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Background: Several studies reported favorable outcomes of small-for-size grafts with graft-to-recipient weight ratio (GRWR) <0.8% in living-donor liver transplantation (LDLT). However, their indications should be carefully determined because they must have been indicated for low-risk cases over larger grafts with 0.8% ≤ GRWR. Furthermore, evidence for minimum requirements of GRWR remains inconclusive. We investigated the safety of small-for-size grafts against larger grafts by adjusting for confounding risk factors, and minimum requirement of graft volume in adult LDLT., Methods: We enrolled 417 cases of primary adult-to-adult LDLT in our center between 2006 and 2019. The outcomes of small grafts (0.6% ≤ GRWR < 0.8%, n = 113) and large grafts (0.8% ≤ GRWR, n = 289) were mainly compared using a multivariate analysis and Kaplan-Meier estimates., Results: The multivariate analysis showed that small grafts were not a significant risk factor for overall graft survival (GS). In the Kaplan-Meier analysis, small grafts did not significantly affect overall GS regardless of lobe selection (versus large grafts). However, GRWR < 0.6% was associated with poor overall GS. Although there were no significant differences between the 2 groups, unadjusted Kaplan-Meier curves of small grafts were inferior to those of large grafts in subcohorts with ABO incompatibility, and donor age ≥50 years., Conclusions: Similar outcomes were observed for small and large graft use regardless of lobe selection. 0.6% in GRWR was reasonable as the minimum requirement of graft volume in LDLT. However, small grafts should be indicated carefully for high-risk cases., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The liver is a unique organ with an abundant regenerative capacity. Therefore, partial hepatectomy (PHx) or partial liver transplantation (PLTx) can be safely performed. Liver regeneration involves a complex network of numerous hepatotropic factors, cytokines, pathways, and transcriptional factors. Compared with liver regeneration after a viral- or drug-induced liver injury, that of post-PHx or -PLTx has several distinct features, such as hemodynamic changes in portal venous flow or pressure, tissue ischemia/hypoxia, and hemostasis/platelet activation. Although some of these changes also occur during liver regeneration after a viral- or drug-induced liver injury, they are more abrupt and drastic following PHx or PLTx, and can thus be the main trigger and driving force of liver regeneration. In this review, we first provide an overview of the molecular biology of liver regeneration post-PHx and -PLTx. Subsequently, we summarize some clinical conditions that negatively, or sometimes positively, interfere with liver regeneration after PHx or PLTx, such as marginal livers including aged or fatty liver and the influence of immunosuppression.

Background: We established a completely novel method of auxiliary xenogeneic partial liver transplantation and examined whether liver grafts procured from Syrian hamsters regenerated in nude rats, which were used as in vivo bioreactors., Methods: The hamsters and the rats were all males (n = 10). Partial liver grafts from hamsters were transplanted into nude rats in an auxiliary manner. We evaluated liver graft injury, rejection, and regeneration during 7 days after auxiliary xenogeneic partial liver transplantation., Results: All rats survived until sacrifice on post-operative day (POD) 1, 3, and 7. HE-staining showed normal at POD1, mild periportal edema, and slight bile duct and venous endothelial inflammation at POD3, and moderate acute cellular rejection at POD7 without parenchymal necrosis. The liver regeneration rates at POD3 and 7 were 1.54 ± 0.23 and 2.54 ± 0.43, respectively. The Ki-67 labeling index was also elevated at POD3 (27.5 ± 4.1%). Serum HGF and VEGF were elevated at POD1 and 3. ATP levels of liver grafts recovered at POD7., Conclusions: These results revealed that with appropriate immunosuppressive therapy, partial liver graft regeneration occurred in a xenogeneic animal, which suggests liver grafts regenerated in xenogeneic environments, such as an in vivo bioreactor, have potential to be transplantable liver grafts for humans., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models., Methods: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 μmol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight., Results: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group., Conclusion: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied., (© 2019 S. Karger AG, Basel.)

