Changing trends in the etiology of liver transplantation in Turkiye: A multicenter study.

Background and Aim: This study aimed to identify the indications for liver transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT. Materials and Methods: We conducted a multicenter cross-sectional observational study across 11 tertiary centers in Turkiye from 2010 to 2020. The study included 5,080 adult patients. Results: The mean age of patients was 50.3±15.2 years, with a predominance of female patients (70%). Chronic viral hepatitis (46%) was the leading etiological factor, with Hepatitis B virus infection at 35%, followed by cryptogenic cirrhosis (24%), Hepatitis C virus infection (8%), and alcohol-related liver disease (ALD) (6%). Post-2015, there was a significant increase in both the number of liver transplants and the proportion of living donor liver transplants (p<0.001). A comparative analysis of patient characteristics before and after 2015 showed a significant decline in viral hepatitis-related LT (p<0.001), whereas fatty liver disease-related LT significantly increased (p<0.001). Conclusion: Chronic viral hepatitis continues to be the primary indication for LT in Turkiye. However, the proportions of non-alcoholic fatty liver disease (NAFLD) and ALD-related LT have seen an upward trend over the years.

Evaluation of the Effects of Immunosuppressive Drugs Following Liver Transplantation on Pregnancy Outcomes: A Retrospective Study.

BACKGROUND: Liver transplantations can be safely performed in women of reproductive age. Women with chronic liver disease may have infertility for various reasons, although fertility returns after recovering >90% of sexual disorders following liver transplantation. The present study examined the effects of immunosuppressive drugs used by women of reproductive age undergoing liver transplantation in our clinic on pregnancy and pregnancy outcomes and evaluated mortality and morbidity in this patient population. METHODS: Among the patients undergoing liver transplantation in our clinic between 1997 and 2020, those conceiving after liver transplantation were evaluated in the present study. Demographic data on maternal and newborn health, as well as mortality and morbidity, were recorded. Maternal transplant indications, graft type, the interval between transplantation and pregnancy, maternal age at pregnancy and the number of pregnancies, the number of living children, complications, delivery mode, immunosuppressive drugs, and blood levels were investigated. RESULTS: A total of 615 liver transplantations (353 from a living donor, 262 from a cadaveric donor) were performed in our clinic. Furthermore, 33 pregnancies occurred in 22 women following transplantation (17 living donor liver transplantations, 5 deceased donor liver transplantations), and the data of these patients were recorded. Tacrolimus and mycophenolate mofetil were used as immunosuppressive therapy. CONCLUSIONS: Liver transplantations can be safely performed in women of reproductive age if indicated, and these patients can be safely followed up throughout the pregnancy and during labor by a multidisciplinary team.

Complications and Long-Term Outcomes in Adult Patients Undergoing Living Donor Liver Transplantation Because of Fulminant Hepatitis.

BACKGROUND: The present study investigates the complications that may occur during long-term follow-up in patients aged 18 years and older undergoing living donor liver transplantation (LDLT) in our clinic because of fulminant hepatitis. METHODS: The study included patients aged 18 years and older with a minimum survival of 6 months who underwent an LDLT between June 2000 and June 2017. The demographic data of the patients were evaluated in terms of late-term complications. RESULTS: Of the 240 patients who met the study criteria, 8 (3.3%) underwent LDLT for fulminant hepatitis. The indication for transplantation in patients with fulminant hepatitis was cryptogenic liver hepatitis in 4 patients, acute hepatitis B infection in 2 patients, hemochromatosis in 1 patient, and toxic hepatitis in 1 patient. Of the 240 patients, 65 (27%) undergoing LDLT underwent a liver biopsy for suspected rejection because of an elevation in liver function test results during follow-up. Histopathologic scoring was carried out according to the Banff scoring system. A diagnosis of late acute rejection was made in only 1 of the 8 patients (12.5%) who underwent LDLT for fulminant hepatitis. CONCLUSION: Patients with fulminant hepatitis must be prepared for an LDLT, if available, while waiting for a cadaveric donor. The results of the present study suggest that LDLTs in patients with fulminant hepatitis are safe, and the outcomes are acceptable in terms of survival and complications.

