Biomedical subjects

Chung-Mau Lo

Publications and source records attributed to Chung-Mau Lo.

At least 37 records · Page 2Linked to original sources

PubMed2003

Over-expression of Id-1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16INK4a/RB pathway.

Inhibitors of differentiation and DNA binding-1 (Id-1) have been demonstrated to oppose Ets-mediated activation of p16INK4a. As p16INK4a protein is inactivated in hepatocellular carcinoma (HCC), we aimed to investigate the role of Id-1 in regulating p16INK4a expression during the development of HCC in HCC patients and direct ectopic Id-1 introduction into the PLC/PRF/5 HCC cell line. Sixty-two HCC samples were recruited for evaluation of Id-1 and proliferating cell nuclear antigen (PCNA) protein expression. The messenger RNA (mRNA) expression of Id-1 and p16INK4a was detected by quantitative reverse transcription-polymerase chain reaction. For in vitro Id-1 transfection, five Id-1 transfected clones were isolated and the effect of ectopic Id-1 introduction was investigated by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, immunostaining and western blot. Our results showed that Id-1 was over-expressed in HCC specimens both at mRNA and protein levels. Over-expression of Id-1 protein was correlated with PCNA (r = 0.334, P = 0.033). HCC samples showing low Id-1 protein expression had a lower Id-1 mRNA level (340.2 versus 1467%, P = 0.039) and higher p16INK4a expression (195 versus -78.6%, P = 0.039) than samples with high Id-1 protein expression. In the PLC/PRF/5 HCC cell line study, ectopic Id-1 expression resulted in proliferation of HCC cells and an increased percentage of S phase cells and PCNA expression. The results showed that over-expression of Id-1 induces cell proliferation in HCC through inactivation of p16INK4a/retinoblastoma pathway. In conclusion, the results provided an insight for the understanding of the role of Id-1 in functional inactivation of p16INK4a in HCC.

Base Sequence↗

PubMed2003

Insulin in University of Wisconsin solution exacerbates the ischemic injury and decreases the graft survival rate in rat liver transplantation.

BACKGROUND: Insulin keeps the liver in a metabolically vigorous state. However, organ preservation aims to decrease the metabolic rate. The objective of this study was to clarify the effect of insulin used in University of Wisconsin (UW) preservation solution on the liver graft. METHODS: The liver grafts were preserved by UW solution with or without insulin for 7, 9, and 24 hr, respectively. The influence of insulin was studied by 7-day survival rate, liver function, morphology, and intragraft gene expression 24 hr after transplantation. Morphology was studied on the preserved grafts. RESULTS: The morphology of the graft in the insulin group showed more severe ischemia-reperfusion injury. The 7-day graft survival rates of the 7-hr subgroups with and without insulin were 55% and 93%, respectively (P=0.02). In the 9-hr subgroups, the survival rates were 0% and 78%, respectively (P=0.002). The serum levels of aspartate aminotransferase (AST) (P=0.008) and alanine aminotransferase (ALT) (P=0.032) were higher in the 7-hr subgroup with insulin. The same trend was found in the 9-hr subgroups (AST, P=0.016; ALT, P=0.016). The expression level of 215 genes were much lower at 24 hr after transplantation in the grafts preserved with insulin than in those preserved without insulin, and most of the genes were related to metabolic activities. CONCLUSIONS: Insulin in UW solution may exacerbate graft ischemic injury and decrease the graft survival rate in rat liver transplantation. Insulin, in the absence of glucose in UW solution, may exhaust the metabolic activity of the liver graft. It is harmful rather than helpful for isolated rat liver grafts preserved in UW solution.

Adenosine↗

PubMed2003

Distinct intragraft response pattern in relation to graft size in liver transplantation.

