Hepatolithiasis:Epidemiology,presentation,classification and management of a complex disease

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.

Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis

Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax

BACKGROUNDHepatic hydrothorax (HH) is an uncommon and difficult-to-manage complicationof cirrhosis with limited treatment options.AIMTo define the clinical outcomes of patients presenting with HH managed withcurrent standards-of-care and to identify factors associated with mortality.METHODSCirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 wereretrospectively identified. HH was defined as pleural effusion in the absence ofcardiopulmonary disease. The primary outcomes were overall and transplant-freesurvival at 12-mo after the index admission. Cox proportional hazards analysiswas used to determine factors associated with the primary outcomes.RESULTSOverall, 84 patients were included (mean age, 58 years) with a mean model forend-stage liver disease score of 29. Management with diuretics alone achievedlong-term resolution of HH in only 12% patients. At least one thoracocentesis wasperformed in 73.8% patients, transjugular intrahepatic portosystemic shuntinsertion in 11.9% patients and 33% patients received liver transplantation within12-mo of index admission. Overall patient survival and transplant-free survival at12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidneyinjury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increasedrisk of mortality.CONCLUSIONCirrhotic patients with HH are a challenging population with a poor 12-mo survival despitecurrent treatments. Current smoking and episodes of AKI are potential modifiable factors affectingsurvival. HH is often refractory of diuretic therapy and transplant assessment should beconsidered in all cases.

Navigating the controversy regarding antibiotic prophylaxis in acute variceal bleeding

Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines.However,with recent evidence arguing against antibiotic prophylaxis,the role of this intervention has become less clear.

Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.

Serum leptin levels and insulin resistance are associated with gallstone disease in overweight subjects

AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD).METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate)stratified by BMI was used to calculate the risk of GD.RESULTS: The multivariate conditional regression analysis revealed a model for those patients with BMI ＜30. The selected variables in the model were HOMA-IR index with OR = 1.31, P= 0.02 and leptin higher than median with OR = 2.11, P= 0.05. In the stratum of BMI ≥30, we did not find a useful model.CONCLUSION: We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.

Point-of-care continuous ^(13)C-methacetin breath test improves decision making in acute liver disease: Results of a pilot clinical trial

AIM: To assess the role of the 13C-methacetin breath test (MBT) in patients with acute liver disease. METHODS: Fifteen patients with severe acute liver disease from diverse etiologies were followed-up with 13C-MBT during the acute phase of their illnesses (range 3-116 d after treatment). Patients fasted for 8 h and ingested 75 mg of methacetin prior to the MBT. We compared results from standard clinical assessment, serum liver enzymes, synthetic function, and breath test scores. RESULTS: Thirteen patients recovered and two patients died. In patients that recovered, MBT parameters improved in parallel with improvements in lab results. Evidence of consistent improvement began on day 3 for MBT parameters and between days 7 and 9 for blood tests. Later convergence to normality occurred at an average of 9 d for MBT parameters and from 13 to 28 d for blood tests. In both patients that died, MBT parameters remained low despite fluctuating laboratory values. CONCLUSION: The 13C-MBT provides a rapid, noninvasive assessment of liver function in acute severe liver disease of diverse etiologies. The results of this pilot clinical trial suggest that the MBT may offer greater sensitivity than standard clinical tests for managing patients with severe acute liver disease.

Pediatric gastrointestinal bleeding: Perspectives from the Italian Society of Pediatric Gastroenterology

There are many causes of gastrointestinal bleeding(GIB) in children, and this condition is not rare, having a reported incidence of 6.4%. Causes vary with age, but show considerable overlap; moreover, while many of the causes in the pediatric population are similar to those in adults, some lesions are unique to children. The diagnostic approach for pediatric GIB includes definition of the etiology, localization of the bleeding site and determination of the severity of bleeding; timely and accurate diagnosis is necessary to reduce morbidity and mortality. To assist medical care providers in the evaluation and management of children with GIB, the "Gastro-Ped Bleed Team" of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition(SIGENP) carried out a systematic search on MEDLINE via Pub Med(http://www.ncbi.nlm.nih.gov/pubmed/) to identify all articles published in English from January 1990 to 2016; the following key words were used to conduct the electronic search: "upper GIB" and "pediatric" [all fields]; "lower GIB" and "pediatric" [all fields]; "obscure GIB" and "pediatric" [all fields]; "GIB" and "endoscopy" [all fields]; "GIB" and "therapy" [all fields]. The identified publications included articles describing randomized controlled trials, reviews, case reports, cohort studies, casecontrol studies and observational studies. References from the pertinent articles were also reviewed. This paper expresses a position statement of SIGENP that can have an immediate impact on clinical practice and for which sufficient evidence is not available in literature. The experts participating in this effort were selected according to their expertise and professional qualifications.

