Publications by authors named "Murat Zeytunlu"

44 Publications

Steatotic and Steatohepatitic Hepatocellular Carcinomas: Features in a Series With Predominantly Viral Etiology.

Am J Surg Pathol 2021 Apr 8. Epub 2021 Apr 8.

Nisantasi Pathology Group, Istanbul Department of Pathology, University of Health Sciences, Bozyaka Training and Research Hospital Departments of Biostatistics and Medical Informatics Anesthesiology and Reanimation General Surgery and Organ Transplantation Center Gastroenterology Pathology, Ege University Faculty of Medicine, Ege University Application and Research Center of Organ Transplantation, Izmir, Turkey.

Hepatocellular carcinomas (HCCs) with steatohepatitis and steatosis are reported with varying definitions and clinicopathologic features. We aimed to search the attributes of steatohepatitic hepatocellular carcinoma (SH-HCC) and steatotic-HCC in our series. A retrospective clinicopathologic analyses of 150 HCCs and immunostaining for C-reactive protein (CRP) and serum amyloid A (SAA) were performed. Tumors were reclassified as all SH-HCC, limited SH-HCC, typical SH-HCC (steatohepatitic features in >5%, 5% to 50%, and ≥50% of the tumor, respectively), steatotic-HCC, and classic HCC (C-HCC). Group comparisons were made using Kruskal-Wallis and Kaplan-Meier tests. The background etiology in all SH-HCCs was pure viral in 51.4%, nonalcoholic steatohepatitis (NASH)/alcoholic liver disease (ALD) alone/mixed in 34.3%, and unidentified in normal liver in 14.3%. All SH-HCCS (n=35, 23.3%) and typical SH-HCCs (n=13, 8.6%) had higher NASH/ALD. Limited SH-HCCs (n=22, 14.6%) had higher ALD (all P<0.05). Typical SH-HCCs tended to have more NASH (P=0.054). Steatotic-HCCs (n=13, 9%) and C-HCCs (n=102, 68%) had higher pure viral etiology and serum CRP (all P<0.05). CRP and SAA were positive in 69% and 27% of the tumors, respectively. SAA positivity correlated with ALD (P=0.026). In the overall group disease-free survival rates at 1, 5, 10, and 20 years were 97.0%, 82.3%, 79.6%, and 77.2%, respectively. Demographics, tumor characteristics, CRP and SAA positivity, and survival were similar between the groups (P>0.05). H-HCC is heterogenous in terms of underlying etiologies, and can be seen in NASH/ALD, pure viral and noncirrhotic/normal background. The ≥50% cutoff for the definition of SH-HCC can lead to overlook ALD-related SH-HCC. Steatotic-HCC seems more similar to C-HCC rather than SH-HCC, but none of them feature as a different prognostic group.
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http://dx.doi.org/10.1097/PAS.0000000000001714DOI Listing
April 2021

Infections developing in patients undergoing liver transplantation: Recipients of living donors may be more prone to bacterial/fungal infections.

Turk J Gastroenterol 2020 12;31(12):894-901

Department of Gastroenterology, Ege University School of Medicine, Bornova, Izmir, Turkey.

Background/aims: Despite surgical advances in liver transplantation and effective prophylactic strategies, posttransplant infections are the most important cause of morbidity and mortality. Diagnosis and management of infections because of developing immunosuppression is difficult and adversely affects mortality. This study aimed to review bacterial and fungal infections in patients after liver transplantation and to reveal the resistance rates.

Materials And Methods: A total of 107 patients who underwent liver transplantation between January 2017 and February 2018 were evaluated retrospectively with regard to demographic characteristics, causes of transplantation, conditions that may lead to infection, postoperative infections, pathogens, and resistance patterns.

Results: Of the 107 patients who underwent liver transplantation, 48 (44.8%) had an infection. Bacterial infections were detected in 41% of the patients, and fungal infections were found in 13%. When we compared living and cadaveric transplants in terms of infection development, these rates were found to be 53% and 33%, respectively (p=0.034). No statistically significant results could be obtained when evaluating conditions such as sex, presence of underlying primary disease, Model for End-Stage Liver Disease MELD score, diabetes status, total parenteral nutrition, and risk factors for infection.

Conclusion: After liver transplantation, infections are often seen in the first month of the postoperative period. Knowing the most common pathogens and resistance states in this process reduces infection-related deaths by providing appropriate treatment regimens at the right time.
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http://dx.doi.org/10.5152/tjg.2020.19286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928243PMC
December 2020

The efficiency of low-dose hepatitis B immunoglobulin plus nucleos(t)ide analogs in preventing posttransplant hepatitis B virus recurrence

Turk J Med Sci 2019 08 8;49(4):1019-1024. Epub 2019 Aug 8.

Department of Liver Transplantation, Kent Hospital, İzmir, Turkey

Background/aim: In this study, the efficiency of using low-dose hepatitis B immunoglobulin (HBIG) plus antiviral treatment according to individual needs has been evaluated in posttransplant hepatitis B virus (HBV) patients.

Materials And Methods: We retrospectively evaluated 179 patients who were admitted between 2009 and 2014. Five thousand IU intravenous HBIG was given in the anhepatic phase, and 400 IU/day intramuscular (IM) HBIG was given in the posttransplant period. After HBsAg seroconversion, 400 IU IM HBIG was continued as prophylaxis every two weeks.

