Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid.

BACKGROUND & AIMS: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.

Rate of non-response to ursodeoxycholic acid in a large real-world cohort of primary biliary cholangitis patients in Italy.

Background and aim: Response to ursodeoxycholic acid (UDCA) is crucial for the prediction of primary biliary cholangitis (PBC) prognosis, and different response criteria were validated and proposed by reference centers for PBC. To date, rates of non-response to UDCA from real-world series are lacking.Methods: Hepatology/Gastroenterology centers belonging to 'Club Epatologi Ospedalieri' (CLEO) and 'Associazione Italiana Gastroenterologi Ospedalieri' (AIGO) were invited to participate in the study, and asked to extract all patients followed for PBC, without any selection or exclusion, and fill in the database provided.Results: Thirty-four centers were enrolled throughout Italy, for a total of 713 patients. None of these centers, except one, had a hepatology outpatient clinic devoted to the care of patients with autoimmune liver diseases. After excluding 79 cases of PBC/autoimmune hepatitis overlaps, 634 patients were analyzed: mean age, 64.4 ± 12.0 years; 91.2% females; F/M 10.3/1. For patients with at least 1 year of UDCA treatment (583), rates of non-response to UDCA were evaluated according to the Paris-I/-II, Toronto and GLOBE criteria, and compared with those in the original cohorts: 27% vs 39% in Paris-I cohort; 39.6% vs 52% in Paris-II; 20.1% vs 43.5% in Toronto; 15.7% vs 30% in GLOBE (age-specific cutoffs). Mean alkaline phosphatase levels on UDCA treatment, and the age-adjusted prevalence of F3/F4 fibrosis, appeared lower in this PBC population than in reference cohorts.Conclusions: A mean ∼15% better response to UDCA is observed in a real-world PBC population, probably due to migration of some of most severe/advanced cases to PBC referral centers.

TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD.

Mechanisms underlying the opposite effects of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C>T polymorphism on liver injury and cardiometabolic risk in nonalcoholic fatty liver disease (NAFLD) are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabolism, glucose homeostasis, and nutrient oxidation in NAFLD. Sixty nonobese nondiabetic normolipidemic biopsy-proven NAFLD patients and 60 matched controls genotyped for TM6SF2 C>T polymorphism underwent: indirect calorimetry; an oral fat tolerance test with measurement of plasma lipoprotein subfractions, adipokines, and incretin glucose-dependent insulinotropic polypeptide (GIP); and an oral glucose tolerance test with minimal model analysis of glucose homeostasis. The TM6SF2 T-allele was associated with higher hepatic and adipose insulin resistance, impaired pancreatic ß-cell function and incretin effect, and higher muscle insulin sensitivity and whole-body fat oxidation rate. Compared with the TM6SF2 C-allele, the T-allele entailed lower postprandial lipemia and nefaemia, a less atherogenic lipoprotein profile, and a postprandial cholesterol (Chol) redistribution from smaller atherogenic lipoprotein subfractions to larger intestinal and hepatic VLDL1 subfractions. Postprandial plasma VLDL1-Chol response independently predicted the severity of liver histology. In conclusion, the TM6SF2 C>T polymorphism affects nutrient oxidation, glucose homeostasis, and postprandial lipoprotein, adipokine, and GIP responses to fat ingestion independently of fasting values. These differences may contribute to the dual and opposite effect of this polymorphism on liver injury and cardiometabolic risk in NAFLD.

Hepatitis delta infection in Italian patients: towards the end of the story?

BACKGROUND: The endemicity of hepatitis delta virus infection in Italy has decreased in the last decades. AIM: To evaluate the current epidemiology of chronic delta infection in Italy and to compare the present findings with the corresponding figures from the previous studies. METHODS: A cross-sectional study involving 16 referral centres scattered all over the country in 2014. RESULTS: Out of the 513 hepatitis B surface antigen-positive subjects enrolled, 61 (11.9%) were anti-delta positive, with a sex ratio (M/F) of 2.05. The majority (80.3%) of them was 50 years or older, while the proportion of subjects younger than 30 years of age was as low as 3.3%. No difference was detected by geographical area of residence. The presence of liver cirrhosis was diagnosed in 52.4% of cases. In comparison to previous studies, a further shift towards the oldest age groups and an increasing proportion of subjects having liver cirrhosis among all anti-delta-positive subjects are observed. CONCLUSIONS: Currently, hepatitis delta infection mostly affects old people who have an advanced but indolent liver disease, reflecting a survival effect. The defective hepatitis delta virus is near to disappear in the country, where it has been discovered in the second half of 70s.