Vascular Complications After Liver Transplantation.

OBJECTIVES: Vascular complications after liver transplant can be lethal. High levels of suspicion and aggressive use of diagnostic tools may help with early diagnosis and treatment. Here, we share our experiences regarding this topic. MATERIALS AND METHODS: Adult and pediatric patients who had liver transplant between February 1997 and June 2018 in our clinic were included in the study. Patients were grouped according to age (pediatric patients were those under 18 years old), male versus female, indication for transplant, type of liver transplant, type of vascular complication, treatment, and survival aftertreatment.We analyzed the statistical incidence of vascular complications according to age, male versus female, and type of liver transplant. RESULTS: Our analyses included 607 liver transplant procedures, including 7 retransplants, with 349 (57.4%) from living donors and 258 (42.6%) from deceased donors. Of total patients, 539 were adults (89.8%) and 61 were children (10.2%). Vascular complications occurred in 25 patients (4.1%), with hepatic artery complications seen in 13 patients (2.1%) (10 adults [1.8%] and 3 children [4.9%]), portal vein complications seen in 9 patients (1.5%) (6 adults [1.1%] and 3 children [4.9%]), and hepatic vein complications seen in 3 patients (0.5%) (2 adults [0.36%] and 1 child [1.6%]). Rate of vascular complications was statistically higher in pediatric patients (11.4% vs 3.3%; P = .007) and higher but not statistically in recipients of livers from living donors (5.2% vs 2.7%; P = .19). Twelve patients (48.8%) were treated with endovascular approach, and 11 (0.44%)required surgicaltreatment. Two patients underwent immediate retransplant due to hepatic artery thrombosis. CONCLUSIONS: Because vascular complications are the most severe complications afterlivertransplant,there must be close follow-up of vascular anastomoses, particularly early postoperatively, with radiologic methods. In cases of vascular complications, emergent treatment, including endovascular interventions, surgery, and retransplant, must be performed.

Outcomes of Surgical Strategies for Living Donor Liver Transplantation in Patients With Portal Vein Thrombosis: A Cohort Study.

BACKGROUND: Adequate portal flow to the liver graft is the requirement of a successful liver transplant (LT). Historically, portal vein thrombosis (PVT) was a contraindication for LT, especially for living donor LT (LDLT), demanding technically more difficult operations and advanced technique. In this study, the outcomes of patients with and without PVT after LDLT were compared. METHODS: Adult LDLTs performed by 2 centers (n = 335) between 2013 and 2020 were included into this large cohort study. PVT was classified based on Yerdel classification grade 1 to 4. RESULTS: Sixty-two patients with PVT constituted 19% of the study cohort of 335 recipients. While mean platelet count was found to be lower (P = .011) in the PVT group, patient age (P = .035), operation duration (P = .001), and amount of intraoperative blood transfusion (P = .010) were found to be higher. Incidence of PVT was higher in female patients than males (22.7% vs 16.1%, P = .037). There was no significant difference in survival between patients with and without PVT on 30-day (P = .285), 90-day (P = .565), 1-year (P = .777), and overall survival (P = .917). Early thrombosis did not show a better survival rate than Grades 2, 3, or 4 PVT. Thrombosis limited to portal vein was not found to bring a survival advantage compared with Grade 3 and 4 thromboses. Eversion thrombectomy was the most common procedure (66%) to overcome PVT intraoperatively. CONCLUSION: Although technically more challenging, PVT is not a contraindication of LDLT. Similar outcomes can be achieved in LDLT in patients with PVT after proper restoration of portal flow, which eliminates the default survival disadvantage of patients with PVT.

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

Does early removal of double J stents reduce urinary infection in living donor renal transplantation?

