Twelve Months with COVID-19: What Gastroenterologists Need to Know.

Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal-oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care.

Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis.

BACKGROUND & AIM: An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. PATIENTS AND METHODS: A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. RESULTS: During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47-6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23-7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05-3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08-4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35-6.09; p = 0.006) were associated with HCC recurrence. CONCLUSION: An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. LAY SUMMARY: This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.

Longitudinal study of interventional radiology activity in a large metropolitan Italian tertiary care hospital: how the COVID-19 pandemic emergency has changed our activity.

OBJECTIVES: To retrospectively analyze interventional radiology (IR) activity changes in the COVID-19 era and to describe how to safely and effectively reorganize IR activity. METHODS: All IR procedures performed between January 30 and April 8, 2020 (COVID-era group) and the same 2019 period (non-COVID-era group) were retrospectively included and compared. A sub-analysis for the lockdown period (LDP: 11 March-8 April) was also conducted. Demographic, hospitalization, clinical, and procedural data were obtained for both groups and statistically compared with univariable analysis. RESULTS: A total of 1496 procedures (non-COVID era, 825; COVID era, 671) performed in 1226 patients (64.9 ± 15.1 years, 618 women) were included. The number of procedures decreased by 18.6% between 2019 and 2020 (825 vs 671, p < .001), with a reduction by 48.2% in LDP (188 vs 363, p < .0001). In the LDP COVID era, bedside procedures were preferred (p = .013), with an increase in procedures from the intensive care unit compared with the emergency department and outpatients (p = .048), and an increased activity for oncological patients (p = .003). No incidents of cross-infection of non-infected from infected patients and no evidence of COVID-19 infection of healthcare workers in the IR service was registered. CONCLUSIONS: Coronavirus disease outbreak changed the interventional radiology activity with an overall reduction in the number of procedures. However, this study confirms that interventional radiology continuum of care can be safely performed also during the pandemic, following defined measures and protocols, taking care of all patients. KEY POINTS: • Coronavirus disease pandemic determined a reduction of interventional radiology activity as compared to the same period of the previous year. • Interventional radiology procedures for life-threatening conditions and non-deferrable oncologic treatments were prioritized as opposed to elective procedures. • Strict adoption of safe procedures allowed us to have until now no incidents of cross-infection of non-infected from infected patients and no evidence of COVID-19 infection of HCWs in the IR service.

Randomised trial of chronic supplementation with a nutraceutical mixture in subjects with non-alcoholic fatty liver disease.

A mixture of natural ingredients, namely, DHA, phosphatidylcholine, silymarin, choline, curcumin and d-α-tocopherol, was studied in subjects with non-alcoholic fatty liver disease (NAFLD). Primary endpoints were serum levels of hepatic enzymes, and other parameters of liver function, the metabolic syndrome and inflammation were the secondary endpoints. The coagulation-fibrinolysis balance was also thoroughly investigated, as NAFLD is associated with haemostatic alterations, which might contribute to increased cardiovascular risk of this condition. The present study involved a double-blind, randomised, multicentre controlled trial of two parallel groups. Subjects with NAFLD (18-80 years, either sex) received the active or control treatment for 3 months. All assays were performed on a total of 113 subjects before and at the end of supplementation. The hepatic enzymes aspartate aminotransferase (AST), alanine aminotransferase and γ-glutamyl transpeptidase decreased from 23·2 to 3·7 % after treatment, only the AST levels reaching statistical significance. However, no differences were found between control and active groups. Metabolic and inflammatory variables were unchanged, except for a slight (less than 10 %) increase in cholesterol and glucose levels after the active treatment. Coagulation-fibrinolytic parameters were unaffected by either treatment. In conclusion, chronic supplementation with the mixture of dietary compounds was well tolerated and apparently safe in NAFLD subjects. The trial failed to demonstrate any efficacy on relevant physiopathological markers, but its protocol and results may be useful to design future studies with natural compounds.

Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS: We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ±â€¯dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION: Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY: There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.

GOALS: The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). BACKGROUND: About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. STUDY: CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. RESULTS: In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. CONCLUSIONS: A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.

The Spectrum of Small Intestinal Lesions in Patients with Unexplained Iron Deficiency Anemia Detected by Video Capsule Endoscopy.

