Portal Hyperperfusion Research Articles

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation

Background/Aim: Liver size regulation is based on the balance between hepatic regeneration and atrophy. To achieve a better understanding of intrahepatic size regulation, we explored the size regulation of a portally deprived liver lobe on a liver subjected to concurrent portal vein ligation (PVL) and partial hepatectomy (PHx). Materials and Methods: Using a surgical rat model consisting of right PVL (rPVL) plus 70% PHx, we evaluated the size regulation of liver lobes 1, 2, 3, and 7 days after the operation in terms of liver weight and hepatocyte proliferation. Portal hyperperfusion was confirmed by measuring portal flow. The portal vascular tree was visualized by injection of a contrast agent followed by CT imaging of explanted livers. Control groups consisted of 70% PHx, rPVL, and sham operation. Results: The size of the ligated right lobe increased to 1.4-fold on postoperative day 7 when subjected to rPVL + 70% PHx. The right lobe increased to 3-fold when subjected to 70% PHx alone and decreased to 0.3-fold when subjected to rPVL only. The small but significant increase in liver weight after the combined procedure was accompanied by a low proliferative response. In contrast, hepatocyte proliferation was undetectable in the right lobe undergoing atrophy after PVL only. The caudate lobe in the rPVL + 70% PHx group increased to 4.6-fold, which is significantly more than in the other groups. This increase in liver weight was paralleled by persisting portal hyperperfusion and a prolonged proliferative phase of 3 days. Conclusions: A discontinued portal blood supply does not always result in atrophy of the ligated lobe. The concurrent regenerative stimulus induced by 70% PHx seemed to counteract the local atrophy after a simultaneously performed rPVL, leading to a low but prolonged regenerative response of the portally deprived liver lobe. This observation supports the conclusion that portal flow is not necessary for liver regeneration. The persisting portal hyperperfusion may be crucial for the specific kinetics of prolonged liver regeneration after rPVL + 70% PHx in the portally supplied caudate lobe. Both observations deserve more attention regarding the underlying mechanism in further studies.

Portosystemic Shunts for "Too Small-for-Size Syndrome" After Liver Transplantation: A Systematic Review.

Portosystemic shunts (PSSs) modulate the portal hyperperfusion against small-for-size syndrome (SFSS) after split or living donor liver transplantation. To find out the results and the limitations of PSSs against SFSS. We searched PubMed and Cochrane databanks for systematic review and analyzed the indications, types, morbidities, and survivals of the PSSs at split or living donor liver transplantations. Total 66 patients were assessed in 16 studies. Main indications for PSS were graft recipient weight ratio (GRWRs) <0.8% and/or portal vein pressure >20mmHg. Five different types of PSSs were described but hemi-portocaval shunts were the most common one. The incidence of SFSS was 12%. Overall 90-day, 1-, and 3-year graft survivals were 80, 70, and 47%, respectively. GRWR <0.65% was found as the only significant parameter on graft survival. The 90-day, 1- and 3-year graft survivals for GRWR <0.65 and ≥0.65% patients were 62.5, 42.8, and 30.0 and 95, 94, and 67%, respectively (p=0.03, p=0.01, and p=0.18). PSSs can modulate the small graft size (GRWR<0.8%) and/or portal hypertension (>20mmHg) after split or living donor liver transplantations sufficiently. However, its protective effect is not unlimited. If the GRWR is below 0.65%, survival decreases significantly despite PSSs.