Results: The average follow-up period was 26 (2–65) months. Seventy patients had hepatocellular carcinoma (HCC). The HBV recurrence was 4.5% in the first year, and 5.8% in the third year. The HBsAg became negative in 11 (2–63) days, and anti-HBs became positive in 9 (1–31) days. HBsAg positivity occurred in 6 patients during the follow-up period. Five of these patients were those who underwent transplantation due to HCC. In 5 of the HCC patients, in whom HBsAg became positive, tumor recurrence was observed after 0.3–9.9 months. HBsAg positivity was more frequently detected in patients with HCC (P = 0.009).

Conclusion: The HBV recurrence should be evaluated as a predictor of the HCC recurrence in patients who were transplanted due to HCC.
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http://dx.doi.org/10.3906/sag-1808-86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018359PMC
August 2019

Hepatitis B and hepatocellular carcinoma recurrence after living donor liver transplantation: The role of the Milan criteria.

Turk J Gastroenterol 2019 01;30(1):75-80

Department of Liver Transplantation, Kent Hospital, İzmir, Turkey.

Background/aims: The aim of this study was to evaluate the effect of the Milan criteria on the hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrence in patients who underwent living donor liver transplantation due to HBV-induced cirrhosis and HCC.

Materials And Methods: We evaluated a total of 142 patients, 88 who underwent transplantation due to HBV-induced cirrhosis and 54 due to HCC, between 2009 and 2014. In the posttranplant period, after the HBsAg seroconversion, 400 IU of hepatitis B immunoglobulin were applied intramuscularly every 2 weeks, and daily nucleos(t)ide analogs were continued as prophylaxis. The HBV recurrence was defined as the presence of HBsAg in serum. Patients were screened for alpha-fetoprotein levels and imaging for evaluation of HCC recurrence.

Results: The average follow-up period was 26 (2-65) months. Fifty-four patients had HCC. The HCC recurrence was observed in 12 patients during the follow-up period. The HBV recurrence was observed in four patients. Three of the patients who developed HBV recurrence had liver transplantation due to HCC. Tumor recurrence was observed 1.4-12 months following the HBV recurrence. The HCC recurrence within the Milan criteria and beyond the Milan criteria was 0% vs. 28.4 % in the first year and 3.4% vs. 47.5% in the third year. The cumulative incidence of the HBV recurrence was 2.8% and 3.7% for the first year and 3.7% for the third year. The HBV recurrence was more frequently detected in patients with HCC (p=0.048), especially with HCC beyond the Milan criteria (p=0.044).

Conclusion: The HBV recurrence should be evaluated as a predictor of the HCC recurrence in patients who underwent liver transplantation due to HCC with exceeding Milan criteria.
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http://dx.doi.org/10.5152/tjg.2018.18794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389300PMC
January 2019

Results of 1001 liver transplantations in 23 years: Ege University experience.

Turk J Gastroenterol 2018 11;29(6):664-668

Liver Transplantation Department of Organ Transplantation and Research Center, Ege University School of Medicine, İzmir, Turkey.

Background/aims: Liver transplantation (LT) is now the standard of care for most end-stage liver diseases. Over the next 30 years, advances in medicine and technology will greatly improve the survival rates of patients after this procedure. The aim of the present study was to analyze retrospectively the results of 1001 patients withLT.

Materials And Methods: Medical reports of 989 patients were analyzed retrospectively. Data were obtained from the patient's data chart. Descriptive statistics were used to describe continuous variables (mean, median, and standard deviation).

Results: A total of 1001 LTs for 989 recipients were performed at Ege University Organ Transplantation and Research Center between 1994 and 2017. Therewere 639 male and 350 female recipients. Among 1001 LTs, there were 438 deceased donors and 563 living donors. The age interval of the patients was 4 months to 71 years old. The median Model for End-Stage Liver Disease score was 20. There were 12 deceased liver donors using the split method. There were 12 cases subject to retransplantation. In living donor LT grafts, 423 right lobes, 46 left lobes, and 94 left lateral sectors were used. In the first monitoring,the total annual mortality rate was 130 cases (13%). The mortality rate in retransplantation was found to be 66%. A 1-year survival rate of 87% was generally stablished.

Conclusion: LThas been improving consistently over the last two decades. Ege University is one of the biggest liver transplant centers in Turkey for both technical and educational perspective.
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http://dx.doi.org/10.5152/tjg.2018.18058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284687PMC
November 2018

Live donor liver transplantation for a child presented with severe hepatopulmonary syndrome and nodular liver lesions due to Abernethy malformation.

Pediatr Transplant 2017 Mar 12;21(2). Epub 2017 Jan 12.

Division of Liver Transplantation, Kent Hospital, Izmir, Turkey.

A 15-year-old boy first presented with severe lung lesions and hypoxia and he was considered as a lung transplant candidate. Upon evaluation, hepatopulmonary syndrome, multiple nodular liver lesions, and Abernethy type 1b malformation were diagnosed. The patient underwent successful right lobe live donor liver transplantation, and all of the symptoms disappeared soon after the transplant. He is currently alive and well with excellent liver and lung functions 4 years after surgery.
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http://dx.doi.org/10.1111/petr.12874DOI Listing
March 2017

Neurophysiological follow-up of two siblings with Crigler-Najjar syndrome type I and review of literature.

Turk J Pediatr 2013 May-Jun;55(3):349-53

Division of Pediatric Neurology, Department of Pediatrics, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.