Background and objectives: Video-capsule endoscopy (VCE) has shown a large range (38⁻83%) of diagnostic yield in unexplained iron deficiency anemia (IDA) and obscure-occult bleeding. Therefore, we retrospectively investigated the VCE-detected spectrum and the prevalence of small bowel injuries and associated risk factors in inpatients with both of the above reported conditions. Methods: We selected inpatients with IDA (hemoglobin <12 g/dL in women, <13 g/dL in men) and obscure-occult bleeding. We excluded VCE indications other than IDA. Complete medical histories and laboratory tests were collected. All subjects underwent PillCam SB2/SB3. The VCE feature Lewis score was calculated when appropriate. We used the t-test and Fisher's exact test for continuous and categorical variables, respectively, in univariate analysis. For multivariate analysis, we used binomial logistic regression. Results: We retrieved 109 patients (female:male ratio of 53:56; age 63.4 ± 18.9 years). Eighty patients (73.4%) showed ≥1 small bowel lesions. The Lewis score was calculated in 41 patients: 13 (31.7%) showed a mild (<135) and 28 (68.3%) a moderate-severe (135⁻790 and >790, respectively) score. In univariate analysis, the small bowel transit time (6.2 ± 2.9 versus 5.2 ± 2.1 h; p = 0.049) and non-steroidal anti-inflammatory drug use for at least two weeks (17.5% versus 0%; p = 0.01) were significantly higher in subjects with injuries. These associations were not confirmed at multivariate analysis. The severity of a lesion directly correlated with proton pump inhibitor (PPI) use and duration (not confirmed in multivariate analysis). VCE can reveal the source of obscure-occult bleeding in a high percentage of unexplained IDAs. A wide spectrum of endoscopic pictures may be found. Known as well as supposed risk factors for small bowel lesions may be detected.

Chemoprevention of inflammation-related colorectal cancer by silymarin-, acetyl-11-keto-beta-boswellic acid-, curcumin- and maltodextrin-enriched dietetic formulation in animal model.

On the basis of preliminary in vitro experience, we assessed whether an enriched nutritional formulation with estrogen receptor (ER)-beta agonist and anti-inflammatory properties may prevent inflammation-associated colorectal cancer (CRC) in an animal model. Study sample enclosed 110 C57BL/6J male mice. Forty underwent dietary supplement safety assessment (20 standard diet and 20 enriched formulation). Seventy were treated with azoxymethane (AOM)/dextran sulfate sodium and divided into two groups: 35 received standard diet and 35 enriched formulation (curcumin, boswellic acids, silymarin and maltodextrins). Miniature colonoscopy demonstrated colitis and solid lesion development in five mice/group 100 days after first AOM injection. Mice were killed after 10 days. In each group, four subgroups received intraperitoneal bromodeoxyuridine (BrdU) injection at 24th/48th/72nd/96th hour before killing. Anti-inflammatory effect and chemoprevention were evaluated by lesion number/size, histological inflammation/dysplasia/neoplasia assessment, pro-inflammatory cytokine messenger RNA (mRNA), ER-beta/ER-alpha/BrdU immunohistochemistry and TUNEL immunofluorescence. Standard formulation assumption was associated with colon shortening compared with enriched one (P = 0.04), which reduced solid lesion number and size (P < 0.001 for both), histological inflammation score (P = 0.04), pro-inflammatory cytokine mRNA expression (P < 0.001), number of low-grade dysplasia (LGD; P = 0.03) and high-grade dysplasia (P < 0.001) areas. CRC was observed in 69.6% in standard and 23.5% in enriched formulation assuming animals (P < 0.001). Enriched formulation induced lower ER-alpha expression in CRC (P < 0.001) and higher ER-beta expression in LGD (P < 0.001) being associated to higher epithelial turnover (BrdU; P<0.001) in normal mucosa and increased apoptosis in LGD and CRC (P < 0.001 for both). Our results are promising for a successful anti-inflammatory and chemopreventive effect of enriched formulation in CRC arising from inflamed tissue.

Chromoendoscopy for Surveillance in Ulcerative Colitis and Crohn's Disease: A Systematic Review of Randomized Trials.