Effects of portal hyperperfusion on partial liver grafts in the presence of hyperdynamic splanchnic circulation: hepatic regeneration versus portal hyperperfusion injury

Effects of portal hyperperfusion on partial liver grafts in the presence of hyperdynamic splanchnic circulation: hepatic regeneration versus portal hyperperfusion injury

Importance of Hepatic Flows in Liver Transplantation

Establishing appropriate dual blood supply in liver transplant is important to ensure optimal graft survival and post-operative outcomes. The hemodynamic changes in cirrhotic patients render the patients with hyperdynamic circulation and this environment raises the portal venous flow through the graft immediately after transplant. In deceased donor liver transplantation, lower hepatic flows are associated with detrimental outcomes. Lower measured hepatic artery flow has been associated with lower graft survival and higher rate of arterial complications. Lower portal venous flow of less than 1-1.3 L/min has been associated with lower graft survival. Lower hepatic artery flow is associated with increased rate of biliary complications after deceased donor transplantation. In live donor liver transplantation, portal hyperperfusion is implicated in small for size syndrome. Maneuvers to decrease portal venous flow such as splenic artery ligation, splenectomy or portacaval shunt have been associated with improved outcomes after live donor liver transplantation. It appears that relationship between higher portal flows and poor outcomes is not yet firmly established in that the live donor liver graft may tolerate higher PV flows when the outflow of the graft is well established and if the higher PV flow is not accompanied by portal hypertension. The importance of blood flow in liver transplantation is undeniable. Further studies are required to establish the relationship between the portal and hepatic arterial flows to biliary and arterial complications after liver transplantation.

How Much Portal Vein Flow Is Too Much for Liver Remnant in a Stable Porcine Model?

BackgroundThere is increasing evidence that the occurrence of small-for-size syndrome (SFSS) depends on portal hemodynamics rather than graft size. The portal hyperperfusion has been regarded as the most important contributing factor to SFSS. However, it is unknown how much portal vein flow (PVF) or what limit of PVF the liver remnant can sustain in extreme hepatectomy. This study aimed to evaluate the limit of portal hyperperfusion in a stable porcine model. MethodsTwenty pigs were subjected to different liver resection volumes of 77%–82% (80% group; n = 6), 83%–87% (85% group; n = 7), and 88%–92% (90% group; n = 7). The survival rate, hemodynamic change, energy metabolism, lipopolysaccharide (LPS)/bacterial translocation, and injury and regeneration of the residual liver were observed after surgery. ResultsAll of the 80% group could sustain ∼4 times baseline PVF per unit volume, energy metabolism, and detoxifying functions, and survived to postoperative day (POD) 14. Only 3 animals in the 85% group, with ∼5.6 times baseline of PVF, were alive on POD 14, and in the 90% group, with >6 times baseline of PVF, undergoing severe hyperperfusion injury and LPS/bacterial translocation, none survived to POD 14. ConclusionsThe deaths of animals in the 85% group supports the hypothesis that the remnant vascular bed with 15% of liver volume represents a critical residual liver parenchyma in pigs, the safe minimum residual liver volume should be >15% of liver volume, indicating that the liver remnant can regenerate successfully in ∼5.6 times baseline of PVF, whereas it fails to regenerate in >5.6 times baseline of PVF.

Portal Hyperperfusion after Extended Hepatectomy Does Not Induce a Hepatic Arterial Buffer Response (HABR) but Impairs Mitochondrial Redox State and Hepatocellular Oxygenation.

Background & AimsPortal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. The underlying mechanisms, however, are still not completely understood. Herein, we analysed whether hepatectomy-associated portal hyperperfusion induces a hepatic arterial buffer response, i.e., an adaptive hepatic arterial constriction, which may cause hepatocellular hypoxia and organ dysfunction.MethodsSprague-Dawley rats underwent 30%, 70% and 90% hepatectomy. Baseline measurements before hepatectomy served as controls. Hepatic arterial and portal venous flows were analysed by ultrasonic flow measurement. Microvascular blood flow and mitochondrial redox state were determined by intravital fluorescence microscopy. Hepatic tissue pO2 was analysed by polarographic techniques. Hepatic function and integrity were studied by bromosulfophthalein bile excretion and liver histology.ResultsPortal blood flow was 2- to 4-fold increased after 70% and 90% hepatectomy. This, however, did not provoke a hepatic arterial buffer response. Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy. Microvascular blood flow increased significantly after hepatectomy and functional sinusoidal density was found only slightly reduced. Major hepatectomy further induced a 2- to 3-fold increase of bile flow. This was associated with a 2-fold increase of bromosulfophthalein excretion.ConclusionsPortal hyperperfusion after extended hepatectomy does not induce a hepatic arterial buffer response but reduces mitochondrial redox state and hepatocellular oxygenation. This is not due to a deterioration of microvascular perfusion, but rather due to a relative hypermetabolism of the remnant liver after major resection.

