Gioacchino Leandro

Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease

BACKGROUND/AIMS In chronic viral hepatitis, liver biopsy is performed for assessing disease activity and fibrosis. In this study, we evaluated the impact of the size of liver biopsy on the grading and staging. METHODS We selected 161 liver biopsies from patients with chronic types B and C hepatitis on the basis of their length (> or =3 cm) and width (1.4 mm). Ishak scoring system was used for grading and staging. The score was blindly repeated reducing the length of the specimen from > or =3 to 1.5 cm and to 1 cm long and width from 1.4 to 1 mm. RESULTS Reducing the length of the biopsy led to an increase of cases with mild grades: 49.7% in > or =3 cm, 60.2% in 1.5 cm and 86.6% in 1 cm long specimens (P<0.001). Similarly, cases staged as having mild fibrosis significantly increased in the shorter specimens: 59% in > or =3 cm, 68.3% in 1.5 cm and 80.1% in 1 cm long specimens (P<0.001). As for the width, both grade and stage were significantly underscored in the 1 mm samples, regardless of their length. CONCLUSIONS Liver biopsy size strongly influences the grading and staging of chronic viral hepatitis. The use of fine needles should be discouraged in this setting.

A Comparison of Five Maintenance Therapies for Reflux Esophagitis

BACKGROUND Patients with reflux esophagitis have a high rate of relapse within one year after therapy is discontinued. METHODS We enrolled 175 adults with endoscopy-confirmed reflux esophagitis in a prospective study comparing five maintenance therapies. All the patients were initially treated with omeprazole (40 mg orally once a day) for four to eight weeks, and healing was confirmed by endoscopy. Participants were then stratified according to their initial grade of esophagitis and randomly assigned to 12 months of treatment with one of the following: cisapride (10 mg three times a day), ranitidine (150 mg three times a day), omeprazole (20 mg per day), ranitidine plus cisapride (10 mg three times a day), or omeprazole plus cisapride. Endoscopy was repeated after 6 and 12 months of treatment; the endoscopists were blinded to the treatment assignments. Remission was defined as the absence of esophageal lesions on scheduled or unscheduled follow-up endoscopy. RESULTS In an intention-to-treat analysis, the numbers of patients in continued remission at 12 months were 19 of 35 (54 percent) in the cisapride group, 17 of 35 (49 percent) in the ranitidine group, 28 of 35 (80 percent) in the omeprazole group, 23 of 35 (66 percent) in the ranitidine-plus-cisapride group, and 31 of 35 (89 percent) in the omeprazole-plus-cisapride group. Omeprazole was significantly more effective than cisapride (P = 0.02) or ranitidine (P = 0.003), and combination therapy with omeprazole plus cisapride was significantly more effective than cisapride alone (P = 0.003), ranitidine alone (P < 0.001), or ranitidine plus cisapride (P = 0.03). Ranitidine plus cisapride was significantly better than ranitidine alone (P = 0.05). CONCLUSIONS For maintenance treatment of reflux esophagitis, omeprazole alone or in combination with cisapride is more effective than ranitidine alone or cisapride alone, and the combination of omeprazole and cisapride is more effective than ranitidine plus cisapride.

Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study.

BACKGROUND/AIMS We studied the influence of biochemical and virologic patterns and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164 (103 treated) consecutive patients, followed-up prospectively for a mean of 6 years (21 months-12 years). METHODS Histology, biochemical and virologic profiles were characterized by monthly monitoring during the first 12 months of follow-up. Thereafter patients underwent blood and clinical controls every 4 and 6 months, respectively. Cirrhosis at follow-up histology or end stage complications of cirrhosis served as end points for the analysis of factors influencing disease progression in patients with baseline chronic hepatitis or cirrhosis, respectively. RESULTS Disease progression was associated with older age (P<0.001), absence of previous HBeAg history (P=0.017) and higher serum HBV-DNA levels (P=0.009) (more frequently observed in unremitting disease profile, P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels (associated with disease exacerbations, P=0.045) correlated with end stage complications in cirrhotics (P=0.011). Disease improved in 14.6 and 1.6% of treated and untreated patients, respectively (P=0.015): interferon slowed disease progression (P<0.001). CONCLUSIONS The outcome of anti-HBe positive chronic hepatitis B is worsened by older age and persistent viral replication or hepatitis exacerbations in chronic hepatitis or in cirrhotic patients, respectively. Interferon reduces by 2.5-folds disease progression.