Crigler-Najjar syndrome type I is an autosomal recessive inherited disease and rarely seen in childhood. Bilirubin neurotoxicity is the morbidity of the disease due to the elevated unconjugated bilirubin levels. Mental retardation, seizures, cognitive dysfunction, oculomotor nerve palsy, ataxia, choreoathetosis, and spasticity may be seen. Due to the high bilirubin levels, alterations in the neurophysiological studies may be detected. In this study, we describe two siblings who were diagnosed with Crigler-Najjar syndrome type I who underwent a successful liver transplantation using a single cadaveric organ, together with their neurophysiological follow-up and review of the literature.
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July 2014

The results of vascular and biliary variations in turks liver donors: comparison with others.

ISRN Surg 2011 28;2011:367083. Epub 2011 Aug 28.

Department of General Surgery, Manisa Merkezefendi State Hospital, 45000 Manisa, Turkey.

Objective. To evaluate liver anatomy with a view to access unerring surgery in liver donors. Summary Background Data. Liver transplantation, the unique curative treatment option for end-stage hepatic failure, has become routinely practicable, which was inconceivable in the past. But, the vascular and biliary anatomy of the liver has not been completely disclosed yet. Methods. From 1994 to 2009, we have done a research on 496 liver donors. The data were accumulated and categorized according to the most widely used classification systems. Results. Of 496 liver donors, 393 (79.1%) underwent the right donor hepatectomy, 98 (19.9%) were performed the left lateral segmentectomy, and 5 donors (1%) underwent the left donor hepatectomy surgery. Given the data regarding to 398 liver donors undergone right and left donor hepatectomy, arteries, bile ducts, and portal vein showed classical anatomy in 107 (21.6%) donors. Variations in all three systems were found in 16 donors (3.2%). In the remaining 275 donors (75.2%), anatomical variations were found at either of arterial, biliary, or portal system. Conclusions. Our study could come up to actual estimate in liver anatomy as any of donors have not been removed in our institute due to high hilar dissection technique.
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http://dx.doi.org/10.5402/2011/367083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197254PMC
November 2011

Postoperative gemcitabine alone and concurrent with radiation therapy in locally advanced pancreatic carcinoma.

Tumori 2010 Jul-Aug;96(4):560-7

Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir, Turkey.

Aims And Background: To evaluate the treatment results of gemcitabine alone and concurrent with radiotherapy after R0/R1 resection of locally advanced pancreatic cancer.

Methods And Study Design: From 1999 to 2005, 55 patients with stage II resected pancreatic cancer treated with gemcitabine-based radiochemotherapy were retrospectively evaluated. Initially, one cycle of induction gemcitabine was administered and followed by weekly gemcitabine concurrent with radiotherapy. After the completion of radiochemotherapy, patients received 3 additional courses of gemcitabine.

Results: Thirteen patients were stage IIA and 42 were stage IIB. Forty-six patients (83.6%) had R0 and 9 patients (16.4%) had R1 resection. All of the patients received induction chemotherapy and radiotherapy, all but 3 received concurrent radiochemotherapy, and 46 (84%) patients received maintenance chemotherapy. During induction, concurrent and maintenance phases of the protocol, 11%, 13.5% and 19.5% of the patients had at least one > or = grade 3 toxicity, respectively. Within a median 47 months (range, 34-105) of follow-up, 4 (7.3%) patients had isolated local recurrence, 5 (9%) patients had local recurrence and distant metastases, and 27 (49%) had only distant metastases. Median disease-free survival and overall survival were 13 (range, 4-105) and 19 months (range, 6-105), respectively. In multivariate analysis, nodal stage, AJCC stage and number of lymph nodes dissected were the significant factors affecting disease-free survival whereas Karnofsky performance status was the only significant factor for overall survival.

Conclusions: The prognosis for pancreatic cancer remains poor despite adjuvant radiochemotherapy. More aggressive treatments should be considered in patients with unfavorable prognostic factors.
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November 2010

Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation.

Liver Transpl 2010 May;16(5):621-30

Department of Pathology, Faculty of Medicine, University of Ege, Izmir, Turkey.

Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP-9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty-nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha-fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP-9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large-vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP-9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP-9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP-9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP-9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP-9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP-9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP-9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP-9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail.
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http://dx.doi.org/10.1002/lt.22028DOI Listing
May 2010

Fat replacement of the malignant pancreatic tissue after neoadjuvant therapy.

Int J Clin Oncol 2010 Feb 21;15(1):88-92. Epub 2010 Jan 21.

Department of General Surgery, Ege University School of Medicine, Izmir, Turkey.

Pancreatic lipomatosis is characterized as massive lipid infiltration of the pancreatic tissue. Although its etiology is ill defined; obesity, diabetes mellitus, chronic pancreatitis, hereditary pancreatitis, and conditions that cause pancreatic ductal obstruction, for example tumors and stones, are related to its pathogenesis. Recently, with the increased use of computerized tomography and magnetic resonance imaging, it has become possible to observe the fat replacement of the pancreas. Herein, we report a 60-year-old man complaining of abdominal pain and weight loss. Preoperative work-up revealed a locally advanced (Stage III) pancreatic adenocarcinoma. Multimodal treatment was carried out and a 100% complete response was detected after neoadjuvant therapy. The patient underwent a standard pancreaticoduodenectomy, without complications. The tissue pathology revealed lipomatosis of the pancreas. He was disease-free and symptom-free at 1 year follow-up. To our knowledge, this is the first report in the literature of pancreatic head carcinoma with total fat replacement of the pancreas after neoadjuvant chemoradiotherapy.
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http://dx.doi.org/10.1007/s10147-009-0001-9DOI Listing
February 2010

Infectious complications in pediatric liver transplantation candidates.