In mammalian livers, sexual dimorphisms are observed in tissue-specific functions and diseases such as hepatocellular carcinoma. We identified sex-dependent differentially methylated regions (S-DMRs) which had been previously been characterized as growth hormone- STAT5 dependent. In this study, we performed genome-wide screening and identified ten additional hypomethylated S-DMR gene regions in male livers. Of these S-DMRs, Uggt2 and Sarnp were hypomethylated in both male and female livers compared to brain and embryonic stem (ES) cells. Similarly, Adam2, Uggt2, and Scp2 were hypomethylated in female embryonic germ (EG) cells and not in male EG cells, indicating that these S-DMRs are liver-specific male hypo-S-DMRs. Interestingly, the five S-DMRs were free from STAT5 chromatin immunoprecipitation (ChIP) signals, suggesting that S-DMRs are independent of the growth hormone-STAT5-pathway. Instead, the DNA methylation statuses of the S-DMRs of Adam2, Snx29, Uggt2, Sarnp, and Rnpc3 genes were under the control of testosterone. Importantly, the hypomethylated S-DMRs of the Adam2 and Snx29 regions showed chromatin decondensation. Epigenetic factors could be responsible for the sexual dimorphisms in DNA methylation status and chromatin structure, as the expression of Dnmt1, Dnmt3b, and Tet2 genes was lower in male mice compared to female mice and TET2 expression recovered following orchidectomy by testosterone treatment. In conclusion, we identified novel male-specific hypomethylated S-DMRs that contribute to chromatin decondensation in the liver. S-DMRs were tissue-specific and the hypomethylation is testosterone-dependent., (Copyright © 2015. Published by Elsevier Inc.)

An insufficient remnant in extended hepatectomy and small-for-size graft in liver transplantation are critical matters in the field of liver surgery, and reliable and reproducible animal models that can provide clinically relevant and reliable data are needed. We herein describe our detailed surgical procedures for performing 70 % hepatectomy in pigs, and discuss the critical anatomical features, key techniques and pitfalls based on our experience. The porcine liver is divided into four lobes. The right lateral lobe (RLL) accounts for 30 % of the liver volume. Important points, such as selective temporal clamping of the arterial branch, confirmation of a related demarcation line, a two-step process to skeletonize Glisson's capsules during liver resection and selective ligation of the portal venous branch to the right medial lobe without inducing any subtle injuries to Glisson's capsules from the RLL to common bile duct, are discussed.

Background: Liver transplant outcomes using grafts donated after cardiac death (DCD) remain poor., Methods: We investigated the effects of ex vivo reconditioning of DCD grafts with venous systemic oxygen persufflation using nitric oxide gas (VSOP-NO) in rat liver transplants. Orthotopic liver transplants were performed in Lewis rats, using DCD grafts prepared using static cold storage alone (group-control) or reconditioning using VSOP-NO during cold storage (group-VSOP-NO). Experiment I: In a 30-min warm ischemia model, graft damage and hepatic expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1) were examined, and histologic analysis was performed 2, 6, 24, and 72 hr after transplantation. Experiment II: In a 60-min warm ischemia model, grafts were evaluated 2 hr after transplantation (6 rats/group), and survival was assessed (7 rats/group)., Results: Experiment I: Group-VSOP-NO had lower alanine aminotransferase (ALT) (P<0.001), hyaluronic acid (P<0.05), and malondialdehyde (MDA) (P<0.001), hepatic interleukin-6 expression (IL-6) (P<0.05), and hepatic tumor necrosis factor-alpha (TNF-α) expression (P<0.001). Hepatic eNOS expression (P<0.001) was upregulated, whereas hepatic iNOS (P<0.01) and ET-1 (P<0.001) expressions were downregulated. The damage of hepatocyte and sinusoidal endothelial cells (SECs) were lower in group-VSOP-NO.Experiment II: VSOP-NO decreased ET-1 and 8-hydroxy-2'deoxyguanosine (8-OHdG) expression and improved survival after transplantation by 71.4% (P<0.01)., Conclusion: These results suggest that VSOP-NO effectively reconditions warm ischemia-damaged grafts, presumably by decreasing ET-1 upregulation and oxidative damage.

