Effect of ursodeoxycholic acid on liver regeneration capacity after living donor hepatectomy: a prospective, randomized, double-blind clinical trial.

OBJECTIVE: Ursodeoxycholic acid (UDCA) has multiple hepatoprotective activities: it modifies the bile acid pool, decreases levels of endogenous, hydrophobic bile acids while increasing the proportion of nontoxic hydrophilic bile acids. It also has cytoprotective, antiapoptotic, and immunomodulatory properties. The aim of this study was to analyze the effect of postoperative administration of UDCA on liver regeneration capacity. PATIENTS AND METHODS: This is a single-center, prospective, randomized, double-blind study that was carried out in our Liver transplant Institute. Sixty living liver donors (LLDs) who underwent right lobe living donor hepatectomy were divided into two groups using computer-generated random numbers: one group received oral UDCA 500 mg 12 hourly for 7 days (UDCA group; n=30) from the first postoperative day (POD) and the other did not receive UDCA (non-UDCA group; n=30). Both groups were compared in terms of the following parameters: clinical and demographic parameters, liver enzymes (ALT, AST, ALP, GGT, total bilirubin, direct Bilirubin), and INR. RESULTS: The median ages in the UDCA and non-UDCA were 31 years (95% CI for median: 26-38) and 24 years (95% CI for median: 23-29), respectively. Liver function tests showed significant differences at various times within the first seven PODs. The INR was lower in UDCA group patients on POD3 and POD4. However, GGT was significantly lower on POD6 and POD7 for the UDCA group. Total bilirubin was also significantly lower on POD3 for the UDCA group patients, but ALP was lower all from POD1 to POD7. A significant difference was also observed in AST on POD3, POD5 and POD6. CONCLUSIONS: Postoperative administration of oral UDCA significantly improves liver function tests and INR among LLDs.

Vessel sealing system vs. conventional knot-tying for hilar dissection during living donor hepatectomy: a prospective, randomized, double-blinded study.

OBJECTIVE: LT has become the gold standard treatment for many liver diseases, especially chronic liver disease. A commonly seen problem, even in donors who do not develop any major complications after living donor hepatectomy (LDH), is the persistent drainage of lymphatic fluid from the hepatectomy site drain, which causes extensive hospitalization and consequent loss to the workforce. To our knowledge, no study has yet been published comparing LVSS and conventional knot-tying methods for hilar dissection, which is an important stage of the LDH procedure. We aimed to prospectively compare the outcomes of these two treatment methods. PATIENTS AND METHODS: Donor candidates were divided into two groups: conventional suture tying (conventional knot tying group; n=34) and Ligasure vessel sealing system (LVSS; n=34). A simple randomization method of drawing lots was used to assign the patients to each group. The following parameters were analyzed for all patients: age, gender, BMI, duration of surgery, postoperative drainage amounts, drain removal times and complications, length of hospital stay, morbidity, and mortality. RESULTS: There were no significant differences in terms of operative times, postoperative drainage levels, hospital stay or drain removal times. CONCLUSIONS: In this study, the use of LVSS in LDH was found to be safe, although it did not offer any advantage over conventional methods. Nevertheless, it seems probable that the use of LVSS could reduce operative time and amounts of lymphatic drainage, especially in centers with minimal experience with LDH, such as new LDH centers.

Hepatitis B/D-Related Hepatocellular Carcinoma. A Clinical Literature Review.

AIM: Given the current literature data, this article aims to shed light on the epidemiological and clinical effects of HBV, as well as its impact on the development of hepatocellular carcinoma (HCC). METHODS: A review of the English language literature based on a MEDLINE (PubMed) database was searched. The keywords were cirrhosis, hepatocellular carcinoma, epidemiology, hepatitis delta virus, hepatitis B virus, and co-infection. All references from retrieved papers were reviewed systematically to find additional collection of reports. RESULTS: The study has broadly confirmed the contribution of HDV viremia to liver disease and cirrhosis. However, uncertainty over the mechanism of action on HCC development remains. As the recent data has demonstrated, the HCC-HDV has a unique molecular profile which is distinct from that of HBV-HCC. CONCLUSION: Owing to the dependence of HDV on HBV, it is not clear whether HCC is a consequence of the cumulative effect of both HBV and HDV, an effect of the underlying cirrhosis, or a direct oncogenic effect of HDV. Many questions concerning the oncogenic role of HDV remain unanswered. To better understand the role of HDV in carcinogenesis, studies at the molecular level that consider genotype differences should be increased. Multicenter, high-volume, and prospective studies that compare HBV/HDV co-infected and HBV-infected individuals will be pivotal in determining the oncogenic role of HDV.