Optimal Central Venous Pressure During the Neohepatic Phase to Decrease Peak Portal Vein Flow Velocity for the Prevention of Portal Hyperperfusion in Patients Undergoing Living Donor Liver Transplantation

BackgroundThe association between intraoperative systemic hemodynamic status and preventing portal hyperperfusion, which induces shear stress on the sinusoidal endothelial cells of liver grafts, resulting in poor graft function in live-donor recipients, has not been identified. This study evaluates the effects of systemic hemodynamic parameters (SHPs) during the neohepatic phase on changes in hepatic hemodynamic parameters (HHPs) between the neohepatic phase and the 1st postoperative day. MethodsThirty-eight patients undergoing living donor liver transplantation (LDLT) were enrolled in this study. HHPs (flow velocities of portal vein and hepatic artery) were measured immediately after hepatic artery and bile duct reconstruction and on the first postoperative day. SHPs (mean arterial pressure, central venous pressure [CVP], cardiac index, stroke volume variation, stroke volume index, systemic vascular resistance index, and central venous oxygen saturation) were recorded and averaged for 5 minutes after the measurement of HHPs. The relationships between the SHPs and HHPs were assessed using linear or quadratic regression analysis. ResultsPeak portal vein flow velocity (PVV) decreased on the 1st postoperative day in 24 patients (63%). There was an inverted-U relationship between CVP and the percentage change in PVV (R2 = 0.241, P = .008). According to the quadratic regression model, the PVV maximally decreased at a CVP of 7.8 mm Hg. No significant correlations were found between the other SHPs and HHPs. ConclusionsMaintaining CVP (approximately 8 mm Hg) during the neohepatic phase was clinically beneficial in decreasing PVV to prevent portal hyperperfusion in the early postoperative period of LDLT.

Safety and efficacy of splenic artery embolization for portal hyperperfusion in liver transplant recipients: a 5-year experience.

Severe portal hyperperfusion (PHP) after liver transplantation has been shown to cause intrahepatic arterial vasoconstriction secondary to increased adenosine washout (hepatic artery buffer response). Clinically, posttransplant PHP can cause severe cases of refractory ascites and hydrothorax. In the past, we reported our preliminary experience with the use of splenic artery embolization (SAE) as a way to reduce PHP. Here we present our 5-year experience with SAE in orthotopic liver transplantation (OLT). Between January 2007 and December 2011, 681 patients underwent OLT at our institution, and 54 of these patients underwent SAE for increased hepatic arterial resistance and PHP (n=42) or refractory ascites/hepatic hydrothorax (n=12). Patients undergoing SAE were compared to a control group matched by year of embolization, calculated Model for End-Stage Liver Disease score, and liver weight. SAE resulted in improvements in hepatic artery resistive indices (0.92±0.14 and 0.76±0.10 before and after SAE, respectively; P<0.001) and improved hepatic arterial blood flow (HAF; 15.6±9.69 and 28.7±14.83, respectively; P<0.001). Calculated splenic volumes and spleen/liver volume ratios were correlated with patients requiring SAE versus matched controls (P=0.002 and P=0.001, respectively). Among the 54 patients undergoing SAE, there was 1 case of postsplenectomy syndrome. No abscesses, significant infections, or bleeding was noted. We thus conclude that SAE is a safe and effective technique able to improve HAF parameters in patients with elevated portal venous flow and its sequelae.

Split liver transplantation: What’s unique?

