal protection factor against acid.

Appropriateness of colonoscopy in a digestive endoscopy unit: a prospective study using ASGE guidelines.

RATIONALE, AIMS AND OBJECTIVES: Appropriate indications for colonoscopy (C) are essential for a rational use of resources. The aim of this study is to evaluate the appropriateness of indication for C according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines and to evaluate whether appropriate use was correlated with the diagnostic yield of C. METHODS: We analysed 677 consecutive C performed over an 11-month period in a digestive endoscopy unit with an open access system. RESULTS: The rate of 'generally indicated' C was 77% and 'generally not indicated' C was 18%. The rate of indication not listed in the ASGE guidelines was 5%. The percentage of generally not indicated C requested by gastroenterologists for outpatients was lower than that requested by primary care surgeons or doctors (9.5%, 29%, 25.3%, respectively). In 38 (7.3%) and in 111 (21.3%) of 520 patients with appropriate C, cancer and polyps larger than 5 mm were found, respectively. Twenty polyps greater than 5 mm were detected in 15 cases (12%) of 122 inappropriate C, with only one case of intramucosal carcinoma; four (12%) polyps measuring over 5 mm were found in C not listed in ASGE guidelines. No advanced stage cancer was detected in the inappropriate group and in C not listed in ASGE guidelines. CONCLUSIONS: Our results showed the high rate of inappropriate procedures, according to ASGE guidelines, requested by surgeons, internists and primary care doctors for both outpatients and inpatients. The proportion of not indicated endoscopic procedures requested by gastroenterologists must be reduced through more carefully application of ASGE guidelines. Endoscopic findings were more stringent in appropriate C.

[Primary cardiac sarcoma. Description of a case]. / Sarcoma primitive del cuore. Descrizione di un caso.

Primary cardiac tumors are rare events. We describe here a case of undifferentiated pleomorphic sarcoma (so-called pleomorphic malignant fibrous histiocytoma) obliterating mostly the left side and the anterior wall of pericardium in a 84-year-old man admitted for mild dyspnea at rest. The diagnosis was suspected after excluding the lung origin of the mass (observed by plain chest radiography) by thorax computed tomography but it was confirmed only by cardiac-gated magnetic resonance imaging and transthoracic biopsy. Considering both patient's age and comorbidity, and local extension of the lesion, after counseling with cardiac surgeons and oncologists, the patient was treated only by conservative medical therapy. The patient died 6 months after the diagnosis due to a superior vena cava syndrome as an effect of infiltration and obstruction of superior vena cava by the tumor at the site of vein entry in the right atrium. This case is an example of a primary cardiac tumor that causes relative myocardial sufferance both by infiltration and by limitation of normal heart diastolic function.

Management of hepatic encephalopathy: role of rifaximin.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops in patients with acute or chronic liver failure. It is widely accepted to be due to impairment of hepatic clearance of toxic products from the gut such as ammonia. Accumulation of ammonia induces a glutamate neurotoxicity leading to an increased tone of the gamma-aminobutyric acid A (GABA-A) receptor system in the brain which results in HE. Factors either increasing the ammonia levels (protein load, constipation, sepsis, or gastrointestinal bleeding) or potentiating the functional activity of the GABAergic system [natural benzodiazepine-like compounds (NBZDs) or exogenous benzodiazepines] may act as precipitating factors of HE. NBZDs are present in trace amounts in the blood of normal subjects and have been found to be increased in the blood of patients with liver cirrhosis, with or without HE. These compounds may derive either from the diet since they have been found in plants, vegetables and animals or from gut bacteria. The observation that intestinal bacterial flora is involved in the production of both primary agent of HE (ammonia) and precipitating factors (NBZDs) suggests that the use of nonabsorbable antibiotics such as rifaximin may be useful in preventing episodes of HE in patients with liver cirrhosis.

Hyperhomocysteinaemia in chronic liver diseases: role of disease stage, vitamin status and methylenetetrahydrofolate reductase genetics.

BACKGROUND/AIMS: The liver plays a key role in sulphur aminoacid metabolism hence, homocysteine metabolism may be impaired in chronic liver diseases. The aim of this study was to investigate, in patients affected by chronic liver diseases, (1) the prevalence of hyperhomocysteinaemia and (2) the role of its determinants such as the stage and the aetiology of disease, vitamin status, genetic documented alterations (methylenetetrahydrofolate reductase deficiency) and presence/absence of documented malignant evolution (hepatocellular carcinoma). MATERIAL AND METHODS: One hundred and thirty patients with chronic liver disease (34 with chronic active hepatitis, 12 with fatty liver and 88 with liver cirrhosis) and 50 healthy age-matched control subjects were included into the study. RESULTS: Hyperhomocysteinaemia was defined as homocysteine plasma levels greater than 12.6 micromol/l. Hyperhomocysteinaemia prevalence in liver cirrhosis group was 40.9%, significantly higher (all P<0.01) with respect to controls (12%), chronic active hepatitis (14.7%) and fatty liver (25%) groups and increased with Child-Pugh stage [Child A: 22.2%, Child B (50%); Child C (58.3%)]. In chronic-active hepatitis and liver cirrhosis, the prevalence of subjects with methylenetetrahydrofolate reductase C677-->T mutation (both as CT and as TT) and hyperhomocysteinaemia results in significantly higher levels with respect to controls. Methylenetetrahydrofolate reductase C677-->T mutation and disease stage showed to be the most important predictive factors of hyperhomocysteinaemia in liver cirrhosis whereas the influence of homocysteine-related vitamin status seems to have a secondary role. CONCLUSIONS: In conclusion hyperhomocysteinaemia is highly prevalent in liver cirrhosis but not in other chronic liver diseases; it may contribute to fibrogenesis and vascular complication of liver cirrhosis.