BACKGROUND & AIMS: Key international guideline agencies recommend dysplasia surveillance in inflammatory bowel diseases with chromoendoscopy. We performed a systematic review of randomized trials comparing chromoendoscopy vs other endoscopic techniques for dysplasia surveillance in inflammatory bowel diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant studies published through September 2016. We estimated risk ratios (RRs) for dichotomous outcomes (all-cause/colorectal cancer-related mortality, time to interval cancer, patients with dysplasia, total/subtypes of dysplastic lesions, dysplasia detected by targeted biopsies, adverse events), mean differences for continuous outcomes (procedural time, costs, total/targeted biopsies), and their 95% confidence intervals (CIs) using a random-effects model. Subgroup analyses included technique compared with chromoendoscopy, type of disease, and type of dye. We estimated sensitivity and specificity of the techniques with reference to histology. RESULTS: We identified 10 randomized trials (n = 1500 participants). There was a higher likelihood of detecting patients with dysplasia with chromoendoscopy compared with other techniques (RR, 1.37; 95% CI, 1.04-1.79). Subgroup analyses confirmed this effect only if chromoendoscopy was compared with standard-definition white-light endoscopy (RR, 2.12; 95% CI, 1.15-3.91). Chromoendoscopy required a significantly longer procedural time compared with other techniques (mean difference, 8.91 min; 95% CI, 1.37-16.45). There was no difference in the likelihood of detecting dysplastic subtypes and dysplasia by targeted biopsies between groups. Test sensitivity and specificity were similar between groups. CONCLUSIONS: In surveillance of inflammatory bowel diseases, chromoendoscopy identifies more patients with dysplasia only when compared with standard-definition white-light endoscopy. It is associated with longer procedural time with no direct evidence of effect on preventing all-cause/cancer-specific mortality or time to interval cancer.

Long-term safety of anti-TNF agents on the liver of patients with spondyloarthritis and potential occult hepatitis B viral infection: an observational multicentre study.

OBJECTIVES: The aim of the study was to retrospectively evaluate the long-term safety profile of anti-tumour necrosis factor (TNF)-α agents on the liver of patients with spondyloarthritis (SpA) and a previously resolved hepatitis B virus (HBV) infection. METHODS: Medical records from 992 consecutive outpatients receiving anti-TNF-α therapy between 2007 and 2015 were retrospectively reviewed. HBV infection was assessed evaluating HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to hepatitis B core (anti-HBc), and HBV-DNA levels. In patients with a previously resolved HBV infection, serum levels of aminotransferase (AST/ALT) were also assessed every three months, while HBsAg and HBV-DNA every six months. RESULTS: We identified 131 consecutive patients (70 males, 61 females) with SpA and resolved HBV infection. At baseline none of the patients were positive for HBV-DNA, and AST/ALT levels were within the normal range with no subsequent increase during the observational treatment period. None received antiviral therapy prior to or during anti-TNF drug administration. At the end of the follow-up period (75.50±33.37 months) no viral reactivation was observed in anti-HBc positive patients, regardless of anti-HBs positivity. During the whole follow-up, HBV-DNA was undetectable in all patients, HBsAg remained negative, and it was not necessary to discontinue biologic therapy because of liver damage. CONCLUSIONS: Our results confirm that pre-emptive antiviral prophylaxis may not be necessary routine, but strict monitoring for AST/ALT levels, as well as for changes in HBV serology and HBV-DNA remain necessary and seem a realistic and cost-effective approach to identify early viral reactivation.

Update on the Medical Management of Gastrointestinal Behçet's Disease.

Behçet's disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis, all of which represent the "stigmata" of disease. However, many other organs including the vascular, neurological, musculoskeletal, and gastrointestinal systems can be affected. The gastrointestinal involvement in Behçet's disease (GIBD), along with the neurological and vascular ones, represents the most feared clinical manifestation of BD and shares many symptoms with inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. Consequently, the differential diagnosis is often a daunting task, albeit the presence of typical endoscopic and pathologic findings may be a valuable aid to the exact diagnosis. To date, there are no standardized medical treatments for GIBD; therefore therapy should be tailored to the single patient and based on the severity of the clinical features and their complications. This work provides a digest of all current experience and evidence about pharmacological agents suggested by the medical literature as having a potential role for managing the dreadful features of GIBD.

Safety of long-term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection.

