Serum glypican-3 for the prediction of survival in patients with hepatocellular carcinoma.

BACKGROUND: Glypican-3 (GPC-3) is a heparan sulfate proteoglycan overexpressed by hepatocellular carcinoma (HCC) cells. Several studies highlighted the diagnostic and prognostic value of GPC-3 expression in liver tissue, while data on the reliability of serum GPC-3 are limited and conflicting. We aimed to evaluate the prognostic value of serum GPC-3 in patients with HCC. METHODS: A total of 449 patients (91 F and 358 M; median age 65 [38-86] years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were retrospectively analyzed. All patients had cirrhosis and the main underlying etiology was viral (N.=323, 72%). Barcelona Clinic Liver Cancer (BCLC) staging system was adopted for patients' classification (BCLC 0/A, N.=293, 65% vs. B/C/D, N.=156, 35%) and treatment allocation. Response to therapy was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: Median overall survival (OS) after HCC diagnosis was 30 months (95% confidence interval [CI]: 27-34). Patients with serum GPC-3>150 pg/mL showed lower overall survival (16; 95%CI: 13-24 months) compared to those with GPC-3≤150 pg/mL (36; 95%CI: 30-56 months) (Log-rank test, P<0.001). At multivariate Cox proportional-hazard regression analysis, presence of ascites (adjusted Hazard Ratio [aHR]=1.84; 95%CI: 1.23-2.74, P=0.003), BCLC stage (aHR=1.65; 95%CI: 1.39-1.97, P<0.001), mRECIST (aHR=0.33; 95%CI: 0.21-0.51, P<0.001) and GPC-3>150 pg/mL (aHR=2.02; 95%CI: 1.47-2.78, P<0.001) resulted significantly associated to overall survival. CONCLUSIONS: Serum GPC-3 resulted an independent prognostic factor for patients with HCC irrespectively from tumor stage and response to therapy.

Effectiveness of Third-Class Biologic Treatment in Crohn's Disease: A Multi-Center Retrospective Cohort Study.

BACKGROUND: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. AIMS AND METHODS: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. RESULTS: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). CONCLUSION: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

Long-term follow-up of diabetic and non-diabetic patients with chronic hepatitis C successfully treated with direct-acting antiviral agents.

BACKGROUND AND AIMS: Clearance of hepatitis C virus (HCV) is associated with improved glycometabolic control in patients with diabetes mellitus (DM) but whether this effect is maintained over the long term with a reduction in liver-related events (LRE) is still debated. To address these issues, we conducted a long-term prospective study on diabetic and non-diabetic patients with chronic hepatitis C cured by direct antiviral agents (DAAs). METHODS: Among 893 recruited patients, 15.7% were diabetic (Group 1) and 84.3% non-diabetic (Group 2); changes in fasting glucose (FG) and glycated haemoglobin (HbA1c) levels were assessed in Group 1 while the incidence of LRE was established in the whole cohort. Differences between groups were evaluated and independent predictors of unfavourable clinical outcome were established. RESULTS: After a mean follow up of 44.5 months, a significant reduction in FG and HbA1c values was found in Group 1. Death was reported in 5.7% of patients in Group 1 vs 1.6% in Group 2 (P = .003), hepatocellular carcinoma (HCC)-free survival was significantly lower in Group 2 (P = .015) as well as LRE-free survival in Group 1 cirrhotic patients (P = .0006). After adjustment for baseline variables, cirrhosis and albumin levels emerged as independent predictors of LRE; low albumin levels, DM and central obesity were associated with HCC risk in cirrhotic patients while insulin therapy emerged as unfavourable predictor among diabetics. CONCLUSIONS: SVR achieved by DAAs is associated with long-term improvement of glycometabolic control in diabetic patients, but among cirrhotics DM still exerts a detrimental effect on the liver.

Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study.

