Non-composite combined liver and intestinal allotransplantation

Introduction Small bowel transplantation has been the optimal choice for patients with irreversible intestinal failure. Advances in total parenteral nutrition (TPN) have allowed patients with short bowel syndrome to survive, but the long-term effects are often complicated by intestinal failure. As a result, many candidates for intestinal transplantation have concomitant cholestatic liver damage. Thus, simultaneous liver and intestinal transplantation is required.[1-5] Herein we present a cas…     

Diet therapy for inflammatory bowel diseases: The established and the new

Although patients with inflammatory bowel diseases(IBD) have a strong interest in dietary modifications as part of their therapeutic management, dietary advice plays only a minor part in published guidelines. The scientific literature shows that dietary factors might influence the risk of developing IBD, that dysbiosis induced by nutrition contributes to the pathogenesis of IBD, and that diet may serve as a symptomatic treatment for irritable bowel syndrome-like symptoms in IBD. The role of nutrition in IBD is underscored by the effect of various dietary therapies. In paediatric patients with Crohn’s disease(CD) enteral nutrition(EN) reaches remission rates similar to steroids. In adult patients, however, EN is inferior to corticosteroids. EN is not effective in ulcerative colitis(UC). Total parenteral nutrition in IBD is not superior to steroids or EN. The use of specific probiotics in patients with IBD can be recommended only in special clinical situations. There is no evidence for efficacy of probiotics in CD. By contrast, studies in UC have shown a beneficial effect in selected patients. For patients with pouchitis, antibiotic treatment followed by probiotics, like VSL#3 or Lactobacillus GG, is effective. When probiotics are used, the risk of bacterial translocation and subsequent bacteremia has to be considered. More understanding of the normal intestinal microflora, and better characterization of probiotic strains at the phenotypic and genomic levels is needed as well as clarification of the mechanisms of action in different clinical settings. A FODMAP reduced diet may improve symptoms in IBD.     

Prolonged small vessel vasculitis with colon mucosal inflammation as first manifestations of Behet’s disease

Behet’s disease is a chronic, relapsing, systemic vasculitis of unknown aetiology. Patients present manifestations of gastrointestinal complications, including mouth lesions, small and large intestinal lesions, and vascular lesions in the abdomen. In some cases, the intestinal ulcers of patients with Behet’s disease are indistinguishable from those of Crohn’s disease, tuberculosis, vasculitis and other diseases. In this article, we present a case of atypical Behet’s disease with a complicated medical history and multisystem damage, for the purpose of better management of this disease.     

Intestinal permeability and its association with the patient and disease characteristics in Crohn's disease

AIM:To assess the intestinal permeability (IP) in patients with Crohn's disease (CD) and study the association of IP with the patient and disease characteristics. METHODS: One hundred and twenty five consecutive patients of CD (Males: 66) were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index (CDAI) was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy controls. RESULTS: Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion (patients vs controls = 12.5% vs 14.2%, P = 0.4652), but lactulose excretion was significantly higher in patients compared to healthy controls (patients vs controls = 0.326% vs 0.293%, P = 0.0391). The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P = 0.0044]. Male patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs 0.022 (95% CI 0.0178, 0.028) (P = 0.0024), though there was no difference in the number of patients with abnormal IP in boththe sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 (95% CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P < 0.001)]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P = 0.0062)]. There was no correlation of IP with age, disease activity, duration of illness, D-xylose absorption, upper GI involvement, perianal disease, and extra- intestinal manifestations. On multiple regression analysis, male gender and ileo-colonic disease were independent factors associated with increased IP. Gender, location, behavior of the disease and upper GI involvement could explain up to 23% of variability in IP (R2 = 0.23). CONCLUSION: IP was increased in 36% of patients with CD. Male gender and an ileo-colonic disease were the independent factors associated with increased IP.     

Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.     

Alcoholic liver disease

Alcohol use disorders affect millions of individuals worldwide.Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs.Alcoholic liver disease(ALD) may take the form of acute involvement(alcoholic hepatitis)or chronic liver disease(steatosis,steatohepatitis,fibrosis and cirrhosis).The severity and prognosis of alcohol-induced liver disease depends on the amount,pattern and duration of alcohol consumption,as well as on the presence of liver inflammation,diet,nutritional status and genetic predisposition of an individual.While steatosis is an almost completely benign disease,liver cirrhosis is associated with marked morbidity,mortal-ity and life expectancy shortening.The median survival of patients with advanced cirrhosis is 1-2 years.Se-vere acute alcoholic hepatitis(AH)is associated with mortality as high as 50%.It has been managed with corticoids,pentoxifylline and enteral nutrition,although evidence based data are still conflicting.Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH.Absolute abstinence is a basic condition for any treatment of acute or chronic ALD,the other therapeutical procedure being of a supportive nature and questionable significance.Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alco-hol dependent patients.Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation,which leads to a markedly pro-longed life expectancy.The crucial step in ALD preven-tion is in the prevention of alcohol abuse,whereas the prevention of liver injury in active alcohol abusers is not clinically applicable.     

