Acoustic Radiation Force Impulse Elastography in Post-transplant Recurrent Hepatitis C in Living Donor Liver Transplantation.

OBJECTIVE: The aim of the study was to evaluate the efficacy of liver fibrosis (LF) with acoustic radiation force impulse (ARFI) elastography for post-transplant (post-LT) HCV recurrence. PATIENTS AND METHODS: We enrolled 89 adult recipients of living donor liver transplantation (LDLT) who had HCV, with or without post-LT HCV recurrence and treated or not treated. The post-LT HCV recurrence was diagnosed on the basis of RNA viral load present. ARFI examination was performed every 3 months for all patients, with shear wave velocity (SWV) obtained quantitatively in m/s and correlated with histopathologic fibrosis scoring of liver biopsy (LB). RESULTS: There were 50 (50 of 89) patients without HCV recurrence and 39 (39 of 89) with post-LT recurrence in the 89 patients studied. The recurrent group had significantly higher median SWVs (1.87 ± 0.52 vs 1.37 ± 0.52 m/s, P < .0001), in which 18 (18 of 39) patients had antiviral drug treatment and obtained significant improvement with SWVs from 1.83 ± 0.49 to 1.68 ± 0.56 m/s, P = .043. The correlations of LF staging between ARFI elastography and Ishak histopathologic LF scores showed great significance, P = .045. The HCV RNA titer after antiviral treatment decreased from 3,831,750 to 0, P < .0001, but the RNA titer of nontreated patients remained high and the median SWV increased. The Ishak LF staging in the nontreated group progressed from stage 1 to 2, P = .012 and SWV increased from 1.69 ± 0.54 to 1.91 ± 0.66 m/s, P = .085 at 1-year follow-up. CONCLUSION: ARFI elastography has efficient quantitative LF monitoring correlated with histopathologic staging for post-LT HCV recurrence. It could be an alternative, noninvasive method for frequent LB in the disease follow-up.

Efficiency of Transluminal Angioplasty of Hepatic Venous Outflow Obstruction in Pediatric Liver Transplantation.

BACKGROUND: Our aim in this study was to evaluate long-term efficiency of hepatic venous balloon angioplasty (BA) and stent placement (SP) for hepatic venous outflow obstruction (HVOO) in pediatric liver transplantation (LT). METHODS: From January 1999 to September 2016, 262 pediatric patients underwent LT at our hospital. Ten were diagnosed with HVOO, which included 8 living donor grafts and 2 split liver grafts. BA and SP were used in management of these 10 patients with HVOO. After intervention, Doppler ultrasound (DUS) was the major follow-up modality for comparing efficiency of BA and SP. RESULTS: The incidence of HVOO was 3.8% (10 of 262) in our pediatric LTs. Of the 10 HVOO cases, 5 had SP, 3 had BA once, 1 had BA twice, and 1 had BA twice along with SP. The patent hepatic vein was maintained after a mean follow-up of 7.4 (range, 0.04-17) years. Recurrent rate of HVOO after BA was 42%. Neither recurrent HVOO nor stent migration occurred after SP and throughout long-term follow-up. CONCLUSION: Hepatic venous SP was found to be more effective and safe than BA for treatment of HVOO in pediatric LT for long-term follow-up.

Donor Outcomes After Liver Donation in Adult to Adult Living Donor Liver Transplantation.

OBJECTIVES: This study aims to investigate postdonation outcomes of adult living donor liver transplantation donors and remnant liver regeneration in different graft types. METHODS: A total of 236 adult living donor liver transplantation donors were classified into different groups: donors with <35% remnant liver volume (group A; n = 56) and donors with remnant liver volume ≥35% (group B, n = 180); left lobe grafts (LLG group; n = 98) including middle hepatic vein (MHV) and right lobe grafts (RLG group; n = 138) without MHV. The 98 LLG group donors were further classified into 2 subgroups based on hepatic venous drainage patterns: MHV-dominant (n = 20) and non-MHV-dominant (n = 78). The demographic data, postoperative laboratory data, complications, graft weight, remnant liver volume, remnant liver growth rate, and remnant liver regeneration rate (RLRR) after partial liver donation were analyzed. RESULTS: The postoperative aspartate aminotransferase, alanine aminotransferase, total bilirubin, intensive care unit stays, and hospitalization stays were higher in A and RLG group donors. All the donor complications in our series were minor complications. The postoperative complication rate was higher in the A and RLG group, but failed to reach statistical significance. There was no significant difference in RLRR between the RLG/LLG and A/B groups. However, the MHV-dominant group had significantly lower RLRR than the non-MHV-dominant group (P < .05). CONCLUSIONS: Small remnant liver volume donors (<35% remnant liver) have higher risks of developing postdonation minor complications. Left lobe liver donation in MHV-dominant donor candidates are a major concern.

