Gyuri Kim

Greater hemodynamic instability with histidine-tryptophan-ketoglutarate solution than University of Wisconsin solution during the reperfusion period in living donor liver transplantation.

OBJECTIVE University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the 2 most commonly used liver preservation solutions. The aim of this study was to compare cardiovascular stability, acid-base status, and potassium concentrations between patients who received grafts preserved in either UW or HTK solution in orthotopic liver transplantation (OLT). PATIENTS AND METHODS In this retrospective study, 87 patients who underwent living donor OLT were divided into 2 groups: UW (n = 28) and HTK (n = 59). Group HTK was subdivided into group NF-HTK (n = 31; nonflushed before reperfusion) and group F-HTK (n = 28; flushed before reperfusion). We determined mean arterial pressure (MAP) and heart rate every minute for 5 minutes after reperfusion and the maximum change in these values and incidence of postreperfusion syndrome (PRS). Body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were compared at 5 minutes before and 5 and 30 minutes after reperfusion. RESULTS The maximum decreases in MAP within 5 minutes after reperfusion were significantly greater in both the NF-HTK and the F-HTK groups. The rate of PRS was significantly greater in the NF-HTK compared with the UW group. Flushing with HTK solution decreased the rate of PRS; there was no significant difference between the F-HTK and UW groups. All serial changes in body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were similar among the 3 groups. CONCLUSIONS The incidence of PRS was greater using HTK compared with UW solution during the reperfusion period. Therefore, careful hemodynamic management is advised when using HTK solution.

Predictors of High Intraoperative Blood Loss Derived by Simple and Objective Method in Adult Living Donor Liver Transplantation

We conducted a risk factor analysis for high intraoperative blood loss (IBL) in 555 living donor liver transplantation (LDLT) cases with a simple and objective method of IBL estimation based on the concept of red cell mass (RCM): Lost RCM (mL) = patients estimated blood volume (mL) × (preoperative hematocrit in % - postoperative hematocrit in %) + (transfused leukocyte-depleted red blood cell in units × 213 × 70%) + (transfused Cell Saver blood in mL × 55%). Analysis of 33 preoperative variables revealed that Model for End-stage Liver Disease (MELD) score, albumin, the presence of ascites, and previous abdominal surgery were correlated with high IBL (lost RCM > 1000 mL) in multivariate logistical regression analysis. In conclusion, we found that MELD score, albumin, the presence of ascites, and previous abdominal surgery were significantly correlated with high IBL during adult LDLT.

The Relationship Between Inhalational Anesthetic Requirements and the Severity of Liver Disease in Liver Transplant Recipients According to Three Phases of Liver Transplantation

PURPOSE Orthotopic liver transplantation (OLT) patients are known to show decreased intraoperative anesthetic requirements compared with patients undergoing other liver surgeries. The aim of this study was to determine the relationship between inhalational anesthetic requirements and the severity of liver disease among OLT patients. METHODS Fifty patients undergoing first living donor OLT were divided into 2 groups: model for end-stage liver disease (MELD) score<20 (low-MELD group; n=25) versus, MELD score>or=20 (high-MELD group; n=25). Anesthesia was maintained with desflurane and inspired concentration was titrated to maintain the bispectral index between 40 and 50. Neither intraoperative opioid nor epidural or intrathecal analgesia was used. End-tidal desflurane concentration (ETdes) was measured every 5 minutes and averaged in 30-minute intervals. These values were divided into 3 phases: preanhepatic (P 0.5 hour, P 1 hour, and P 1.5 hours), anhepatic (A 0.5 hour, A 1 hour, A 1.5 hours, and A 2 hours), and postreperfusion (R 0.5 hour, R 1 hour, R 1.5 hours, R 2 hours, R 2.5 hours, and R 3 hours). Results were compared between the 2 groups. RESULTS The demographic and intraoperative data were similar between the 2 groups. ETdes to maintain comparable anesthetic depth was significantly lower during the preanhepatic and anhepatic phases in the high-MELD than the low-MELD group, but there was no significant difference during the postreperfusion period. CONCLUSIONS OLT patients with high MELD scores showed less inhalational anesthetic requirements during the preanhepatic and the anhepatic periods than those with low MELD scores.

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case-control study

Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population–based nested case–control study was conducted within the National Health Insurance Service National Sample Cohort 2002–2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow–up time, and the date of diabetes diagnosis at a five–to–one ratio. Odds ratios (ORs) for associations of statin use with HCC were calculated using conditional logistic regression. After at least a 5‐year HCC–free period, there were 229 incident HCC cases and 1,145 matched controls from 47,738 patients with incident diabetes. Of these 229 incident HCC cases, 27 (11.8%) were statin users, whereas 378 (33.0%) were statin users among 1,145 controls. Statin use was associated with a reduced risk of HCC development (adjusted OR [AOR]= 0.36, 95% confidence interval [CI] 0.22–0.60) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area. Risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non–users (AORs 0.53, 0.36, 0.32, and 0.26 in ≤60, 60–180, 181–365, and >365cDDD, respectively; P for trend <0.0001). The risk reduction was apparent in the presence of liver disease (AOR = 0.27, 95% CI 0.14–0.50), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (AOR = 0.64, 95% CI 0.32–1.29). Among patients with new onset T2DM, statin use before HCC diagnosis may have a beneficial inhibitory effect on HCC development in a dose–dependent manner, especially in individuals with liver disease.