Is paracetamol responsible for fatal acute liver failure in pediatric patients after hip dysplasia surgery?

OBJECTIVE: It is well known that local complications, such as avascular necrosis and arthrosis can develop after surgery for developmental dysplasia of the hip (DDH). Thus far, systemic complications that may develop in such cases have not been identified in the literature. This study is the first case series to evaluate acute liver failure (ALF) development after DDH surgery in pediatric patients. PATIENTS AND METHODS: Six patients, five female and one male, who underwent DDH surgery were selected for this study. Perioperative fasting time, laboratory values, treatments, histopathological evaluations, and prognoses after ALF in these patients were evaluated retrospectively. RESULTS: All the patients were administered paracetamol and sevoflurane in therapeutic doses. The patients were referred postoperatively to our pediatric emergency department after 5 ± 1.67 days (range = 3-7 days) on average. The average perioperative fasting time was 9.3 ± 0.82 hours (range = 8-10 hours). Due to the very high aminotransferases and use of paracetamol, intravenous N-acetylcysteine was administered alongside supportive treatments to all the patients. After liver transplantation, two of three patients with grade 3 encephalopathy, died in the early postoperative period. Histopathological evaluations of the three patients' explants were compatible with toxic hepatitis due to paracetamol. CONCLUSIONS: Paracetamol is a commonly used analgesic after pediatric surgery. The therapeutic dose of paracetamol remains uncertain in children who have been fasting for a long time and have been exposed to hepatotoxic drugs due to previous surgery. In conclusion, caution should be exercised in the use of paracetamol in children with DDH who will undergo surgery, and careful perioperative clinical and laboratory monitoring for ALF is essential.

Aborted donor hepatectomy in living donor liver transplantation: lessons learned.

BACKGROUND: Aborted donor hepatectomy (ADH) during any stage of living donor hepatectomy (LDH) is a rare event. We describe our experience and discuss the lessons from these events. METHODS: From September 2005 to January 2019, 77 of 2 031 (3.79%) LDH were aborted at various stages of surgical procedure due to donor or recipient related reasons. Demographic and clinical data of aborted donor candidates and the clinical course of their potential recipients were analysed. RESULTS: LDH of 77 donor candidates was aborted due to donor (n = 53) or recipient (n = 24) related reasons. The most common donor related reason was the quality of liver parenchyma (n = 31). The most common recipient related reason was haemodynamic instability (n = 11). Twenty-three recipients underwent either living donor liver transplantation (LDLT) (n = 21) or deceased donor liver transplantation (DDLT) (n = 2) at a median of 6 days following ADH. In one aborted due to a donor reason and two aborted for recipient reasons, LDLT was performed using the same donor candidates. Thirty-six recipients had no liver transplantation (LT) and died a median of 17.5 days following ADH. CONCLUSIONS: We believe that ADH will decrease with experience and meticulous preoperative clinical and radiological evaluations. Abandoning the donor hepatectomy is always a valid option at any stage of the surgery when the unexpected is encountered.

Effect of a honey and arginine-glutamine-hydroxymethylbutyrate mixture on the healing of colon anastomosis in rats immunosuppressed with tacrolimus.

We compared the effect of honey and a mixture of arginine-glutamine-hydroxymethylbutyrate (AGHMB) on healing of a descending colon anastomosis in rats that were immunosuppressed with tacrolimus (Tac). Sprague-Dawley rats were divided into four groups: untreated control, Tac, Tac + honey and Tac + AGHMB. Colon resection and anastomosis were performed on day 14 and re-laparotomy was performed on the day 21 of the study. Anastomotic bursting pressure, macroscopic adhesion score, weekly body weight changes, histopathological features and immunohistochemical staining of TGF-ß1 were determined for all groups. We found no significant difference in anastomotic bursting pressure among the experimental groups. We found significant weekly increases in body weight for the Tac + honey group. We found no significant difference in the weekly body weight measurements for the Tac + AGHMB group. We found significant increases in TGF-ß1 expression in the Tac + honey group compared to the control and Tac groups. No significant differences in inflammatory cell infiltration, fibroblast proliferation or collagen deposition were found between the Tac + honey and Tac + AGHMB groups; however, a significant difference in neovascularization between these groups was found. Neovascularization in the Tac + honey group was significantly greater than for the Tac + AGHMB group. We found that both honey and the AGHMB mixture were beneficial for anastomotic wound healing in rats that were immunosuppressed using Tac.

Significance and outcome of living-donor liver transplantation in acute mushroom intoxication.