Che-1 attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis by upregulation of Nrf2 signaling.

OBJECTIVE: Hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis plays a critical role in the development of myocardial infarction. Che-1 has been reported as an anti-apoptotic gene in response to various cellular stresses. However, whether Che-1 regulates cardiomyocyte apoptosis in myocardial infarction remains unclear. In this study, we aimed to investigate the role of Che-1 in regulating H/R-induced cardiomyocyte apoptosis and the underlying molecular mechanism. MATERIALS AND METHODS: The expression of mRNA and protein was detected by Real-time quantitative polymerase chain reaction and Western blot. Cell viability was detected by cell counting kit-8 assay. Cell cytotoxicity was measured by lactate dehydrogenase assay. Cell apoptosis was assessed by caspase-3 activity assay. Intracellular ROS generation was determined using a Reactive Oxygen Species Assay Kit. The activity of antioxidant response elements was detected by luciferase reporter assay. RESULTS: We found that Che-1 expression was significantly upregulated in cardiomyocytes in response to H/R treatment. Functional experiments showed that silencing of Che-1 promoted H/R-induced cell apoptosis and oxidative stress. By contrast, overexpression of Che-1 significantly alleviated H/R-induced cell apoptosis and oxidative stress. Interestingly, we found that Che-1 promoted the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the activity of antioxidant response elements. Moreover, Che-1 significantly upregulated the expression of Nrf2 downstream target genes, including heme oxygenase-1 and NADPH-quinone oxidoreductase 1. CONCLUSIONS: Our results showed that Che-1 alleviates H/R-induced cardiomyocyte apoptosis by upregulation of Nrf2 signaling. Our study suggests that Che-1 may serve as a potential and promising therapeutic target for the treatment of myocardial infarction.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. AIM: To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. METHODS: Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. RESULTS: A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). CONCLUSIONS: In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC.

Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway.

Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear. Here, we found that PDIA4 expression was upregulated in a variety of tumor cell lines and human lung adenocarcinoma tissues. Knockdown and overexpression of PDIA4 in tumor cells showed that PDIA4 facilitated cell growth via the reduction of caspases 3 and 7 activity. Consistently, Lewis lung carcinoma cells overexpressing PDIA4 grew faster than did parental cells in tumor-bearing mice, as shown by a reduced survival rate, increased tumor size and metastasis, and decreased cell death and caspases 3 and 7 activity. PDIA4 knockdown resulted in opposite outcomes. Moreover, results obtained in mice with spontaneous hepatoma indicated that PDIA4 deficiency significantly reduced hepatic tumorigenesis and cyst formation and increased mouse survival, tumor death, and caspases 3 and 7 activity. Mechanistic studies illustrated that PDIA4 negatively regulated tumor cell death by inhibiting degradation and activation of procaspases 3 and 7 via their mutual interaction in a CGHC-dependent manner. Finally, we found that 1,2-dihydroxytrideca-5,7,9,11-tetrayne, a PDIA4 inhibitor, reduced tumor development via enhancement of caspase-mediated cell death in TSA tumor-bearing mice. These findings characterize PDIA4 as a negative regulator of cancer cell apoptosis and suggest that PDIA4 is a potential therapeutic target for cancer.

Higher risk for thyroid diseases in physicians than in the general population: a Taiwan nationwide population-based secondary analysis study.