Pediatr Transplant 2010 Feb 11;14(1):82-6. Epub 2009 Mar 11.

Faculty of Medicine, Department of Pediatric Gastroenterology, Ege University, Bornova, Izmir, Turkey.

We analyzed infections that occurred within one month prior to LT, identified factors associated with their occurrence and effect of infections on post-transplant mortality. The study group included 40 consecutive children who underwent LT. Sites and types of infection and culture results were recorded prospectively. IID was assessed. Risk factors for the infectious events were analyzed. Forty infection episodes were found in 24 patients (60%); 90% were bacterial, 7.5% fungal, and 2.5% viral. Overall, IID was 38.2 per 1000 patient days. Sites of bacterial infection were urinary tract in 13 events (36.1%) and blood stream in 11 events (30.5%). Bacteremia (culture positive infection episodes) was identified in 19 events (52.7%). Gram-negative isolates were twice as frequent as Gram-positive infections (63.1% vs. 36.9%). Risk factors for the infectious complications were young age, low body weight, prior abdominal surgery, chronic liver disease related to biliary problems, presence of ascites, portal hypertension and cirrhosis, and high PELD score (p < 0.05 for all). Infectious complications in pediatric LT candidates are common. Preventive measures are important not only to reduce the infectious complications but also to prevent the post-operative mortality.
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http://dx.doi.org/10.1111/j.1399-3046.2009.01136.xDOI Listing
February 2010

The effects of the Pringle maneuver on the pancreas: can octreotide be protective?

JOP 2009 May 18;10(3):284-91. Epub 2009 May 18.

Department of General Surgery, Ege University School of Medicine, Izmir, Turkey.

Objective: The aim of this study was to evaluate the negative effects of the Pringle maneuver on pancreatic tissue with respect to the time of performing the maneuver. Moreover, the efficacy of octreotide therapy on pancreatic changes at the time of the Pringle maneuver was assessed.

Animals: Fifty male Wistar Albino rats were randomized into 5 groups.

Design: The groups were formed as follows: Group A: sham operation, Group B: Pringle maneuver for 30 min plus octreotide (PM30-OCT), Group C: Pringle maneuver for 60 min plus octreotide (PM60-OCT) and Group D: Pringle maneuver for 30 min plus 0.9 % saline solution (PM30-SS), Pringle maneuver for 60 min plus 0.9 % saline solution (PM60-SS, Group E).

Main Outcome Measures: Blood samples for the evaluation of both amylase and lipase levels were taken via the portal vein. Levels of glutathione, glutathione reductase, catalase, myeloperoxidase, nitric oxide, xanthine oxidase, malondialdehyde, tumour necrosis factor alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) were assessed in the excised pancreatic tissue.

Results: In the octreotide-treated groups, the catalase level was significantly higher in Group B (PM30-OCT) as compared to Group C (PM60-OCT). Amylase, lipase, NO and IL-1 beta levels were higher in Group C (PM60-OCT). In the saline solution-treated groups, the catalase level was significantly higher in Group E (PM60-SS) than in Group D (PM30-SS) while nitric oxide and glutathione levels were found to be significantly lower in Group E (PM60-SS) than in Group D (PM30-SS). Comparison of those groups using the Pringle maneuver for 30 minutes, the octreotide-treated group (Group B, PM30-OCT) was found to have a higher degree of edematous change than the saline-treated group (Group D, PM30-SS). Among the treatment groups, TNF-alpha expression decreased with increasing occlusion time.

Conclusion: In this study, pancreatic damage and the duration of the Pringle maneuver are directly proportional to each other. Moreover, the administration of octreotide prior to the Pringle maneuver contributed to the pancreatic damage.
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May 2009

Biliary intraductal papillary mucinous neoplasia: three case reports.

Virchows Arch 2009 May 4;454(5):589-94. Epub 2009 Apr 4.

Department of Pathology, Faculty of Medicine, University of Ege, Izmir, Turkey.

Intrahepatic cholangiocarcinoma is subdivided as mass-forming, periductal-infiltrating, and intraductal-growing types. Intraductal-growing type is an entity described in recent years as mucin-producing intrahepatic cholangiocarcinoma or intrahepatic (biliary) intraductal papillary mucinous neoplasia (b-IPMN). b-IPMN is classified as adenoma, borderline tumor, carcinoma in situ, and carcinoma, from benign to malignant. Using a different classification, b-IPMNs are subdivided into intestinal, pancreatobiliary, gastric, or oncocytic based on morphology of the cells forming the lesion and expression of MUC1, MUC2, and MUC5 gene proteins in the mucin family. The clinical and histopathological features of b-IPMN diagnosed in three cases are presented herein. Case 1 was classified as borderline. Case 2 was diagnosed as carcinoma in situ. Case 3 had large invasive areas, and was diagnosed as carcinoma. In all three cases, immunohistochemical investigation revealed MUC1 and MUC5AC to be positive, and MUC2 to be negative. We present herein three cases diagnosed with the clinical and pathological findings of a new entity in the literature, b-IPMN, and we discuss the macroscopic, histological, and immunohistochemical features.
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http://dx.doi.org/10.1007/s00428-009-0767-1DOI Listing
May 2009

Can hyperbaric oxygenation decrease doxorubicin hepatotoxicity and improve regeneration in the injured liver?

J Hepatobiliary Pancreat Surg 2009 17;16(3):346-52. Epub 2009 Mar 17.