INTRODUCTION: Mushroom intoxication (MT) can lead to acute liver injury which may result in Mushroom intoxication-related liver failure (M-ALF) requiring liver transplantation (LT). In the present study, we want to share the experience of our institute regarding living-donor LT (LDLT) due to mushroom poisoning. AIM: The aim of this study is to identify the predictors of poor prognosis in patients with ALF secondary to mushroom intoxication requiring LDLT. MATERIALS AND METHODS: All patients with MT between 2008 and 2016 were evaluated. Demographics, symptoms, interval between symptoms and admission to our institute, laboratory data, model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) scores, clinical course, and outcomes of supportive therapy and LT were evaluated. There were two groups in the study: Group A = responsive to supportive therapy (n = 9) versus Group B = unresponsive to supportive therapy (n = 9). RESULTS: During the study, a total of 18 patients were admitted with M-ALF. Twelve (66.7%) of them were female, and the mean age was 39.9 ± 18.2 years. All of the nine patients in Group A fully recovered with supportive therapy. In Group B, one patient died during waiting period for LT and 8 patients received LDLT LDLT. Three of the eight patients who were transplanted died in the postoperative early period within postoperative 5 days. The patients in Group B had significantly higher MELD/PELD scores and encephalopathy rate than in Group A (P < 0.05). International normalized ratio (INR), bilirubin, ammonium levels, and platelet count were significantly different between groups (P < 0.05). The patients in Group B had significantly longer interval before admission to our institute (P < 0.05). CONCLUSION: The presence of encephalopathy, higher MELD/PELD, INR, bilirubin, ammonium levels, and lower platelet count was related to poor prognosis in MT. LDLT provides a good therapeutic option in patients with M-ALF. The time is a crucial factor in successful treatment of MT. Early admission to a tertiary referral center with expertise in LT results in a better prognosis and increased survival following M-ALF.

Pregnancy After Liver Transplantation: Risks and Outcomes.

OBJECTIVE: The aim of this study was to evaluate the outcomes of liver transplant recipients who became pregnant after transplantation. METHODS: The clinical data of all patients who underwent liver transplantation between January 2007 and December 2016 in our liver transplantation institute were reviewed. The following data were analyzed: indications for transplantation, recipient age at the beginning of pregnancy, the interval between transplantation and pregnancy, maternal and fetal complications, type of delivery, the health condition of neonates, and modifications in immunosuppressive therapy. RESULTS: During the study period, 1890 patients underwent liver transplantation. There were 185 women (9.8%) in childbearing age (15-45 years old), and 18 (9.7%) of them became pregnant during the study period. There were a total of 26 pregnancies. The mean age of patients at the time of operation was 25.3 ± 5.2 years, and the mean interval between operation and conception was 32.7 ± 15.3 months. Seventeen pregnancies (65.4%) ended in a live birth in the study. Six pregnancies (23%) resulted with no maternal or fetal complications. The most frequent maternal complication during pregnancy was pregnancy-induced hypertension (n = 3; 16.6%). CONCLUSIONS: Despite advances in immunosuppressive therapy and increasing experience in the management of these patients, pregnancies in liver transplant recipients are still more risky than in the general population for both the mother and the fetus. Thus, the issues related to fertility should be comprehensively discussed with the patients and their partners, preferably before transplantation, and pregnancies in liver transplant recipients should be followed up more carefully by a multidisciplinary team.

Telescopic Biliary Reconstruction in Patients Undergoing Liver Transplantation With 1-Year Follow-up.

BACKGROUND: Biliary complications are important during liver transplantation because of their effect on recipient and graft survival, incidence, and the long treatment period. These complications are associated with 50% morbidity and 30% mortality rates in recent studies. One of the most important reasons for biliary anastomosis complications is arterial ischemia. We present the results of our telescopic biliary anastomosis technique performed on the mucosa of the main biliary duct. PATIENTS AND METHODS: Fifty-six cases of telescopic biliary reconstruction were performed in 203 patients during 2015. Fifty cases and 52 patients who underwent standard reconstruction were chosen and compared. All patients had been scanned retrospectively. Statistical analyses were conducted with χ2 and Mann-Whitney U tests for the complications that occurred during the first 3 months. A P value <.05 was considered significant. RESULTS: No clinical or demographic differences were detected between the groups. About 90% of both groups were living donor liver transplantation cases. Five (10%) anastomotic leaks occurred in telescopic reconstruction group (n = 50), and 13 (25%) occurred in the standard reconstruction group (n = 52; P < .05). CONCLUSION: The arterial blood supply is better if the biliary anastomosis is made on the mucosal side of the main biliary duct. Early period anastomotic leaks may decrease significantly.

Surgical Treatment of Portal Vein Thrombosis With the Use of Cadaveric Venous Patch After Donor Hepatectomy: A Case Report.