BACKGROUND: Physicians have high work stress, responsibility for night shifts and chances of exposure to medical radiation, which may increase the risk for thyroid diseases. AIM: We conducted this study to assess the risk for thyroid diseases in physicians, which remain unclear. DESIGN: We used a secondary analysis of the Taiwan National Health Insurance Research Database for this study. METHODS: After excluding thyroid diseases occurring before 2006 and residents, physicians and general population were identified by matching with age and sex in 2009 in a 1:2 ratio. The risk for thyroid diseases was compared between the physicians and general population and among physicians by tracing their medical histories between 2006 and 2012. RESULTS: In total, 28,649 physicians and 57,298 general population were identified. Physicians had a higher risk for overall thyroid diseases than the general population [odds ratio (OR): 1.27; 95% confidence interval (CI): 1.10-1.47], including individual thyroid disease: thyroid cancer (OR: 1.89; 95% CI: 1.22-2.95), hypothyroidism (OR: 1.64; 95% CI: 1.23-2.18) and thyroiditis (OR: 1.48; 95% CI: 1.00-2.19). CONCLUSIONS: We showed that physicians had a significantly higher risk for thyroid diseases than the general population. This reminds us to pay more attention to thyroid diseases in physicians. Further studies about the underlying mechanisms are warranted.

Impact of Different Dominant Hepatic Vein Patterns in Left-Lobe Donors of Adult Living Donor Liver Transplantation.

OBJECTIVE: Optimal hepatic venous tributary flow is correlated with liver function and regeneration. In left-lobe graft living donor liver transplantation, the stump of segment 5 and 8 hepatic veins (S5V and S8V) are ligated without performing hepatic tributary reconstruction. The aim of this article was to evaluate the different dominate hepatic vein patterns that affect left-lobe living donor safety. MATERIALS AND METHODS: A total of 44 donors who underwent left-lobe hepatectomy were divided into 2 groups, middle hepatic vein (MHV) dominance (group 1) and right hepatic vein (RHV) dominance (group 2), according to the dominant venous territory drainage from S5V and S8V or RHV. The clinical pathological data, postoperative laboratory data, complication, remnant liver volume and remnant liver regeneration rate at 6 months after surgery were compared. RESULTS: No difference was found in blood loss, postoperative liver function such as alanine transaminase value, complications, and hospital stays between groups. Group 1 had slightly higher total bilirubin level than group 2 (1.99 vs 1.79; P = .49). Group 2 had significantly better remnant liver regeneration rate than group 1 (89.2% vs 82.5%; P = .026). CONCLUSION: It is important to recognize the dominant MHV group. Ligation large S5V and S8V in dominant MHV donors led to lower remnant liver regeneration in our series. This might be critical in extremely small RHV territory and potential large remnant liver congestion donors. Adjusting surgical planning, such as hepatic vein reconstruction, in this kind of donor might be appropriate for donor safety.

Magnetic Resonance Spectroscopy in Living-Donor Liver Transplantation.

OBJECTIVE: The purpose of this study is to evaluate the accuracy rate of the one breath-hold single voxel hydrogen-1 magnetic resonance spectroscopy (MRS) in comparison with intraoperative biopsy for liver fat quantification in living-donor liver transplantation. MATERIALS AND METHODS: A total of 80 living liver donors participated in this study. Each patient underwent both MRS and intraoperative biopsy for evaluation of liver fatty content. MRS was performed using 1.5-T magnetic resonance imaging and placed in segments 2-4, 5-8, and left lateral segment for each donor. Accuracy was assessed through receiver operating characteristic curve analysis. Sensitivity and specificity of MRS fat fractions were also calculated. RESULTS: Eighty living-donor liver transplantation donors were enrolled in this study. There was no fatty liver in 59 subjects (73.8%), 5% to 10% fatty liver in 17 subjects, 11% to 15% fatty liver in 3 subjects, and >16% fatty liver in 1 subject. MRS fat fraction showed excellent parameters to predict between normal liver and fatty liver groups (1.85% ± 0.98, 8.13% ± 3.52, respectively; P < .0001). Linear regression between MRS fat fraction and pathology grading showed high correlation (R(2) = 0.7092). Pearson correlation revealed high correlation between MRS and pathology results (r = 0.936), poor correlation between body mass index and pathology results (r = 0.390). The sensitivity and specificity for detection of liver steatosis in MRS fat fraction were 95.2% and 98.3%, respectively. CONCLUSION: (1)H MRS fat fraction is a highly precise and accurate method in quantification of hepatic steatosis for the living donor and can be finished in a single breath-hold.

Drug-Eluting Bead Transarterial Chemoembolization as Bridge Therapy for Hepatocellular Carcinoma Before Living-Donor Liver Transplantation.

