Falling Rates of Hospital Admissions for Alcoholic Liver Disease in Northeast Italy: A Retrospective Study on a Large Database.

AIM: To describe recent trends in hospital admission rates for alcoholic liver disease (ALD) in the Veneto region of Italy. METHODS: This retrospective cohort study is based on anonymous hospital discharge records (HDRs) for 2000-2017 from all public and accredited private hospitals operating within the context of the Regional (Veneto) Health Services that are conserved in National/Regional database. It examined the HDR's of all the hospitalizations of the residents of the Veneto region that were registered under an ALD diagnosis. These were classified under three subheadings: acute alcoholic hepatitis Alcoholic liver cirrhosis and 'other ALD'. RESULTS: During 2000-2017, 30,089 hospital admissions (out of a total regional population of 4,900,000) were registered for ALD. Hospitalization stratified by age showed that the percentage attributable to acute alcoholic hepatitis is higher in younger age groups: 42% in 15-24-year-old (odds ratios (ORs): 14.74; CI95%: 7-30.86; P < 0.000) and 15% in the 25-44-year-old (OR: 3.51; CI95%: 3.12-3.94; P < 0.000). A longitudinal analysis of hospitalization patterns showed a 7% increase in average age in both sexes (from 58.8 ± 9.2 to 62.4 ± 9.7) and a substantial decrease (63.5%) in standardized hospitalization rates (HRs, χ2 trend: 4099.827; P < 0.000) and a smaller decrease (47%) in standardized mortality rates (χ2 trend: 89.563; P < 0.000). CONCLUSIONS: The fall in the overall ALD-related HR in the Veneto region can be explained by a decrease in population alcohol consumption. Increase in the HRs for acute alcoholic hepatitis in the age group 15-44 suggests an ongoing need for strategies to prevent alcohol abuse by young people.

Clean Colon Software Program (CCSP), Proposal of a standardized Method to quantify Colon Cleansing During Colonoscopy: Preliminary Results.

BACKGROUND AND STUDY AIMS: Neoplastic lesions can be missed during colonoscopy, especially when cleansing is inadequate. Bowel preparation scales have significant limitations and no objective and standardized method currently exists to establish colon cleanliness during colonoscopy. The aims of our study are to create a software algorithm that is able to analyze bowel cleansing during colonoscopies and to compare it to a validate bowel preparation scale. PATIENTS AND METHODS: A software application (the Clean Colon Software Program, CCSP) was developed. Fifty colonoscopies were carried out and video-recorded. Each video was divided into 3 segments: cecum-hepatic flexure (1st Segment), hepatic flexure-descending colon (2nd Segment) and rectosigmoid segment (3rd Segment). Each segment was recorded twice, both before and after careful cleansing of the intestinal wall. A score from 0 (dirty) to 3 (clean) was then assigned by CCSP. All the videos were also viewed by four endoscopists and colon cleansing was established using the Boston Bowel Preparation Scale. Interclass correlation coefficient was then calculated between the endoscopists and the software. RESULTS: The cleansing score of the prelavage colonoscopies was 1.56 ±â€Š0.52 and the postlavage one was 2,08 ±â€Š0,59 (P < 0.001) showing an approximate 33.3 % improvement in cleansing after lavage. Right colon segment prelavage (0.99 ±â€Š0.69) was dirtier than left colon segment prelavage (2.07 ±â€Š0.71). The overall interobserver agreement between the average cleansing score for the 4 endoscopists and the software pre-cleansing was 0.87 (95 % CI, 0.84 - 0.90) and post-cleansing was 0.86 (95 % CI, 0.83 - 0.89). CONCLUSIONS: The software is able to discriminate clean from non-clean colon tracts with high significance and is comparable to endoscopist evaluation.

Intrahepatic cholestasis of pregnancy: new insights into its pathogenesis.

AIM: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome. METHODS: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique. RESULTS: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene). CONCLUSIONS: Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.

A 35-year follow-up of a large cohort of patients with primary biliary cirrhosis seen at a single centre.

BACKGROUND: The natural history of primary biliary cirrhosis (PBC) is still debated. AIMS: To evaluate: (i) long-term survival in a large cohort of PBC patients observed prospectively at a single centre and (ii) mortality in relation to baseline characteristics and ursodeoxycholic acid (UDCA) treatment. METHODS: We considered all consecutive patients between 1973 and 2007 (327 subjects; 310 females, 17 males). RESULTS: The mean follow-up was 9.1±7.7 years. The patients' age at diagnosis for representative periods (1973-1980, 1981-1990, 1991-2000, 2001-2007) increased progressively from 47.7±1.5 to 53.2±1.2, to 65.2±2.1 and then 63.6±2.9 years. The proportion of asymptomatic patients at diagnosis increased from 30 to 48% in the last decade, while associated symptoms of extrahepatic autoimmunity remained unchanged. Eighty patients (24.4%) died, 74 of them because of liver failure (12 patients developed hepatocellular carcinoma); nine patients underwent liver transplantation. From 1988 onwards, all patients were treated with UDCA (n=288). The mean age at death for the sample as a whole was 67.2±1.3 years. The survival probability at 20 years was 82% for patients with histological stages I-II at entry, 64% for those with stage III and 42% for those with stage IV (P=0.0007). Mortality was significantly reduced in patients treated with UDCA (P=0.012), whereas it was independently associated with oesophageal varices (P=0.015). Patients treated with UDCA had a better prognosis than those untreated, irrespective of the histological stage. Early treated subjects with a good response to UDCA have an 85% chance of survival at 20 years. CONCLUSIONS: The clinical presentation of PBC has been changing over the years. Its early detection and early treatment improve the related survival rates.

Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: comparative analysis from two centers.

UNLABELLED: The limited information and divergent results on the prevalence, incidence, and risk factors for hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) may be due to the low prevalence of the disease and geographical and environmental differences. Therefore, we analyzed the incidence, prevalence, survival, and risk factors for HCC in patients with PBC from two European centers (389 from Barcelona, Spain, and 327 from Padova, Italy) followed up for 9.3 +/- 6.5 years. Gender, age, smoking habit, alcohol consumption, presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (anti-HCV), and advanced histological stage (III-IV) were evaluated as risk factors for tumor development. Twenty-four patients (13 from Barcelona and 11 from Padova) developed HCC. The prevalence of HCC was similar in Barcelona (3.34%) and Padova (3.36%). The incidence was 0.35 and 0.37 per 100 patient-years, respectively. Male gender, age >52 years, smoking habit, alcohol >40 g/day, HBsAg, and anti-HCV were not associated with HCC. Advanced histological stage was the only factor associated with the development of HCC (odds ratio [OR]: 5.80, 95% confidence interval [CI]: 2.34-14.38, P < 0.001). When analyzing the two series separately, male gender was associated with higher likelihood of HCC in Padova (OR: 8.09, 95% CI: 1.93-33.8, P < 0.01). The median survival after the diagnosis of HCC was 36 months. CONCLUSION: The prevalence and incidence of HCC is similar in Spain and Italy and the advanced histological stage is the only risk factor associated with the development of HCC in PBC. The slight disparities observed between the two series might be explained by patient features on diagnosis of liver disease.

Fatal hepatic decompensation in a bone marrow transplant recipient with HBV-related cirrhosis following lamivudine withdrawal.

Lamivudine is a nucleoside analogue with a potent antiviral activity used as prophylaxis against hepatitis B virus reactivation in patients with chronic HBV infection receiving chemotherapy. No standard guidelines exist, however, for the duration of lamivudine treatment. We report a clinical case of a 56-year-old patient with HBeAg-negative cirrhosis who developed a multiple myeloma. He was treated with lamivudine for 1 year while receiving chemotherapy and a subsequent bone marrow transplant. Complete remission from multiple myeloma was achieved. Four months after lamivudine was withdrawn, he experienced HBV reactivation with jaundice, though no YMDD mutations were detected. The patient rapidly developed fatal decompensation with septicemia and renal failure. In conclusion, this case shows that physicians should avoid discontinuing nucleoside therapy in patients with HBV infection who undergo immunosuppression for concomitant neoplastic conditions.

Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome.

UNLABELLED: Autoimmune hepatitis/primary sclerosing cholangitis (AIH/PSC) overlap syndrome is a relatively uncommon variant of PSC. AIM: To evaluate the natural history of AIH/PSC overlap syndrome compared to a group of "classical" PSC. METHODS: Forty-one consecutive PSC patients, with a regular follow-up of at least 2 years, were prospectively included in the study. Among these, 7 fulfilled the criteria for AIH/PSC overlap syndrome. RESULTS: The AIH/PSC overlap group significantly differed from the "classical" PSC group in the following parameters: mean age at presentation (21.4 +/- 5.0 vs 32.3 +/- 10 years, p < 0.01), AST 191.0 +/- 14.8 vs 48.9 +/- 34.5 U/L, p < 0.005), ALT (357.0 +/- 26.5 vs 83.7 +/- 60.7 U/L, p < 0.005) and serum IgG (25.6 +/- 4.7 vs 12.9 +/- 6.0 mg/dl, p < 0.0001). The mean follow-up was similar in the 2 groups (93.3 +/- 65.9 vs 98.1 +/- 65.9 months respectively). Treatment included immunosuppression + ursodeoxycholic acid (UDCA) in the AIH/PSC overlap patients, and UDCA in the "classical" PSC group. Deaths were recorded only in the classical PSC group. The median survival in the latter group was 207 months (95% C.I. 87.6-326.4). The major events during the follow-up included: OLTx (1/7 vs 6/34), and neoplasms (only in the group of "classical" PSC). The new Mayo score prognostic index only increased significantly during follow-up in the "classical" PSC group (r2 0.8117, p < 0.01) CONCLUSION: Patients with AIH/PSC overlap syndrome seem to benefit from immunosuppression + UDCA therapy, survival is apparently better than in "classical" PSC condition.