When the graft volume is too small to satisfy the recipient's metabolic demand, the recipient may thus experience small-for-size syndrome (SFSS). Because the occurrence of SFSS is determined by not only the liver graft volume but also a combination of multiple negative factors, the definitions of small-for-size graft (SFSG) and SFSS are different in each institute and at each time. In the clinical setting, surgical inflow modulation and maximizing the graft outflow are keys to overcoming SFSS. Accordingly, relatively smaller-sized grafts can be used with surgical modification and pharmacological manipulation targeting portal circulation and liver graft quality. Therefore, the focus of the SFSG issue is now shifting from how to obtain a larger graft from the living donor to how to manage the use of a smaller graft to save the recipient, considering donor safety to be a priority.

The increasing shortage of donor organs has led to the increasing use of organs from non-heart-beating donors. We aimed to assess the impact of venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the cold storage (CS) of warm ischemia (WI)-damaged experimental liver grafts. Rat livers (n = 5 per group) were retrieved after 30 minutes of WI induced by cardiac arrest (the WI group) and were thereafter preserved for 24 hours by CS in histidine tryptophan ketoglutarate solution. During CS, gaseous oxygen was insufflated via the caval vein with 40 ppm NO (the VSOP-NO group) or without NO (the VSOP group). Cold-stored livers without WI served as controls. Liver viability was assessed after the preservation period by normothermic isolated reperfusion for 45 minutes with oxygenated Krebs-Henseleit buffer. After 45 minutes of reperfusion, the VSOP-NO-treated livers showed significantly lower alanine aminotransferase values than the WI-damaged livers (10.2 ± 0.2 versus 78.2 ± 14.6 IU/L), whereas the control livers showed no differences from the VSOP-NO-treated livers. The mitochondrial enzyme release was lower in the VSOP-NO group (4.0 ± 0.7 IU/L) versus the WI group (18.2 ± 4.9 IU/L). An increased portal vein pressure was observed throughout reperfusion (45 minutes) in the WI group (21.7 ± 0.2 mm Hg) versus the VSOP-NO group (12.2 ± 0.8 mm Hg) and the control group (19.9 ± 0.4 mm Hg). Furthermore, the NO concentration in the perfusate after 5 minutes of reperfusion was highest in the VSOP-NO group. The release of malondialdehyde into the perfusate was significantly reduced in the VSOP-NO group (0.9 ± 0.1 nmol/mL) versus the WI group (31.3 ± 5.3 nmol/mL). In conclusion, the resuscitation of livers after 30 minutes of WI to a level comparable to that of nonischemically damaged livers is possible with VSOP supplemented with NO gas. Moreover, the application of VSOP with NO minimizes the extent of injuries caused by oxygen free radicals during preservation., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Background: Due to the severe shortage of deceased donors, demand for living-donor liver transplantation (LDLT) has increased worldwide. Here, we compared POLYSOL, a recently developed low-viscosity preservation solution, and histidine-tryptophan-ketoglutarate (HTK) for cold storage of partial liver graft in this study., Methods: Partial liver transplantations with 30% of the native liver were performed in Lewis rats. The graft livers were flushed with either HTK or POLYSOL (n = 25, respectively) and stored in the respective solution for 3 h at 5°C. Graft function was evaluated regarding ischemia-reperfusion injury and regeneration at 1, 3, 24, and 168 h after reperfusion., Results: POLYSOL preservation resulted in improvement of portal venous flow (HTK versus POLYSOL; mean ± SEM: 16.8 ± 2.2 versus 21.6 ± 2.1 mL/min; P = 0.005), microcirculation (383 ± 63 versus 532 ± 64 Flux; P = 0.045), ALT (310.2 ± 56.1 versus 181.8 ± 17.0 IU/L; P = 0.0262), LDH (4052.4 ± 764.4 versus 2494.1 ± 410.0 IU/L; P = 0.0215), total bilirubin (21.6 ± 14.2 versus 4.0 ± 0.6 IU/L; P = 0.0236), malondialdehyde (100.0 ± 4.3 versus 69.2 ± 4.0 nmol/mL; P = 0.0015), as well histologic findings at 24 h. Liver regeneration was improved in POLYSOL with regards to liver weight (4.0 ± 0.2 versus 4.3 ± 0.3 g; P = 0.038) and Ki-67 labeling index (9.67 ± 2.17 versus 1.10 ± 0.14%; P < 0.0001) at 24 h with higher up-regulation of portal VEGF (31.55 ± 5.78 versus 91.94 ± 9.27 pg/mL; P = 0.0052)., Conclusions: This study showed that POLYSOL improves microcirculation and thus improves the preservation quality of partial liver transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Infectious complications such as bacteremia after living donor liver transplantation (LDLT) are associated with significant morbidity and mortality. We retrospectively analyzed the frequency and characteristics of posttransplant bacteremia in 181 adult LDLT recipients between April 2006 and November 2009, and we evaluated the risk factors for posttransplant bacteremia. One hundred seventeen episodes of bacteremia occurred in 62 of 181 recipients (34.3%) within 12 days (median) after transplantation (range = 1-71 days). The most frequently isolated pathogens were Pseudomonasaeruginosa (26 episodes), methicillin-resistant coagulase-negative staphylococci (22 episodes), and Enterococcus sp. (11 episodes). The overall survival rate at 1 year for patients with bacteremia (n = 62) was significantly lower than the rate for patients without bacteremia (n = 119; 69.6% versus 92.3%, respectively, P < 0.0001). Multivariate analysis showed that Child-Pugh class C (P = 0.0002), preoperative massive pleural effusion or ascites requiring drainage (P = 0.0384), postoperative cytomegalovirus infection (P = 0.0014), ABO incompatibility (P = 0.0188), and older donor age (P = 0.015) were independent risk factors for postoperative bacteremia. In conclusion, bacteremia occurred at a high rate after adult LDLT and induced a higher mortality rate in those who developed it. Infection control may play a pivotal role in improving early outcomes after LDLT., (Copyright © 2010 American Association for the Study of Liver Diseases.)