The intraoperative management of split liver transplantation (SLT) has some unique features as compared to routine whole liver transplantations. Only the liver has this special ability to regenerate that confers benefits in survival and quality of life for two instead of one by splitting livers. Primary graft dysfunction may result from small for size syndrome. Graft weight to recipient body weight ratio is significant for both trisegmental and hemiliver grafts. Intraoperative surgical techniques aim to reduce portal hyperperfusion and decrease venous portal pressure. Ischemic preconditioning can be instituted to protect against ischemic reperfusion injury which impacts graft regeneration. Advancement of the technique of SLT is essential as use of split cadaveric grafts expands the donor pool and potentially has an excellent future.

Somatostatin Therapy Protects Porcine Livers in Small-for-Size Liver Transplantation

Small-for-size (SFS) injury occurs in partial liver transplantation due to several factors, including excessive portal inflow and insufficient intragraft responses. We aim to determine the role somatostatin plays in reducing portal hyperperfusion and preventing the cascade of deleterious events produced in small grafts. A porcine model of 20% liver transplantation is performed. Perioperatively treated recipients receive somatostatin and untreated controls standard intravenous fluids. Recipients are followed for up to 5 days. In vitro studies are also performed to determine direct protective effects of somatostatin on hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). At reperfusion, portal vein flow (PVF) per gram of tissue increased fourfold in untreated animals versus approximately threefold among treated recipients (p = 0.033). Postoperatively, markers of hepatocellular, SEC and HSC injury were improved among treated animals. Hepatic regeneration occurred in a slower but more orderly fashion among treated grafts; functional recovery was also significantly better. In vitro studies revealed that somatostatin directly reduces HSC activation, though no direct effect on SEC was found. In SFS transplantation, somatostatin reduces PVF and protects SEC in the critical postreperfusion period. Somatostatin also exerts a direct cytoprotective effect on HSC, independent of changes in PVF.

Reduced hepatic arterial perfusion impairs the recovery from focal hepatic venous outflow obstruction in liver-resected rats.

Extended partial hepatectomy (PH) in patients is leading to portal hyperperfusion but reduced hepatic arterial perfusion (HAP), and is invariably causing focal hepatic venous outflow obstruction (FHVOO). We observed in a rat model that PH in combination with right median hepatic vein ligation (RMHV-L) caused confluent parenchymal necrosis interspersed with viable portal tracts in the obstructed territory and large sinusoidal vascular canals in the border zone. Lack of HAP impaired the spontaneous course of recovery in terms of enlarged parenchymal necrosis, delayed regeneration, and the absence of draining vascular canals. We aimed to investigate whether pharmacological intervention modulates the imbalance between portal venous and hepatic arterial inflow, aggravates the liver damage, and delays the recovery process after FHVOO in liver-resected rats. Male Lewis rats were subjected to 70% PH and RMHV-L. Molsidomine or NG-nitro-L-arginine methyl ester (L-NAME) or saline were applied daily. Hepatic damage, microcirculation, regeneration, and vascular remodeling were evaluated at postoperative days 1, 2, and 7. Animals subjected to RMHV-L only were used as "no HAP" control. Significant increase of portal venous inflow with a concomitant decrease in HAP was observed in all groups after PH. Molsidomine treatment did neither affect hepatic hemodynamics nor the spontaneous recovery. In contrast, L-NAME treatment further decreased HAP which impaired hepatic microcirculation, aggravated parenchymal damage, decelerated recovery, and impaired the formation of sinusoidal canals. Reduction of HAP through inhibition of nitric oxide production worsened the recovery from FHVOO. Drugs increasing HAP need to be evaluated to reverse the hyperperfusion-induced impairment of the spontaneous course after FHVOO.