Department of General Surgery, Ege University Hospital, 3rd Floor, Bornova, 35100, Izmir, Turkey.

Background/purpose: Portal vein embolization is used in the treatment of hepatocellular cancer, with the purpose of enhancing resectability. However, regeneration is restricted due to hepatocellular injury following chemotherapeutics (e.g. doxorubicin). The aim of this study was to investigate whether hyperbaric oxygenation (HBO) can alleviate the hepatotoxicity of chemotherapy and improve regeneration in the injured liver.

Methods: Rats were allocated to four experimental groups. Group I rats were subjected to right portal vein ligation (RPVL); rats in groups II and III were administered doxorubicin prior to RPVL, with group III rats being additionally exposed to HBO sessions postoperatively; group IV rats was sham-operated. All rats were sacrificed on postoperative day 7, and liver injury was assessed by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Protein synthetic ability was determined based albumin levels and liver regeneration by the mitotic index (MI).

Results: The AST and ALT values of group II rats were significantly higher than those of group I, but not those of group III. Rats treated with doxorubicin and HBO (groups II and III) showed slightly but not significant differences in albumin levels than those subjected to only RPVL or sham-operated. The MI was significantly increased in groups I, II, and III, with the MI of group III rats significantly higher than those of group I rats.

Conclusions: Based on our results, we conclude that HBO treatment has the potential to diminish doxorubicin-related hepatotoxicity and improve regeneration in the injured liver.
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http://dx.doi.org/10.1007/s00534-009-0059-9DOI Listing
August 2009

Liver transplantation for acute liver failure due to toxic agent ingestion in children.

Pediatr Transplant 2009 Dec 6;13(8):1034-40. Epub 2009 Feb 6.

Department of Pediatric Gastroenterology Hepatology and Nutrition, Ege University, Bornova, Izmir, Turkey.

ALF is characterized by sudden onset, impaired liver function, jaundice and encephalopathy, without previous liver disease. We analyzed the patients who underwent LT due to toxic agent induced ALF to raise community awareness about preventing the toxic agent induced ALF. Five children (three boys, two girls) underwent LT due to toxic agent ingestion. Toxic agents were mushroom poisoning (n = 2), Datura stramonium (n = 1), yellow phosphorous (n = 1) and INH (n = 1). On admission, one patient had stage IV, two had stage III and two had stage II hepatic encephalopathy but worsened during the follow-up. One patient had renal failure, and three patients required mechanical ventilation. Three patients underwent LRLT and others from a DD. Post-operative complications were managed by supportive managements successfully, and overall all the patients are alive (100% survival) without any organ sequelae. Although outcome of these patients are excellent, ALF may be prevented in these cases by educating the public about consuming mushrooms and toxic effects of wild plants, prohibiting fireworks and serial liver enzyme measurements after initiating INH.
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http://dx.doi.org/10.1111/j.1399-3046.2008.01119.xDOI Listing
December 2009

A rare cause of recurrent gastrointestinal bleeding: mesenteric hemangioma.

World J Emerg Surg 2009 Jan 29;4. Epub 2009 Jan 29.

Ege University Medical Faculty Department of General Surgery, Organ Transplantation and Research Center, Izmir, Turkey.

Lower gastrointestinal hemorrhage accounts for approximately 20% of gastrointestinal hemorrhage. The most common causes of lower gastrointestinal hemorrhage in adults are diverticular disease, inflammatory bowel disease, benign anorectal diseases, intestinal neoplasias, coagulopathies and arterio-venous malformations. Hemangiomas of gastrointestinal tract are rare. Mesenteric hemangiomas are also extremely rare.We present a 25-year-old female who was admitted to the emergency room with recurrent lower gastrointestinal bleeding. An intraluminal bleeding mass inside the small intestinal segment was detected during explorative laparotomy as the cause of the recurrent lower gastrointestinal bleeding. After partial resection of small bowel segment, the histopathologic examination revealed a cavernous hemagioma of mesenteric origin.Although rare, gastrointestinal hemangioma should be thought in differential diagnosis as a cause of recurrent lower gastrointestinal bleeding.
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http://dx.doi.org/10.1186/1749-7922-4-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654482PMC
January 2009

Surgical management of Mirizzi syndrome.

Turk J Gastroenterol 2008 Dec;19(4):258-63

Departments of General Surgery and Gastroenterology, Ege University, School of Medicine, Izmir.

Background/aims: Mirizzi syndrome is an unusual presentation of prolonged cholelithiasis. This study aimed to analyze the diagnostic methods, operative strategies, and outcome of the surgical treatment of patients with Mirizzi syndrome.

Methods: We retrospectively evaluated the patients with Mirizzi syndrome treated in our General Surgery Clinic. The data collected included demographic variables, clinical presentation, diagnostic methods, surgical procedures, and postoperative complications.

Results: The study included 13 male and 21 female patients, with a mean age of 67.2 years. The incidence of Mirizzi syndrome was determined as 0.6% (34/5632), and type II was more frequently observed (52.9%); no patient was determined as type IV. The incidences of types I and III were 35.2% and 11.7%, respectively. Among the preoperative diagnostic evaluations, ultrasonography was the initial imaging study that was performed in all patients. Computerized tomography, magnetic resonance cholangiopancreatography, and endoscopic retrograde cholangiopancreatography were the other radiological studies. Surgical procedures included cholecystectomy for 83% of the patients with type I. The remaining cases and 14 of the type II patients (77.7%) underwent choledochotomy and T-tube insertion following cholecystectomy. Four of the patients with type II variety and all of the type III patients underwent cholecystectomy and roux-en-Y hepaticojejunostomy. All of the patients had complete recovery, with a morbidity rate of 5.8%, and there was no hospital mortality.