Tissue-specific expression of transporters is tightly linked with their physiological functions through the regulation of the membrane transport of their substrates. We hypothesized that epigenetic regulation underlies the tissue-specific expression of mouse liver-specific transporters (Oatp1b2/Slco1b2, Ntcp/Slc10a1, Bsep/Abcb11, and Abcg5/g8). We examined their DNA methylation and histone modification profiles near the transcriptional start site (TSS) in the liver, kidney, and cerebrum. Genome-wide DNA methylation profiling with tissue-dependent differentially methylated region profiling with restriction tag-mediated amplification and subsequent bisulfite genomic sequencing demonstrated that the CpG dinucleotides around the TSS of Oatp1b2 (from -515 to +149 CpGs), Ntcp (from -481 to +495 CpGs), Bsep (from -339 to +282 CpGs), and Abcg5/g8 (from -161 to +5 CpGs for Abcg5, i.e., from -213 to -48 CpGs for Abcg8) were hypomethylated in the liver and hypermethylated in the kidney and cerebrum. The opposite pattern was observed for Pept2/Slc15a2 (from -638 to +4 CpGs), which was expressed in the kidney and cerebrum but not in the liver. These DNA methylation profiles are consistent with the tissue distribution of these transporters. A chromatin immunoprecipitation assay demonstrated that the histone H3 associated with Oatp1b2, Ntcp, Bsep, and Abcg5/g8 promoters was hyperacetylated in the liver but was acetylated very little in the kidney and cerebrum, whereas the upstream region of Pept2 was hyperacetylated only in the kidney and cerebrum. These results suggest the involvement of epigenetic systems in the tissue-specific expression of mouse transporters Oatp1b2, Ntcp, Bsep, Abcg5/g8, and Pept2.

