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Inflammatory bowel disease in liver transplanted patients

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World Journal of Gastroenterology 2017年第18期23卷 3214-3227页

作者： Tajana Filipec Kanizaj Maja Mijic Department of Gastroenterology University Hospital MerkurSchool of MedicineUniversity of Zagreb University Hospital Merkur

Most common hepatobiliary manifestation of inflammatory bowel disease(IBD) are primary sclerosing cholangitis(PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation(LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Antitumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.

关键词：煽动性的肠疾病 Anti-TNF alpha 治疗肝移植 Immunomodulatory 治疗免疫力的抑制 Proctoproctocolectomy 冒险因素

Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review

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World Journal of Gastroenterology 2017年第20期23卷 3589-3606页

作者： Kuan-Yin Lin Guan-Jhou Chen Yu-Lin Lee Yi-Chia Huang Aristine Cheng Hsin-Yun Sun Sui-Yuan Chang Chun-Eng Liu Chien-Ching Hung Department of Medicine National Taiwan University Hospital Jin-Shan Branch Department of Internal Medicine National Taiwan University Hospital Department of Internal Medicine Changhua Christian Hospital National Taiwan University College of Medicine Department of Clinical Laboratory Sciences and Medical Biotechnology National Taiwan University College of Medicine Department of Laboratory Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Department of Parasitology National Taiwan University College of Medicine Department of Medical Research China Medical University Hospital China Medical University

Hepatitis A virus(HAV)is one of the most common infectious etiologies of acute hepatitis *** virus is known to be transmitted fecal-orally,resulting in symptoms ranging from asymptomatic infection to fulminant *** can also be transmitted through oral-anal *** from regions of low endemicity for HAV infection often remain susceptible in their ***,clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV *** duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus(HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis *** guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV(such as from injecting drug use,oral-anal sex,travel to or residence in endemic areas,frequent clotting factor or blood transfusions)or with increased risks of fulminant disease(such as those with chronic hepatitis).The seroconversion rates following the recommended standard adult dosing schedule(2doses of HAVRIX 1440 U or VAQTA 50 U administered6-12 mo apart)are lower among HIV-positive individuals compared to HIV-negative *** the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose,the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.

关键词：传染病学病毒的肝炎尖锐肝炎烘便口头的传播口头肛门的性与人性交的人注射药使用免疫力的抑制免疫

Hepatosplenic T-cell lymphoma in a 47-year-old Crohn's disease patient on thiopurine monotherapy

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World Journal of Gastroenterology 2016年第47期22卷 10465-10470页

作者： Maartje M van de Meeberg Lauranne AAP Derikx Harm AM Sinnige Peet Nooijen D Lucette Schipper Loes HC Nissen Department of Gastroenterology and Hepatology Jeroen Bosch Hospital Department of Hematology Jeroen Bosch Hospital Department of Pathology Jeroen Bosch Hospital

Hepatosplenic T-cell lymphoma(HSTCL) is a rare nonHodgkin lymphoma with a high mortality rate. Higher incidence is reported in patients with inflammatory bowel disease, specifically in male patients that are younger than 35 years, and have been treated with thiopurine and tumor necrosis factor(TNF)-α inhibitor combination therapy for over 2 years. In this case report we describe a 47-year-old patient with Crohn's disease(CD) who developed HSTCL after having been treated with thiopurine monotherapy for 14 years. To our best knowledge, only eleven cases exist of patients with CD who developed HSTCL while on thiopurine monotherapy. We report the first patient with CD, older than 35 years, who developed HSTCL while on thiopurine monotherapy. This emphasizes that HSTCL risk is not limited to young men receiving both thiopurines and TNF-α inhibitors.