Conclusions: The essential part of the management of patients with Mirizzi syndrome is to determine the best surgical procedure in the preoperative period. In type I patients, simple cholecystectomy is generally enough, but sometimes T-tube insertion may be required, while the cases with types II-IV require more complex surgical approach, such as cholecystectomy and bilioenteric anastomosis. Roux-en-Y hepaticojejunostomy is an appropriate procedure with good outcome.
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December 2008

Management of renal cell carcinoma with intracardiac extension.

J Card Surg 2008 Nov-Dec;23(6):754-8

Department of Cardiovascular Surgery, Ege University Hospital, Bornova, Izmir, Turkey.

Renal cell carcinoma extended to the right atrium was operated by using cardiopulmonary bypass and deep hypothermic circulatory arrest. Hypothermic circulatory arrest provides bloodless surgical field for tumor thrombus removal and adequate visceral and brain protection. The surgical technique that we used in a patient was reported in light of the literature.
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http://dx.doi.org/10.1111/j.1540-8191.2008.00664.xDOI Listing
April 2009

Incidence and diagnosis of active toxoplasma infection among liver transplant recipients in Western Turkey.

Liver Transpl 2008 Oct;14(10):1526-32

Department of Parasitology, Ege University Medical School, Bornova/Izmir, Turkey.

Toxoplasmosis is a serious and potentially life-threatening disease in liver transplant recipients while they are immunosuppressed. We report the clinical and laboratory findings related to active toxoplasma infection associated with 40 immunosuppressed liver transplant procedures that took place over a 12-month period at a major transplant unit in Izmir, Turkey. Twenty-seven (67.5%) of the 40 transplant recipients were found to be seropositive for toxoplasma infection and therefore at risk of reactivated infection. From the serological status of the donors, which was ascertained in 38 of 40 cases, we identified 3 (7.9%) of 38 transplants to be from a seropositive donor to a seronegative recipient. In 10 (26.3%) of 38 transplants, both the donor and recipient were seronegative, and this excluded toxoplasma as a risk. A comparison of real-time polymerase chain reaction (PCR) and nested PCR was undertaken in combination with a range of serological assays (the Sabin-Feldman dye test, enzyme immunoassay immunoglobulin M, and immunosorbent agglutination assay immunoglobulin M). Ethylene diamine tetraacetic acid blood samples from 3 of the 30 recipients at risk from toxoplasma were found positive by PCR, but only 1 of these was found positive in both assays. Among the 3 PCR-positive patients, immunoglobulin M and immunoglobulin G antibody levels increased in only 1 patient. Correlations between symptoms, laboratory findings, and clinical management (use of anti-toxoplasma therapy) are presented. Our findings suggest that toxoplasma presents a significant risk to our liver transplant population and that PCR is a helpful addition in identifying active infections and hence in informing clinical management decisions.
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http://dx.doi.org/10.1002/lt.21558DOI Listing
October 2008

Timing of Roux-en-Y limb reconstruction for pediatric live donor liver transplantation.

Transplantation 2008 May;85(10):1431-5

Ege University School of Medicine, Organ Transplantation and Research Center, Izmir, Turkey.

Background: Roux-en-Y (R-Y) hepaticojejunostomy is usually accepted as the standard method of choice for biliary reconstruction in pediatric cases though the potential risks for gastrointestinal complications are higher. In this study, we examined gastrointestinal complications in pediatric patients by comparing two different strategies of R-Y reconstruction with respect to the portal clampage time.

Methods: Forty-three pediatric recipients who underwent Live Donor Liver Transplantation with R-Y for biliary reconstruction between March 2001 and December 2006 in our transplantation center were divided into two groups regarding the time of dissection and creation of the roux limb. R-Y limb reconstruction was performed before clampage of the portal vein in group A-preclampage group. In group B, because of prolonged catheterization period, R-Y limb was reconstructed after implantation of the graft (Group B- postclampage group).

Results: Overall, seven patients (16%) had gastrointestinal bleeding in the postoperative period, all in group B (0/20 vs. 7/23, P<0.01). One of those three cases who were diagnosed after endoscopy and one another were performed surgical treatment. Although remaining three cases had multiple bleeding episodes but no diagnostic findings by endoscopic/colonoscopic interventions, conservative treatment was successful and therefore, plausible R-Y limb bleeding was considered for these cases. The timing of removal of nasogastric tube and postoperative oral intake were also significantly earlier (P<0.01) in Group A than in Group B.

Conclusion: In Live Donor Liver Transplantation, if recipient team may have enough time until the donor team got ready for the recovery of the graft, dissection and preparation of the R-Y limb should be performed. This approach can be helpful to avoid gastrointestinal complications due to the reconstruction of the R-Y limb.
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http://dx.doi.org/10.1097/TP.0b013e31816f1b17DOI Listing
May 2008

A new technique of biliary reconstruction after "high hilar resection" of hilar cholangiocarcinoma with tumor extension to secondary and tertiary biliary radicals.

Ann Surg Oncol 2008 Jul 3;15(7):1871-9. Epub 2008 May 3.

Organ Transplantation and Research Center, Ege University School of Medicine, Izmir, Turkey.