BACKGROUND: The molecular mechanism of small-for-size graft injury remains unclear. The aim of this study is to investigate the gene expression pattern of acute phase response in relation to graft size in a rat-liver transplantation model. METHODS: A rat orthotopic liver transplantation model using 30%, 50%, and whole grafts was used. The graft survival rates and liver morphology were compared among the three groups. Two transcription factors, nuclear factor (NF)-kappaB (p65) and early growth response (Egr-1), and their downstream genes were compared. RESULTS: According to the graft size, the rats were grouped as follows: group 1 (n=20), 32% (24-47%); group 2 (n=10), 56% (50-65%); and group 3 (n=10), 104% (89-120%). The 7-day survival rates were 20% (P=0.039 vs. group 2, P=0.000 vs. group 3), 60%, and 100% in groups 1, 2, and 3, respectively. Dilation of hepatic sinusoids and vacuolization of hepatocytes were observed in group 1. Up-regulation of Egr-1 and endothelin (ET)-1 and over-expression of nitric oxide synthase (iNOS) was found in group 1, but heme oxygenase (HO)-1 and A20 were down-regulated. At 24 hours after reperfusion, the intragraft protein level of heat-shock protein (Hsp)-70 was significantly lower in group 1 than that in group 3 (12.4 vs. 17.0 ng/mL, P=0.04). More apoptotic nuclei were found in group 1. CONCLUSIONS: Small-for-size graft injury was related to early over-expression of Egr-1 associated with up-regulation of ET-1 and deterioration of intracellular homeostasis reflected by down-regulation of Hsps and A20.

Acute-Phase Reaction↗

PubMed2003

Hepatic venoplasty in living-donor liver transplantation using right lobe graft with middle hepatic vein.

Inclusion of the middle hepatic vein in a right lobe graft from a living-donor may improve venous drainage and avoid graft dysfunction, but reconstruction of the middle hepatic vein is technically difficult. We developed a hepatic venoplasty technique, which was applied in eight consecutive right lobe liver transplantations. The right and middle hepatic veins of the graft were joined together to form a triangular cuff for a single anastomosis to the recipient's inferior vena cava. Hepatic venoplasty was successful in all cases, and no interposition graft was required. Venovenous bypass was not used. All grafts showed immediate function, and no hepatic venous outflow obstruction was observed. There was no reoperation and the graft survival rate was 100%. This hepatic venoplasty technique can be applied systemically as a standard one in right lobe liver graft with the middle hepatic vein to simplify the recipient hepatectomy and to obviate venous outflow obstruction.

Adult↗

PubMed2003

Ethics and rationale of living-donor liver transplantation in Asia.

Living-donor liver transplantation took root in Asia as a natural result of circumstances, because the supply of organs from the cadaveric pool remained scarce over the years. In contrast to Western countries, the majority of organs for liver transplantation in Asia come from live donations. As the expertise of the transplant teams grows, patient outcomes improve, and public awareness increases, the option of live donation of the liver is increasingly chosen. Although no live liver donor death has yet been reported from Asia, the risk is not eliminated and remains a major consideration in the potential donor's decision to donate. The low morbidity and mortality rate could be attributed to the extensive experience of surgeons in liver surgery, because surgical liver disease is highly prevalent in Asia. Although the donor risk is estimated to be low, live organ donation should be absolutely voluntary, with consent given on the basis of unbiased information and chosen only when the option for obtaining a cadaveric graft is practically nil. It is only under these conditions that living-donor liver transplantation should be perpetuated. Although the disease-donation-transplantation process involves a complex interplay of psychosocial and family dynamics, the potential candidate's perception will necessarily depend on the surgeon's explanation. The ethical soundness of the practice of living-donor liver transplantation rests primarily on the ones who deliver the service.

Asia↗

PubMed2003

Complications and long-term outcome of living liver donors: a survey of 1,508 cases in five Asian centers.