Gastric dysplasia: the Padova international classification.

A worldwide-accepted histologic, classification of the gastric carcinomatous and precancerous lesions is a prerequisite for a consistent recording of epidemiologic data and for both developing and evaluating primary and secondary preventive efforts. Different nomenclatures have been proposed for gastric precancerous lesions in eastern countries and in Japan. This article presents a classification of gastric precancerous lesions resulting from an international consensus conference involving pathologists of different countries. Five main diagnostic categories are identified. To allow comparisons with the nomenclature proposed by the Japanese Research Society for Gastric Cancer, each category was also assigned a numeric identification: 1 = normal, 2 = indefinite for dysplasia, 3 = noninvasive neoplasia, 4 = suspicious for invasive cancer, and 5 = cancer. The interobserver reproducibility of the histologic classification was tested in a series of 46 cases. By collapsing benign alterations (categories 1+2) versus noninvasive neoplasia (category 3) versus suspicious for invasive cancer and fully appearing carcinomatous lesions (categories 4+5), the general agreement value was 77.7%, whereas kappa coefficient was 0.63. By examining gastric precancerous lesions from diverse populations, the authors agreed that the gastric precancerous process is universal and the differences in nomenclatures are merely semantics. The international Padova classification of the gastric precancerous lesions is submitted to the attention of the international scientific community, which is invited to test and to improve on it.

Steatosis affects chronic hepatitis C progression in a genotype specific way

Background and aims: Liver steatosis is frequent in chronic hepatitis C, particularly in patients infected with hepatitis C virus (HCV) genotype 3. The aim of this study was to determine the relationship between steatosis and fibrosis in chronic hepatitis C as a function of viral genotype. Methods: A multivariable logistic regression analysis was carried out in 755 chronic hepatitis C patients (mean body mass index (BMI) 24.11 kg/m2; 178 with genotype 3), consecutively admitted to three referral hospitals. Liver histology showed steatosis in 315 and fibrosis in 605 patients, of whom 187 had cirrhosis (78 compensated and 109 decompensated). Results: Steatosis was independently associated with fibrosis (p<0.001), genotype 3 (p<0.001), BMI (p<0.001), ongoing alcohol abuse (p<0.001), and age (p = 0.001). Fibrosis was associated with the Metavir activity score (p<0.001), age (p<0.001), steatosis (p = 0.001), past alcohol abuse for >5 years (p = 0.015), and BMI (p = 0.034). When regression analysis was repeated on patients divided according to viral genotype (that is, 3 v non-3) to identify type specific risk factors, steatosis was associated with ongoing alcohol abuse (p<0.001) and age (p = 0.01) only in non-3 genotype infected patients and with Metavir activity (p = 0.044) only in genotype 3 infected patients. Similarly, fibrosis was associated with steatosis only in genotype 3 infected individuals (p = 0.018), and with past alcohol abuse (p = 0.003) and (marginally) diabetes (p = 0.078) only in non-3 genotype infected patients. Conclusions: Steatosis influences chronic hepatitis C progression in a genotype specific way. Patients infected with genotype 3 and histologically confirmed steatosis should not be deferred from effective antiviral therapy.

Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children.