Background: In adult living-donor liver transplantation (LDLT), the assessment of the graft functional reserve is very important. We evaluated the graft functional reserve by technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl-human serum albumin ((99m)Tc-GSA) liver scintigraphy., Patients and Method: From May 2003 to September 2006, (99m)Tc-GSA studies were performed in 27 adult recipients on two, four wk after LDLT, the receptor index [ratio of liver to heart-plus-liver radioactivity at 15 minutes (LHL15)] (LHL15) was calculated. Recipients were divided into two groups according to LHL15 on two wk after LDLT (group H; >0.935, group L; <0.935). Liver functional tests and recipients' background parameters were evaluated between the two groups., Result: Group L accompanied higher preoperative model for end-stage liver disease (MELD) score (p = 0.038), lower graft-recipient weight ratio (GRWR) (p = 0.032) and older donor age (p = 0.003) compared with group H. There was no significant difference in the graft regeneration rate between two groups. The three-yr cumulative survival rate was 76.1% in group L and 88.9% in group H., Conclusion: In LDLT, LHL15 has the potential to assess the graft function and predict the recipients' outcome. Graft function after LDLT may be related closely to the pretransplant MELD score, GRWR, and donor age.

Aim: To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation (LDLT), and to clarify how systemic hemodynamics impact on local graft circulation after LDLT., Methods: Systemic hemodynamics, indocyanine green (ICG) elimination rate (K ICG) and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry (PDD) and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output (CO) to blood volume (BV) and mean transit time (MTT), defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function., Results: Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance (TPR) were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and MTT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased K ICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow., Conclusion: We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.

In adult living-donor liver transplantation (LDLT), the assessment of the allograft functional reserve is important for adequate graft regeneration. From March 2002 to December 2003, 30 adult recipients underwent right lobe LDLT. Mean CT attenuation values (CT-AVs) in the graft were measured on unenhanced CT for 6 months after LDLT. The histological features of the graft parenchyma were evaluated with post-operative liver biopsy specimens. Mean CT-AVs after LDLT were decreased significantly from the pre-operative values, recovered to over 60 HU within 6 months. There was a positive linear correlation between the CT-AVs and the receptor index (LHL15) in technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl-human serum albumin ((99m)Tc-GSA) liver scintigraphy (r = 0.803, p = 0.005). The recipients were divided into two groups according to the CT-AV at one post-operative week (group H; > or =55HU, group L; <55HU). The low CT-AVs, under 55 HU, in group L were prolonged for 3 months compared with those in group H (p < 0.05). The 1-year cumulative survival rate was 94.7% and 45.5% in groups H and L, respectively (p = 0.014). Histological findings revealed that the parenchymal damage was severe in the grafts with low CT-AVs. The CT-AVs in the grafts may be a useful parameter for assessing the allograft functional reserve.

Aim: Direct‐acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post‐living donor liver transplantation (LDLT). Methods: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post‐LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. Results: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4–15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus‐related cirrhosis, of which two were treated with direct‐acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody‐positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19–463] days). Conclusion: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody‐positive grafts, should be carefully followed by surveillance of the liver graft. [ABSTRACT FROM AUTHOR]