A multicenter survey was conducted regarding the safety and outcome of living liver donors in Asia. Five Asian liver transplant centers reported a total of 1,508 living donor liver transplantations (LDLT) performed between January 1990 and December 2001. The recipients consisted of 766 adults and 742 children. The graft types were left lateral or extended left lateral segment in 605, left lobe in 334, right lobe or right lateral sector in 561, and not classified in eight cases. The donor blood loss was less than 1,000 mL in 94.1% of the cases, and 0.53% of the donors received banked blood transfusion. The overall donor complication rate was 15.8%, and 1.1% of donors underwent reoperation. The complication rate was higher in right lobe (28%) than in left lateral segment (9.3%) or left lobe (7.5%) donors. In particular, right lobe donors had more serious complications such as cholestasis (7.3%), bile leakage (6.1%), biliary stricture (1.1%), portal vein thrombosis (0.5%), intra-abdominal bleeding (0.5%), and pulmonary embolism (0.5%). There was no hospital mortality, but there was one late donor death 3 years after operation. Long-term follow-up beyond 3 months was available in 15.1% of the donors only. The data from the multicenter study set the standard for the safety of living liver donors in high-volume liver transplant centers in Asia and provide further justification for the continued application of LDLT in the face of the critical organ shortage in Asia. The long-term outcome of liver donation, however, remains unknown, and transplant centers should continue their follow-up of donors.

Adult↗

PubMed2003

Prophylaxis and treatment of recurrent hepatitis B after liver transplantation.

Chronic hepatitis B virus (HBV) infection is the leading cause of end-stage liver disease in Asia. The results of liver transplantation in these patients have significantly improved to a level comparable to those of other recipients as a result of the rapid evolution in the strategies of prevention and treatment of recurrent hepatitis B over the past decade. Hepatitis B immune globulin (HBIG) and lamivudine, either alone or in combination, are effective in preventing reinfection, but the most cost-effective dosing regimen with optimum efficacy without the prohibitive cost remains to be determined, an issue that is particularly relevant to liver transplant centers with serious financial constraints in Asia. The idea of active immunization is attractive, but the results have been conflicting to date. The newer nucleoside analogs appear most promising, and a combination of two or more antiviral agents is likely to represent the future strategy of choice in the prophylaxis and treatment of recurrent hepatitis B after liver transplantation.

Antiviral Agents↗

PubMed2003

Living-donor liver transplantation for high-urgency situations.

Patients in high-urgency situations for liver transplantation have a high mortality rate while on the waiting list for cadaveric grafts. In countries where cadaveric organ donation is scarce, the use of living-donor liver transplantation (LDLT) provides the only chance of survival for both pediatric and adult patients. It results in a satisfactory overall survival, from approximately 60% to 75% in pediatric patients and from 70% to 90% in adult patients. Patients who had early LDLT were shown to have a better survival outcome than those who waited for cadaveric organ donation, because a timely graft was available to them before they deteriorated further to multiple organ failure. Patients who were in high-urgency situations for liver transplantation and opted for LDLT were also shown to have significantly better survival outcomes than those who did not opt for this procedure. Although left lobe liver graft can be used successfully in adult-to-adult LDLT in high-urgency situations, there is a trend toward a more frequent use of the larger mass provided by the right lobe of the liver. Adequate venous drainage of the anterior segment of the right lobe liver graft is also considered essential for the favorable outcome of the recipients. Although donor morbidity has been reported to be low in LDLT and no donor death has been reported from Asian transplant centers, standardized definitions of morbidity and better methods for observing and measuring outcomes are necessary to understand and to potentially reduce morbidity.

Adult↗

PubMed2003

Value of live donor liver transplantation experience in major hepatectomy for hepatocellular carcinoma.