Italian survey on non-steroidal anti-inflammatory drugsand gastrointestinal bleeding in children

AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was needed.CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in

Concise review on the comparative efficacy of endoscopic ultrasound-guided fine-needle aspiration vs core biopsy in pancreatic masses, upper and lower gastrointestinal submucosal tumors

Endoscopic ultrasound(EUS)-guided fine needle aspiration with or without biopsy(FNA/FNB) are the primary diagnostic tools for gastrointestinal submucosal tumors. EUS-guided fine needle aspiration(EUS-FNA) is considered a first line diagnostic method for the characterization of pancreatic and upper gastrointestinal lesions, since it allows for the direct visualization of the collection of specimens for cytopathologic analysis. EUSFNA is most effective and accurate when immediate cytologic assessment is permitted by the presence of a cytopathologist on site. Unfortunately, the accuracy and thus the diagnostic yield of collected specimens suffer without this immediate analysis. Recently, a EUS-FNB needle capable of obtaining core samples(fine needle biopsy, FNB) has been developed and has shown promising results. This new tool adds a new dimension to the diagnostic and therapeutic utility of this technique. The aim of the present review is to compare the efficacy of EUS-FNA to that afforded by EUS-FNB in the characterization of pancreatic masses and of upper and lower gastrointestinal submucosal tumors.

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

Learning from a rare phenomenon — spontaneous clearance of chronic hepatitis C virus post-liver transplant: A case report

BACKGROUND Hepatitis C virus(HCV)can lead to chronic liver damage resulting in cirrhosis and hepatocellular carcinoma.Spontaneous clearance of HCV has been documented after an acute infection in 20%-45%of individuals.However,spontaneously resolved chronic hepatitis C following liver transplant(LT)is rare and has been documented only in a few case reports.The phenomenon of spontaneous clearance of chronic hepatitis C occurs together with other meaningful events,which are typically associated with significant changes in the host immunity.CASE SUMMARY We report three cases of spontaneous resolution of chronic hepatitis C following liver transplantation.These patients either failed or had no HCV treatment prior to transplant,but had spontaneous resolution of HCV post-LT as documented by undetectable polymerase chain reaction(PCR).Diagnosis of HCV was based on viremia through PCR or liver biopsy.All three patients currently undergo surveillance and have no recurrence of HCV.CONCLUSION Examining each patient’s clinical course,we learned about many viral,host and cellular-factors that may have enhanced the host’s immunity leading to spontaneous clearance of HCV.Though HCV treatment has excellent cure rates,understanding this mechanism may provide clinicians with insights regarding timing and duration of treatment.

Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients

BACKGROUND While clinical guidelines recommend hepatocellular carcinoma(HCC)surveillance for at-risk individuals,reported surveillance rates in the United States and Europe remain disappointingly low.AIM To quantify HCC surveillance in an Australian cohort,and assess for factors associated with surveillance underutilisation.METHODS All patients undergoing HCC surveillance liver ultrasounds between January 1,2018 to June 30,2018 at a tertiary hospital in Melbourne,Australia,were followed until July 31,2020,or when surveillance was no longer required.The primary outcome was the percentage of time up-to-date with HCC surveillance(PTUDS).Quantile regression was performed to determine the impact of factors associated with HCC surveillance underutilisation.RESULTS Among 775 at-risk patients followed up for a median of 27.5 months,the median PTUDS was 84.2%(IQR:66.3%-96.3%).85.0%of patients were followed up by specialist gastroenterologists.Amongst those receiving specialist care,quantile regression demonstrated differential associations at various quantile levels of PTUDS for several factors.Older age at the 25th quantile(estimate 0.002 per percent,P=0.03),and cirrhotic status at the 75th quantile(estimate 0.021,P=0.017),were significantly associated with greater percentage of time up-to-date.African ethnicity(estimate-0.089,P=0.048)and a culturally and linguistically diverse(CALD)background(estimate-0.063,P=0.01)were significantly associated with lower PTUDS at the 50th quantile,and again for CALD at the 75th quantile(estimate-0.026,P=0.045).CONCLUSION While median PTUDS in this Australian cohort study was 84.2%,awareness of the impact of specific factors across PTUDS quantiles can aid targeted interventions towards improved HCC surveillance.