BACKGROUND: The long-term course of ulcerative colitis after a severe attack is poorly understood. Second-line rescue therapy with cyclosporine or infliximab is effective for reducing short-term colectomy but the impact in the long-term is controversial. OBJECTIVE: The purpose of this study was to evaluate the long-term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy. METHODS: This was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow-up visit or death. The primary end-point was long-term colectomy rate in patients avoiding early colectomy. RESULTS: From the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow-up was 44 months (interquartile range, 21-85). Colectomy-free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid-responders (log-rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long-term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2-0.8), while previous exposure to antitumour necrosis factor-α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5-5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%). CONCLUSIONS: Patients with acute severe ulcerative colitis avoiding early colectomy are at risk of long-term colectomy, especially if previously exposed to antitumour necrosis factor-α agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

Moving towards core antigen for the management of patients with overt and occult HBV infection.

Chronic Hepatitis B virus (HBV) infection encompasses a wide virologic and clinical spectrum with heterogeneous outcomes. The natural history of chronic HBV infection ranges from an inactive carrier state (hepatitis B e antigen-negative chronic infection) to progressive chronic hepatitis that may evolve in end-stage liver disease and hepatocellular carcinoma. The issue becomes even more complicated when we consider the unique biology of the virus; the HBV covalently-closed-circular DNA, that acts as virus transcription template, is the key factor responsible of the persistence of the infection even after hepatitis B surface antigen loss. In the last decade, novel serological and immunological biomarkers associated to the core protein of HBV have been approached in different clinical conditions. Remarkable results have been obtained both in the setting of overt and occult HBV infection. Here, we reviewed the meaning and the potential clinical applications of the measurement of core antigen and antibodies.

Management of functional dyspepsia in 2020: a clinical point of view.

Dyspepsia is a disorder that refers mainly to central upper abdominal pain or discomfort. When a cause of this symptom is not identified the condition is termed functional dyspepsia (FD), that affects a large part of the general population. The relevance of FD is due to its high prevalence, but also to its chronic or intermittent course. This induces a significant burden for each national healthcare system. The pathogenesis of FD is complex and multifactorial, depending on cultural, environmental, and biological factors. Although considered of main importance in the pathophysiology of several gastroduodenal diseases, in the context of FD Helicobacter pylori (H. pylori) infection plays a limited role. The diagnosis of FD requires the exclusion of organic gastroduodenal diseases as well as H. pylori infection. Thus, the diagnostic workup includes a complete anamnesis, biochemical tests, and endoscopy with biopsy (when requested), and the satisfaction of clinic criteria recommended by the Rome IV consensus. The treatment of FD is also challenging, in fact more and more studies focused on a wide range of different therapies, with a multitude of results. The aim of this literature review is to provide an update of the new evidences useful for diagnosis and management of FD.

Proctitis: a glance beyond inflammatory bowel diseases.

Proctitis is an inflammation involving the anus and the distal part of the rectum, frequently diagnosed in the context of inflammatory bowel diseases (IBD). Nevertheless, when the standard therapy for IBD is ineffective, it becomes necessary for the clinician to review alternative etiologies, beginning from the broad chapter of infectious causes up to rare causes such as radiation, ischemia, diversion and traumatisms. While it is possible to find infectious proctitides caused by pathogens generally inducing extensive colitis, the growing incidence of both sexually transmitted infections and isolated proctitis reported in the recent years require a lot of attention. The risk appears to be higher in individuals participating in anal intercourse, especially men having sex with men (MSM) or subjects who use sex toys and participate to sex parties, dark rooms and so on. The commonest implicated pathogens are Neysseria gonorrhoeae, Chlamydia trachomatis, Herpes Simplex virus and Treponema pallidum. Herpes and Chlamydia infections mainly occur in HIV-positive MSM patients. Since symptoms and signs are common independently from etiology, performing a differential diagnosis based on clinical manifestations is complicated. Therefore, the diagnosis is supported by the combination of clinical history and physical examination and, secondly, by endoscopic, serologic and microbiologic findings. Particular emphasis should be given to simultaneous infections by multiple organisms. The involvement of experts in infectious diseases and in sexual health is crucial for the diagnostic and therapeutic management. The available therapies, empirically initiated or specific, in many cases are able to guarantee a good prognosis and to prevent relapses.