Gut hormones, and short bowel role of glucagon-like peptide-2 in adaptation syndrome： The enigmatic the regulation of intestinal

Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenterai nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenterai nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.     

Rifaximin and Crohn’s disease

In a recent article,Longman and Swaminath analyzed our paper on the use of rifaximin in patients with moderately active Crohn’s disease(CD).Here we report some considerations concerning their article.The exploratory post-hoc subgroup analysis showed that early-stage disease and,differently from that written by Longman and Swaminath,also colonic involvement seemed to be associated with a significant higher efficacy of rifaximin-EIR 800 mg twice daily.Early-stage disease is generally considered as the more easily treatable phase of CD,and the better response to rifaximin in Crohn’s colitis is in accordance with the high concentration of bacteria in the colon.In addition,patients with C reactive protein level>5 mg/L achieved remission more significantly than patients with normal values,thus suggesting that the symptoms were probably caused by inflammation instead of by non-inflammatory causes.We also analyze the role of rifaximin against gut bacteria and the clinical situations that could obtain the best results from antibiotics.     

Skin cancer in immunosuppressed transplant patients: Vigilance matters

Liver transplantation(LT) is a widely-accepted, definitive therapy of irreversible liver diseases including hepatitis C, alcoholic liver disease and metabolic liver disease. After transplantation, patients generally use a variety of immunosuppressive medications for the rest of their lives to prevent rejection of transplanted liver. Mortality after LT is mainly caused by recurrence of alcoholic hepatitis which is mostly seen in the patients who resume heavy drinking. On the other hand, de-novo malignancies after LT are not seldom. Skin cancers make up 13.5% of the de-novo malignancies seen in these patients. Malignancies tend to affect survival earlier in the course with a 53% risk of death at 5 years after diagnosis. We aimed to report a case who underwent LT secondary to alcoholic liver disease and developed squamous cell carcinoma of the skin eighteen years after transplantation. In summary, transplant recipients are recommended to be educated on self examination for skin cancer; health care providers should be further suspicious during routine dermatological examinations of the transplant patients and biopsies of possible lesions for skin cancer is warranted even many years after transplantation.     

Portopulmonary hypertension in liver transplant candidates

Pulmonary vascular disorders including portopulmonary hypertension(PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure(PAP) and liver transplant surgery, survival of patients with Po PHT and advanced liver disease is significantly improved. Because of the prognostic significance of Po PHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild Po PHT can safely undergo liver transplant surgery. In cases of moderate to severe Po PHT, right heart catheterization(RHC) should be performed. In patients with moderate to severe Po PHT on RHC(mean PAP 35-45 mm Hg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed.     

Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn’s disease

The concept of fecal microbiota transplantation(FMT)has been used in traditional Chinese medicine at least since the 4thcentury.Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease.We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease.However,there were no reports of FMT used in patients with severe Crohn’s disease(CD).Here,we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula,residual Barium sulfate and formation of intraperitoneal large inflammatory mass.As far as we know,this is the first case of severe CD treated using FMT through mid-gut.     

Crohn’s disease complicated by multiple stenoses and internal fistulas clinically mimicking small bowel endometriosis

We report a 31-year-old woman with Crohn's disease complicated by multiple stenoses and internal fistulas clinically misdiagnosed as small bowell endometriosis, due to the patient's perimenstrual symptoms of mechanical subileus for 3 years; at first monthly, but later continuous, and gradually increasing in severity. We performed an exploratory laparotomy for small bowel obstruction, and found multiple ileal strictures and internal enteric fistulas. Because intraoperative findings were thought to indicate Crohn's disease, a right hemicolectomy and partial distal ileum resection were performed for obstructive Crohn's ileitis. Histopathology of the resected specimen revealed Crohn's disease without endometrial tissue. The patient made an uneventful recovery from this procedure and was discharged home 10 d post-operatively. The differential diagnosis of Crohn's diease with intestinal endometriosis may be difficult pre-operatively. The two entities share many overlapping clinical, radiological and pathological features. Nevertheless, when it is difficult to identify the cause of intestinal obstruction in a woman of child-bearing age with cyclical symptoms suggestive of small bowel endometriosis, Crohn's disease should be included in the differential diagnosis.     

Liver transplantation for Wilson disease

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options mayinclude hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD.     

Management of patients with hepatitis C infection and renal disease

Hepatitis C virus(HCV) infection in patients with end-stage renal disease(ESRD) is associated with more rapid liver disease progression and reduced renal graft and patients’ survival following kidney transplantation. Evaluations and management of HCV in patients with renal disease are challenging. The pharmacokinetics of interferons(IFN), ribavirin(RBV) and some direct acting antiviral(DAA), such as sofosbuvir, are altered in patients with ESRD. With dose adjustment and careful monitoring, treatment of HCV in patients with ESRD can be associated with sustained virological response(SVR) rates nearly comparable to that of patients with normal renal function. DAA-based regimens, especially the IFNfree and RBV-free regimens, are theoretically preferred for patients with ESRD and KT in order to increase SVR rates and to reduce treatment side effects. However, based on the data for pharmacokinetics, dosing safety and efficacy of DAA for patients with severe renal impairment are lacking. This review will be focused on the evaluations, available pharmacologic data, and management of HCV in patients with severe renal impairment, patients who underwent KT, and those who suffered from HCV-related renal disease, according to the available treatment options, including DAA.     