The Safe Minimally Ischemic Liver Remnant for Small-for-Size Syndrome in Porcine Hepatectomy

BackgroundThe minimal functional remnant liver mass or graft after an ischemic injury in hepatectomy or living donor liver transplantation (LDLT) is not clear. This study sought to determine the minimal remnant liver (MRL) size after 20 minutes hepatic inflow occlusion (HIO) and the maximal portal flow with which the liver remnant can sustain in a porcine model. MethodsTwenty pigs that underwent massive hepatectomy were randomly divided into 3 groups: 30% group, the remnant constituted about 30% of total liver volume (TLV); 35%+O group, the remnant constitute about 35% of TLV with 20 minutes HIO, and 30%+O group, the remnant constituted about 30% of TLV with 20 minutes of HIO. We evaluated survival rates, kinetic portal vein pressures (PVP), hemodynamics, hepatocyte metabolism, and injury. ResultsThe 14-day survival rate in the 30%+O group was significantly reduced compared with that of either the 30% group or the 35%+O group: l00% versus 28.6% versus 85.7% respectively (P = .009). The tissue, serum analyses, and PVP in the 30%+O group were significantly different compared with the measurements among the other groups (P < .05), revealing that the liver remnant in 30%+O group could not sustain more than 3 times baseline portal flow, whereas in 35%+O group it could sustain 2.8 times baseline portal flow. ConclusionsIntraoperative ischemia can injure the sinusoidal endothelium, decreasing its ability to regulate portal hyperperfusion, causing less than 30% to 35% of TLV to show small-for-size syndrome or postoperative liver failure.

Attenuation of Portal Hypertension by Continuous Portal Infusion of PGE1 and Immunologic Impact in Adult-to-Adult Living-Donor Liver Transplantation

Small-for-size syndrome remains the greatest limiting factor of expanding segmental liver transplantation from living donors. Portal hyperperfusion is considered to substantially contribute to small-for-size syndrome. We investigated the impact of continuous portal infusion of prostaglandin E1 (PGE1) on small-for-size grafts (SFSGs) in adult-to-adult living-donor liver transplantation (LDLT). From July 2003 to December 2009, LDLT was performed in 122 patients. We introduced continuous portal infusion of PGE1 to five SFSG patients (PG group) from November 2007 to December 2009 and retrospectively compared them with a historical control group of eight relevant SFSG patients without PGE1 infusion (non-PG group) from July 2003 to October 2007 to determine the safety and efficacy of continuous PGE1 portal infusion for SFSGs. Splenectomy cases were excluded from analysis. The PG group demonstrated significantly lower postoperative portal pressure than the non-PG group. Moreover, the PG group demonstrated significantly improved liver function in the early posttransplantation period and significantly better recovery from hyperammonemia at 1 week after transplantation and from hyperbilirubinemia in the late posttransplantation period. Overall survival was significantly better in the PG group than in the non-PG group. Three patients in the non-PG group died of rejection-related reasons. Interestingly, immunomonitoring assay revealed that antidonor immune responses were significantly accelerated in the non-PG group compared with the PG group after LDLT. In contrast, the PG group showed well-suppressed antidonor immune responses. Continuous portal infusion of PGE1 for SFSG attenuated portal hypertension, improved graft function, and suppressed antidonor immune responses, resulting in better survival.

Liver dysfunction due to “portal hyperperfusion” after mesenteric revascularization

The post-operative course after mesenteric revascularization for chronic mesenteric ischemia is associated with significant morbidity (5%–30%) and mortality (5%–12%), since many of these patients develop significant liver dysfunction, with cholestasis and transaminitis, and a vitamin-K resistant coagulopathy with a fall in platelet count. An elderly male underwent mesenteric revascularization and developed ascites, jaundice, transaminitis and coagulopathy with thrombocytopenia; which gradually recovered over 7–10 days. The post-operative findings are remarkably similar to that seen in portal hyperperfusion, or small for size syndrome (SFSS) after living donor liver transplantation. Mesenteric revascularization results in improved blood blow through the splanchnic circulation, and results in an increased portal blood flow after repair. The portal hyperperfusion may explain the manifestations seen after mesenteric revascularization, including the liver dysfunction, coagulopathy and in extreme cases renal and pulmonary dysfunction.