关键词： Hepatosplenic T 房间淋巴瘤 Thiopurine Crohn’ s 疾病免疫力的抑制

Duplicate publication bias weakens the validity of metaanalysis of immunosuppression after transplantation

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World Journal of Gastroenterology 2017年第39期23卷 7198-7200页

作者： Cameron J Fairfield Ewen M Harrison Stephen J Wigmore Department of Clinical Surgery University of Edinburgh Royal Infirmary of Edinburgh

Duplicate publication can introduce significant bias into a meta-analysis if studies are inadvertently included more than once. Many studies are published in more than one journal to maximize readership and impact of the study findings. Inclusion of multiple publications of the same study within a meta-analysis affords inappropriate weight to the duplicated data if reports of the same study are not linked together. As studies which have positive findings are more likely to be published in multiple journals this leads to a potential overestimate of the benefits of an intervention. Recent advances in immunosuppression strategies following liver transplantation have led to many studies investigating immunosuppressive regimes including immunosuppression monotherapy. In this letter we focus on a recently published meta-analysis by Lan et al investigating studies assessing immunosuppression monotherapy for liver transplantation. The authors claim to have identified fourteen separate randomised studies investigating immunosuppression monotherapy. Seven of the references appear to relate to only three studies which have been subject to duplicate publication. Several similarities can be identified in each of the duplicate publications including similar authorship, identical immunosuppression regimes, identical dates of enrolment and citation of the original publication in the subsequent manuscripts. We discuss the evidence of the duplicate publication inclusion in the meta-analysis.

关键词：肝移植免疫力的抑制元分析复制出版偏爱

Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

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World Journal of Hepatology 2016年第35期8卷 1569-1575页

作者： Siddharth Sood Lijia Yu Kumar Visvanathan Peter William Angus Paul John Gow Adam Gareth Testro Department of Gastroenterology and Hepatology University of Melbourne Royal Melbourne Hospital Liver Transplant Unit Victoria University of Melbourne Innate Immune Laboratory University of Melbourne St Vincent’s Hospital

AIM To investigate whether a novel immune function biomarker Quanti FERON-Monitor(QFM) can identify cirrhotic patients at greatest risk of infection. METHODS Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47(52%) transplanted on the day of their QFM. The remaining 44(48%) were monitored for infections until transplant, death, or census date of 1st February *** Cirrhotic patients express a median QFM significantly lower than healthy controls(94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely *** factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient's immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13(29.5%) experienced a pre-transplant infection a median 20 d(range 2-182) post-test. QFM < 214 IU/mL was associated with HR = 4.1(P = 0.01) for infection. A very low QFM < 30 IU/mL was significantly associated(P = 0.003) with death in three patients who died while awaiting transplantation(HR = 56.6).CONCLUSION QFM is lower in cirrhotics, allowing objective determinations of an individual's unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.

关键词：感染 Biomarker 有免疫力的机能障碍有免疫力的功能免疫力的抑制肝免疫系统肝硬化死亡

Use of everolimus in liver transplantation

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World Journal of Hepatology 2017年第23期9卷 990-1000页

作者： Mei-Ling Yee Hui-Hui Tan Department of Pharmacy Singapore General Hospital Department of Gastroenterology and Hepatology Singapore General Hospital

In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation(LT) setting. The efficacy of everolimus(EVR) in de novo LT is established and a reasonable time to initiate EVR is 30d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor(CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy. Adverse effects of proteinuria, hypercholesterolemia and hyperlipidemia are significantly higher as compared to standard CNI and long-term implications on graft and patient survival in LT is still unclear. Future research to explore strategies to minimise EVR adverse effects will be crucial for the success of EVR as an important alternative or adjunct immunosuppressive therapy in LT.

关键词： Everolimus rapamycin 禁止者的哺乳动物的目标免疫力的抑制肝移植 Nephrotoxicity

Hepatitis B reactivation in the setting of chemotherapy and immunosuppression- prevention is better than cure

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世界肝病学杂志：英文版（电子版） 2015年第7期7卷 954-967页

作者： Venessa Pattullo Department of Gastroenterology Royal North Shore Hospital Sydney Medical School University of Sydney

Due to the inherent relationship between the immune system and the hepatitis B virus(HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation(HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations' guidelines and the best available evidence to date.

关键词：免疫力的抑制肝炎 B 肝炎 B 病毒复活预防 Lamivudine 化疗 Entecavir Tenofovir Rituximab