Tigecycline-Associated Hepatic Steatosis After Liver Transplant: A Case Report.

Tigecycline is a parenteral glycycline antibiotic that is used to treat severe infections caused by susceptible organisms, butitis also associated with hepatotoxicity. We present 2 similar patients with hepatic steatosis possibly associated with early tigecycline after transplant. In the first case, a 61-year-old woman underwent liver transplant for acute severe hepatitis; 6 days posttransplant, because of nonroutine resistant fever, the patient received tigecycline combined with daptomycin. Retransplant was applied to the patient on day 12 posttransplant because of acute liver failure secondary to hepatic vein thrombosis. After retransplant, biochemical levels gradually increased, exceeding the upper limit of normal. In liver biopsy, the patient had macrovesicular steatosis in 70% to 80% ofthe parenchyma. In the second case, a 53-yearold woman underwent liver transplant for liver cirrhosis. Tigecycline was added to the treatment because of recurrent fever on day 6 after transplant, with treatment also comprising piperacillin-tazobactam and meropenem. On day 15 of the patient's tigecycline treatment, her liver function tests were elevated. In liver biopsy, the patient had 30% to 40% macrovesicular steatosis and canalicular cholestasis in the parenchyma, especially in zone 3. Reports of hepatic steatosis associated with early tigecycline after transplant are quite new to the literature.

Effect of Pretransplant Sarcopenia on Mortality in Liver Transplant Recipients.

OBJECTIVES: Sarcopenia is an important metabolic disorder associated with end-stage liver disease and is an independent predictor of mortality in liver transplant candidates. We evaluated effects of pretransplant muscle mass, muscle quality, and visceral adipose tissue on mortality after liver transplant. MATERIALS AND METHODS: For 2015-2020, we included 65 liver transplant recipients whose records contained pretransplant liver computed tomography images. We calculated skeletal muscle mass index (muscle tissue area in centimeters squared divided by height in meters squared), visceral-to-subcutaneous fat ratio (visceral adiposity indicator), and intramuscular adipose tissue content ratio (muscle quality indicator). RESULTS: Median age was 55 years (IQR, 45-63 years), and 48 (73.8%) patients were men. During follow-up, 53 (81.5%) study group patients survived; mean survival time was 71.73 ± 3.81 months. The deceased patient group had a statistically higher pretransplant visceral-to-subcutaneous fat ratio than the survival group (P = .046). Survival was 100% for 1 positive indicator, 86.2% for 2 positive indicators, and 70.4% for 3 positive indicators (P = .096). Positive correlation was confirmed between pretransplant skeletal muscle mass index and age (P = .043) and pretransplant body mass index (weight in kilograms divided by height in meters squared) (P < .001). There was a moderate positive correlation between pretransplant intramuscular adipose tissue content ratio and age (R = 0.529, P ≤ .001) and a weak positive correlation with pretransplant body mass index (R = 0.361, P = .003). Furthermore, pretransplant visceral- tosubcutaneous fat ratio showed a weak positive correlation with age (R = 0.306, P = .013) and a weak negative correlation with the Model for End-Stage Liver Disease score (R = -0.301, P = .016). CONCLUSIONS: Pretransplant sarcopenia is an important indicator to predict mortality and morbidity in posttransplant follow-up. Visceral-to-subcutaneous fat ratio is an important parameter to evaluate sarcopenia in liver transplant patients.

Biliary Complications in Living Liver Donors After Donor Hepatectomy: A Single-Center Experience.

OBJECTIVES: The most frequent postoperative morbidity following living donor liver transplant is biliary complications, which can happen for both anatomical and procedural reasons. MATERIALS AND METHODS: We conducted a retrospective analysis of 104 patients who were living liver donors undergoing hepatectomy from January 2011 to April 2022. We evaluated all perioperative finding such as age, sex, remnant liver volume, biliary anatomy, theduration of operation time and hospitalization, and blood loss. RESULTS: Clavien-Dindo classification grade III complications were observed in 24% of all donors, with rate of biliary complications of 7.6% (n = 8). All biliary complications were typified as biliary leakage, and an endoscopic retrograde cholangiopancreatography procedure was performed for 5 patients. We analyzed the clinical and surgical features and discovered that the duration of hospitalization was longer in the biliary leakage group than the group without leakage (15.7 ± 5.8 days vs. 30.8 ± 9.3 days, respectively; P < .08). There was no significant statistical relationship between age, the duration of operation time, intraoperative blood loss, and remnant liver volume versus biliary leakage (P = .074, P = .217, P = .219, and P = .363, respectively). CONCLUSIONS: Early detection and treatment of complications are ensured during the perioperative process by carefuldonor selection andaccurate identification of the patient atrisk for biliary complications.

Investigating Whether the Severity of SARS-CoV-2 Infection Is Higher in Liver Transplant Recipients: A Single-Center Experience.