Oral iron supplementation with Feralgine® in inflammatory bowel disease: a retrospective observational study.

BACKGROUND: Inflammatory bowel disease (IBD) is a relapsing chronic disease of the gastrointestinal (GI) tract. Among IBD patients, anemia is more frequent than in general population. Recent studies demonstrated a good iron absorption using Feralgine®, a compound of ferrous bysglicinate chelate and alginic acid, oral supplementation with both good compliance rate and efficacy in treating iron deficiency anemia especially due to its high oral bioavailability. In this study we evaluated hemoglobin (Hb) improvement after Feralgine® supplementation in patients with IBD and anemia. METHODS: This is a retrospective observational study. All data were derived from the patients' registry of the Inflammatory Bowel Disease Center, San Giovanni Antica Sede-Molinette Hospital, Turin, Italy. All IBD patients suffering from anemia and treated with Feralgine® (Tecnofer Plus), 1 capsule daily, were selected. RESULTS: Mean Hb value increased from 11 g/dL (95% confidence interval [CI]: 10.72-11.47) to 12.2 g/dL (95% CI: 11.6-12.52, P=0.0001), after three months of Feralgine® supplementation. While 90% of the patients did not report adverse events, 10% experienced dyspepsia and worsening of diarrhea. Only 6% of patients suspended oral iron supplementation due to GI intolerance (adherence rate 94%). CONCLUSIONS: Oral supplementation with Feralgine® induced a significant improvement in Hb levels, suggesting that in IBD patients with mild or moderate anemia, oral iron supplementation could be considered the first line therapy. We suggest further studies on larger cohorts to assess iron, ferritin and transferrin saturation improvement after this treatment.

The role of topical therapy for perianal fistulizing Crohn's disease: are we forgetting something?

INTRODUCTION: Rectal inflammation is the principal risk factor for the development of perianal fistulizing Crohn's disease. However, no topical therapy direct to rectal healing is discussed in European' guidelines. The aim of this systematic review was to evaluate the role of topical therapy in healing the rectal inflammation in Crohn's disease. EVIDENCE ACQUISITION: A MEDLINE search of all studies published in English until December 2018 was conducted. Articles were identified using the strings "Crohn's disease and topical therapy" or "perianal Crohn's disease and topical therapy." EVIDENCE SYNTHESIS: Contradictory results about the efficacy of topical metronidazole were present. No benefit from topical tacrolimus use was demonstrated. Mesalazine suppositories induced and maintained remission of rectal inflammation in 50% of patients with rectal Crohn's disease. Few data were available about the role of local therapy for the fistulous tract in Crohn's disease. Local mesenchymal stem cells therapy could be a promising new approach. CONCLUSIONS: Due to the disappoint success rate of current strategy in perianal fistulizing Crohn's disease, the role of rectal inflammation as a causative factor and the fair success rate of topical therapy with mesalazine suppositories in the healing of rectal inflammation without relevant side effects, more studies are advisable in this field.

Serum zonulin in patients with inflammatory bowel disease: a pilot study.