MicroRNA expression in relation to different dietary habits: a comparison in stool and plasma samples.

MicroRNAs (miRNAs), a class of small non-coding RNAs, are fundamental for the post-transcriptional regulation of gene expression. Altered expression of miRNAs has been detected in cancers, not only in primary tissue but also in easily obtainable specimens like plasma and stools. miRNA expression is known to be modulated by diet (micro and macronutrients, phytochemicals) and possibly by other lifestyle factors; however, such influence has not yet been exhaustively explored in humans. In the present study, we analysed the expression levels of a panel of seven human miRNAs in plasma and stool samples of a group of 24 healthy individuals characterised by different dietary habits (eight vegans, eight vegetarians and eight subjects with omnivorous diet, all groups with similar age and sex distribution). The dual aim of the study was to identify possible differences in miRNA expression due to diet (or other lifestyle factors recorded from questionnaires) and to compare results in both types of specimens. miR-92a was differentially expressed in both plasma and stool samples and with the same trend, among the three groups with different diets (P = 0.0002 and P = 0.02, respectively, with expression levels of vegans>vegetarians>omnivores). miR-92a was also associated with low body mass index (P = 0.04 and P = 0.05, respectively) in both types of specimens, and with several dietary factors. Other analysed miRNAs (miR-16, miR-21, mir-34a and miR-222) were associated with dietary and lifestyle factors, but not consistently in both stool and plasma. Our pilot study provides the first evidence of miRNA modulation by diet and other factors, that can be detected consistently in both plasma and stools samples.

Nonalcoholic steatohepatitis versus steatosis: adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). Though liver-related risk seems confined to NASH, it is currently unclear whether NASH has a higher risk of cardiovascular disease (CVD) and diabetes than SS as a result of the coexistence of obesity and other cardiometabolic confounders. Adipose tissue is an emerging modulator of liver disease in NAFLD and of cardiometabolic disease in the general population. We evaluated in SS and NASH (1) glucose homeostasis and cardiovascular risk profile and (2) the effect of adipose tissue dysfunction, assessed in fasting conditions and postprandially, on liver injury, glucose and lipoprotein metabolism, and markers of early atherosclerosis. Forty nonobese, nondiabetic, normolipidemic biopsy-proven NAFLD patients (20 with SS and 20 with NASH) and 40 healthy subjects, matched for overall/abdominal adiposity and metabolic syndrome, underwent an oral fat load test, with measurement of plasma triglyceride-rich lipoproteins, oxidized low-density lipoproteins, adipokines, and cytokeratin-18 fragments, and an oral glucose tolerance test with minimal model analysis to yield glucose homeostasis parameters. Circulating endothelial adhesion molecules were measured, and adipose tissue insulin resistance (adipose IR) index and visceral adiposity index were calculated. Despite similar fasting values, compared to SS, NASH showed a more atherogenic postprandial lipoprotein profile, an altered adipokine response (i.e., higher resistin increase and an adiponectin fall), and hepatocyte apoptosis activation after fat ingestion. Adipose IR index, endothelial adhesion molecules, and hepatic insulin resistance progressively increased across NAFLD stages. NASH, but not SS, showed an impaired pancreatic ß-cell function. On multiple regression analysis, adipose IR index and postprandial adiponectin independently predicted liver histology and altered cardiometabolic parameters. CONCLUSION: Adipose tissue dysfunction, including a maladaptive adipokine response to fat ingestion, modulates liver injury and cardiometabolic risk in NAFLD.

Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. METHODS: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. RESULTS: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). CONCLUSIONS: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. LAY SUMMARY: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.

Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: a multicenter study of 664 patients and 1992 healthy controls.

Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multicenter case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and sex, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR), 3.3; 95% confidence interval (CI), 2.4-4.5] and DRB1*02 (OR 0.9; 95% CI 0.8-1.2) were significantly associated with PBC, whereas alleles DRB1*11 (OR 0.4; 95% CI 0.3-0.4) and DRB1*13 (OR 0.7; 95% CI 0.6-0.9) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. Associated DRB1 alleles were found only in a minority of patients, whereas an additive genetic model is supported by the gene dosage effect for DRB1*11 allele and the interaction of DRB1*11,*13, and *08. Lastly, no significant associations were detected between specific DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. In conclusion, we confirm the role for HLA to determine PBC susceptibility and suggest that the effect of HLA is limited to patient subgroups. We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease.

Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis.

BACKGROUND: The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation. OBJECTIVE: Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis. DESIGN: We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis. RESULTS: Females were older than males (p<0.01) and less frequently showed HBV and alcoholic aetiology (p<0.01). In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01). An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06-24.56) exceeds the sum (4.14) of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake). No interaction is observed in male sex. CONCLUSIONS: The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males.

Etiological factors of chronic hepatitis in Italy: a 2014 national survey.

BACKGROUND: The last Italian prevalence survey on chronic hepatitis (CH) conducted in 2001 showed that the hepatitis C virus (HCV) was the main agent associated with CH. AIM: The aim of this study was to evaluate epidemiological changes in CH occurring after 13 years. PATIENTS AND METHODS: Enrollment of 1392 CH consecutive patients referred to 16 Italian liver units in 2014 scattered all over the country (four in the North, four in the Center, four in the South, and four in the Islands) was performed. RESULTS: The mean age of the patients was 58.3 years, with a sex ratio (male/female) of 1.5. HCV infection (also with other etiologies) continues to be the most prevalent etiology (58.1%). However, this prevalence was lower (P<0.01) than the corresponding figure (76.5%) for 2001. The proportion of hepatitis B virus-related cases almost doubled over time from 12.2% in 2001 to 22.5% in 2014 (P<0.01), most probably biased because of the distribution of entecavir and tenofovir free of charge at outpatient hospital clinics after 2001. Patients reporting risky alcohol intake (also with other etiologies) accounted for 12.4% of cases, a figure lower than that reported in 2001: 19.2% (P<0.01). The proportion of nonalcoholic fatty liver disease cases nearly doubled over time (3.6% in 2001 and 6.2% in 2014; P<0.05), reflecting the greater attention over time devoted to this syndrome. CONCLUSION: The decreasing role of HCV infection as an etiologic factor of CH in Italy is good news considering the high cost of the directly acting antiviral agents for HCV eradication. Metabolic factors warrant greater attention in the near future.

Inflammatory bowel disease: Traditional knowledge holds the seeds for the future.

Despite the level of sophistication they have reached nowadays, the available tools for treatment of inflammatory bowel disease (IBD) can at best chronicize the disease but not cure it. Chances to make leap forward from this hold-back may include designs to reach personalized treatment strategies taking advantage of modern genome associated studies, and shift resources towards unfolding inciting pathogenetic steps rather than continuing to develop drugs that address down-stream phenomena. We have arbitrarily chosen to scrutinize a few projects that may make their way in 2015 and mark the history of IBD research. The list includes: the role of appendix as a regulating factor in pathogenesis of ulcerative colitis/proctitis; the reappraisal of (auto)immune phenomena in the era of microbiome; projects to treat IBD by stem cell infusion; recognition of the crucial pathogenetic role of gut microbiome, and attempts to modify it to treat enteric diseases, from clostridium difficile infection to IBD.

6-Mercaptopurine for Azathioprine Intolerant Inflammatory Bowel Disease: Literature Search and Reappraisal of Own Data.

Thiopurines have been shown to effectively maintain remission of both Crohn's disease (CD) and ulcerative colitis (UC), and to behave as disease modifiers if used for >12 months in UC. Gastric intolerance manifesting as nausea constitutes a demanding drawback of thiopurines, at times forcing treatment discontinuance. A few studies have now indicated that some patients might tolerate mercaptopurine (6-MP) for azathioprine. In this paper, we review the literature, and reappraise our own data against the published figures. The data which form the basis for this study span over all visit reports that were released between January 2008 and December 2011 in a primary care Hospital, in Turin, Italy. For the aim of this study we searched our own database and the MedLine using the key-words "azathioprine", "mercaptopurine", "thiopurine", "inflammatory bowel disease", "Crohn's disease", "ulcerative colitis". We retrieved 85 azathioprine prescriptions for 42 UC, 37 CD, and 6 miscellaneous patients. There were 10 episodes of gastric intolerance to azathioprine, which were switched to 6-MP: 6 out of 10 (60%) responded and tolerated the switch drug in a median follow-up of 66 months. Female gender prevailed (p=0.038) in the azathioprine intolerant subset. A trial with 6-MP is worth being offered to azathioprine intolerant inflammatory bowel disease subjects at any center matching the standard figures of specific performance.