OBJECTIVES: Liver transplant recipients have been reported to be a high-risk population for severe disease from COVID-19 infection. In this crosssectional, single-center study, we investigated whether liver transplant increased the risk of death and severe disease in patients with SARS-CoV-2 infection. MATERIALS AND METHODS: We collected data and serum anti-SARS-CoV-2 immunoglobulin M and immunoglobulin G results of 91 liver transplant recipients seen from September 2020 to March 2021. Liver transplant recipients were enrolled during presentation for scheduled routine follow-up visits. All patients who required serum anti-SARS-CoV-2 immunoglobulin M and immunoglobulin G tests completed a ques-tionnaire on clinical symptoms during the previous 6 months. RESULTS: Among the 91 patients with SARS-CoV-2 immunoglobulin M and G results, 7 patients had a known history of symptomatic COVID-19 during the previous 6 months. Of the 84 participants who completed the questionnaire, 21 (25%) had positive anti-SARS-CoV-2 immunoglobulin M and G results. These 21 patients also received COVID-19 polymerase chain reaction tests, which were negative in all 21 patients. Overall, only 7 patients stated that they experienced flu-like upper respiratory tract infection symptoms or diarrhea. CONCLUSIONS: We documented past SARS-CoV-2 infection in only 25% of our outpatient liver transplant recipients, and most were asymptomatic. We found no significant relationship between symptoms and seropositivity for SARS-CoV-2.

Complete Recovery After Immunosuppressive Treatment Change in a Patient With Posttransplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative diseases are a rare but important cause of morbidity and mortality secondary to immunosuppression after solid-organ or bone marrow transplant. Generally, posttransplant lymphoproliferative diseases develop in the first 2 years after transplant, when immunosuppressive therapy is the most intense. Change or reduction in immunosup - pressive treatment is an option for treatment of posttransplant lymphoproliferative diseases. We evaluated the treatment of a patient with posttransplant lymphoproliferative disease after liver transplant. A 64-year-old man underwent liver transplant from a living donor (the patient's son) in 2011 to treat hepatocellular cancer secondary to chronic hepatitis B. Tacrolimus and mycophenolate mofetil were used for immunosuppression through 9 years after liver transplant. In the abdominal computed tomography performed in response to abdominal pain during follow-up in March 2019, multiple solid lesions were observed. A liver biopsy revealed posttransplant lymphoproliferative disease with diffuse large B-cell lymphoma. Fluorine-18 positron emission tomography/computed tomography imaging of the patient showed no pathology in favor of primary lymphoproliferative disease. Mycophenolate mofetil and tacrolimus treatment was changed to everolimus. In the follow-up dynamic magnetic resonance imaging examination that was performed at 3 months after treatment change, we observed that the lesion at liver segment 6 had regressed to 30 mm and several lesions with similar features were observed in the right lobe of the liver. Additional liver biopsy results were compatible with complete remission. The patient's clinical symptoms had fully regressed at 18 months after the diagnosis of PTLD, at the time of this writing. Ongoing radiological and clinical follow-up has shown complete remission. Change from calcineurin treatment to treatment with an inhibitor of the mechanistic target of rapamycin may be an essential and new option for treatment of posttransplant lymphoproliferative disease after liver transplant.

Multidrug-Resistant Infections After Liver Transplantation, Etiology and Risk Factors: A Single-Center Experience.

OBJECTIVES: Patients undergoing liver transplant are at an increased risk of morbidity and mortality due to the development of infections. We aimed to evaluate the risk factors affecting the incidence of infectious diseases after liver transplant and to present the epidemiological data. MATERIALS AND METHODS: We investigated patients aged ≥18 years who underwent liver transplant between 2012 and 2020 at our center. We collected infections, causative microorganisms, and antibacterial resistance patterns seen during the first 6 months posttransplant. Risk factors affecting the development of infectious diseases were also analyzed and evaluated. RESULTS: Of 112 patients included in our study, 76 (67.9%) were men, and the median age was 50 years (range, 20-66 years). Within month 1 and month 6 after transplant, at least 1 episode of infection occurred in 67 (59.8%) and 80 (71.4%) patients, respectively. Bacterial infections were the most common type (n = 78, 95.1%), followed by fungal (n = 2, 2.4%) and viral (n = 2, 2.4%) infections. The rate of multidrug resistance in bacterial infections was high (n = 38, 52.7%) and was also a risk factor for mortality in the first 6 months after transplant (P < .001). Pretransplant values of international normalized ratio, creatinine, bilirubin, and posttransplant intensive care unit stay, as well as the presence of encephalopathy, were shown to increase the risk of infection after transplant. CONCLUSIONS: Multidrug-resistant bacterial infections are a significant risk factor for mortality in liver transplant patients. Many risk factors that contribute to the development of infections aftertransplant have been included in prognostic scoring systems of liver failure. Consequently, the severity of end-stage liver failure is directly related to the risk of posttransplant infections.