Rosiglitazone Use and the Risk of Bladder Cancer in Patients With Type 2 Diabetes

AbstractPatients with diabetes have a higher incidence of bladder cancer; however, the association between thiazolidinedione use and bladder cancer risk has been controversial. We aimed to investigate whether pioglitazone or rosiglitazone use is associated with bladder cancer risk in patients with type 2 diabetes mellitus.This nationwide nested case-control study used data set obtained from the Korean National Health Insurance Service National Sample Cohort 2002 to 2013. Among the 47,738 patients with incident diabetes, 85 cases of newly diagnosed bladder cancer and 850 controls (1:10 matched by age, sex, index year, and diabetes diagnosis year) were recruited. Type 2 diabetes mellitus and bladder cancer were diagnosed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision code.More cases of bladder cancer were diagnosed in men (81.2%), and the stratified age peaked at 70 to 79 years old. Exclusive rosiglitazone use raised the incidence of bladder cancer (odds ratio [OR] = 3.07, 95% confidence interval [CI ] = 1.48–6.37). The risk of bladder cancer started to increase after less than 3 months use (OR = 3.30, 95% CI = 1.02–10.70) and peaked at 3 to 12 months of rosiglitazone use (OR = 4.48, 95% CI = 1.51–13.31). Patients were first exposed to exclusive rosiglitazone within 1 year (OR = 11.74, 95% CI = 2.46–56.12) and those who had consistently used it for 1 year (OR = 4.48 95% CI = 1.51–13.31), had higher risks of bladder cancer compared with nonthiazolidinedione users. Neither pioglitazone use nor exclusive pioglitazone use were associated with an increased incidence of bladder cancer.Rosiglitazone use is associated with an increased risk of incident bladder cancer independent of age and sex in patients with type 2 diabetes mellitus. The highest odds of bladder cancer in rosiglitazone users was seen in those with <1 year of exposure.

Which Score System Can Best Predict Recipient Outcomes after Living Donor Liver Transplantation

INTRODUCTION Many scoring systems have been suggested to predict the outcomes of deceased donor liver transplantations. The aims of this study were to compare the Model for End-Stage Liver Disease (MELD) score with respect to other scores among patients who underwent living donor liver transplantation (LDLT) seeking to evaluate the best system to correlate with postoperative outcomes after LDLT. METHODS We analyzed retrospectively data from 202 adult patients who underwent LDLT from January 2008 to July 2010. We calculated preoperative MELD, MELD-sodium, MELD to serum sodium ratio (MESO), integrated MELD, United Kingdom MELD, Child-Turcotte-Pugh, Acute Physiology and Chronic Health evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores in all patients. We analyzed the correlation of each score with postoperative laboratory results, as well as survival at 1, 3, 6 and 12 months after LDLT. RESULTS There was significant positive correlation between all scores and peak total bilirubin during the first 7 days after LDLT. The MELD score showed the greatest correlation with peak total bilirubin (r=0.745). APACHE II and SOFA scores at 6 months and 1 year after LDLT and MESO score at 1 year after LDLT showed acceptable discrimination performance {area under the receiver operating characteristic curves (AUC)>0.7, while other scoring systems showed poor discrimination. However, the AUCs of each score were not significantly different from the MELD score AUC. CONCLUSION The MELD score most correlated with total bilirubin after LDLT, while the APACHE II and SOFA scores seemed to correlate with mortality after LDLT.

Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia

Beneficial effects of omega-3 fatty acid (O3FA) supplementation in a wide range of disease condition have been well studied. However, there is limited information regarding the effects of O3FAs on chronic kidney disease (CKD), especially in diabetic nephropathy (DN) with hypertriglyceridemia. We investigate whether O3FA supplementation could help maintain renal function in patients with diabetes and hypertriglyceridemia. Total 344 type 2 diabetic patients with a history of O3FA supplementation for managing hypertriglyceridemia were included. Reduction in urine albumin to creatinine ratio (ACR) and glomerular filtrate rate (GFR) were examined. Subgroup analyses were stratified according to the daily O3FA doses. Serum total cholesterol, triglyceride, and urine ACR significantly reduced after O3FA supplementation. Overall, 172 (50.0%) patients did not experience renal function loss, and 125 (36.3%) patients had a GFR with a positive slope. The patients treated with O3FAs at 4g/day showed greater maintenance in renal function than those treated with lower dosages (p < 0.001). This dose dependent effect remains significant after adjustment for multiple variables. O3FA supplementation in diabetic patients with hypertriglyceridemia shows benefits of reducing albuminuria and maintaining renal function. The effects are dependent on the dose of daily O3FA supplementation.

Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis

Oxidative stress is important for the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a chronic disease that ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The nuclear factor erythroid 2-related factor 2-Kelch-like ECH associated protein 1 (Nrf2-Keap1) pathway is essential for cytoprotection against oxidative stress. In this study, we found that oxidative stress or inflammatory biomarkers and TUNEL positive cells were markedly increased in NASH patients compared to normal or simple steatosis. In addition, we identified that the hepatic mRNA levels of Nrf2 target genes such as Nqo-1 and GSTA-1 were significantly increased in NASH patients. Ezetimibe, a drug approved by the Food and Drug Administration for the treatment of hypercholesterolemia, improves NAFLD and alleviates oxidative stress. However, the precise mechanism of its antioxidant function remains largely unknown. We now demonstrate that ezetimibe activates Nrf2-Keap1 pathway which was dependent of autophagy adaptor protein p62, without causing cytotoxicity. Ezetimibe activates AMP-activated protein kinase (AMPK), which in turn phosphorylates p62 (p-S351) via their direct interaction. Correspondingly, Ezetimibe protected liver cells from saturated fatty acid-induced apoptotic cell death through p62-dependent Nrf2 activation. Furthermore, its role as an Nrf2 activator was supported by methione- and choline- deficient (MCD) diet-induced NASH mouse model, showing that ezetimibe decreased the susceptibility of the liver to oxidative injury. These data demonstrate that the molecular mechanisms underlying ezetimibes antioxidant role in the pathogenesis of NASH.

The protective effect of ischemic preconditioning against hepatic ischemic-reperfusion injury under isoflurane anesthesia in rats.

PURPOSE Apoptosis is a central mechanism of ischemic-reperfusion injury (IRI) to the liver. Among the methods to reduce IRI, ischemic preconditioning (IP) has been shown to confer protection. Therefore, the aim of this study was to determine if IP conferred protection against hepatic IRI under isoflurane anesthesia in rats and to investigate underlying protective mechanisms. MATERIALS AND METHODS Twenty-three rats weighing 270 to 300 grams were randomly divided into three groups: (1) the sham operated group (n = 5); (2) the non-IP group (n = 9; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion); and (3) the IP group (n = 9); IP induced by 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of prolonged hepatic ischemia). Anesthesia was maintained with isoflurane (1.5%). We compared the degrees of hepatic injury and expressions of B cell lymphoma 2 (Bcl-2) and caspase 3 and 8 mRNAs. RESULTS The IP group showed significantly lower levels of aspartate transaminase and alanine transaminase as well as reduced histological grades of hepatocyte injury compared with the non-IP group at 2 hours after reperfusion. At the corresponding time, the Bcl-2 mRNA level was 2-fold higher in the IP group. Caspase 3 mRNA levels were highest in the non-IP group significantly compared with the sham cohort. Similarly, caspase 8 mRNA levels were highest in the Non_IP group albeit not significancely. CONCLUSION IP protected against hepatic IRI under isoflurane anesthesia in rats. The mechanism of protection appeared to involve upregulation of Bcl-2 expression resulting in inhibited apoptosis.

Effect of active airway warming on body core temperature during adult liver transplantation.

INTRODUCTION Active inspired gas humidification (AH) preserves body heat and maintains normothermia intraoperatively. However, it is unclear whether AH shows comparable influences during liver transplantation (OLT), which may be affected by both large internal heat loss and external heat supply. Thus, the aim of this study was to evaluate the effect of AH compared with passive humidification (PH) on body temperature in OLT. MATERIALS AND METHODS Thirty-four adult patients undergoing living donor OLT were randomly enrolled into two groups: those given AH using a heated humidifier (HH group, n = 17) and those using a heat-and-moisture exchanger (HME group, n = 17). Both core and skin temperatures (Tc and Ts), as well as respiratory parameters, including static/dynamic lung compliances and PaO(2), were recorded at predetermined times. RESULTS Both Tc and Ts were consistently higher among the HH versus the HME group after 2 hours of anesthesia. Differences in Tc and Ts between the two groups increased gradually over time. The overall Tc during surgery was higher among the HH than the HME group (P = .023). The incidences of hypothermia were lower in the HH group at 3 hours of anesthesia, 1 and 3 hours of reperfusion, and at the end of surgery (P = .037, 0.024, 0.005, and 0.010 respectively). The duration of hypothermia was lower in the HH than the HME group (3.9 ± 3.5 hours versus 6.7 ± 3.3 hours, P = .025). Both groups showed no significant intraoperative changes in respiratory parameters; there were no postoperative respiratory complications. CONCLUSION Active humidification warms the patients body effectively, lessening the incidence and duration of hypothermia during OLT with no respiratory risks.