Exocrine pancreatic insufficiency in adults:A shared position statement of the Italian association for the study of the pancreas

This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas(AISP).We covered the main diseases associated with exocrine pancreatic insufficiency(EPI)which are of common interest to internists/gastroenterologists,oncologists and surgeons,fully aware that EPI may also occur together with many other diseases,but less frequently.A preliminary manuscript based on an extended literature search(Medline/PubMed,Cochrane Library and Google Scholar)of published reports was prepared,and key recommendations were proposed.The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012.Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached.The final draft of the manuscript was then sent to the AISP Council for approval and/or modification.All concerned parties approved the final version of the manuscript in June 2013.

Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition

The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance(SVR),halt disease progression,and prevent re-infection of the liver graft.However,while the medical need is great,the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias.We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis,due to hepatitis C virus(HCV) infection.In cases presenting with bridging fibrosis or cirrhosis,current regimens of antiviral therapy have attained a 44%-48% rate of SVR.In cirrhotic patients with portal hypertension,the SVR rate was 22% overall,12.5% in patients with genotype 1,and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin.In patients with decompensated cirrhosis,full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall,16% in patients with genotype 1 and 4,and 59% in those with genotype 2 and 3.Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects.Major benefits after HCV eradication were partial recovery of liver metabolic activity,prevention of hepatitis C recurrence after transplantation,and removal of some patients from the waiting list for liver transplant.Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve(Child-Pugh-Turcotte score ≥ 10).Although SVR rates are low indecompensated cirrhotics due to hepatitis C,these patients have the most to gain as successful antiviral therapy is potentially lifesaving.

Enteropathic spondyloarthropathy:A common genetic background with inflammatory bowel disease?

The association between spondyloarthropathy and in flammatory bowel disease(IBD) is largely established, although prevalence is variable because of different population selection and diagnostic methodologies.Most studies indicate that as many as 10%15% of cases of IBD are complicated by ankylosing spondylitis(AS) or other forms of spondylarthritis(SpA).Of note, ileal inflammation resembling IBD has been reported in up to two thirds of cases of SpA, and it has been suggested that the presence of ileitis is associated with the chronic ity of articular complications.Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of patients with SpA by ileocolonos copy is not indicated in the absence of gut symptoms, as only a small proportion of patients with subclinical gut inflammation will develop overt IBD over time.The existence of familial clustering of both IBD and AS, the coexistence of both conditions in a patient, the evidence of an increased risk ratio among f irstand seconddegree relatives of affected AS or IBD patients and f inally, the increased crossrisk ratios between AS and IBD, strongly suggest a shared genetic background.So far, however, IL23R is the only identified susceptibility gene shared by both IBD and AS.Although functional studies are still needed to better understand its pathogenic role, great ef fort is being spent therapeutically targeting this pathway that may prove effective for both disorders.

Comparison of four proton pump inhibitors for the short-term treatment of esophagitis in elderly patients

AIM: To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients.METHODS: A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk: (1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d; (3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d. Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated.RESULTS: Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole = 93.5% (P = 0.04 vs omeprazole) and 90.0% (P = 0.02 vs omeprazole), rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates: 81.8% vs 100%, 100% and 100%, respectively, P = 0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001)and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P < 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P < 0.05) in decreasing epigastric pain.CONCLUSION: In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms. H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI.

Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis

AIM: To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD). METHODS: All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT). RESULTS: At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21). CONCLUSION: BMI helps identify children with NASH who might have fibrotic deposition in the liver.

Lack of association between UGT1A7,UGT1A9,ARP,SPINK1 and CFTR gene polymorphisms and pancreatic cancer in Italian patients

AIM: To investigate simultaneously UGT1A7, UGT1A9, ARP, SPINK and CFTR genes to verify whether genetic polymorphisms predispose to the development of pancreatic cancer (PC). METHODS: Genomic DNA of 61 pancreatic cancer patients and 105 healthy controls (HC) were analyzed. UGT1A7 genotyping was determined by PCR-RFLP analysis. Specific PCR and sequencing were used to analyze genetic variants of UGT1A9, ARP, SPINK1 and CFTR genes. RESULTS: Four different alleles (*1: WT; *2: N129K and R131K; *3: N129K, R131K, and W208R; and *4: W208R) in UGT1A7 and three different alleles (*1: WT; *4: Y242X; and *5: D256N) in UGT1A9 were detected. All UGT1A polymorphisms were observed at similar frequency in PC patients and HC. Seven different alleles in ARP were found in PC patients and HC at similar frequency. The SPINK1 mutations N34S and P55S occurred in five PC patients with a prevalence (4.1%) not significantly different from that observed (2.0%) in HC. The only CFTR ΔF508 mutation was recognized in three PC patients with a prevalence (4.9%) similar to HC. CONCLUSION: UGT1A7, UGT1A9, ARP, SPINK1 and CFTR gene polymorphisms are not associated with PC in Italian patients.