Washed microbiota transplantation reduces proton pump inhibitor dependency in nonerosive reflux disease

BACKGROUND The pathogenesis of gastroesophageal reflux disease(GERD)is closely associated with the intestinal bacteria composition and their metabolites.AIM To investigate whether washed microbiota transplantation(WMT)improves symptoms of nonerosive reflux disease(NERD)with proton pump inhibitor(PPI)dependency.METHODS Patients with recurrent NERD and PPI dependency at the First Affiliated Hospital of Guangdong Pharmaceutical University from 2017 to 2018 were included and divided into a WMT or PPI group treated with PPI with/without WMT.The endpoint was NERD symptom frequency evaluated 1 mo after WMT using reflux disease questionnaire(RDQ)and GERD questionnaire(GERDQ)scores,remission time,PPI dose,and the examination of intestinal mucosal barrier function.RESULTS In the WMT(n=15)and PPI(n=12)groups,the total remission rate at 1 mo after treatment was 93.3%vs 41.7%.Compared with the PPI group,the WMT group showed better results in GERDQ(P=0.004)and RDQ(P=0.003)and in remission months(8 vs 2,P=0.002).The PPI dose was reduced to some extent for 80%of patients in the WMT group and 33.3%in the PPI group.In 24 patients,intestinal mucosal barrier function was examined before treatment,and changes in the degree of damage were observed in 13 of these patients after treatment.Only one of the 15 patients had minor side effects,including a mushy stool two or three times a day,which resolved on their own after 1 wk.CONCLUSION This study is the first to demonstrate that WMT may be safe and effective for relieving NERD symptoms and reducing PPI dependency and recurrence.     

Use of antibiotics in the treatment of Crohn’s disease

Many data coming from animal models and clinical observations support an involvement of intestinal microbiota in the pathogenesis of Crohn’s disease(CD). It is hypothesized in fact,that the development of chronic intestinal inflammation is caused by an abnormal immune response to normal flora in genetically susceptible hosts.The involvement of bacteria in CD inflammation has provided the rationale for including antibiotics in the therapeutic armamentarium.However, randomized controlled trials have failed to demonstrate an efficacy of these drugs in patients with active uncomplicated CD,even if a subgroup of patients with colonic location seems to get benefit from antibiotics. Nitroimidazole compounds have been shown to be efficacious in decreasing CD recurrence rates in operated patients,and the use of metronidazole and ciprofloxacin is recommended in perianal disease.However,the appearance of systemic side effects limits antibiotic long-term employment necessary for treating a chronic relapsing disease.Rifaximin,characterized by an excellent safety profile,has provided promising results in inducing remission of CD.     

Nonalcoholic fatty liver disease and vascular disease:State-of-the-art

Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.     

Differences in clinical features of Crohn’s disease and intestinal tuberculosis

AIM: To investigate the clinical features of Crohn’s disease(CD) and intestinal tuberculosis(ITB) with a scoring system that we have developed.METHODS: A total of 25 CD and 40 ITB patients were prospectively enrolled from August 2011 to July 2012.Their characteristics and clinical features were recorded. Laboratory, endoscopic, histologic and radiographic features were determined. The features with a high specificity were selected to establish a scoring system. The features supporting CD scored +1, and those supporting ITB scored-1; each patient received a final total score. A receiver operating characteristic(ROC) curve was used to determine the best cut-off value for distinguishing CD from ITB.RESULTS: Based on a high specificity of differentiating between CD and ITB, 12 features, including longitudinal ulcers, nodular hyperplasia, cobblestone-like mucosa, intestinal diseases, intestinal fistula, the target sign, the comb sign, night sweats, the purified protein derivative test, the interferon-γ release assay(T-SPOT.TB), ring ulcers and ulcer scars, were selected for the scoring system. The results showed that the average total score of the CD group was 3.12 ± 1.740, the average total score of the ITB group was-2.58 ± 0.984, the best cutoff value for the ROC curve was-0.5, and the diagnostic area under the curve was 0.997, which was statistically significant(P < 0.001). The patients whose total scores were higher than-0.5 were diagnosed with CD; otherwise, patients were diagnosed with ITB. Overall, the diagnostic accuracy rate and misdiagnosis rate of this scoring system were 97% and 3%, respectively. CONCLUSION: Some clinical features are valuable for CD and ITB diagnosis. The described scoring system is key to differentiating between CD and ITB.     

Management of hepatitis C virus infection in HIV/HCV co-infected patients： Clinical review

Nearly one fourth of individuals with human immunodeficiency virus （HIV） infection have hepatitis C virus （HCV） infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti- HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection （33% vs 72%, P = 0.07）. A betterunderstanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome, and survival.