Gastrinomas mainly occur in the duodenum and pancreas. Primary hepatic gastrinoma is rare and difficult to diagnose because the liver is a frequent site of metastatic gastrinomas. Clinical factors were assessed in a 28-year-old man with diarrhea and heartburn who was hospitalized for recurrent duodenal ulcers. Abdominal ultrasound, endoscopic ultrasound and computed tomography ( CT) could not detect a tumor in the duodenum or pancreas. His gastrin level was 846 pg/mL and magnetic resonance imaging showed a mass 12 mm in diameter in the right robe of the liver. A selective intra-arterial calcium injection ( SACI) test and 68-gallium edotreotide positron emission tomography CT ( Ga- DOTATOC PET-CT) were therefore performed. Calcium gluconate injection into the proper hepatic artery resulted in a marked increase in serum gastrin concentration in the right hepatic vein, with Ga- DOTATOC PET-CT showing uptake only by the liver mass. Following a diagnosis of primary hepatic gastrinoma, the tumor was resected. A histopathological examination indicated gastrinoma. Six months postoperatively, he has no symptoms, is not taking proton-pump inhibitors and his gastrin level remains within the normal range. The SACI test and the clinical course of this patient strongly suggest that the tumor was a primary hepatic gastrinoma. The SACI test is helpful in the diagnosis of primary hepatic gastrinoma. [ABSTRACT FROM AUTHOR]

Background: After extensive hepatectomy, excessive portal venous flow (PVF) and elevated portal venous pressure (PVP) may lead to postoperative liver damage. We have evaluated the use of portocaval shunt (PCS) to control PVF and PVP following partial hepatectomy (PH) to reduce the postoperative liver damage. Method: Twenty-four pigs were divided into two Groups: Group C (n = 10) underwent 70% PH alone and Group S (n = 14) underwent 70% PH with PCS. The changes in PVF, PVP, serum liver function tests, and histology were evaluated. Results: PVP and PVF per unit of remnant liver weight and serum total bilirubin levels in Group S were significantly lower than those in Group C postoperatively (P < 0.05). Histology showed that there were significant differences in hepatocyte ballooning, necrosis, and neutrophil aggregation between the two groups (P < 0.05). In particular, hepatic necrosis was observed in zone 3 of Group C as centrilobular necrosis. These results suggest that hepatic and sinusoidal damage after 70% PH were more severe in Group C than in Group S, with the latter group maintaining an almost normal ultrastructural appearance. Hepatocyte apoptotic index differed significantly between the two groups (P < 0.0001). Conclusion: After 70% PH, extensive centrolobular necrosis and neutrophil aggregation were present and may have caused liver damage, manifested as hyperbilirubinemia and coagulopathy. The delayed liver regeneration with PCS may reduce the postoperative liver damages rather than the rapid liver hypertrophy. The diversion of PVF with PCS to maintain adequate PVP is a very effective procedure for avoiding the postoperative liver failure after extensive hepatectomy. [Copyright &y& Elsevier]

The Pringle maneuver (PM) has been widely used to control blood loss during liver resection. However, hepatic inflow occlusion can also result in hepatic ischemia–reperfusion injury (IRI), especially in patients with a cholestatic, fibrotic, or cirrhotic liver. Here we investigate a nitric oxide synthase (NOS) inhibitor N-Nitroarginine methyl ester (L-NAME) on IRI after the PM and partial hepatectomy of cholestatic livers induced by bile duct ligation (BDL) in rats. Control group (non-BDL/no treatment), BDL + T group (BDL/L-NAME treatment) and BDL group (BDL/no treatment) were analyzed. Cholestasis was induced by BDL in the L-NAME and BDL group and a 50% partial hepatectomy with PM was performed. L-NAME was injected before PM in the BDL + T group. Hepatocellular damage, portal venous flow, microcirculation, endothelial lining, and eNOS, iNOS, interleukin (IL)-6, and transforming growth factor-β (TGF-β) were evaluated. Microcirculation of the liver in the BDL + T group tended to be higher. Liver damage and apoptotic index were significantly lower and Ki-67 labeling index was higher in the BDL + T group while iNOS and TGF-β expression was decreased. This was corroborated by a better preserved endothelial lining. L-NAME attenuated IRI following PM and improved proliferation/regeneration of cholestatic livers. These positive effects were considered as the result of improved hepatic microcirculation, prevention of iNOS formation, and TGF-β mRNA upregulation. [ABSTRACT FROM AUTHOR]