Background: Radical operation for hilar cholangiocellular carcinoma, including extended hepatic resection, seems to improve prognosis by increasing the surgical curability rate. Nevertheless, high postoperative morbidity and mortality have been reported in patients with obstructive jaundice. We describe the technique of "high hilar resection" and a modification of bilioenteric anastomosis for drainage of the multiple secondary or tertiary biliary radicals.

Methods: Ten patients with advanced hilar cholangiocellular carcinoma underwent a high hilar resection with complete parenchymal preservation, and the biliary drainage was reconstructed by a sheath-to-enteric hepaticojejunostomy. Because of the technical difficulty caused by anastomosis line in the range of the biliary sheath, a modification was performed by dividing the biliary apertures of segments 5 and 4b.

Results: A high hilar resection was successfully performed, and all patients were discharged from the hospital in good condition. No patient died postoperatively. The proximal resection margin was tumor-free in all patients. One patient died after 29 months of peritoneal carcinomatosis. None of the patients developed local recurrence around the hepaticojejunostomy. The remaining nine patients are alive after a mean follow-up of 28.8 months after surgery without any signs of recurrence.

Conclusion: In highly selected patients with advanced hilar cholangiocellular carcinoma, a high hilar resection is technically safe and oncologically justifiable. In combination with our new technique of sheath-to-enteric anastomosis, the patients considerably benefit from the preservation of liver parenchyma with low postoperative morbidity and very short in-hospital stay.
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http://dx.doi.org/10.1245/s10434-008-9926-xDOI Listing
July 2008

The optimal treatment of hydatid cyst of the liver: radical surgery with a significant reduced risk of recurrence.

Turk J Gastroenterol 2008 Mar;19(1):33-9

Department of General Surgery, Ege University, School of Medicine, Izmir.

Background/aims: The management of hydatid cyst of the liver, which is still endemic in Turkey, varies from medical treatment or percutaneous drainage to different surgical procedures. In this study, we aimed to compare the efficacy of radical surgical procedures and conservative interventions with respect to recurrence rates.

Methods: Patients who underwent any type of surgical treatment between March 1994 and March 2007 due to liver cyst hydatid were retrospectively evaluated. Data collection included demographic variables, diagnostic methods, surgical procedures, and morbidity and mortality rates.

Results: 242/258 (93.8%) patients with liver hydatid cyst underwent surgery, and the characteristics of 221 (91.3%) (123 female, 98 male) of these patients matched the criteria of the study. The mean age of the patients was 51 years (18-82 years). The diagnostic methods primarily included abdominal ultrasonography and computed tomography with a rate of 61.8% and magnetic resonance imaging in 12% of the patients. The patients were divided into two groups with respect to the treatment modality: Group A (n=92) - radical surgical treatment and Group B (n=129) - conservative surgery. The overall rate of recurrence was 15.3%. In Group B, this rate was 24% (n=31), whereas only 3.2% of the patients (n=3) in Group A had recurrence in the follow-up (p<0.05). The morbidity rate of the patients who underwent radical surgical modalities was also significantly lower.

Conclusions: Although conservative surgical procedures are considered simpler and safer to perform, the rate of postoperative complications such as biliary fistula, residual cavity and recurrence, and cavity suppuration has been reported to be about 35%. On the other hand, radical surgery can be performed with low risk of recurrence (3.2%). We believe radical surgical procedures present a lower rate of recurrence and less morbidity, and thus should be the surgical treatment of choice for hepatic hydatid disease.
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March 2008

Bimanual 'bi-finger' liver hanging maneuver: an alternative and safe technique for liver hanging.

HPB (Oxford) 2007 ;9(3):195-8

Department of General Surgery, Ege University School of Medicine, Izmir, Turkey.

Background: Currently, a popular method for right hepatectomy is hepatic resection with the liver hanging maneuver. The aim of this study is to present an alternative and safe approach during this maneuver without using any instrument, thus avoiding injury.

Patients And Methods: From March 2005 to April 2006, a bimanual 'bi-finger' liver hanging maneuver (BBLHM) was planned in 22 right hepatectomies and the data were collected prospectively after operation.

Results: BBLHM was performed in 21/22 patients (95%). The maneuver was stopped in one patient, due to manual detection of an accessory hepatic vein during finger dissection in the retrohepatic space. This vein did not allow completion of the BBLHM. The indications for right hepatectomy included 11 primary hepatic tumors (52%), 8 metastatic right hepatic tumors (38%), and 2 hydatid cysts (9%). Intraoperative ultrasound (IOUS) demonstrated the normal anatomical configuration type of the hepatic veins. Bleeding occurred in one patient (4%), which was interrupted with the use of continuous 6/0 polypropylene suture.

Discussion: The most important step during the liver hanging maneuver is to develop the avascular space without any complication. In the present study, the index fingers were used instead of forceps during the blind dissection. BBLHM not only reduced the rate of damage to the hepatic veins but was also predictive for the presence of any accessory vein by its manual detection prior to injury. This maneuver allowed easier clamping of the hepatic veins and controllable hepatic resection. Dissection of retrohepatic space with the BBLHM produces a safer method, using both index fingers instead of a surgical instrument.
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http://dx.doi.org/10.1080/13651820701216208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063600PMC
May 2010

Management of hemorrhage of retro hepatic inferior vena cava injury during piggy-back technique for liver transplantation.

Indian J Surg 2008 Feb 19;70(1):19-24. Epub 2008 Mar 19.

Organ Transplantation and Research Center, Ege University School of Medicine, Izmir, 35100 Turkey.