BACKGROUND: Live donor liver transplantation (LDLT) mandates conversance in liver anatomy and major hepatectomy. Hepatocellular carcinoma is most reliably treated by hepatectomy. HYPOTHESIS: The outcomes of major hepatectomy for hepatocellular carcinoma are influenced by the surgeon's LDLT experience. DESIGN: We collected prospective cohort study data on patient and disease characteristics. SETTING: Tertiary referral center. PATIENTS: A retrospective study was performed on 250 patients who underwent major hepatectomy for hepatocellular carcinoma from January 16, 1996, through December 28, 2001. MAIN OUTCOME MEASURES: Overall and disease-free survival and outcomes including blood loss, blood transfusion, and complications. RESULTS: The 3 liver transplantation surgeons (LTSs) performed 102 major hepatectomies; the 4 hepatobiliary and pancreatic surgeons (HBPSs), 148 major hepatectomies. Patients in both groups had similar baseline characteristics. The mean +/- SD blood loss in the LTS and HBPS groups was 1.36 +/- 1.37 and 2.21 +/- 2.40 L, respectively (P<.001). The mean +/- SD blood transfusion in the LTS and HBPS groups was 0.27 +/- 0.82 and 0.51 +/- 0.94 L, respectively (P =.001). Fewer patients in the LTS group required blood transfusion (17/102 [16.7%]; HBPS group, 57/148 [38.5%]; P<.001). We found no difference in overall and disease-free survival between the groups. The median overall survival was 55.8 months for the nontransfused group, and 34.3 months for the transfused group (P =.06). Median disease-free survival was 16.1 months for the nontransfused group compared with 12.4 months for the transfused group (P =.25). Cox regression multivariate analysis showed that transfusion, cirrhosis, and venous invasion worsened overall survival. Venous invasion, cirrhosis, and tumor size adversely affected disease-free survival. CONCLUSIONS: The LTS group lost less blood and required less blood transfusions than the HBPS group. Blood transfusion worsened overall survival. The significantly lower blood transfusion requirement of the LTS group contributes to a potential advantage in their overall survival.

Aged↗

PubMed2003

Hepatic venoplasty in right lobe live donor liver transplantation.

Inclusion of the middle hepatic vein (MHV) in a right lobe graft is essential to guarantee uniform venous drainage and optimum function of the graft, but end-to-end recipient-to-donor MHV anastomosis may result in outflow obstruction. To avoid outflow obstruction, we designed the venoplasty technique. From September 2000 to November 2002, 65 adult patients received right lobe live donor liver transplantation (LDLT) with grafts containing the right hepatic vein (RHV) and MHV. In the first 34 recipients, the graft RHV and MHV were anastomosed to the recipients' RHV and MHV/left hepatic vein, respectively. For the subsequent 31 recipients, the MHV was joined to the RHV at the back table to form a triangular common orifice. The septum in between the two hepatic veins was divided at the middle and sutured transversely to remove the ridge in between and to create a large opening. The common orifice was anastomosed to a matched-size triangular opening in the recipient's inferior vena cava. After reperfusion, the presence of triphasic pulsatility on spectral Doppler tracing was regarded as a sign of perfect reconstruction. In the first group, Doppler study showed little flow in the MHV in 3 patients, absent pulsatility in the MHV after portal vein reperfusion in 4 patients, and absent pulsatility in the MHV after hepatic artery reperfusion in 5 patients. In the second group, excellent triphasic pulsatility was seen in all except 1 patient (12 of 34 versus 1 of 31, P =.001). A significant increase in the peak flow velocity was seen in the MHV in the second group (median, 19.45 cm/sec versus 31.4 cm/sec, P<.001). Less time was required to complete the hepatic vein anastomoses in the second group (40 minutes versus 27 minutes, P<.001). In conclusion, hepatic venoplasty technique facilitates the implantation of the right lobe graft and guarantees outflow in the MHV.

Adolescent↗

PubMed2003

Development of antibody to hepatitis B surface antigen after liver transplantation for chronic hepatitis B.

Patients with chronic hepatitis B virus (HBV) infection have a defective HBV-specific immune response, and the spontaneous development of antibody against hepatitis B surface antigen (anti-HBs) after liver transplantation has not been observed. We report the spontaneous production of anti-HBs in 21 of 50 (42%) patients receiving lamivudine monoprophylaxis after liver transplantation. Seroconversion to anti-HBs status (>10 mIU/mL) was found at a median of 8 days (range, 1 to 43 days) after transplantation. In each case, serial serum samples showed a >100% increase in antibody titer as compared with that of day 7 after transplantation in the absence of any blood product transfusion. The anti-HBs titer increased to a maximum within 3 months, and the peak titer was <100 mIU/mL in 10 patients, 100 to 1000 mIU/mL in 5 patients, and >1,000 mIU/mL in 6 patients. In 12 patients, anti-HBs disappeared from serum at a median of 201 days (range, 24 to 414 days), whereas the other 9 patients remained positive for anti-HBs at a median of 221 days (range, 94 to 1,025 days) after transplantation. Patients in whom anti-HBs in serum developed had a more rapid clearance of serum hepatitis B surface antigen (HBsAg) (log rank test, P =.011). Using logistic regression analysis, the only predictor of anti-HBs production was an HBV-immune donor (odds ratio, 18.9; 95% confidence interval, 3.2 to 112.4; P =.001). In conclusion, patients who undergo liver transplantation for chronic hepatitis B using lamivudine prophylaxis may develop anti-HBs spontaneously. The antibody is likely to be of donor origin, suggesting the possibility of adoptive immunity transfer through a liver graft.