Enhanced recovery for liver transplantation: recommendations from the 2022 International Liver Transplantation Society Consensus Conference: towards better clinical care in transplant hepatology

Liver transplantation(LT)was first performed over six decades ago and is currently the standard of care for patients with end-stage liver disease and life-threatening complications.There have been significant advances in the area of LT;however,it remains a highly morbid,restrictive,expensive and resource-intensive intervention(1).Early recovery for LT(ERAS4OLT.org)is a multimodal concept aimed at promoting faster recovery in patients undergoing LT.The development of a dedicated protocol for early recovery following LT has been challenging due to the complexity of developing a treatment approach,patient comorbidities associated with decompensated cirrhosis,and low case volume.

Clinical relevance of sarcopenia in patients with cirrhosis

The most commonly recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, susceptibility for infections, kidney dysfunction, and hepatocellular carcinoma; however, severe muscle wasting or sarcopenia are the most common and frequently unseen complications which negatively impact survival, quality of life, and response to stressor, such as infections and surgeries. At present, D&#x02019;Amico stage classification, Child-Pugh, and MELD scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of assessing the nutritional and functional status. Currently, numerous methods are available to evaluate the nutrition status of the cirrhotic patient; nevertheless, most of these techniques have limitations primarily because lack of objectivity, reproducibility, and prognosis discrimination. In this regard, an objective and reproducible technique, such as muscle mass quantification with cross-sectional imaging studies (computed tomography scan or magnetic resonance imaging) constitute an attractive index of nutritional status in cirrhosis. Sarcopenia is part of the frailty complex present in cirrhotic patients, resulting from cumulative declines across multiple physiologic systems and characterized by impaired functional capacity, decreased reserve, resistance to stressors, and predisposition to poor outcomes. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis. Also, we analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in patients with cirrhosis and their impact after liver transplantation. Finally, we discuss existing and potential novel therapeutic approaches for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in an effort to reduced morbidity related and improved survival in cirrhosis.

Metabolic syndrome as a risk factor for gallstone disease

AIM: To establish an association between the presence of metabolic syndrome and the development of gallstone disease. METHODS: We carried out a cross-sectional study in a check-up unit in a university hospital in Mexico City. We enrolled 245 subjects, comprising 65 subjects with gallstones (36 women, 29 men) and 180 controls (79 women and 101 men without gallstones). Body mass index, waist circumference, blood pressure, plasma insulin, and serum lipids and lipoproteins levels were measured. Insulin resistance was calculated by homeostasis model assessment. Unconditional logistic regression analysis (univariate and multivariate) was used to calculate the risk of gallstone disease associated with the presence of at least three of the criteria (Adult Treatment Panel Ⅲ). Analyses were adjusted for age and sex. RESULTS: Among 245 subjects, metabolic syndrome was present in 40% of gallstone disease subjects, compared with 17.2% of the controls, adjusted by age and gender (odds ratio (OR) = 2.79; 95%CI, 1.46-5.33; P= 0.002), a dose-dependent effect was observed with each component of metabolic syndrome (OR=2.36, 95%CI, 0.72-7.71; P= 0.16 with one component and OR = 5.54, 95%CI, 1.35-22.74; P = 0.02 with four components of metabolic syndrome). Homeostasis model assessment was significantly associated with gallstone disease (adjusted OR = 2.25; 95%CI, 1.08-4.69; P= 0.03). CONCLUSION: We conclude that as for cardiovascular disease and diabetes mellitus, gallstone disease appears to be strongly associated with metabolic syndrome.

