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Influence of donor age on liver transplantation outcomes: A multivariate analysis and comparative study

World Journal of Gastrointestinal Surgery 2024年第2期16卷 331-344页

作者： Miran Bezjak Ivan Stresec Branislav Kocman Stipislav Jadrijević tajana filipec kanizaj Miro Antonijević Bojana Dalbelo Bašić Danko Mikulić Department of Surgery University Hospital MerkurZagreb 10000Croatia Department of Electronics MicroelectronicsComputer and Intelligent SystemsFaculty of Electrical Engineering and ComputingZagreb 10000Croatia Department of Gastroenterology University Hospital MerkurZagreb 10000Croatia Development of Software Nanobit Ltd.Zagreb 10000Croatia

BACKGROUND The growing disparity between the rising demand for liver transplantation(LT)and the limited availability of donor organs has prompted a greater reliance on older liver grafts.Traditionally,utilizing livers from elderly donors has been associated with outcomes inferior to those achieved with grafts from younger donors.By accounting for additional risk factors,we hypothesize that the utili-zation of older liver grafts has a relatively minor impact on both patient survival and graft viability.AIM To evaluate the impact of donor age on LT outcomes using multivariate analysis and comparing young and elderly donor groups.METHODS In the period from April 2013 to December 2018,656 adult liver transplants were performed at the University Hospital Merkur.Several multivariate Cox propor-tional hazards models were developed to independently assess the significance of donor age.Donor age was treated as a continuous variable.The approach involved univariate and multivariate analysis,including variable selection and assessment of interactions and transformations.Additionally,to exemplify the similarity of using young and old donor liver grafts,the group of 87 recipients of elderly donor liver grafts(≥75 years)was compared to a group of 124 recipients of young liver grafts(≤45 years)from the dataset.Survival rates of the two groups were estimated using the Kaplan-Meier method and the log-rank test was used to test the differences between groups.RESULTS Using multivariate Cox analysis,we found no statistical significance in the role of donor age within the constructed models.Even when retained during the entire model development,the donor age's impact on survival remained insignificant and transformations and interactions yielded no substantial effects on survival.Consistent insigni-ficance and low coefficient values suggest that donor age does not impact patient survival in our dataset.Notably,there was no statistical evidence that the five developed models did not adhere to the proportional hazards assumption.When c

关键词： Liver transplantation Elderly donors Survival analysis Postoperative complications Cox proportional hazard models

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Liver regeneration as treatment target for severe alcoholic hepatitis

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World Journal of Gastroenterology 2022年第32期28卷 4557-4573页

作者： Lucija Virovic-Jukic Dominik Ljubas Sanja Stojsavljevic-Shapeski Neven Ljubičić tajana filipec kanizaj Ivana Mikolasevic Ivica Grgurevic Department of Gastroenterology and Hepatology Sisters of Charity University Hospital CenterZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of MedicineZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of Dental MedicineZagreb 10000Croatia Department of Gastroenterology Merkur University HospitalZagreb 10000Croatia Department of Gastroenterology Rijeka University Hospital CenterRijeka 51000Croatia Department of Internal Medicine University of Rijeka School of MedicineRijeka 10000Croatia Department of Gastroenterology Hepatology and Clinical NutritionDubrava University HospitalZagreb 10000Croatia

Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high mortality.Supportive medical care with corticosteroids in selected patients is the only currently available treatment option,often with poor outcomes.Based on the insights into the pathogenetic mechanisms of AH,which are mostly obtained from animal studies,several new treatment options are being explored.Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target.Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor(G-CSF)on liver regeneration and immunomodulation in animal models,several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH.Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH,these effects were not confirmed by a recently published multicenter randomized trial,suggesting that other options should rather be pursued.Stem cell transplantation represents another option for improving liver regeneration,but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing,with established lack of efficacy in patients with compensated cirrhosis.In this review,we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration.The lack of high-quality studies and evidence is a major obstacle in further treatment development.New insights into the pathogenesis of not only liver injury,but also liver regeneration processes are mandatory for the development of new treatment options.A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing,and data obtained from animal studies are essential for future research.

关键词： Severe alcoholic hepatitis Alcohol-related liver disease Treatment Liver regeneration Granulocyte colony-stimulating factor Stem cell transplantation

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Helicobacter pylori:Future perspectives in therapy reflecting three decades of experience

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World Journal of Gastroenterology 2014年第3期20卷 699-705页

作者： tajana filipec kanizaj Nino Kunac Department of gastroenterology University hospital MerkurSchool of MedicineUniversity of Zagreb University hospital Merkur

The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated,and their contribution to eradication failure is estimated.For a long time being considered the cornerstone eradication scheme,the standard triple therapy has been replaced with novel,more efficient regimens,namely sequential and concomitant,along with the emergence of a new design of bismuth quadruple therapy.A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant(clarithromycin and metronidazole)H.pylori.Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy,making eradication success close to originally desirable rates.Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes,so various probiotic compound supplements are taken into consideration.Finally,we summarize the emerging efforts and obstacles in creating efficientH.pylori vaccine.

关键词： Helicobacter pylori Eradication therapy Antibiotic

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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

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Role of total pancreatectomy in the treatment of paraduodenal pancreatitis:A case report

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World Journal of Gastrointestinal Surgery 2019年第6期11卷 296-302页

作者： Danko Mikulic Tomislav Bubalo Anna Mrzljak Anita Skrtic Stipislav Jadrijevic tajana filipec kanizaj Branislav Kocman Division of Abdominal Surgery and Organ Transplantation Department of Surgery University Hospital Merkur Division of Gastroenterology Department of Internal Medicine University of Zagreb School of Medicine University Hospital Merkur Department of Pathology and Cytology University of Zagreb School of Medicine University Hospital Merkur

BACKGROUND Paraduodenal pancreatitis(PP)is a rare form of chronic pancreatitis presenting with symptoms of duodenal obstruction.Conservative treatment is often unsuccessful and pancreaticoduodenectomy is the preferred surgical approach.A mini review of the outcomes of surgical therapy for PP shows that the results of pancreaticoduodenectomy are predominantly favorable.CASE SUMMARY In our case report of PP,we describe an unusual course first presenting with the symptoms of chronic pancreatitis and a pseudocyst of the pancreatic tail.A pseudocystojejunostomy was performed and the late postoperative course was complicated with the symptoms of duodenal obstruction.At laparotomy,PP was found and the patient was treated with a total pancreatectomy.The postoperative course was uneventful and good weight gain with resolution of pain was demonstrated at follow up visits.CONCLUSION Surgery is currently the optimal treatment option for PP.It is also the best diagnostic tool in distinguishing between pancreatitis and pancreatic adenocarcinoma.

关键词： Paraduodenal pancreatitis Groove pancreatitis Chronic pancreatitis Total pancreatectomy Case report

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Constrictive pericarditis as a cause of refractory ascites after liver transplantation:A case report

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World Journal of Clinical Cases 2019年第20期7卷 3266-3270页

作者： Miran Bezjak Branislav Kocman Stipislav Jadrijevic Hrvoje Gasparovic Anna Mrzljak tajana filipec kanizaj Darko Vujanic Tomislav Bubalo Danko Mikulic Division of Abdominal Surgery and Organ Transplantation Department of SurgeryUniversity Hospital MerkurZagreb 10000Croatia Division of Cardiology Department of Internal MedicineUniversity Hospital Centre ZagrebZagreb 10000Croatia Division of Gastroenterology Department of Internal MedicineUniversity Hospital MerkurZagreb 10000Croatia Division of Cardiology Department of Internal MedicineUniversity Hospital MerkurZagreb 10000Croatia

BACKGROUND Refractory ascites is a rare complication following orthotopic liver transplantation(OLT).The broad spectrum of differential diagnosis often leads to delay in diagnosis.Therapy depends on recognition and treatment of the underlying cause.Constrictive pericarditis is a condition characterized by clinical signs of right-sided heart failure.In the advanced stages of the disease,hepatic congestion leads to formation of ascites.In patients after OLT,cardiac etiology of ascites is easily overlooked and it requires a high degree of clinical suspicion.CASE SUMMARY We report a case of a 55-year-old man who presented with a refractory ascites three months after liver transplantation for alcoholic cirrhosis.Prior to transplantation the patient had a minimal amount of ascites.The transplant procedure and the early postoperative course were uneventful.Standard posttransplant work up failed to reveal any typical cause of refractory post-transplant ascites.The function of the graft was good.Apart from atrial fibrillation,cardiac status was normal.Eighteen months post transplantation the patient developed dyspnea and severe fatigue with peripheral edema.Ascites was still prominent.The presenting signs of right-sided heart failure were highly suggestive of cardiac etiology.Diagnostic paracentesis was suggestive of cardiac ascites,and further cardiac evaluation showed typical signs of constrictive pericarditis.Pericardiectomy was performed followed by complete resolution of ascites.On the follow-up the patient remained symptom-free with no signs of recurrent ascites and with normal function of the liver graft.CONCLUSION Refractory ascites following liver transplantation is a rare complication with many possible causes.Broad differential diagnosis needs to be considered.

关键词： Constrictive pericarditis Liver transplantation Refractory ascites Case report

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Nonalcoholic fatty liver disease and liver transplantation-Where do we stand?

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World Journal of Gastroenterology 2018年第14期24卷 1491-1506页

作者： Ivana Mikolasevic tajana filipec-kanizaj Maja Mijic Ivan Jakopcic Sandra Milic Irena Hrstic Nikola Sobocan Davor Stimac Patrizia Burra Department of Gastroenterology UHC Rijeka School of Medicine University of Rijeka Department of Gastroenterology University Hospital MerkurSchool of Medicine University of Zagreb Department of Internal medicine General Hospital Pula Pula School of Medicine University of Rijeka and Zagreb Multivisceral Transplant Unit Department of Surgery Oncology and Gastroenterology Padua University Hospital

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation(LT), on patients on the waiting list for transplant, on posttransplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome(Met S) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of Met S and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.

关键词： nonalcoholic steatohepatitis chronic liver disease liver transplantation nonalcoholic fatty liver disease outcome

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Hepatitis C:New challenges in liver transplantation

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World Journal of Gastroenterology 2015年第19期21卷 5768-5777页

作者： tajana filipec kanizaj Nino Kunac Department of Gastroenterology University Hospital Merkur School of Medicine University of Zagreb University Hospital Merkur

In an era of great achievements in liver transplantation, hepatitis C viral infection(HCV) remains an unsolved problem. As a leading indication for liver transplantation in Western countries, HCV poses a significant burden both before and after transplantation. Post-transplant disease recurrence occurs in nearly all patients with detectable pretransplant viremia, compromising the lifesaving significance of transplantation. Many factors involving the donor, recipient and virus have beenevaluated throughout the literature, although few have been fully elucidated and implemented in actual clinical practice. Antiviral therapy has been recognized as a cornerstone of HCV infection control; however, experience and success are diminished following transplantation in a challenging cohort of patients with liver cirrhosis. Current therapeutic protocols surpass those used previously, both in sustained viral response and side-effect profile. In this article we review the most relevant and contemporary scientific evidence regarding hepatitis C infection and liver transplantation, with special attention dedicated to novel, more efficient and safer antiviral regimens.

关键词： Hepatitis C Liver transplantation Treatmentprotocols Pegylated interferon Ribavirin Direct actingantivirals

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Noninvasive markers of liver steatosis and fibrosis after liver transplantation-Where do we stand?

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World Journal of Transplantation 2021年第3期11卷 37-53页

作者： Ivana Mikolasevic Sanja Stojsavljevic Filip Blazic Maja Mijic Delfa Radic-Kristo Toni Juric Nadija Skenderevic Mia Klapan Andjela Lukic tajana filipec kanizaj Department of Gastroenterology Clinical Hospital Centre RijekaRijekaCroatiaDepartment of GastroenterologyClinical hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of RijekaRijekaCroatia Department of Gastroenterology University Hospital Center“Sestre Milosrdnice”Zagreb 10000Croatia Department of Gastroenterology University Hospital Center RijekaRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagreb 10000Croatia Department of Hematology University Hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of ZagrebZagrebCroatia School of Medicine School of MedicineRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of ZagrebZagrebCroatia

In the last two decades,advances in immunosuppressive regimens have led to fewer complications of acute rejection crisis and consequently improved shortterm graft and patient survival.In parallel with this great success,long-term posttransplantation complications have become a focus of interest of doctors engaged in transplant medicine.Metabolic syndrome(MetS)and its individual components,namely,obesity,dyslipidemia,diabetes,and hypertension,often develop in the post-transplant setting and are associated with immunosuppressive therapy.Nonalcoholic fatty liver disease(NAFLD)is closely related to MetS and its individual components and is the liver manifestation of MetS.Therefore,it is not surprising that MetS and its individual components are associated with recurrent or“de novo”NAFLD after liver transplantation(LT).Fibrosis of the graft is one of the main determinants of overall morbidity and mortality in the post-LT period.In the assessment of post-LT steatosis and fibrosis,we have biochemical markers,imaging methods and liver biopsy.Because of the significant economic burden of post-LT steatosis and fibrosis and its potential consequences,there is an unmet need for noninvasive methods that are efficient and cost-effective.Biochemical scores can overestimate fibrosis and are not a good method for fibrosis evaluation in liver transplant recipients due to frequent post-LT thrombocytopenia.Transient elastography with controlled attenuation parameter is a promising noninvasive method for steatosis and fibrosis.In this review,we will specifically focus on the evaluation of steatosis and fibrosis in the post-LT setting in the context of de novo or recurrent NAFLD.

关键词： Steatosis Fibrosis Noninvasive methods Transient elastography Transplantation Nonalcoholic fatty liver disease

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Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage:A prospective case control study

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World Journal of Clinical Cases 2022年第17期10卷 5551-5565页

作者： tajana Pavic Stipe Pelajic Nina Blazevic Dominik Kralj Milan Milosevic Ivana Mikolasevic Ivan Lerotic Davor Hrabar Department of Gastroenterology and Hepatology University Hospital Center Sestre MilosrdniceZagreb 10000Croatia Andrija Stampar School of Public Health WHO Collaborative Centre for Occupational Health University of ZagrebSchool of MedicineZagreb 10000Croatia Department of Gastroenterology University Hospital Center RijekaRijeka 51000Croatia

BACKGROUND Biliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually.Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality,it is important to identify factors and mechanisms involved in its development.AIM To determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status.METHODS This was a prospective case control study performed in a tertiary center in Zagreb,Croatia.Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled.After excluding patients who developed procedure related complications or were lost in the follow-up,out of initial 73 patients,55 patients were included in the analysis,including 34 with benign and 21 with malignant disease.Meanwhile,40 non-jaundiced controls were also included.Appetite,nutritional status,and serum ghrelin,cholecystokinin(CCK),interleukin 6(IL-6),and tumor necrosis factorα(TNF-α)were determined at admission,48 h and 28 d after internal biliary drainage.Chi square test was used for categorical variables.Continuous variables were analysed for normality by Kolmogorov-Smirnov test and relevant non-parametric(Mann-Whitney,Kruskal-Wallis,and Friedman)or parametric(t-test and analysis of variance)tests were used.RESULTS Patients with obstructive jaundice were significantly malnourished compared to controls,regardless of disease etiology.Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice.Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α,but had no correlation with CCK concentrations.After internal biliary drainage,a significant improvement of nutritional status was observed although serum concentrations of ghrelin,IL-6,and TNF-α remained significantly elevated even 28 d after the procedure.CCK levels in patients without malnutrition remained elev

关键词： Ghrelin Cholecystokinin Biliary obstruction Malnutrition

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