The overlap syndrome between primary biliary cirrhosis and primary sclerosing cholangitis.

BACKGROUND: The overlap syndrome between primary biliary cirrhosis and primary sclerosing cholangitis is an extremely rare condition that has been reported in only six published cases so far. METHODS: Here we report two cases showing the clinical manifestations of both primary biliary cirrhosis and primary sclerosing cholangitis. RESULTS: In one case the overlap condition was associated with psoriatric arthritis, and the patient successfully underwent dual treatment with ursodeoxycholic acid and the anti-tumour necrosis factor-alpha agent adalimumab. In the second case, the predominant condition was, initially, an antimitochondrial antibody-negative primary biliary cirrhosis with progressive course towards end-stage liver disease; the patient then developed either antimitochondrial antibody positivity or changes in the biliary tree compatible with primary sclerosing cholangitis. CONCLUSIONS: These two cases add information on a controversial issue in the literature, and indicate the importance of recognizing a possible overlap syndrome to optimize treatment.

Association of single nucleotide polymorphisms of the interleukin-10 promoter gene and susceptibility to primary biliary cirrhosis: immunogenetic differences in Italian and Japanese patients.

Several lines of data suggest that genetic factors play an important role in the onset and/or progression of primary biliary cirrhosis (PBC). Since PBC is an autoimmune disease, it is reasoned to assume that genes encoding cytokines may confer susceptibility to disease. Amongst these factors, interleukin-10 (IL-10) has received significant attention. The promoter region of IL-10 gene has three single nucleotide polymorphisms (SNPs) at positions -1082, -819 and -592. To elucidate the association of the three SNPs of IL-10 promoter region with susceptibility of PBC in two different genetic populations, 159 unrelated patients with PBC (94 Italian and 65 Japanese) and 143 local controls (72 Italian and 71 Japanese) were enrolled. SNPs were determined using allele-specific PCR/RFLP. In Italian PBC patients, the frequency of homozygosity for G/G at position -1082 was significantly higher than that of local controls (p < 0.041, OR = 2.44, 95% C.I.; 1.02-5.86). The frequencies of haplotype GCC in PBC patients, possibly linked to higher IL-10 production, were also significant higher than local controls (p < 0.033). However, in Japanese population, there were no significant differences in the three SNPs and haplotypes between PBC patients and controls. Excessive production of IL-10 may play an important role in some populations in modulating the onset of PBC. Further, immunogenetic studies of PBC should take into account ethnic and geographic variations; this makes such studies in heterogeneous population, like the USA, more difficult.

Source of exhaled nitric oxide in primary biliary cirrhosis.

BACKGROUND: Exhaled nitric oxide (NO) levels may be elevated in patients with liver cirrhosis and autoimmune diseases. Primary biliary cirrhosis (PBC) is often associated with keratoconjunctivitis sicca (Sjogren syndrome [SS]), an extrahepatic autoimmune manifestation. The aim of this study was to evaluate the source of increased exhaled NO (ie, alveolar vs airway) in patients with PBC, whether associated with SS or not, and to evaluate its impact on oxygenation abnormalities. DESIGN: Observational controlled study. SETTING: University hospital. METHODS: The fractional alveolar NO concentration (FANO) and airway flux of NO (QbrNO) were measured by the multiple flows technique in 34 patients with PBC, 12 with associated SS, and were compared to 20 control subjects and 12 patients with primary SS. RESULTS: FANO was significantly higher in patients with PBC, associated with SS (mean [+/- SEM], 8.9 +/- 0.8 parts per billion [ppb]) or not (mean, 7.7 +/- 0.7 ppb) compared to healthy control subjects (mean, 4.6 +/- 0.5 ppb; p < 0.001) and to patients with primary SS (mean, 4.3 +/- 0.5 ppb; p < 0.001). FANO was significantly higher in cirrhotic patients with increased alveolar-arterial oxygen pressure difference (P[A-a]O(2)) compared to patients with normal P(A-a)O(2) values (9.8 +/- 0.8 vs 7.3 +/- 0.7, respectively; p = 0.018). When compared with control subjects and with patients with PBC not associated with SS, QbrNO was significantly increased in patients with both primary SS and SS associated with PBC. CONCLUSIONS: Increased exhaled NO levels found in PBC are from both alveolar and airway sources in patients with associated SS, but only FANO is associated with oxygenation impairment.

Lack of association between seroprevalence of Helicobacter pylori infection and primary biliary cirrhosis.

AIM: To determine the association between seroprevalence of Helicobacter pylori (H pylori) infection and primary biliary cirrhosis (PBC). METHODS: In this case-control study, 149 consecutive patients (10 males, 139 females, mean age 58.2+/-11 years, range 26-82 years) suffering from PBC and 619 consecutive healthy volunteer blood donors (523 males, 96 females, mean age 47+/-5.3 years, range 18-65 years) attending the Hospital Blood Bank and residing in the same area were recruited. A commercial enzyme linked immunosorbent assay was used to detect anti-H pylori (IgG) antibodies in serum. RESULTS: Antibodies to H pylori were present in 78 (52.3%) out of 149 PBC-patients and in 291 (47%) out of 619 volunteers (P = 0.24, OR 1.24, 95% CI 0.85-1.80). In the subjects less than 60 years old, the prevalence of H pylori infection among PBC-patients (40/79) was slightly higher than in controls (50.6% vs 46.2%) P = 0.46, OR = 1.19, 95% CI: 0.72-1.95). In those over 60 years, the prevalence of H pylori infection was similar between PBC-patients and controls (54.2% vs 57.8%, P = 0.7, OR 0.86, 95% CI 0.36-2.07). CONCLUSION: There is no association between seroprevalence of H pylori infection and primary biliary cirrhosis.

Inflammatory bowel diseases: Current problems and future tasks.

Current knowledge on inflammatory bowel disease (IBD) is mainly endorsed by controlled trials and epidemiologic studies. Yet, we seldom look at the messages from real-world practice. Among a patient population followed since 2008, we looked at an unselected sample of 64 IBD patients [26 Crohn's disease (CD) and 38 ulcerative colitis (UC)] who had been seen as out-patients in the last year. Inducing remission, mesalamines (86% for UC/69% for CD/33%-16% as MMX formulation) prevailed as prescriptions; steroids (55%/19% for UC/CD) ranked second. Prescription of third-party drugs (antibiotics, NSAIDs, biologics) and adherence, were issues in the maintenance. 34% of CD, and 23% of UC patients showed accompanying immunologic diseases: CD-associated familiar psoriasis (4:9) ranked first. Main Message. The association between IBD (CD mainly) and psoriasis, now found in our practice, matches current basic science gathering IBD together with psoriasis (and perhaps chronic respiratory disease) under the comprehensive term "barrier organ disease" wherein an epithelial surface with sensor systems rules contacts between outer antigens and a reactive underneath tissue, with the balance between inflammation and quiescence kept at any time by mucosal permeability. IBD is thus viewed as a polyfactorial/polygenic/syndromic disorder, embedded into a galaxy of immune conditions offering multiple points of attack. This mindset of splitting the IBDs into pathogenic categories may allow overcoming the uniformly targeting of a single cytokine by biological drugs, in favor of demarcating the boundaries between different disease-subtype-specific indications, and paving the way to future personalized strategies.

Antibiotics and non-steroidal anti-inflammatory drugs in outpatient practice: indications and unwanted effects in a gastroenterological setting.

OBJECTIVE: To explore the type and frequency of the unwanted effects following use of non-steroidal antiinflammatory drugs (NSAIDs) and antibiotics in a gastroenterological out-patient setting. METHODS: We analyzed a gastroenterological database which includes 151 inflammatory bowel disease (IBD) patients followed between January 2008 and December 2009. The key-words included NSAIDs and antibiotics. RESULTS: Of 19 cases treated with NSAIDs, 8 displayed convincing evidence linking them with the subsequent development of IBD. Of 44 antibiotic mentions, 7 documents alluded to macrolide prescriptions, which were followed by induction or relapse of IBD in 5; all of the newly diagnosed cases of IBD were endoscopically proven, and one ran a fulminant course requiring emergency colectomy; 4 of 5 prescriptions of amoxycillin/clavulanic acid were accompanied by toxicity (three hepatitides and one reactivated IBD). Overall, the frequency of unwanted effects was 36% for both NSAIDs and antibiotics. CONCLUSION: We suggest that NSAIDs and antibiotics (specifically of the macrolide structure) can induce gut and hepatic damage, significantly enhancing co-morbidities in gastroenterologic out-patients, with break of cost-containment guidelines. Therefore, caution is advisable in prescribing NSAIDs and antibiotics in this setting. Though retrospective and possibly biased, the current data coincide with both bench work and epidemiological evidence.