COVID-19 infection frequency and clinical course in patients with liver transplantation: Results of a single transplant center in Türkiye.

Objectives: In this paper, it was tried to determine the incidence of COVID-19, course of the disease, and mortality rate in liver transplant patients by evaluating all patients operated on in our center. In addition, the results of liver transplantation performed in our center during the pandemic period were also presented. Material and Methods: All patients who had undergone liver transplantation in our liver transplant center were questioned about their history of COVID-19 either at their routine controls in the clinic or by phone interview. Results: Our liver transplant unit had 195 registered liver transplantation patients (2002-2020), and 142 of these were still alive and under follow-up. During the pandemic period, 80 patients referred to our outpatient clinic for follow-up, and their records were evaluated retrospectively in January 2021. Among 142 liver transplant patients, a total of 18 (12.6%) COVID-19 patients were identified. While 13 of these patients were males, mean age of the patients at the time of interviews was 48.8 years (22-65 years). Nine of the patients had living donor liver transplant, and the rest had cadaveric liver transplant. The most common COVID-19 associated symptom in the patients was fever. During the pandemic period, 12 liver transplant operations were performed in our center. Nine of them were living donor liver transplantation and the remainder were cadaveric liver transplantations. Two of our patients got COVID-19 positive during this period. One of them who was transplanted after COVID treatment was followed-up in intesive care for a long time and was lost not related to COVID-19. Conclusion: The incidence of COVID-19 is higher in liver transplant patients than in the general population. Nonetheless, mortality rates are low. During the pandemic period, liver transplantation can be continued by following general precautions.

Evaluation of epicardial adipose tissue and carotid intima-media thickness as a marker of atherosclerosis in patients with inflammatory bowel disease.

BACKGROUND AND AIM: this study aimed to compare carotid intima media (CIMT) and epicardial adipose tissue (EAT) measurements, which are considered as markers for the detection of early atherosclerosis in healthy controls and inflammatory bowel disease (IBD) cases. METHODS: a total of 60 IBD patients (25 Crohn's disease and 35 ulcerative colitis) and 60 healthy patients (as a control group) were included in the study. The measurements of CIMT and EAT were performed using echocardiography and ultrasonography, respectively. Statistical analysis was used to determine the relationship between the parameters. RESULTS: the thickness of bilateral (right and left) CIMT and EAT were significantly higher in IBD than in the control group (p < 0.05). There was a positive correlation between EAT and bilateral (right and left) CIMT in IBD patients (p < 0.05). CONCLUSION: IBD is associated with an increased thickness of EAT and CIMT. Chronic inflammation in IBD may increase the risk of atherosclerotic heart disease. Thus, only measuring the thickness of EAT and CIMT can be used as an objective, easy, simple, affordable, non-invasive and accessible assessment method in order to screen for this risk.

Bezoar in upper gastrointestinal endoscopy: A single center experience.

BACKGROUND/AIMS: We aimed to investigate the association of bezoar with endoscopic findings, risk factors for bezoar occurrence, and the success of endoscopic treatment in a tertiary center. MATERIALS AND METHODS: This retrospective study was conducted between January 2012 and December 2015. Overall, 8200 endoscopy records were examined and 66 patients with bezoar were included in the study. RESULTS: We enrolled 29 (44%) female and 37 (56%) male patients in this study. The mean age of the patients was 63±9.4 years. The most frequent risk factors were history of gastrointestinal surgery (23%), diabetes mellitus (17%), trichophagia (9%), and anxiety disorder (6%). Gastric ulcer, duodenal ulcer, erosive gastritis, and reflux esophagitis were present in 27%, 11%, 20%, and 23% of the patients, respectively. While bezoars were most commonly observed in the stomach (70%), the majority of them were phytobezoars (91%). The mean number of interventions for each patient was 1.5 (range, 1-6). Endoscopy was successful in removing bezoars in 86.5% of the patients. Among those referred to surgery, seven patients underwent gastrostomy (10.5%); one (1.5%) patient underwent gastroenterostomy because of concomitant pyloric stenosis; and one (1.5%) patient underwent fistula repair surgery due to the development of duodenal fistula caused by bezoar. CONCLUSION: The findings of this study indicated that bezoars are more common among subjects with history of gastrointestinal surgery, diabetes mellitus, or psychiatric disorders; bezoars are closely related to peptic ulcer and reflux esophagitis; and they can be successfully treated with endoscopy.

A bioactive product lipoxin A4 attenuates liver fibrosis in an experimental model by regulating immune response and modulating the expression of regeneration genes.