BACKGROUND: In recent years it has been supposed that impaired intestinal permeability represents an early event preceding the onset of inflammatory bowel disease (IBD). Since zonulin has been proposed as a biomarker of intestinal permeability, we investigated its role in patients with IBD and the correlation between serum and fecal zonulin. METHODS: A total of 118 IBD patients (86 Crohn's disease [CD] and 32 ulcerative colitis [UC]) and 23 healthy controls (HC) were prospectively enrolled. A serum sample was collected for all the subjects included in the study. A stool specimen collected in the same day of blood drawing was available for a subgroup of 33 IBD patients. Serum and fecal zonulin were tested by ELISA. Non-parametric statistical tests were used for data analysis. RESULTS: Serum zonulin concentration was higher in IBD patients compared to HC (34.5 [26.5-43.9] ng/mL vs. 8.6 [6.5-12.0] ng/mL, P<0.001) showing an area under the curve of 0.98 for their discrimination. No difference in serum zonulin concentration was observed between patients with CD and those with UC (P=0.074). An inverse correlation was observed between serum zonulin concentration and disease duration (rs=-0.30, P=0.001); no correlation was observed between serum and fecal zonulin (rs=0.15, P=0.394). CONCLUSIONS: Serum zonulin is highly sensitive for the evaluation of intestinal permeability in IBD patients. There is no correlation between zonulin values in serum and feces.

Management of Helicobacter pylori in Piedmont, Italy.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium, usually acquired during childhood, whose natural habitat is the gastric lumen. H. pylori is accepted as the most important cause of gastritis and peptic ulcer in humans. Nevertheless, its important role in the pathogenesis of gastric cancer as well as in several extra-gastroduodenal diseases has been confirmed. The aim of this work is to discuss, for the first time in a single article, all publications concerning H. pylori infection arising from Piedmont region, Italy, where in 1893 Giulio Bizzozero was the first who observed and described spiral organisms in the stomach of animal models. A systematic review of all publications on the management of H. pylori in adults in Piedmont, based on a PubMed and a Scopus research from 1965 to 2017 was performed. The discussed aspects are the epidemiology, the study on gastric and extragastric diseases related to H. pylori, the diagnostic methods, the treatment of H. pylori infection, and the possibility of reinfection. In conclusions, with almost 70 publications, Piedmont has proudly maintained the tradition of the father of the H. pylori.

Fecal calprotectin: beyond intestinal organic diseases.

Fecal calprotectin (FC) is a calcium-binding protein with antimicrobic, imunomodulatory and antiproliferative properties that is mainly found in the cytoplasm of neutrophil granulocytes. During the last decades, FC became an increasingly useful tool both for gastroenterologists and for general practitioners for distinguishing inflammatory bowel disease (IBD) from irritable bowel syndrome. FC correlates with clinical scoring systems and endoscopic lesions in IBD and is considered a reliable biomarker for the prediction of clinical relapse or remission. However, FC elevation could be observed also in other gastrointestinal pathological conditions including infective colitis, microscopic colitis, eosinophilic colitis, adenomas and colorectal cancer. In addition, there are several non-pathological conditions that can lead to altered FC values. In this review, we aimed to point out individual, environmental and method-related factors that can affect FC measurement and thus its clinical interpretation.

A 2016 panorama of Helicobacter pylori infection: key messages for clinicians.

The discovery that the bacterium Helicobacter pylori (H. pylori) lives in the stomach has rendered out-of-date the concept of inhospitality of the gastric environment. H. pylori is able to survive in this organ through mechanisms of acid resistance and colonization factors. The prevalence of H. pylori infection varies depending on age, socioeconomic class, and country. Currently, in the context of a decreased trend in H. pylori prevalence, it is estimated that about 50% of the world's human population are carriers of the microorganism, with a higher rate in developing countries than in developed countries. In this review, the authors provide an overview on the current status of knowledge on the clinical aspects of H. pylori infection, with a focus on diagnostic and therapeutic challenges. In particular, the choice of the test to diagnose H. pylori infection, defined as invasive or non-invasive based on the need or not of biopsy specimens obtained during an endoscopy, depends on the clinical context. Regarding bacterial eradication, it is important that treatment should be decided locally on the basis of local antibiotic usage, documented antibiotic resistance and outcome data. For patients having previously received a clarithromycin-containing regimen, this drug should be avoided as a second-line therapy. In this case, the tailored therapy (to test clarithromycin susceptibility before prescribing drugs) or the so-called quadruple therapy, and triple levofloxacin-based therapy should be proposed. Rifabutin- and furazolidone-based treatments should be reserved for further treatment.