BACKGROUND: The majority of hepatocellular carcinoma (HCC) patients is diagnosed in late stages and therefore becomes ineligible for potentially curative treatment such as resection or liver transplantation. Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads, Biocompatibles, Farnham, United Kingdom) has been proven with less side effects and better efficacy than conventional TACE, especially among patients with poor liver function. PURPOSE: The aim of this study is to evaluate outcomes of HCC patients who received TACE with DC beads, which resulted to eligibility for liver transplantation. METHODS AND MATERIALS: From January 2012 to June 2015, 60 patients with HCC received pre-liver transplantation evaluation whose cases were managed with TACE using DC beads at Kaohsiung Chang Gung Memorial Hospital were included in the study. DC beads loaded with doxorubicin were used. RESULTS: Forty percent of the patients had complete tumor response. Thirty-three percent of the patients had partial tumor response, of which 15% showed stable disease, 11.7% exhibited disease progression including 3 with portal vein thrombosis, 1 with both hepatic vein and portal vein thrombosis, and 3 with increase in tumor size. Twenty-three patients were beyond University of California, San Francisco (UCSF) criteria initially. The successful downstage rate was 73.9% (17 of 23). Thirty-seven patients fit the USCF criteria initially. The 3-, 6- and 12-month drop rates of these patients were 0%, 3.9%, and 16.8%, respectively. Twenty-four (40%) patients successfully underwent liver transplantation. Three patients (12.5%) demonstrated recurrent HCC after liver transplantation. CONCLUSION: TACE with DC bead can effectively induce tumor necrosis and appears to be a successful approach as bridge therapy for patients with advanced HCC and poor liver function.

Noncontrast Magnetic Resonance Angiography Using Inflow Sensitive Inversion Recovery Technique for Vascular Evaluation in Pre-liver Transplantation Recipients.

OBJECTIVE: Vascular anatomy is essential in pretransplantation survey. The purpose of this study is to investigate the feasibility and diagnostic performance of inflow sensitive inversion recovery (IFIR) magnetic resonance angiography (MRA) to evaluate the recipient's hepatic vasculature before liver transplantation. MATERIALS AND METHODS: Thirty-one pre-liver transplantation patients underwent both IFIR and conventional contrast-enhanced MRA using a 1.5T MR scanner from December 2012 to December 2014. The contrast-to-noise ratios (CNRs) between liver parenchyma and hepatic vasculature were calculated. The image sets of IFIR and contrast-enhanced MRA were assessed for subjective image quality and depiction of hepatic vasculature on vessel-to-vessel basis by two independent radiologists. RESULTS: The quantitative results of CNR for hepatic arteries on IFIR were significantly lower than contrast-enhanced MRA, whereas CNR for portal veins and inferior vena cava on IFIR were significantly higher than contrast-enhanced MRA. For subjective assessment of image quality, the overall agreement of scores of IFIR and contrast-enhanced MRA was substantial (kappa values ranged from 0.650 to 0.767). There was no significant difference in the image quality for portal veins between IFIR and contrast-enhanced MRA. The quality scores of IFIR were significantly lower than contrast-enhanced MRA for hepatic arteries. For inferior vena cava evaluation, the scores of IFIR were significantly higher than contrast-enhanced MRA. CONCLUSION: IFIR MRA is a reproducible and noninvasive tool to assess the hepatic vasculature that can provide adequate to good image quality. In pre-liver transplantation patients, IFIR MRA becomes even more useful if contrast medium is a contraindication due to impaired renal and liver functions.

Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Diagnosis and Prognosis After Resection or Transplantation.

BACKGROUND: Primary liver malignancy is the leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) representing the majority. Combined HCC-CC, in contrast, accounts for less than 5% of these liver cancers and has not been clearly characterized by imaging, making diagnosis and management difficult. MATERIALS AND METHODS: This retrospective study investigated 32 patients with early-stage combined HCC-CC tumor who underwent hepatectomy (n = 24) or liver transplantation (n = 8). Preoperative imaging and pathologic reports were retrospectively reviewed and correlated. Survival and recurrence rates were then analyzed. RESULTS: Twelve patients with more than 50% CC component showed typical CC enhancement, whereas 17 patients with less than 50% CC component exhibited typical HCC enhancement. Those with equivocal imaging findings resulted near equal tumor component. The majority demonstrated either heterogeneous or peripheral enhancement. Considering the major tumor component, 66% of the images were consistent with histopathology. The over-all 3-year recurrent rate was 59%, with a mean time to recurrence of about 7 months. The 3-year survival rate of combined tumor after hepatectomy was 76% and after transplant was 75%, regardless of major tumor component. However, patients with more than 50% CC component showed a decrease in 3-year survival rate to 50% when transplantation was performed. CONCLUSION: The overall survival rate for combined tumor after either hepatectomy or transplantation seems to be satisfactory but carries a high risk of recurrent when compared to pure HCC. On the other hand, a major CC component tumor after transplantation is associated with poor survival outcome; thus, liver transplantation has no role and is not a good management option.