INTRODUCTION: Prophylactic use of double J (DJ) stents in recipients is highly accepted in renal transplantation. In this study, the association between the frequency of urologic complications (UC) and urinary tract infections (UTI), and the early or late removal of DJ stents was investigated. MATERIAL AND METHODS: A total of 116 live-donor renal transplant patients were included in the study during a 4-year period, with a mean follow-up of 29.2 ±15.3 months. In all, DJ stents were used. All patients were clinically monitored for graft function by assessment of the complete blood count, renal biochemistry, urine analysis and blood drug level according to our follow-up protocol. RESULTS: The patients were divided into 2 groups according to the time of their stent removal: group I (n = 44), removal within the first 14 days; and group II (n = 72), removal after 14 days. No urinary leaks were detected in either of the groups. Three patients suffered from anastomotic stricture (group I, n = 1; group II, n = 2). The rates of UTI were similar in groups I and II (13.6% vs. 16.6%, respectively, p = 0.79). The rate of UTI in women was found to be 3.8 times higher than in men. CONCLUSIONS: The results of our study demonstrated that DJ stent removal within 14 days did not reduce the risk of UTI when compared to stent removal after 14 days. Similar effects on complication rates for ureteral stenting for these 2 removal periods were observed.

Comparison of intestinal ischemia after on-pump versus off-pump coronary artery bypass grafting surgery

Background/aim: Acute mesenteric ischemia (AMI), one of the gastrointestinal system complications, which occurs following cardiac surgery, is challenged in the literature with a diminished incidence of AMI by heart surgery without cardiopulmonary bypass (CPB) or with pulsatile CPB. This study aims to compare the incidence and mortality rate of mesenteric ischemia in a series of consecutive patients undergoing coronary artery bypass grafting (CABG) through on-pump and off-pump techniques. Materials and methods: This study included patients who underwent CABG between 1 January 2010 and 31 June 2016. All patients were divided into two groups: Group 1 comprised 6396 CABG patients operated on with the off-pump technique. Group 2 included 1210 patients who received CABG with the on-pump technique. Preoperative data were collected on the studied variables. Postoperative data included the development of intestinal ischemia and in-hospital mortality. Results: Of 7606 consecutive CABG patients, a total of 31 (0.4%) developed intestinal ischemia. The incidence of postoperative mesenteric ischemia was 0.28% in Group 1 and 1.07% in Group 2 (P = 0.000). The survival rates after AMI were 61.1% in Group 1 (off-pump) and 7.7% in Group 2 (on-pump) (P = 0.003). Time from the first occurrence of nonspecific GI complaints to laparotomy was similar in the off-pump and on-pump groups and had no effect on mortality. Conclusions: With regard to the incidence of mesenteric ischemia and survival after laparotomy, off-pump CABG patients revealed significant improvement compared with those operated on with the on-pump technique.

Prevention and acute management of biliary injuries during laparoscopic cholecystectomy: Expert consensus statement.

Gallstone disease is very common and laparoscopic cholecystectomy is one of the most common surgical procedures all over the world. Parallel to the increase in the number of laparoscopic cholecystectomies, bile duct injuries also increased. The reported incidence of bile duct injuries ranges from 0.3% to 1.4%. Many of the bile duct injuries during laparoscopic cholecystectomy are not due to inexperience, but are the result of basic technical failures and misinterpretations. A working group of expert hepatopancreatobiliary surgeons, an endoscopist, and a specialist of forensic medicine study searched and analyzed the publications on safe cholecystectomy and biliary injuries complicating laparoscopic cholecystectomy under the organization of Turkish Hepatopancreatobiliary Surgery Association. After a series of e-mail communications and two conferences, the expert panel developed consensus statements for safe cholecystectomy, management of biliary injuries and medicolegal issues. The panel concluded that iatrogenic biliary injury is an overwhelming complication of laparoscopic cholecystectomy and an important issue in malpractice claims. Misidentification of the biliary system is the major cause of biliary injuries. To avoid this, the "critical view of safety" technique should be employed in all the cases. If biliary injury is identified intraoperatively, reconstruction should only be performed by experienced hepatobiliary surgeons. In the postoperative period, any deviation from the expected clinical course of recovery should alert the surgeon about the possibility of biliary injury.