Adoptive Transfer↗

PubMed2003

High frequency of chimerism in transplanted livers.

Recent studies have shown that primitive stem cells can mobilize and differentiate into hepatocytes. We investigated the time and extent in which cells of recipient origins could differentiate into hepatocytes and other cells in human liver allografts. Microsatellite analysis, which can assess quantitatively the proportions of recipient and donor DNA, was performed in posttransplantation liver biopsy specimens from 17 patients at various times. Combined fluorescence in situ hybridization (FISH) for Y chromosome and immunofluorescence for different cell types was also performed in 10 of these cases with sex mismatch. Organ chimerism in the transplanted livers was found to be of variable extent, and the recipients' DNA in the posttransplantation liver biopsy specimens (excluding portal tracts) amounted up to 50%. The recipient DNA in the posttransplantation liver biopsy specimens increased after liver transplantation by as early as 1 week, peaked at around 30 to 40 weeks, and could be shown 63 weeks after transplantation. Most (64%-75%) of the recipient-derived cells showed macrophage/Kupffer cell differentiation. Only up to 1.6% of the recipient-derived cells in the liver grafts showed hepatocytic differentiation in the liver grafts and made up 0.62% of all hepatocytes of both donor and recipient origins. These livers had mild or minimal injury histologically. In conclusion, our results show that most of the recipient-derived cells in the liver allografts were macrophages/Kupffer cells and only a small proportion of hepatocytes was recipient derived. However, with regard to recipient-derived hepatocytes, our data cannot distinguish between transdifferentiation and cell fusion.

Adult↗

PubMed2003

Intragraft gene expression profiles by cDNA microarray in small-for-size liver grafts.

The aim of this study is to identify the molecular mechanism of small-for-size graft injury through large-scale expression measurement of intragraft gene profile by carrier DNA (cDNA) microarray screening in liver transplantation. The studies compared 1,081 intragraft genes expression profiles using cDNA microarray of small-for-size grafts (<30% of recipient liver weight) with those of whole grafts (control group) 1, 3, and 24 hours after reperfusion in a rat liver transplantation model. Intragraft gene expression was detected by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hepatic ultrastructural features were shown by electron microscopy. In the small-for-size grafts, by cDNA microarray study, the vasoconstriction genes were found up-regulated together with adhesion molecules at 1 hour after reperfusion. Three and 24 hours after reperfusion, the vasopressin genes were found up-regulated together with adhesion molecules, inflammatory mediators and cell death signals, accompanied with down-regulation of the genes related to energy metabolism. By quantitative RT-PCR, intragraft messenger RNA (mRNA) expression of endothelin-1 (ET-1) and endothelin-1 receptor A (ETA) was up-regulated during the first 24 hours after reperfusion accompanied with down-regulation of heme oxygenase-1 (HO-1). The intragraft mRNA and plasma levels of inflammatory cytokines (interleukin [IL]-6, IL-15, tumor necrosis factor [TNF]-alpha) also were overexpressed during the first 24 hours after reperfusion. Sinusoidal congestion and disruption were found accompanied with mitochondrial swelling during the first 24 hours after reperfusion. The up-regulation of intragraft vasoconstriction genes accompanied by early overexpression of adhesion molecules and apoptotic signals, as well as down-regulation of HO-1 in small-for-size grafts may be related to sinusoidal injury leading to graft damage in liver transplantation.

Animals↗

PubMed2003

Portal hyperperfusion injury as the cause of primary nonfunction in a small-for-size liver graft-successful treatment with splenic artery ligation.