BACKGROUND/AIMS: Lipoxin A4 (LXA4), an anti-inflammatory lipid mediator, regulates leukocyte cellular activity and activates gene transcription. The therapeutic effect of LXA4 on liver fibrosis and its mechanism on the immune system are largely unknown. Because the regenerative capacity of hepatocytes in acute and chronic liver failure models of mouse increases by silencing MKK4, we aimed to investigate the effect of parenteral administration of LXA4 on the genes responsible for regeneration of liver, namely MKK4, MKK7, and ATF2, and visualize the therapeutic effects in an experimental model. MATERIALS AND METHODS: Fibrosis was induced in mice by administration of thioacetamide (TAA). LXA4 was administered during the last two weeks of fibrosis induction. The fibrosis level was measured by Knodell scoring. The liver function was measured by analyzing serum ALT, AST, and AP levels. Expression levels of genes responsible for liver fibrosis (TGF-α) and cell regeneration (MKK4, MKK7, and ATF2) have been measured by RT-PCR analysis. Inflammatory and anti-inflammatory cytokine levels were measured in serum samples and liver homogenates by Enzyme Linked Immunosorbent Assay (ELISA). Ultrathin sections were examined using a transmission electron microscope and analyzed. RESULTS: We observed significant healing in liver of the LXA4-treated group, histologically. This finding was in parallel with reduction of serum ALT, AST, but not AP levels. TGF-α and MKK4 expressions were significantly reduced in the LXA4-treated group. Administration of LXA4 caused significant elevation of IL-10 in systemic circulation; however, that elevation was not detected in liver homogenates. Nevertheless, significant reductions in TNF-α and IL-17 have been observed. CONCLUSION: The anti-inflammatory effect of LXA4 maintains the regenerative capacity of liver during fibrosis in an experimental liver fibrosis model. LXA4 may be therapeutically beneficial in liver fibrosis.

Endosonogragphic features of lesions suggesting gastricectopic pancreas: experience of a single tertiary center.

BACKGROUND/AIM: We aimed to present the endoscopic ultrasound (EUS) features of gastric lesions suggesting gastric ectopic pancreas during upper gastrointestinal endoscopy that were diagnosed in our gastroenterology unit, which is a tertiary center for endoscopic procedures in Turkey. MATERIALS AND METHODS: The data of patients who underwent upper gastrointestinal EUS in our center between April 2012 and July 2014 were retrospectively analyzed. RESULTS: All of the lesions suggesting gastric ectopic pancreas were localized in the gastric antrum. Thirty-six of 44 lesions (81.1%) showed central dimpling. Lesion borders were shown to be definite in 10 (22.7%) lesions, whereas the borders of 34 lesions (77.3%) were indefinite. Thirty-nine lesions (88.6%) had heterogeneous and 5 lesions (11.4%) had homogeneous echo patterns; whereas 29 lesions (65.9%) were hypoechoic, 9 lesions (20.5%) were hyperechoic and 6 lesions (13.6%) had mixed echogenicity. Forty-two lesions (95.5%) were shown to affect only a single sonographic layer of the gastric wall. CONCLUSION: EUS features of lesions that strongly suggest gastric ectopic pancreas endoscopically, without any histopathological evidence and without either endoscopic or surgical resection, are as follows: indefinite border appearance, minimal heterogeneous hypoisoechoic echo pattern, existence of anechoic duct-like structures inside the lesion, common localization in the submucosal layer, and existence of umbilication.

Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis.

BACKGROUND/AIMS: Because of several limitations and complications of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells for liver diseases. In this study, we assessed the impact of autologous mesenchymal stem cell transplantation on liver tissue and liver chemistry. MATERIALS AND METHODS: Twenty-five patients with biopsy-proven liver cirrhosis were enrolled in the study. Patients received 1×106 autologous mesenchymal stem cells/kg via a peripheral vein. Biochemical parameters were checked monthly. Periodical radiological screening and liver biopsies before mesenchymal stem cell transplantation were performed after 6 months. Liver specimens were assessed by a pathologist. RESULTS: No side effect was observed and the mesenchymal stem cell transplantation procedure was well tolerated. Twelve patients completed the study. In 8 patients, improvements in Model for End-Stage Liver Disease (MELD) scores were observed. Serum albumin levels markedly increased in the third month. In patients with non-responder hepatitis C, HCV RNA levels both became negative after mesenchymal stem cell transplantation. Histopathological examinations of liver tissues before and at 6 months after transplantation revealed no change in liver tissue regeneration or fibrosis. However, in 5 patients, hepatitis activity index scores decreased. CONCLUSION: Autologous mesenchymal stem cell transplantation via peripheral vein is safe and feasible. Consecutive liver biopsy examinations suggested that mesenchymal stem cells could not reach the liver in a sufficient amount. Improvement in patients and clearance of HCV RNA may have occurred through immunomodulatory mediators secreted by transplanted mesenchymal stem cells, namely the "endocrine" effect.