OBJECTIVES:Eradication rates with triple therapy (TT) for Helicobacter pylori infection have declined to unacceptable levels. Sequential therapy (ST) is a novel treatment that has shown promise in several controlled trials. Our aim was to assess the efficacy of ST in adults and children compared with that of TT by performing a systematic review and meta-analysis.METHODS:We performed an electronic search of the following: Cochrane Trial Register (until Issue 4, 2008), MEDLINE (1966 to 21 October 2008), EMBASE (1980 to 21 October 2008), and abstracts from the major US, European, and Asian gastroenterology conferences. Randomized controlled trials (RCTs) and controlled clinical trials with a parallel group design comparing the ST with a TT lasting at least 7 days were used.RESULTS:Ten RCTs enrolled 3,006 adult patients and the odds ratio (OR) for eradication of H. pylori with ST compared with TT was 2.99 (95% confidence interval (CI): 2.47–3.62), giving a number needed to treat (NNT) of 6 (95% CI: 5–7) favoring ST. There was no publication bias. The OR for eradication with ST compared with 10-day TT was 2.92 (95% CI: 1.95–4.38), yielding an NNT of 8 (95% CI: 6–12), favoring ST. In patients with clarithromycin resistance, the OR for eradication with ST was 10.21 (95% CI: 3.01–34.58) compared with TT, but the numbers studied are small. Three RCTs enrolled 260 children and adolescents, and the OR for eradication was 1.98 (95% CI: 0.96–4.07). There was no difference in the rate of side effects between the ST and the TT (OR, 1.01; 95% CI: 0.78–1.30).CONCLUSIONS:ST appears to be better than TT in the eradication of H. pylori. This is a promising therapy, but further trials are needed in other European countries and North America before it can be recommended as a first-line treatment.

Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading

Background and aims : Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the following aims: (i) to generate an acceptable definition and a simple reproducible classification of gastric atrophy; and (ii) to develop guidelines for the recognition of atrophy useful for increasing agreement among observers.

Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials.

OBJECTIVES:Radiofrequency thermal ablation (RF) and percutaneous ethanol injection (PEI) have been employed in the treatment of small hepatocellular carcinoma (HCC) as curative treatments. The aim of the study was to review the available evidence comparing RF to PEI for small HCC.METHODS:Search strategy: Cochrane, MEDLINE, CANCERLIT, and ENBASE databases were used. Selection criteria: randomized clinical trials evaluating RF vs. PEI. Data were extracted from each randomized controlled trial (RCT). Primary outcomes were overall survival and local recurrence. Meta-analysis software was used and risk differences (RDs) and their 95% confidence intervals and Q-test for heterogeneity were calculated.RESULTS:Five RCTs were identified including 701 patients. The overall survival was significantly higher in patients treated with RF than in those treated with PEI (RD 0.116, 95% CI 0.173/0.060; heterogeneity not present). Local recurrence rate is significantly higher in patients treated with PEI than in those treated with RF. In the RF group the 1, 2, and 3 years cancer-free survival rates were significantly better than in the PEI-treated patients (respectively: RD 0.098—95% CI 0.006/0.189; heterogeneity P=0.57; RD 0.187, 95% CI 0.082/0.293; heterogeneity P=0.98; RD 0.210, 95% CI 0.095/0.325; heterogeneity P = 0.78). A small number of adverse events were reported in the two treatments.CONCLUSIONS:RF ablation is superior to PEI in the treatment of small HCC with respect to overall survival, 1, 2, and 3 years survival rates, 1, 2, and 3 cancer-free survival rates, and tumor response. RF shows a significantly smaller risk of local recurrence.

Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit.

Background  Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients.

Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: A prospective study

BACKGROUND/AIMS In humans, the role of liver cell dysplasia as a preneoplastic lesion is still debated. A prospective, long-term, multicenter study was performed to establish whether liver cell dysplasia in cirrhosis is associated with an increased risk for hepatocellular carcinoma (HCC). METHODS A cohort of 307 consecutive patients in whom liver cirrhosis was diagnosed by histology was investigated for development of HCC at 6-month intervals by ultrasonography and determination of alpha-fetoprotein levels. RESULTS At enrollment, liver cell dysplasia was found in 75 patients (24%) and in 53% (P < 0.01) of those positive for hepatitis B surface antigen (HBsAg). After a mean follow-up of 46 months, HCC was detected in 45 cases, and it was significantly more frequent in patients with liver cell dysplasia (P < 0.01) and HBsAg-serum positivity (P < 0.01). Multivariate analysis showed that liver cell dysplasia was the most important risk factor correlated with HCC development. HBsAg positivity and age over 60 years were also independent risk factors for HCC. CONCLUSIONS These results indicate that liver cell dysplasia is a major risk factor for HCC, and it should be looked for carefully by pathologists in liver biopsy specimens to identify patients requiring more intensive observation.