Active form of AKT controls cell proliferation and response to apoptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. Deregulation of the AKT signaling pathway has been found in HCC. However, the effect of AKT activation on the proliferation and apoptosis in HCC is not clear. Herein, expression of phosphorylated form of AKT (Ser 473) was investigated in HCC tumor (n=73), cirrhosis (n=17), normal liver (n=22) samples and in HCC cell lines (n=8). The results showed that expression of p-AKT was higher in tumor (53%) than in cirrhotic tissues (12%) while it was absent in normal liver (p<0.0001). p-AKT expression was also associated with number of tumor nodules and differentiation status (p<0.05). LY294002 induced cell cycle arrest at G0/G1 in SNU-449 and Mahlavu cells by decreasing expression of CDK2, CDK4, CycD1, CycD3, CycE, CycA and increasing expression of p21 and p27 as well; it also caused a decrease in the E2F1 transcriptional activity through declining phosphorylated Rb. LY294002 did not affect the basal level of apoptosis; however, it amplified cisplatin-induced apoptosis in SNU-449 cells. When the p-AKT level was decreased specifically after transfection with the DN-AKT plasmid, SNU-449 cells became more sensitive to cisplatin-induced apoptosis. HuH-7 cells with no basal p-AKT, were markedly affected by the treatment of doxorubicin. Thus, Akt signaling controls growth and chemical-induced apoptosis in HCC and p-AKT may be a potential target for therapeutic interventions in HCC patients.

The efficacy and safety of tenofovir in the prevention of hepatitis B virus recurrence following liver transplantation.

BACKGROUND/AIMS: In this study, a tenofovir disoproxil fumarate (TDF) + hepatitis B immunoglobulin (HBIG) regimen was compared with lamivudine (LAM) + HBIG to determine the efficacy and safety of TDF in the prevention of hepatitis B virus (HBV) recurrence following liver transplantation (LT). MATERIALS AND METHODS: Thirty-six patients, 18 treated with TDF+HBIG (TDF group) and 18 with LAM+HBIG (LAM group), were evaluated retrospectively over a median 36-month follow-up in the Liver Transplantation Outpatient Unit of Dokuz Eylül University after having an LT. In the TDF group, TDF treatment was initiated in six patients due to resistance to LAM, in one patient due to relapse, in three patients to prevent relapse, and in eight patients due to de novo hepatitis. In the LAM group, LAM therapy was initiated in two patients due to de novo hepatitis and in 16 patients to prevent relapse. RESULTS: In the TDF group, an increase of greater than 0.5 mg/dL in creatinine values was observed in two patients. In the LAM group, creatinine values did not increase to greater than 0.5 mg/dL. No cases of acute renal failure associated with TDF or LAM, mild or serious adverse events, or HBV recurrence were observed among the patients. Glomerular filtration rates (GFRs) of these patients were calculated with a modification of renal disease (MDRD) formulation. There was no significant difference (p<0.05) in the GFRs between the two groups. CONCLUSION: The results of this study, after a 36-month follow-up period, were encouraging and demonstrated that TDF therapy is safe and efficacious in treating HBV-positive organ transplant patients. However, patients should be monitored carefully in terms of renal function. Given the limited experience with TDR in LT, this study is of importance due to its long follow-up period.

Prevalence and risk factors for obesity after liver transplantation: a single-center experience.