Sonographic Evaluation of Post-transplantation Portal Vein Stenosis in Pediatric Living-donor Liver Transplant Recipients With Left-liver Grafts.

INTRODUCTION: Portal vein (PV) stenosis is not uncommon in post-transplantation pediatric living-donor liver transplant (PLDLT) recipients. The purpose of this study was to identify specific ultrasound criteria that may be used to detect PV stenosis in PLDLT with left-liver grafts. PATIENTS AND METHODS: From January 2010 to October 2014, 87 pediatric recipients underwent PLDLT with left lobes or left lateral segments at our hospital. All patients underwent routine liver Doppler ultrasound (DUS) as follow-up protocol. The morphologic narrowing and mean time averaged velocity (TAV) at the PV anastomotic site, change in anastomotic/pre-anastomotic TAV (ΔTAV), and the umbilical portal width were evaluated and analyzed. Ultrasound findings were correlated with computed tomography angiography where PV stenosis was suspected. RESULTS: In the liver graft follow-up study, 80.4% (70 of 87 patients) of PV anastomosis was well visualized and measured by Doppler ultrasound. The optimal threshold values for TAV and ΔTAV were 49.6 cm/s and 30 cm/s, respectively, for significant PV anastomosis stenosis. In the other 19.5% (17/87), the PV anastomosis could not be identified properly. The PV anastomosis was not always visible with ultrasound; however, the optimal dilated umbilical portion of the PV indicating possible PV anastomosis narrowing threshold was umbilical portal width >1.5 cm. CONCLUSIONS: Increased anastomotic TAV and ΔTAV are useful features for diagnosing PV stenosis. The identification of a dilated umbilical portion of the left PV helps in detection of PV stenosis in PLDLT recipients especially when the anastomotic narrowed region cannot be visualized.

Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells.

The antitumor drug etoposide (ETO) is widely used in treating several cancers, including adrenocortical tumor (ACT). However, when used at sublethal doses, tumor cells still survive and are more susceptible to the recurring tumor due to centrosome amplification. Here, we checked the effect of sublethal dose of ETO in ACT cells. Sublethal dose of ETO treatment did not induce cell death but arrested the ACT cells in G2/M phase. This resulted in centrosome amplification and aberrant mitotic spindle formation leading to genomic instability and cellular senescence. Under such conditions, Chk2, cyclin A/CDK2 and ERK1/2 were aberrantly activated. Pharmacological inactivation of Chk2, CDK2 or ERK1/2 or depletion of CDK2 or Chk2 inhibited the centrosome amplification in ETO-treated ACT cells. In addition, autophagy was activated by ETO and was required for ACT cell survival. Chloroquine, the autophagy inhibitor, reduced ACT cell growth and inhibited ETO-induced centrosome amplification. Chloroquine alleviated CDK2 and ERK, but not Chk2, activation and thus inhibited centrosome amplification in either ETO- or hydroxyurea-treated ACT cells. In addition, chloroquine also inhibited centrosome amplification in osteosarcoma U2OS cell lines when treated with ETO or hydroxyurea. In summary, we have demonstrated that chloroquine inhibited ACT cell growth and alleviated DNA damage-induced centrosome amplification by inhibiting CDK2 and ERK activity, thus preventing genomic instability and recurrence of ACT.

The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells.

Epigenetic modifying enzymes have a crucial role in the pathogenesis of acute myeloid leukemia (AML). Methylation of lysine 9 on histone H3 by the methyltransferase G9a and SUV39H1 is associated with inhibition of tumor suppressor genes. We studied the effect of G9a and SUV39H1 inhibitors on viability and differentiation of AML cells and tested the cytotoxicity induced by combination of G9a and SUV39H1 inhibitors and various epigenetic drugs. The SUV39H1 inhibitor (chaetocin) and the G9a inhibitor (UNC0638) caused cell death in AML cells at high concentrations. However, only chaetocin-induced CD11b expression and differentiation of AML cells at non-cytotoxic concentration. HL-60 and KG-1a cells were more sensitive to chaetocin than U937 cells. Long-term incubation of chaetocin led to downregulation of SUV39H1 and reduction of H3K9 tri-methylation in HL-60 and KG-1a cells. Combination of chaetocin with suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor) or JQ (a BET (bromodomain extra terminal) bromodomain inhibitor) showed synergistic cytotoxicity. Conversely, no synergism was found by combining chaetocin and UNC0638. More importantly, chaetocin-induced differentiation and combined cytotoxicity were also found in the primary cells of AML patients. Collectively, the SUV39H1 inhibitor chaetocin alone or in combination with other epigenetic drugs may be effective for the treatment of AML.