Dysfunction of a small-for-size graft is an important clinical problem after living donor liver transplantation in adults. We report a case of primary nonfunction after a small-for-size right lobe living donor liver transplant that was successfully salvaged by reduction of portal pressure and blood flow after splenic artery ligation. The case established portal hyperperfusion injury as a cause of primary nonfunction in a small-for-size graft and we recommend that portal pressure be measured when clinical suspicion arises. Splenic artery ligation is a technically simple procedure that can be applied for the prevention or treatment of such injury.

Adult↗

PubMed2003

Safety and outcome of hepatitis B core antibody-positive donors in right-lobe living donor liver transplantation.

We studied the safety of right-lobe donor hepatectomy in living donors with a positive serological test result for antibody against hepatitis B core antigen (anti-HBc). Of 54 right-lobe living liver donors, serum anti-HBc was positive in 29 donors (54%) and negative in 25 donors (46%). None had a history of hepatitis and all had normal liver biochemistry test results before surgery. Surgical data, postoperative liver function, and outcome of donors were compared according to anti-HBc status. Donors positive for anti-HBc were significantly older (median age, 42 v 31 years; P <.001), but there was no difference in other demographics and liver size. Median blood loss was greater in anti-HBc-positive donors (600 v 350 mL; P =.007). Histological examination showed no difference in degree of portal fibrosis or fatty change in liver grafts. There was no significant difference in postoperative serum transaminase levels or prothrombin times; however, anti-HBc-positive donors had greater serum bilirubin levels day 6 (26 v 21 micromol/L; P =.01) and day 7 (22 v 15 micromol/L; P =.004) after surgery. Postoperative complications developed in 10 anti-HBc-positive and 6 anti-HBc-negative donors (P =.4). All donors who developed cholestasis were positive for anti-HBc, aged 45 years or older, and had mild fatty changes of the liver. Hospital stays were similar. All donors had completely normal liver function at a median follow-up of 31 months (range, 21 to 76 months). A positive serological test result for anti-HBc should not be regarded as a contraindication for right-lobe liver donation.

Adult↗

PubMed2003

Impact of right-lobe live donor liver transplantation on patients waiting for liver transplantation.

Right-lobe live donor liver transplantation (LDLT) is accepted for adult patients, but the incremental benefit of LDLT over cadaveric donor liver transplantation (CDLT) is unknown. We evaluated prospectively the impact of right-lobe LDLT on patients listed for CDLT. Between January 1999 and December 2001, a total of 152 patients with chronic liver disease were listed for liver transplantation. The options of LDLT and CDLT were given after listing. Sixty-five patients (43%) had volunteers and 87 patients (57%) did not have volunteers. The groups with and without volunteers were similar in terms of age, diagnosis of liver disease, and Model for End-Stage Liver Disease score. The group with volunteers had a shorter waiting time for transplantation (median, 38 v 344 days; P <.001), greater transplantation rate (72% v 20%; P <.001), and lower mortality rate while waiting for a transplant (15% v 30%; P =.037). Overall, right-lobe LDLT was performed in 44 patients (29%). It increased the transplantation rate from 13% to 42%. On follow-up until December 2002 (median follow-up, 17.4 months), survival rates of the groups with and without volunteers were 68% and 51%, respectively (P =.034). One- and 3-year survival rates were 72.3% and 66.4% for the group with volunteers and 61.9% and 45.6% for the group without volunteers, respectively (P =.028). In conclusion, right-lobe LDLT offers patients listed for transplantation an incremental benefit by tripling the transplantation rate and improving overall survival.

Humans↗

PubMed2003

Live donor liver transplantation for fulminant hepatic failure in children.

