Sustained virological responses following standard anti-viral therapy in decompensated HCV-infected cirrhotic patients.

BACKGROUND: Little data is available about predictors of sustained virological response (SVR) during anti-viral therapy of patients with decompensated HCV cirrhosis. AIMS: To determine whether rapid and early virological responses (RVR and EVR) could predict SVR and help optimize treatment in these patients. METHODS: A total of 94 cirrhotics underwent treatment with peg-interferon alfa-2b (1.5 microg/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for genotypes 1/4 or genotypes 2/3, respectively. RESULTS: Overall, SVR was achieved in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 (P < 0.01). At treatment week 4, 34 patients had undetectable HCV-RNA, 10 with genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%), 6 and 18 with genotypes 1 and non-1. At the multivariate analysis, only EVR, genotypes 2 and 3, and adherence to full course and dosage of therapy retained their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0-217.3), 4.2 (95% CI 1.2-15.3) and 9.1 (95% CI 2.2-38.0), respectively. CONCLUSION: In decompensated cirrhotic patients, anti-viral therapy with current regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment ought to be pursued among patients who attain an EVR, and maintain a full course and dosage of therapy.

Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients: a pilot study.

BACKGROUND: In chronic hepatitis B, long-term use of alpha interferon is hampered by side effects, and long-term treatment with nucleos(t)ide analogues is burdened by drug-resistant mutants. We hypothesized that alternate rounds of lamivudine and alpha interferon might circumvent previous shortcomings. AIM: To evaluate efficacy of sequential lamivudine or IFN-alpha2b monotherapies in preventing occurrence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants and achieving virological and biochemical response. METHODS: Fifteen patients with hepatitis B surface antigen, anti-HBe-positive chronic hepatitis received four consecutive rounds of monotherapy with lamivudine (100 mg/day), IFN-alpha2b (5MU/tiw), lamivudine, IFN-alpha2b. Serum HBV-DNA levels were evaluated during and off treatment, HBV polymerase and pre-core/core regions sequenced. RESULTS: End-of-treatment response was achieved in 10 patients (67%). One patient did not respond, a second developed genotypic resistance at week 24. A rebound in viremia occurred in three patients at week 48. Six patients (40%) remained sustained responders. Triple promoter mutations at nucleotides 1762-1764-1896 prevailed in non-responders (60%) as compared to responders (20%). L180M/M204V mutations were identified during virological breakthrough. CONCLUSION: Sequential approach of alternate rounds of lamivudine or interferon may help patients to tolerate a prolonged schedule of therapy and protect them from emergence of viral strains.

Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis.

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.

HLA-DRB1 alleles may influence disease phenotype in patients with inflammatory bowel disease: a critical reappraisal with review of the literature.

PURPOSE: The HLA region has been implicated in determining the disease susceptibility or the clinical phenotype of inflammatory bowel disease. The aim of this study was to assess the relation between HLA-DRB1 alleles with the clinical features of Crohn's disease and ulcerative colitis and the presence of anti-neutrophil cytoplasmic and anti-Saccharomyces cerevisiae antibodies. METHODS: Blood samples were obtained from 102 Crohn's disease patients, 114 ulcerative colitis patients, and 264 unrelated healthy controls. Anti-neutrophil cytoplasmics were detected by a standard immunofluorescence method, and anti-Saccharomyces cerevisiaes were examined by an enzyme-linked immunosorbent assay immunoglobulin G/immunoglobulin A commercial assay. HLA-DRB1 typing of 26 alleles was performed by polymerase chain reaction sequence-specific primes. Patients were phenotyped according to gender, disease location, extent, and behavior, surgical resection, need of steroid, and anti-neutrophil cytoplasmic/anti-Saccharomyces cerevisiae status. RESULTS: As a whole, after applying Bonferroni's correction for multiple comparisons, no significant association of HLA-DRB1 alleles with Crohn's disease or ulcerative colitis was found. After stratifying HLA-DRB1 alleles by clinical phenotypes of patients with ulcerative colitis, an excess of DRB1*1309*1320*1325*1329 allele (DR13) was found in conjunction with pancolitis (P < 0.0001), surgical resection (P < 0.0003), and extraintestinal manifestations (P < 0.0001). In Crohn's disease patients, an excess of DRB1*0304*0305*0307*0309 allele (DR3) was found in those with colonic disease (P < 0.0001) and patients with extraintestinal manifestations (P = 0.0003). This statistical association, however, emerged in only 3 of 114 patients with ulcerative colitis and in 3 of 102 patients with Crohn's disease. We found no association with the presence of anti-Saccharomyces cerevisiae or anti-neutrophil cytoplasmic. CONCLUSIONS: Some clinical features of Crohn's disease and ulcerative colitis may be influenced by specific HLA-DR alleles; in particular, in ulcerative colitis some alleles appear to segregate with more aggressive disease, whereas in Crohn's disease different alleles cosegregate in patients with colonic disease and extraintestinal manifestations.

Proton-pump inhibitors and outcome of endoscopic hemostasis in bleeding peptic ulcers: a series of meta-analyses.

OBJECTIVE: To perform meta-analyses of studies on outcome of bleeding ulcers of different proton-pump inhibitors (PPIs) regimens, after stratification of patients by endoscopic stigmata, and analysis of studies with and without endotherapy. METHODS: A total of 35 randomized trials comparing PPIs to placebo and/or H2-receptor antagonists (H2RAs) in 4,843 patients with high-risk endoscopic stigmata were retrieved. Outcomes were rebleeding, surgery, and mortality. RESULTS: Monotherapy with oral or bolus PPIs was superior to placebo and H2RAs in reducing rebleeding in both bleeders and nonbleeders at index endoscopy; the need for surgery was reduced only when compared to H2RAs. In nonbleeders, PPI monotherapy was as effective as a combination of endotherapy with H2RAs. A combination of endotherapy with PPIs was superior to monotherapy in reducing bleeding and surgery, and superior to endotherapy alone in minimizing rebleeding, but not surgery; the benefit was lost when confronted to endotherapy plus H2RAs, whether PPIs were given as infusion or bolus. By pooling data from studies comparing high doses of PPIs as continuous infusion versus regular doses as intermittent bolus, rebleeding, surgery, and mortality were not significantly different. CONCLUSIONS: Combination of endotherapy with either PPIs or H2RAs is indicated for nonbleeding ulcers at endoscopy with the intent to reduce rebleeding and surgery. Its value may extend to bleeding lesions, but current data are scanty. The benefit appears to be independent from route and doses of PPIs, as oral, bolus, or infusional methods are all effective.

Linkage analysis identifies gene carriers among members of families with hereditary nonpolyposis colorectal cancer.

BACKGROUND & AIMS: Uncertainty about genetic risk in hereditary nonpolyposis colorectal cancer (HNPCC) may lead to unnecessary screening. The aims of this study were to show how gene linkage findings can elucidate who is at risk and requires intensive screening and how cancer control can be enhanced by screening high-risk family members. This information can be useful given the public health magnitude of HNPCC. METHODS: An extended family with HNPCC was studied using formal linkage analysis with DNA extraction from blood samples, followed by genotyping with polymerase chain reaction technique for microsatellite markers. Sixty-one blood relatives of a family with HNPCC, 5 of whom had colorectal cancer, and 12 unrelated family members underwent DNA sampling for genetic analysis. RESULTS: Linkage analysis showed that all 5 affected individuals had a haplotype with the same alleles 10/7/9, which was also detected in 13 first-degree healthy gene carriers and absent in the remaining 43 non-gene carriers. In the asymptomatic subjects screened, one incidental colorectal cancer and four adenomas were detected in 3 of 6 gene carriers. An adenoma was found in 1 of 17 noncarriers; the remaining 16 noncarriers have undergone 67 unnecessary colonoscopies. CONCLUSIONS: Linkage analysis can differentiate gene carriers from non carriers. Colorectal cancer screening should be restricted to gene carriers.

Acromegaloid facial appearance (AFA) syndrome: report of a second family.

A family is reported in which the 'acromegaloid facial appearance' (AFA) phenotype was segregating through two generations. The five affected persons showed a striking resemblance to the patients previously reported, including progressively coarse acromegaloid-like facial appearance, narrow palpebral fissures, bulbous nose, and thickening of the lips and intraoral mucosa, resulting in exaggerated rugae and frenula. These patients also had increased birth weight and dull mentality. It is unclear if the differences between the two families mark distinct syndromes or simply extend the AFA phenotype.

Gallbladder function and gastric liquid emptying in achalasia.

Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4% +/- 30.4 vs 80.3 +/- 8.3 of controls, mean +/- SD, P = 0.007) and a slower than normal ejection phase (9.1%/min +/- 6.6 vs 18.1 +/- 4.5, P = 0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min +/- 15.4 vs 74.7 min +/- 11.5 in the controls (P = 0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative charges of extraesophageal nerve fibers as well as their clinical significance require further investigations.

Are the lower oesophageal sphincter relaxations in achalasia always incomplete? A manometric and scintigraphic study.

In two patients with achalasia we found intermittent, complete lower oesophageal sphincter (LES) relaxations at manometric evaluation. These patients had no weight loss, minimal oesophageal dilation, lower LES pressure and faster radionuclide oesophageal emptying when compared with other achalasia patients. Concurrent performing of radionuclide oesophageal emptying and manometry showed that the complete relaxations (CRs) were too short and functionally unsuccessful. Our findings suggest that these patients may be at an earlier disease stage and that intermittent CRs of LES may occasionally occur in achalasia.

[ERCP in the diagnosis of bilio-pancreatic pathology. Comparison with echography and CT]. / L'ERCP nella diagnostica della patologia bilio-pancreatica. Raffronto con ecografia e TC.

The authors have evaluated both sensitivity and specificity of ERCP in comparison with other imaging methods, such as US and CT, on the basis of a study of 63 patients with suspected pancreatobiliary pathologies. Our results show ERCP of chronic pancreatitis to have 83% sensitivity and 66% specificity. As for biliary pathologies, sensitivity was 94% and specificity 88%. In pancreatic pathologies, CT sensitivity was 99% and its specificity was 70%. The combined use of ERCP and CT determines a considerable rise in the percentages, and allows the evaluation of both the excretory tree and the parenchyma. As for biliary pathologies, the role of ERCP is fundamental, since its combination with the other methods (CT: sensitivity 72%, specificity 3.5%; US: sensitivity 70%, specificity 3.5%) has not determined but a slight increase in sensitivity, and no significant increase in specificity.

Long-term treatment of duodenal ulcer with pirenzepine; gastric pH values and incidence of relapses: an open pilot study.

Twenty-three endoscopically healed duodenal ulcer patients entered a long-term treatment with pirenzepine for 1 year (two 25-mg tablets at breakfast and two tablets at bedtime). One day before and 7 days after the long-term treatment started, gastric pH and BAO were measured in each patient after fasting. The patients were clinically examined monthly and underwent endoscopy 4, 8 and 12 months after the trial started or when they complained of ulcer symptoms. Blood and urine laboratory tests were carried out before treatment began and 6 and 12 months afterwards. Eighteen of the 22 patients that completed the trial (82%) did not relapse. The statistical analysis tended to show a relationship between absence of pH increase and relapses. No severe side-effects or changes in the results of laboratory tests were observed.