UNLABELLED: European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long-term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti-HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1× upper normal limit at least once during follow-up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti-tumor necrosis factor-alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1× upper normal limit but not when aminotransferase levels >2× upper normal limit were considered. CONCLUSION: Among patients with a prHBV infection and rheumatologic indications for long-term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost-effective in this clinical setting.

Helicobacter pylori DNA isolation in the stool: an essential pre-requisite for bacterial noninvasive molecular analysis.

PURPOSE: Real-time polymerase chain reaction (RT-PCR) is a widely used technique for bacterial and viral infection diagnosis. Herein, we report our preliminary experience in retrieving H. pylori genetic sequences in stools and analyzing genotypic clarithromycin resistance by RT-PCR (noninvasive), with the aim of comparing this procedure with that performed on biopsy samples (invasive). MATERIALS AND METHODS: After 'in vitro' demonstration of H. pylori DNA detection from pure and stool-mixed bacteria, 52 consecutive patients at the first diagnosis of infection were investigated. DNA was extracted from biopsy tissue and stool samples (THD® Fecal Test, Italy). RT-PCR was performed to detect 23S rRNA encoding bacterial subunit gene and search A2143G, A2142C, A2142G point mutations for clarithromycin resistance assessment. RESULTS: RT-PCR showed H. pylori positive DNA in all infected patients with full concordance between tissue and stool detection (100%). We found A2143G mutation in 10 (19.2%), A2142G in 4 (7.7%) and A2142C in 5 (9.6%) patients; there was a full agreement between biopsy and fecal samples. A2143G was found in all the four A2142G positive cases and in three out of the five A2142C positive strains. Overall clarithromycin resistance rate in our series was 23%. CONCLUSIONS: Despite the need of confirmation on large sample, stool RT-PCR analysis could represent a feasible tool to detect H. pylori DNA sequences and antibiotic resistance point mutations. As compared to tissue molecular analysis, this technique is noninvasive, with potential advantages such as improvement of patient compliance, reduction of diagnostic procedure time/cost and improvement of therapeutic outcome.

Prognostic role of 25-hydroxyvitamin D in patients with liver metastases from colorectal cancer treated with radiofrequency ablation.

BACKGROUND AND AIM: Vitamin D is implicated in the etiology of several neoplastic diseases, but its relationship with colorectal cancer survival is still unclear. Aim of this study was to determine whether vitamin D levels influence survival outcomes in colorectal cancer liver metastases patients treated with percutaneous radiofrequency ablation. METHODS: We measured 25-hydroxyvitamin D levels in 143 patients with 215 colorectal liver metastases who underwent radiofrequency ablation between 1999 and 2011 at our institution. The influence of 25-hydroxyvitamin D levels on overall survival and time to recurrence was evaluated in univariate and multivariate Cox analyses. RESULTS: Median age was 68 years (range 41-85), and median number of nodules was 2 (1-3) with a median maximum diameter of 26 mm (10-48). Median survival was 44 months (36-62), and survival rate was 91.4%, 46.5%, and 42.2% at 1, 4, and 5 years in the whole cohort. Median survival was 65 months (52-74) if 25-hydroxyvitamin D >20 ng/mL and 34 months (24-41) if ≤20 ng/mL (P < 0.001). In the whole cohort, median time to recurrence was 34 months (26-47), 50 months (36-62) in the case of 25-hydroxyvitamin D >20 ng/mL and 24 months (20-32) if ≤20 ng/mL (P < 0.001). Nodule size and 25-hydroxyvitamin D resulted as significant predictors of both overall survival and time to recurrence in multivariate analysis. CONCLUSIONS: Our study provides support for the use of 25-hydroxyvitamin D as a new predictor of outcome for colorectal liver metastases patients.

Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: Solid demonstrations of superior efficacy of drug-eluting beads transarterial chemoembolization with respect to conventional chemoembolization in hepatocellular carcinoma patients are lacking. The aim of the study was to compare these two techniques in two large cohorts of unresectable hepatocellular carcinoma patients. METHODS: A single center series of 249 early/intermediate hepatocellular carcinoma patients who underwent "on demand" chemoembolization in the period 2007-2011 was analyzed. Overall survival, time to progression, tumor response rate, and safety were compared between 104 patients who underwent conventional chemoembolization and 145 who underwent drug-eluting beads chemoembolization. Time-to-event data were analyzed using the Cox univariate and multivariate regression. RESULTS: The two cohorts resulted balanced for liver function and tumor stages. Objective response rate was 85.3% after conventional and 74.8% after drug-eluting beads chemoembolization (P = 0.039), and median time to progression was 17 (95% confidence interval: 14-21) versus 11 months (9-12), respectively (P < 0.001). Treatment regimen was the sole independent predictor of progression at multivariate analysis (hazard ratio = 2.01; 1.45-2.80; P < 0.001). Median survival was 39 (32-47) and 32 (24-39) months in the two groups, respectively (hazard ratio = 1.33; 0.94-1.87; P = 0.10), but conventional chemoembolization was significantly associated with a survival advantage in patients with bilobar neoplasia, portal hypertension and alpha fetoprotein above normal limits. No significant differences in severe adverse events were found. CONCLUSION: In a large series of Western hepatocellular carcinoma patients, drug-eluting beads chemoembolization with 100-300 µm particles did not seem to improve survival in comparison with conventional chemoembolization, which in turn provided better tumor responses and time to progression.

Helicobacter pylori, liver cirrhosis, and portal hypertension: an updated appraisal.

OBJECTIVE: Helicobacter pylori (H. pylori) is the most common cause of gastritis and peptic ulcer. However, H. pylori is even involved in extragastric diseases, and it has been hypothesized that H. pylori could be a risk factor for several hepatic diseases. For instance, a direct involvement of H. pylori in the development of portal hypertension (PH) in cirrhotic patients has been postulated. METHODS: We performed a literature search in major databases to elucidate the relationship between H. pylori, portal hypertension, and liver cirrhosis. RESULTS: The effect of H. pylori on PH may be multifactorial. Endothelial dysfunction, alterations in the vasodilating dynamics, and neoangiogenesis are the most appealing theories about this issue, but the proofs come mainly from experimental studies, therefore a solid pathophysiological basis is still to be demonstrated. Congestive gastropathy (CG) and gastric antral vascular ectasia (GAVE) are two common endoscopic entities responsible for acute/chronic upper gastrointestinal bleeding, and a link with H. pylori has been hypothesized: the gastric mucosa, exposed to H. pylori, could develop both inflammatory microcirculatory alterations and thrombi, resembling the histologic pattern of GAVE. CONCLUSIONS: Despite clues for an association between H. pylori and PH have been shown, these evidences are mostly experimental, therefore, in the absence of a direct proof on human beings, the role of H. pylori in the development of PH is uncertain. However, since this germ may be a cause of peptic ulcer, it should be found and eradicated in cirrhotic patients to reduce the risk of blood loss anemia.

Polidocanol injection decreases the bleeding rate after colon polypectomy: a propensity score analysis.

BACKGROUND: EMR is the standard of care for the resection of large polyps. OBJECTIVE: To compare the efficacy and safety profile of submucosal polidocanol injection with epinephrine-saline solution injection for colon polypectomy with a diathermic snare. DESIGN: After 1-to-1 propensity score caliper matching, comparison of submucosal epinephrine injection was performed with polidocanol injection. SETTING: Endoscopic suite at the University of Foggia between 2005 and 2014. PATIENTS: Of 711 patients who underwent endoscopic resection of colon sessile polyps 20 mm or larger, 612 were analyzed after matching. INTERVENTIONS: Submucosal epinephrine injection in 306 patients and polidocanol injection in 306 patients. MAIN OUTCOME MEASUREMENTS: Univariate and multivariate logistic regression models aimed at identifying independent predictors of postpolypectomy bleeding (PPB). RESULTS: The 2 groups presented similar baseline clinical parameters and lesion characteristics. All patients had a single polyp 20 mm or larger; the median size was 32 mm (interquartile range [IQR], 25-38) in the polidocanol group and 32 (IQR, 24-38) in the epinephrine group (P=.7). Polidocanol was more effective in preventing both immediate and delayed PPB (P<.001 and P=.003, respectively), and its efficacy was confirmed in almost all of the subgroups, regardless of polyp size and histology. Postprocedure perforation was observed in 2 patients (0.3%), both in the epinephrine group (P=.49). The 2 groups did not differ in the number of snare resections of lesions or the procedure duration (P=.24 and .6, respectively). LIMITATIONS: Absence of randomization. CONCLUSION: The submucosal injection of polidocanol for colon EMR is effective and significantly lowers the PPB rate.