The mortality rate among children with fulminant hepatic failure (FHF) on the waiting list for cadaveric donor liver transplantation (CDLT) is high. Results of emergency CDLT in this situation often are unsatisfactory, and a long-term survival rate less than 30% has been reported. Live donor liver transplantation (LDLT) for FHF in children has been advocated, but is reported rarely. We present our experience with LDLT in children with FHF. Between September 1993 and December 2002, primary LDLT was performed for 26 children; 8 of these children had FHF. Patient demographics, clinical and laboratory data, surgical details, complications, and graft and patient survival are reviewed. Four boys and four girls received left-lateral segment (n = 7) and full left-lobe (n = 1) grafts. Mean age was 2.9 +/- 1.2 years (range, 3 months to 11 years). Causes of FHF were drug induced in 2 patients and idiopathic in 6 patients. One child received a blood group-incompatible graft. Two patients died; 1 patient of cytomegalovirus infection at 8.6 months and 1 patient of recurrent hepatitis of unknown cause at 2.8 months after LDLT. The child who received a mismatched graft had refractory rejection and underwent a second LDLT with a blood group-compatible graft 19 days afterward. He eventually died of lymphoproliferative disease. Another patient developed graft failure related to venous outflow obstruction and survived after retransplantation with a cadaveric graft. With a median follow-up of 13.2 months (range, 2.8 to 60.3 months), actuarial graft and patient survival rates were 50% and 62.5%, respectively. Survival results appear inferior compared with those of 18 children who underwent LDLT for elective conditions during the same study period (graft survival, 89%; P =.051; patient survival, 89%; P =.281). Although survival outcomes are inferior to those in elective situations, LDLT is a timely and lifesaving procedure for children with FHF.

Child↗

PubMed2003

Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression.

OBJECTIVE: To investigate the degree and mechanism of hepatic sinusoidal injury in different graft sizes in right lobe live donor liver transplantation (LDLT). SUMMARY BACKGROUND DATA: Liver grafts from living donors are likely to be small-for-size for adult recipients. Graft injury after reperfusion is common, but the mechanism and degree of injury remain unclear. The hepatic sinusoidal injury in different graft sizes and its relationship with portal hemodynamics and intragraft gene response at the early phase after reperfusion have not been studied in right lobe LDLT. METHODS: From May 2000 to November 2001, 40 adults receiving right lobe LDLT had portal pressure measured continuously before and after reperfusion. Liver biopsies were taken before and after reperfusion for detection of vasoregulatory genes (endothelin-1 and endothelial nitric oxide synthase) and heat shock genes (heat shock protein 70 and heme oxygenase-1), and electron microscope examination. Blood samples from the portal vein and suprahepatic inferior vena cava were taken for the measurement of plasma nitric oxide level. RESULTS: The recipients were grouped according to the ratio of graft weight to estimated standard liver weight: group 1 (n = 10), less than 40%; group 2 (n = 21), 40% to 60%; and group 3 (n = 9), more than 60%. The portal pressures recorded after reperfusion in group 1 were significantly higher within 30 minutes of reperfusion than those in groups 2 and 3. After reperfusion, the intragraft endothelin-1 mRNA level in group 1 increased by 161% of the basal level but decreased by 31.5% and 62% of the basal level in groups 2 and 3, respectively. The intragraft mRNA level of heme oxygenase-1 in groups 1 and 2 decreased by 75.5% and 25.3% of the basal level respectively but increased by 41% of basal level in group 3. The intragraft protein level of heat shock protein 70 decreased by 50 ng/mL after reperfusion in group 1 but increased by 12.4 ng/mL and 0.6 ng/mL in groups 2 and 3, respectively. The portal vein plasma nitric oxide level decreased more significantly after reperfusion in group 1 than in group 2. Electron microscope examination of liver biopsies in group 1 showed tremendous mitochondrial swelling as well as irregular large gaps between the sinusoidal lining cells. There were two hospital deaths in group 1 and none in the other two groups. CONCLUSIONS: Patients implanted with grafts less than 40% of standard liver weight suffered from transient portal hypertension early after reperfusion. The phenomenon was accompanied by intragraft upregulation of endothelin-1 and ultrastructural evidence of sinusoidal damage. The transient portal hypertension after reperfusion, subsequent endothelin-1 overexpression, and plasma nitric oxide level reduction, together with downregulation of heme oxygenase-1 and heat shock protein 70, may account for the small-for-size graft injury.

Adolescent↗