Portal venous pressure in adult living donor liver transplantation.

OBJECTIVE: The relationship between portal pressure and small-for-size syndrome (SFSS) is unsettled. The purpose of this study was to evaluate the role of portal pressure in predicting SFSS. METHODS: Thirty-four patients with end-stage liver disease who received adult-to-adult living-donor liver transplantation (ALDLT) were included. Recipients were grouped based on whether they received portal flow modulation or not. The intraoperative portal vein flow volume (PVFV) and portal venous pressure (PVP) between the 2 groups were compared. The relationship of PVP to PVFV, graft weight-to-recipient weight ratio (GRWR), and graft weight-to-recipient spleen size ratio (GRSSR) were analyzed. RESULTS: Persistent portal hypertension was found after ALDLT. The PVP was linearly correlated with PVFV but not with GRWR or GRSSR. With the use of the following criteria, (1) PVFV >250 mL/min/100 g graft weight, (2) GRWR <0.8%, and (3) GRSSR <0.6, modulation of the portal flow was performed in 3 cases. The receiver operating characteristic analysis showed that 23 mm Hg was the cutoff point for PVP, with a sensitivity of 83% and specificity of 43%. CONCLUSIONS: PVP is a weak parameter to use for portal flow modulation after ALDLT. It is sensitive but not specific to predict SFSS.

Graft regeneration in pediatric living donor liver transplantation.

OBJECTIVE: Due to the shortage of cadaver liver grafts in Asia, more than 90% of biliary atresia (BA) patients require living donor liver transplantation (LDLT), but the factors that influence liver graft regeneration in pediatric patients are still unclear. The aim of this study was to evaluate the potential predisposing factors that encourage liver graft regeneration in pediatric liver transplantation (LT). METHODS: Case notes and Doppler ultrasound and computed tomography studies performed before and 6 months after transplantation of 103 BA patients who underwent LDLT were reviewed. The predisposing factors that triggered liver regeneration were compiled from statistical analyses and included the following: age, gender, body weight and height, spleen size, graft weight-to-recipient weight ratio (GRWR), post-transplantation total portal flow, and vascular complications. RESULTS: Seventy-two pediatric recipients were enrolled in this study. The liver graft regeneration rate was 29.633 ± 36.61% (range, -29.53-126.27%). The size of the spleen (P = .001), post-transplantation portal flow (P = .004), and age (P = .04) were correlated lineally with the regeneration rate. The GRWR was negatively correlated with the regeneration rate (P = .001) and was the only independent factor that affected the regeneration rate. When the GRWR was >3.4, patients tended to have poor and negative graft regeneration (P = .01). CONCLUSION: Large-for-size grafts have negative effect on regeneration rates because liver grafts that are too large can compromise total portal flow and increase vascular complications, especially when the GRWR is >3.4. Thus, optimal graft size is more essential than other factors in a pediatric LDLT patient.

Diphenhydramine dependence through deep intramuscular injection resulting in myonecrosis and prolonged QT interval.

WHAT IS KNOWN AND OBJECTIVE: Diphenhydramine (DPH) is a first-generation antihistamine, which is useful in treating allergic reaction, and is usually considered innocuous. We describe a retired nurse with history of depression, who began to develop drug-seeking behaviour after her first receiving of an intramuscular (IM) DPH injection due to urticaria. CASE SUMMARY: The 49-year-old patient had developed IM DPH dependence within 4 months. She needed to receive psychiatric inpatient treatment because of depressive mood, serious myonecrosis over injected sites, and prolongation of QT interval. WHAT IS NEW AND CONCLUSION: This is the first reported case of DPH dependence through the IM route. Second-generation antihistamines might be better choices for patients with psychiatric illness by reason of their lower effects on central nervous system and lower risk of abuse.