Liver stiffness and portal blood flow modifications induced by a liquid meal consumption: pathogenetic mechanisms and clinical relevance.

OBJECTIVE: The correlation between liver stiffness (LS) variations and portal blood flow (PBF) modifications induced by a standardized liquid meal consumption and the clinical relevance of this matter are two aspects not yet fully elucidated. Herein, we evaluated the variations of LS and PBF after a standardized liquid meal intake in patients with chronic liver disease. MATERIAL AND METHODS: PBF and LS were determined after an overnight fasting period in 54 patients. They were divided in three groups according to baseline LS (absent, moderate, and severe). They consumed 200 ml of water and a standardized liquid meal (300 Kcal/200 ml) after 60 min. PBF and LS were measured at 30 min after water and liquid meal consumption. RESULTS: In all groups, LS and PBF values significantly increased only after meal consumption. A significant correlation between baseline LS values and post-meal increase of LS was observed. Moreover, higher basal stiffness values were associated to a larger increase of LS variation after meal consumption. The effect of the meal on LS remained statistically significant after multiple regression analysis. A significant correlation between increase of LS and PBF was found in patients with absent and moderate baseline LS. Nine patients (17%) switched from a lower to a higher level of LS after meal consumption. CONCLUSION: A low calories/low-volume meal is capable of significantly increasing LS regardless of the grade of stiffness, determining a reclassification rate of 17%. In presence of minimal or moderate stiffness, the increase of LS is significantly correlated with the augment of PBF.

Conditional survival analysis of hepatocellular carcinoma patients treated with radiofrequency ablation.

AIM: Survival estimates are commonly reported as survival from the first observation, but future survival probability changes based on the survival time already accumulated after therapy, otherwise known as conditional survival (CS). The aim of the study was to describe CS according to different prognostic variables in hepatocellular carcinoma (HCC) patients treated with radiofrequency ablation (RFA). METHODS: Data on 125 very early/early HCC patients treated with RFA between 1999 and 2007 were analyzed. Actuarial survival estimates were computed by means of Kaplan-Meier method and compared by log-rank test. The 5-year CS was calculated with stratification by several predictors for patients who had already survived up to 5 years from diagnosis. RESULTS: Median overall survival (OS) was 72 months (95% confidence interval [CI], 58-86). Age, Child-Pugh (CP), α-fetoprotein (AFP), Cancer of the Liver Italian Program (CLIP) score and type of recurrence (early vs late) were significant predictors of OS. The 5-year CS rates of the entire study cohort assessed at 1, 2, 3 and 5 years from the treatment were 49%, 48%, 30% and 34%, respectively. Subgroup analysis confirmed age and CP as significant predictors of CS at all time points, while the CS of subgroups stratified by AFP and CLIP did not differ significantly from the 3rd year after RFA onward, as more advanced patients had probably escaped early recurrence. CONCLUSION: CS analysis showed that the impact of different variables influencing OS is not linear over time after RFA. Information derived from the study can improve the current management of HCC patients.

Angiotensin receptor blockers improve survival outcomes after radiofrequency ablation in hepatocarcinoma patients.

BACKGROUND AND AIM: Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. The aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. METHODS: Data on 153 patients were reviewed. The study population was classified into three groups: 73 (47.8%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 49 (32%) patients treated with angiotensin-converting enzyme inhibitors (group 2), and 31 (20.2%) patients treated with sartans (group 3). Survival outcomes were analysed by means of Kaplan-Meier analysis and compared with log-rank test. RESULTS: In the whole study population, 85.6% of patients were in Child-Pugh A class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10-40) and alpha fetoprotein was 25 (1.1-2100) UI/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (95% confidence interval: 31-58) in group 1, 72 months (49-89) in group 2, and 84 months (58-92) in group 3 (P = 0.02). Median time to recurrence was 26 (15-42), 44 (33-72), and 69 (44-74) months in the three groups, respectively (P = 0.02). Sartan therapy was a significant predictor of longer overall survival and delayed time to recurrence on multivariate analysis. CONCLUSION: Sartans significantly improved overall survival and time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients.