Assessment of liver fibrosis in the clinical setting: something is changing?

Clinical management of compensated chronic liver diseases (CLD) requires precise definition of the stage of liver fibrosis which is the key histologic predictor of progression to cirrhosis. Several methods are used to assess liver fibrosis. Among those, percutaneous liver biopsy is still the gold standard. However, the recent introduction of liver imaging techniques, the rising of statistical tests able to classify CLD noninvasively, and a reconsideration of its potential complications, have contributed to an audit of the evolving role of liver biopsy. At present, there is an increasing interest for noninvasive approaches to evaluate the stage of liver fibrosis in the clinical work-up of patients with CLD. Transient elastography (FibroScan) is a new, noninvasive method to assess liver stiffness and, consequently, the degree of liver fibrosis. Since its use in the clinical setting is of great interest, further studies should define the exact role of this procedure.

Decreasing eradicaton rate of Helicobacter pylori infection with metronidazole-based triple therapy. A randomised study.

BACKGROUND: Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of duodenal ulcer (DU) disease. Low DU recurrences and reinfection rates were universally described, when treatment was effective. It has been suggested that short-term triple therapy, comprising a proton pump inhibitor plus two antibiotics (clarithromycin, amoxicillin or a nitroimidazole), should be used as first choice in treating H. pylori infection. Nevertheless, conflicting results have been reported on using these treatment regimens in different countries, due to the resistance of H. pylori against one or more antibiotics. Our aim was to compare the efficacy, for H. pylori eradication, of 1-week triple therapy versus 10 and 14-day triple schedules, in patients with a history of recurrent DU. METHODS: A total of 159 patients (85 males, mean age 59.2+/-3.2 years) was randomly treated with a triple therapy including a standard dose of omeprazole twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily. Fifty-three patients received 1-week triple therapy (Group I), 53 subjects were treated with 10-day triple therapy (Group II) and 53 others with 14-day triple therapy (Group III). H. pylori infection at entry and eradication, at least 4 weeks after therapy had ended, was assessed by 13C urea breath test and histology on biopsies from the antrum and the corpus. RESULTS: Of the 159 subjects randomised into the study, 6 (3 in group II and 3 in group III) were excluded from the per protocol (PP) analysis because of discontinuations. At the end of the course of treatment, the overall H. pylori eradication rate in the intention-to-treat analysis, was 73.5% (39/53) in group I, 71.6% (38/53) in group II and 73.5% (39/53) in group III, without any statistically significant difference. Moreover, the PP analysis also showed no statistical differences, with an eradication rate of 73.5% (39/53) in group I, 76% (38/50) in group II and 78% (39/50) in group III. The reported frequency of side-effects was evenly distributed between the groups, but 6 patients (3.7%) stopped because of adverse events only in groups II and III. CONCLUSIONS: The present study shows that there is no significant difference between the three regimens although the 14-day triple therapy shows a slightly higher H. pylori eradication rate. There is a strong need, in our region, to put forward surveillance programmes to monitor the prevalence of local resistant strains and to guide treatment on the basis of resistance patterns.

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease: do they recognize different subsets of a heterogeneous disease?

OBJECTIVE: To evaluate the prevalence of anti-neutrophil cytoplasmic antibodies in a series of patients with inflammatory bowel disease, the discriminatory value of these antibodies in differentiating between ulcerative colitis and Crohn's disease, their antigen specificity and their correlation with epidemiological and clinical variables. METHODS: Serum anti-neutrophil cytoplasmic antibodies were evaluated by indirect immunofluorescence and immunoblotting using neutrophils isolated from peripheral blood and by enzyme-linked immunosorbent assays (ELISAs) using proteinase 3 and myeloperoxidase as antigens. RESULTS: Anti-neutrophil cytoplasmic antibodies were detected by immunofluorescence in 43 (39.8%) of 108 patients with ulcerative colitis, in 11 (11.9%) of 92 patients with Crohn's disease (P < 0.001) and 5 (6.8%) of 73 control patients. The predominant pattern was perinuclear staining around neutrophil nuclei (44 of 59, 75%); a homogeneous cytoplasmic staining was present in 15 (25%) of 59 sera, mainly among Crohn's disease and control patients. The ELISAs gave no positive results. Recognition of proteins of relative molecular masses 27,000 and 49,000 at immunoblotting was common to ulcerative colitis, Crohn's disease and control sera. The proteins of relative molecular masses 32,000 and 106,000 were recognized exclusively by 11% of anti-neutrophil-positive ulcerative colitis sera. No significant correlation was found between the presence of anti-neutrophil cytoplasmic antibodies and the demographic and clinical characteristics of the patients. CONCLUSION: Anti-neutrophil cytoplasmic antibodies are detectable in a large proportion of patients with ulcerative colitis, but their prevalence in a limited proportion of patients with Crohn's disease reduces their discriminatory capability. The persistence of anti-neutrophil cytoplasmic antibodies after total colectomy and the absence of a correlation between the activity of the disease and the presence or titre of these antibodies support the hypothesis that anti-neutrophil cytoplasmic antibodies are not simply an epiphenomenon of colonic inflammation.

Cell-mediated cytotoxicity to autologous hepatocytes in HBsAg positive liver disease: an analysis of the killing specificity and of the clinical use of the test.

The specificity of a system measuring cell-mediated cytotoxicity as effector-induced target cell detachment from plastic recently adopted to study autologous hepatocyte killing in liver disease, was examined in 17 HBsAg positive liver patients whose hepatocytes (after biopsy digestion with collagenase) were incubated in Terasaki plates with the corresponding blood lymphocytes over two days. The hepatocyte viability and the specificity of the effectors were evaluated as determinants of the clinical value of the test. We found that: (a) hepatocytes in all experiments showed membrane damage owing to the lytic action of collagenase on the small liver core; (b) patients' lymphocytes detached diseased autologous hepatocytes more efficiently than did normal lymphocytes with healthy hepatocytes; (c) in eight patients cytotoxicity appeared equally distributed between a population enriched in T cells and one enriched in non-T cells; yet the mean cytotoxic index of the latter subset was higher than that of the former; (d) cytotoxicity was not blocked by the addition of either aggregated IgG or purified HBsAg; (e) protein synthesis seemed required to promote hepatocyte detachment, for lymphocytes treated with Actinomycin D were no longer active. Poor target viability detracts from the specificity and the clinical value of the test, that therefore turns out to be a major problem of liver cell culture.