Background: Injury to large abdominal vessels is still one of the most terrifying results of trauma or intraoperative faults, as the management of the hemorrhage is hardly difficult due to being torrentially and unaware of the proper reparation. The controversial problem is which technique should be preferred in case of injury to RHIVC and how can it be managed with minimal risk.

Patients And Methods: Over two-year period, we retrospectively analyzed the patients who had undergone adult-to-adult liver transplantation and collected data about the injuries to RHIVC during recipient hepatectomy. All patients were treated with the same surgical technique including digital compression and continuous suturing the tear.

Results: Twenty five patients (21 male, 4 female) were detected. The causative factors for end stage liver disease included hepatitis B, hepatitis C with or without hepatocellular carcinoma, autoimmune hepatitis, alcoholic hepatitis, cryptogenic hepatitis, Wilson disease, and nonalcoholic steatohepatitis. Mean diameter of the injury was measured 0.5 cm (range: 0.2-1.6). Only three patients (12%) had more than one injury. Mean amount of blood loss between injury and repair was 130 cc (40-350 cc). There was no operative mortality.

Conclusion: Calmness of the operative team followed by the appropriate surgical approach is the key of the success in case of any injury to RHIVC. Digital compression technique can be enough to prevent massive bleeding and repair the injury tract without any vascular exclusion that may result with serious postoperative complications. We proposed this technique because of its ability by most surgeon and easy to perform in a safe way.
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http://dx.doi.org/10.1007/s12262-008-0004-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3452594PMC
February 2008

A new surgical technique for hepatic vein reconstruction in pediatric live donor liver transplantation.

Pediatr Transplant 2008 Sep 16;12(6):677-81. Epub 2008 Jan 16.

Department of Surgery, Ege University Hospital, Bornova, Izmir, Turkey.

The hepatic venous reconstruction is one of the corner stones of pediatric LDLT. However, problems associated with hepatic venous outflow still remain to be an issue. In this study, we aimed at comparing two methods used in hepatic venous reconstruction. Between November 1999 and December 2006, 61 consecutive left lateral segment pediatric LDLT were performed at Ege University Organ Transplant Center, and two methods were used for hepatic venous reconstruction. In the former group (group 1: 32 patients) continuous anastomosis was performed between the donor LHV and common orifice of the recipient HV. In the later group (group 2: 29 patients), the posterior wall of the anastomosis was sutured continuously while the anterior wall was sutured with interrupted sutures. HV thrombosis was detected in one patient and stenosis was detected in four patients in group 1. No hepatic venous outflow obstruction was detected in group 2 (p < 0.05). In both groups, mortality was not associated with hepatic venous outflow obstruction. As our results indicate, the novel technique used in this study is a simple and safe anastomosis procedure that has contributed into overcoming hepatic venous outflow problems in pediatric LDLT.
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http://dx.doi.org/10.1111/j.1399-3046.2007.00877.xDOI Listing
September 2008

Is it more dangerous to perform inadequate packing?

World J Emerg Surg 2008 Jan 14;3. Epub 2008 Jan 14.

Ege University School of Medicine, Department of General Surgery, Izmir, Turkey.

Peri-hepatic packing procedure, which is the basic damage control technique for the treatment of hepatic hemorrhage, is one of the cornerstones of the surgical strategy for abdominal trauma. The purpose of this study was to evaluate the efficacy of the perihepatic packing procedure by comparing the outcomes of appropriately and inappropriately performed interventions. Trauma patients with liver injury were retrospectively evaluated. The patients who had undergone adequate packing were classified as Group A, and the patients who had undergone inappropriate packing, as Group B. Over a five-year period, nineteen patients underwent perihepatic packing. Thirteen of these patients were referred by other hospitals. Of 13 patients, 9 with inappropriate packing procedure due to insertion of intraabdominal drainage catheter (n=4) and underpacking (n=5) were evaluated in Group B, and the others (n=10) with adequate packing were assessed in Group A. Mean 3 units of blood were transfused in Group A and unpacking procedure was performed in the 24th hour. Only 3 (30%) patients required segment resection with homeostasis, and the mortality rate was 20% (2/10 patients). In Group B, 4 patients required repacking in the first 6 hrs. Mean 8 units of blood were transfused until unpacking procedure. The mortality rate was 44% (4/9 patients). The length of intensive care unit stay and requirement of blood transfusion were statistically significantly lower in Group A (p < 0.05). The mortality rate of this group was also lower. However, the difference between the groups for mortality rates was not statistically significant. This study emphasizes that efficacy of the procedure is one of the determinants that affects the results, and inadequate or inappropriate packing may easily result in poor outcome.
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http://dx.doi.org/10.1186/1749-7922-3-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2263028PMC
January 2008

Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis.

J Gastroenterol Hepatol 2007 Dec;22(12):2130-4

Department of Gastroenterology, Ege University Medical School, Bornova, Izmir, Turkey.

Background: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG.

Method: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients.

Results: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy.

Conclusion: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.
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http://dx.doi.org/10.1111/j.1440-1746.2006.04609.xDOI Listing
December 2007

Living donor liver transplantation for hepatitis B cirrhosis.

J Gastroenterol Hepatol 2007 Dec;22(12):2124-9

Department of Gastroenterology, Ege University Medical School, Bornova, Izmir, Turkey.

Background And Aim: Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection.

Methods: A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir.

Results: In a median follow up of 20 months (range 1-66 months), there was no donor mortality. One-year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft.

Conclusion: The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.
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http://dx.doi.org/10.1111/j.1440-1746.2006.04782.xDOI Listing
December 2007