Live donors should be the priority of transplant professionals to prevent surgery-related morbidity and mortality during living-donor liver transplantation. Portal vein thrombosis after donor hepatectomy is an important complication which can be prevented by careful preoperative as well as perioperative evaluation. If portal vein thrombus occurs after donor hepatectomy, anticoagulation and surgical thrombectomy and even portal vein reconstruction should be kept in mind. Cadaveric venous patches can be used for the reconstruction of narrowed and angulated portal veins. Here we report the surgical treatment of a donor with a cadaveric venous patch who developed portal vein thrombosis after donor hepatectomy.

Progressive Multifocal Leukoencephalopathy after Three Consecutive Liver Transplantations.

Progressive multifocal leukoencephalopathy (PML) is a lytic infection of the central nervous system caused by the reactivation of John Cunningham Virus (JCV) in severely immunosuppressed patients. Occurrence of PML after solid organ transplantations, especially after liver transplantation, is rare. If a patient has poor prognostic factors such as atypical radiological involvements or high viral load in cerebrospinal fluid (CSF), overall survival rates could be poor. Herein, we report on a patients who underwent liver transplantation three times and developed PML with unexpected radiological findings; he was also positive for JCV DNA with a high viral load. Although there are limited data about efficacy of cytarabine against JCV, it was given to the patient for five days. Despite the initiation of cytarabine and complete cessation of the immunosuppressive therapy, we lost the patient, unfortunately.

Evaluation of Potential Donors in Living Donor Liver Transplantation.

INTRODUCTION: Correct donor selection in living donor liver transplantation (LDLT) is essential not only to decrease the risks of complications for the donors but also to increase the survival of both the graft and the recipient. Knowing their most frequent reasons of donor elimination is so important for transplantation centers to gain time. In this study we evaluated the effectiveness of potential donors in LDLT and studied the reasons for nonmaturation of potential liver donors at our transplantation center. PATIENTS AND METHODS: We studied the outcomes of 342 potential living donor candidates for 161 recipient candidates for liver transplantation between January 2013 and June 2014. Donor candidates' gender, age, body mass index (BMI), relationship with recipient, and causes of exclusion were recorded. RESULTS: Among 161 recipients, 96 had a LDLT and 7 had cadaveric liver transplantation. Twelve of the 342 potential donors did not complete their evaluation; 106 of the remaining 330 donor candidates were accepted as suitable for donation (32%) but 10 of these were excluded preoperatively. The main reasons for unsuitability for liver donation were small remnant liver size (43%) and fatty changes of the liver (38.4%). Other reasons were arterial anatomic variations, ABO incompatibility, and Gilbert syndrome. Only 96 of the candidates (29% of the 330 candidates who completed the evaluation) underwent donation. Effective donors were 29% of potential and 90.5% of suitable donors. CONCLUSIONS: In our center, 106 of 330 (32%) donor candidates were suitable for donation and the main reasons for unsuitability for liver donation were small remnant liver size and fatty changes of the liver.

Acquired IgE-mediated food allergy after liver transplantation in children.

BACKGROUND: In recent years, the number of studies regarding newly-diagnosed food allergies after liver transplantation has been increasing. In this study, we aimed to investigate the frequency, aetiology, risk factors, and severity of IgE-mediated food allergies after liver transplantation in children. METHODS: Paediatric patients who underwent liver transplantation at Inonu University Faculty of Medicine, Organ Transplantation Institute were included in the study. RESULTS: Forty-nine paediatric patients were enrolled in the study; 26 (53.1%) were female, the median age at transplantation was five years, and median follow-up time after transplantation was 16 months. Six patients (12.2%) developed IgE-mediated food allergies after transplantation; four had urticaria and/or angio-oedema and two developed anaphylaxis after food intake. Patients with and without IgE-mediated food allergies were similar in terms of sex, age at transplantation, comorbid atopic disease, immunosuppressant therapy with tacrolimus, and blood tacrolimus level (p>0.05 for each). Serum total IgE levels ≥100 IU/mL (p=0.02) and peripheral eosinophilia (p=0.026) were more common in the patients who developed IgE-mediated food allergies. In five of the six patients who developed IgE-mediated food allergies, reaction occurred within the first year after transplantation; the risk of developing a reaction was 2.7 times higher within the first year after transplantation than in subsequent years (95% CI, 1.546-4.914; p=0.026). No Epstein-Barr virus or cytomegalovirus infections were detected in any of the patients who developed IgE-mediated food allergies after liver transplantation. CONCLUSION: The risk of developing IgE-mediated food allergies is approximately three times higher within the first year after transplantation than in subsequent years.