BACKGROUND: The study of weight gain after transplantation and its associated factors is necessary to propose strategies to prevent and treat this problem. OBJECTIVES: This study aims to investigate factors affecting the development of obesity after liver transplantation (LTx). PATIENTS AND METHODS: Medical records of 343 liver transplantation cases, which were followed between January 2001 and January 2010 at Dokuz Eylul University, were retrospectively analyzed. Patient pre-liver transplantation height, body weight, body mass index (BMI) measurements, as well as changes in body weight at the beginning, 6 months, 12 months, and 5 years post-transplantation were observed. BMI measurements with records of immunosuppressive therapies were obtained. RESULTS: The study was carried out with the records of 226 patients. 151 patients (66.8%) were male; 75 (33.2%) were female. The mean age was 46.19 ± 10.2 years. 123 of these liver transplants were performed from living donors, while 103 were from cadaveric donors. The causes of liver transplantation were hepatitis D virus (HDV) infection (28%), hepatitis B virus (HBV) infection (24%), hepatitis C virus (HCV) infection (24%), alcoholic liver disease (9%), cryptogenic liver disease (9%), autoimmune hepatitis (4%), and other (2%). In this study, the prevalence of obesity was 21% at the end of the second year, decreasing to 14% by the end of the fifth year. The mean BMI gradually increased during the follow-ups, reaching 25.1 kg/m² and 26 kg/m² six months after liver transplantation and at the end of the first year, respectively (P < 0.002). Obesity developed in 18.2% of post-transplant patients who were receiving a calcineurin inhibitor (CNI). Regarding the development of obesity after transplantation, no statistically significant difference was found between patients using cyclosporine (CsA) and tacrolimus (TAC) (P = 0.07). Six months after liver transplantation, the mean body weight gain in the groups receiving steroids and not receiving steroids were 4.71 kg and 2.7 kg, respectively (P = 0.03). In the post-transplant period, there was no significant difference in patients who had received TAC and CsA for development of diabetes mellitus (DM), hypertension (HT), or hyperlipidemia (HL) (P = 0.30). CONCLUSIONS: Obesity prevalence before and after liver transplantation was comparable. Education of obese patients prior to surgery and recommendation of medical nutrition therapy should be appropriate. Similar medical care for the non-obese subjects could prevent increase in obesity prevalence. Non-corticosteroid immunosuppressive agents had no significant effect on the development of weight gain and obesity. Avoiding the use of long-term steroid therapy and obesity education are the key measures for preventing obesity after liver transplantation.

Cystic solitary fibrous tumor of the liver: a case report.

Solitary fibrous tumors are unusual neoplasms that are rarely found in the liver parenchyma. They are usually described as hard, grayish white, well-defined lesions. Predominant cystic change in a solitary fibrous tumor is an unexpected finding, with only a few previous cases reported in the literature, two of which are localized in the head and neck region. Herein, we report a unique case of solitary fibrous tumor of the liver in a 38-year-old female with predominant multiloculated cystic appearance, and discuss the histopathologic differential diagnosis.

Effects of blood products on nosocomial infections in liver transplant recipients.

OBJECTIVES: Infection is the most severe complication after an organ transplant. Blood cell transfusion is an independent risk factor for adverse events, including infection in the recipient. This study sought to evaluate the effect of blood product transfusions on nosocomial infections in liver transplant patients. MATERIALS AND METHODS: Patients who underwent a liver transplant at our hospital between 2003 and 2010 were recruited for this study. Exclusion criteria were incomplete records, patients who were hospitalized for more than 48 hours during the 4 weeks before transplant, and pediatric transplants. Incidence of nosocomial infections, which were defined as infections occurring within 30 days after transplant was the primary endpoint. RESULTS: The incidence of nosocomial infections was 28.7%. The number of transfusions of packed red blood cells and fresh frozen plasma was significantly higher in patients with nosocomial infection compared with patients without nosocomial infection (P = .018 and P = .039). Blood products dose-dependently contributed to nosocomial infections. Transfusions of ≥ 7.5 units of red blood cells (odds ratio: 2.8) or ≥ 12.5 units of fresh frozen plasma (odds ratio: 3.27) were associated with nosocomial infections (P = .042 and P = .015). The infection-related mortality rate was 10.3%. CONCLUSIONS: Blood product transfusions are associated with an increased rate of nosocomial infections, which contributes to higher morbidity and mortality.

Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism.

CD40 expression in pancreatic cancer.

BACKGROUND: CD40, a tumor necrosis factor receptor family member, is expressed in a variety of cell types. This widespread expression suggests that CD40 may play an important role in normal physiology and disease pathogenesis. The objective of the current study was to investigate the expression of CD40, and its association with clinicopathological features and survival in patients with pancreatic ductal adenocarcinoma. METHODOLOGY: CD40 expression was assessed in 53 pancreatic ductal adenocarcinoma surgical specimens by immunohistochemistry, and expression was correlated with patient clinicopathological parameters and outcome. RESULTS: Among 53 pancreatic cancer specimens, CD40 expression was detected in 13 specimens (24.5%), and peritumoral lymphocytes were present in 45 specimens (84.9%). Patients with CD40-positive tumors exhibited prolonged median disease-free survival (DFS) compared with patients with CD40-negative tumors (15.60 +/- 3.87 versus 10.03 +/- 1.92); however, this was not significant (p = 0.845). Patients with peritumoral lymphocytic reaction exhibited prolonged median DFS compared with patients without peritumoral lymphocytes (10.96 +/- 1.40 vs. 7.60 +/- 0.47); however, this was not significant (p = 0.624). Patients with peritumoral lymphocytic reaction exhibited higher median overall survival compared with patients without peritumoral lymphocytes (15.20 +/- 1.78 vs. 10.13 +/- 1.39); however, again this was not significant (p = 0.100). CONCLUSIONS: These results suggest that CD40 expression on pancreatic cancer cells and peritumoral lymphocytic reaction may serve as prognostic markers.

Retrospective analysis of risk factors affecting pacreatic fistula formation after the closure of the pancreatic stump with sutures in distal pancreatectomy.

BACKGROUND/AIMS: Development of pancreatic fistula after distal pancreatectomy is still a major problem. Various methods have been defined to prevent the development of the fistula. In this study, the results of suture closure of pancreatic duct and closure of pancreatic stump with "U" sutures passing through each other and the risk factors affecting the development of fistula are studied. METHODOLOGY: Fifty-one patients with prospectively collected data were included in the study. In all patients, pancreatic stump was closed with the same surgical technique. Risk factors that may affect fistula formation were studied between groups with and without fistula. Pancreatic fistula definition was made according to the International Study Group on Pancreatic Fistulas classification. RESULTS: Eight (15.7%) of the 51 patients had fistula. Clinically significant fistula ratio was 9.8% (according to ISGPF B and C). Additional organ resections were performed in 18 patients (35.3%). In multivariate analysis, the soft texture of pancreatic parenchyma (OR: 12.420, p = 0.048) and over 150 mL of blood loss (OR: 1.003, p = 0.043) were found as risk factors for the development of fistula. CONCLUSIONS: Closure of pancreatic stump after distal pancreatectomy with "U" shaped sutures passing through each other is a method that can be performed safely.

[Ocular toxoplasmosis developed after liver transplantation]. / Karaciger Transplantasyonu Sonrasi Gelisen Oküler Toksoplazmoz.

Ocular toxoplasmosis after solid organ transplantation occurs usually within the first three months of primary infection or reactivation of latent infection. There are a few reports of ocular toxoplasmosis following liver transplantation in the literature, however, no reports were detected in the national data. In this report a 35-year-old female patient diagnosed as ocular toxoplasmosis following reactivation in the second year after liver transplantation, was presented. The case was successfully treated with trimethoprim/sulfamethoxazole and clindamycin. This case was presented to emphasize late presentation of toxoplasmosis in transplantation patients and to withdraw attention to the importance of serological investigations done before transplantation.

Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

BACKGROUND: Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. RESULTS: MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of ß-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. CONCLUSIONS: These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the ß-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.