Different profile of cytokine synthesis according to the severity of acute pancreatitis

AIM: To evaluate the cellular synthetic ability of cytokines involved in pro- and anti-inflammatory reactions in patients with AP.METHODS: Sixty-seven patients with AP (16 severe,51 mild) and 10 controls were included in the study.Cultures of whole blood were performed in samples obtained within the first 72 h from the onset of pain.Serum levels of interleukins (IL) 6, 8, 10, and TNF-α were measured at baseline and in the supernatant of cultures with (functional reserve) or without stimulation with phytohemaglutinin.RESULTS: Basal levels of cytokines were significantly higher in patients with severe AP. A significant increase of all pro-inflammatory cytokines vs basal levels was observed in the supernatant after 24 h of whole blood cultures in patients, but not in controls. In contrast, IL-10 increased significantly in the supernatant of cultures only in patients with mild AP. Cells showed a statistically significant functional reserve for all IL in patients with mild, but only for pro-inflammatory cytokines in patients with severe AP.CONCLUSION: A marked activation of immune system may be observed in patients with AP, being balanced between pro- and anti-inflammatory cytokines in patients with mild but not severe AP. A reduced functional reserve for the synthesis of IL-10 may be observed in patients with severe AP, which might lead to a worst prognosis.

Gastric stimulation for weight loss

The prevalence of obesity is growing to epidemic proportions,and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss.Behavior and lifestyle therapy are safe treatments for obesity in the short term,but the durability of the weight loss is limited.Although promising obesity drugs are in development,the currently available drugs lack efficacy or have unacceptable side effects.Surgery leads to long-term weight loss,but it is associated with morbidity and mortality.Gastric electrical stimulation(GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders.GES is a promising,minimally invasive,safe,and effective method for treating obesity.External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time.In addition,data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES.This may involve alteration of secretion of hormones associated with hunger or satiety.Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome.Here,we review the current status,potential mechanisms of action,and possible future applications of gastric stimulation for obesity.

One fifth of hospitalizations for peptic ulcer-related bleeding are potentially preventable

AIM: To calculate the proportion of potentially preventable hospitalizations due to peptic ulcer disease (PUD), erosive gastritis (EG) or duodenitis (ED).

Oral mixture of autologous colon-extracted proteins for the Crohn's disease: A double-blind trial

AIM: To evaluate the safety and efficacy of oral administration of AlequelTM, an autologous proteincontaining colon extract.a randomized,placebo-controlled,double-blind trial.Patients were orally administered with autologous protein-containing colon extract three doses of autologous study drug per week for 15 wk,for a total of45 doses.Patients were followed for safety parameters.Remission was defined as a Crohn’s disease activity index(CDAI)score of less than or equal to 150.All patients were followed for changes in subsets of T cells by fluorescence-activated cell sorting analysis.RESULTS:Analysis was performed on a total number of evaluable patients of 14 in the study drug group and15 in the placebo group.Treatment was well tolerated by all patients.No major treatment-related adverse events were reported or observed in any of the treated patients during the feeding or follow-up periods.Between weeks 6 and 9 of the study,six of the 14(43%)evaluable subjects who received the study drug achieved a CDAI of 150 or lower.In contrast,five of the 15(33%)evaluable subjects in the placebo group achieved remission.Between weeks 9 and 12,the remission rates were 50%and 33%for the drug group and placebo group,respectively.Among the drug-treated subjects who achieved remission,the effect of the drug was judged as stable in eight of the 14 subjects as measured by at least two CDAI scores indicating remission in the 15-wk treatment period.A decreased percentage of peripheral natural killer T regulatory cells(a decrease of 28%vs an increase of 16%)and an increased ratio of CD4+/CD8+T lymphocytes(an increase of 11%vs a decrease of9%)were noted in subjects with a significant clinical response.CONCLUSION:Oral administration of the autologous colonic extract could be a safe and effective for the treatment of patients with moderate to severe Crohn’s disease.