Exploitation of host clock gene machinery by hepatitis viruses B and C

Many aspects of cellular physiology display circadian(approximately 24-h)rhythms.Dysfunction of the circadian clock molecular circuitry is associated with human health derangements,including neurodegeneration,increased risk of cancer,cardiovascular diseases and the metabolic syndrome.Viruses triggering hepatitis depend tightly on the host cell synthesis machinery for their own replication,survival and spreading.Recent evidences support a link between the circadian clock circuitry and viruses’biological cycle within host cells.Currently,in vitro models for chronobiological studies of cells infected with viruses need to be implemented.The establishment of such in vitro models would be helpful to better understand the link between the clock gene machinery and viral replication/viral persistence in order to develop specifically targeted therapeutic regimens.Here we review the recent literature dealing with the interplay between hepatitis B and C viruses and clock genes.

Hepatitis C virus,mitochondria and auto/mitophagy:Exploiting a host defense mechanism

Hepatitis C virus(HCV)is the major reason for liver transplantation and the main cause of liver-related morbidity and mortality in a great number of countries.As for the other viruses,this pathogen interferes in more than one process and in more than one way with host cell biology.A mounting body of evidence points,in particular,toward the drastic alterations of mitochondrial physiology and functions that virus is able to induce,albeit the mechanisms have partly remained elusive.Role of the mitochondria in immunity and in quality control systems,as autophagy,as well as the strategies that HCV has evolved to evade and even to manipulate mitochondrial surveillance for its benefit,highlights the importance of deepening the mechanisms that modulate this virus-mitochondrion interaction,not only to intensify our knowledge of the HCV infection pathogenesis but also to design efficient antiviral strategies.

Comparison of a monoclonal antigen stool test (Hp StAR) with the ^(13)C-urea breath test in monitoring Helicobacter pylori eradication therapy

AIM: To evaluate the agreement between a mAb-based stool test (HP StAR) and the urea breath test (UBT) in monitoring (H pylori) infection after eradication therapy.METHODS: Patients with discordant results on UBT and Hp StAR underwent endoscopy with biopsies for rapid urease test, culture, and histology to confirm H pylori status.RESULTS: Among 250 patients (50±14 years), 240 (96.0%) had concordant UBT and Hp StAR tests with a significant correlation between DOB and A values (R = 0.87; P＜0.0001).The remaining 10 (4.0%) patients had discordant tests (positive Hp StAR and negative UBT) with the Hp StAR inaccurate in five cases (false positive) and UBT inaccurate in the other five cases (false negative). The 'maximal expected' sensitivity, specificity, +PV, -PV, +LR, and -LR were 91%, 100%, 100%, 97.4%, ∞, and 8.2 respectively,for the UBT, and 100%, 97.4%, 91%, 100%, 38.8, and 0,respectively, for the Hp StAR. Overall accuracy for both tests was 98%.CONCLUSION: Both the UBT and the Hp StAR are equally accurate in monitoring H pylori infection. Nowadays,the choice of the 'best' non-invasive H pylori test in the post-treatment setting should be done not only in terms of diagnostic accuracy but also in view of cost and local facilities.

Boceprevir or telaprevir in hepatitis C virus chronic infection:The Italian real life experience

AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-Taq Man2.0(Roche, LLQ 25 IU/m L). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57(range 18-78), of whom 18.3% were over 65; mean body mass index 25.6(range 16-39); genotype 1b(79.4%); diagnosis of cirrhosis(38.2%); and fibrosis F3/4(71.2%). The following drugs were used: Telaprevir(66.2%) and PEG-IFN-alpha2a(67.6%). Patients were na?ve(24.4%), relapsers(30.5%), partial responders(14.8%) and null responders(30.3%). Overall, adverse events(AEs) occurred in 617 patients(73.9%) during the treatment. Anemia was the most frequent AE(52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure(15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.

How evidence-based are current guidelines for managing patients with peptic ulcer bleeding?

Current guidelines for managing ulcer bleeding state that patients with major stigmata should be managed by dual endoscopic therapy(injection with epinephrine plus a thermal or mechanical modality) followed by a high dose intravenous infusion of proton pump inhibitors(PPIs).This paper aims to review and critically evaluate evidence supporting the purported superiority of a continuous infusion over less intensive regimens of PPIs administration and the need for adding a second hemostatic endoscopic procedure to epinephrine injection.Systematic searches of PubMed,EMBASE and the Cochrane library were performed.There is strong evidence for an incremental benefit of PPIs over H2receptor antagonists or placebo for the outcome of patients with peptic ulcer bleeding following endoscopic hemostasis.However,the benefit of PPIs is unrelated to either the dosage(intensive vs standard regimen) or the route of administration(intravenous vs oral).There is significant heterogeneity among the 15 studies that compared epinephrine with epinephrine plus a second modality,which might preclude the validity of reported summary estimates.Studies without second look endoscopy plus re-treatment of re-bleeding lesions showed a signif icant benef it of adding a second endoscopic modality for hemostasis,while studies with second-look and re-treatment showed equal efficacy between endoscopic mono and dual therapy.Inconclusive experimental evidence supports the current recommendation of the use of dual endoscopic hemostatic means and infusion of high-dose PPIs as standard therapy for patients with bleeding peptic ulcers.Presently,the combination of epinephrine monotherapy with standard doses of PPIs constitutes an appropriate treatment for the majority of patients.