Small-for-size syndrome in adult liver transplantation: A review

Small-for-size syndrome remains the greatest limiting factor for the expansion of liver transplantation (apart from cadaveric organ donation) and has been the major cause of worse short-term prognoses after LDLT. The size of the graft, ( GRWR < 0.8 or graft to SLV ratio <30–40%, portal hyperperfusion, obstructed hepatic venous drainage, MELD score, and graft steatosis may be responsible for the pathogenesis of SFSS. Sinusoidal shear stress may be the principal common pathway in the pathogenesis. Living donor grafts with portal pressure more than 20 mmHg or portal flow exceeding 250 mL/min per 100 g have a higher risk of graft failure. The role of decrease arterial flow in response to portal hyperflow remains to be elucidated. Acute portal hypertension and increased shear stress caused by a partial hepatectomy triggers the regeneration of the remaining liver, though liver dysfunction is seen to be due to sudden portal hypertension, microcirculatory ischemia, reduced oxygen delivery, and hepatocellular dysfunction. The differences in sinusoidal pressure, or differences in the hepatotropic substances delivered to the graft or the liver remnant may be the difference between grafts that survive and grafts that don't. We need to find the threshold level of hyperperfusion that does more harm than good.

“Small-for-flow” syndrome: Shifting the “size” paradigm

The “small-for-size” syndrome and “post-hepatectomy liver failure” refers to the development of liver failure (hyperbilirubinemia, coagulopathy, encephalopathy and refractory ascites) resulting from the reduction of liver mass beyond a certain threshold. This complication is associated with a high mortality and is a major concern in liver transplantation involving reduced liver grafts from deceased and living donors as well as in hepatic surgeries involving extended resections of liver mass. The limiting threshold for liver resection or transplantation is currently predicted based on the mass of the remnant liver (or donor graft) in relation to the body weight of the patient, with a ratio above 0.8 being considered safe. This approach, however, has proved inaccurate, because some patients develop the “small-for-size” syndrome despite complying with the “safe” threshold while other patients who surpass the threshold do not develop it.We hypothesize that the development of the “small-for-size” syndrome is not exclusively determined by the ratio of the mass of the liver remnant (or graft) to the body weight, but it is instead strictly determined by the hemodynamic parameters of the hepatic circulation. This hypothesis is based in recent clinical and experimental reports showing that relative portal hyperperfusion is a critical factor in the development of the “small-for-size” syndrome and that maneuvers that manipulate the hepatic vascular inflow are able to prevent the development of the syndrome despite liver-to-body weight ratios well below the “limiting” threshold. Measurements of hepatic blood flow and pressure, however, are not routinely performed in hepatic surgeries.Focusing on the “flow” rather than in the “size” may improve our understanding of the pathophysiology of the “small-for-size” syndrome and “post-hepatectomy liver failure” and it would have important implications for the clinical management of patients at risk. First, hepatic hemodynamic parameters would have to be measured in hepatic surgeries. Second, these parameters (in addition to liver mass) would be the principal basis for deciding the “safe” threshold of viable liver parenchyma. Third, the hepatic hemodynamic parameters are amenable to manipulation and, consequently, the “safe” threshold may also be manipulated. Shifting the paradigm from “small-for-size” to “small-for-flow” syndrome would thus represent a major step for optimizing the use of donor livers, for expanding the indications of hepatic surgery, and for increasing the safety of these procedures.

Liver function impairment in liver transplantation and after extended hepatectomy

Extended hepatectomy, or liver transplantation of reduced-size graft, can lead to a pattern of clinical manifestations, namely "post-hepatectomy liver failure" and "small-for-size syndrome" respectively, that can range from mild cholestasis to irreversible organ non-function and death of the patient. Many mechanisms are involved in their occurrence but in the recent past, high portal blood flow through a relatively small liver vascular bed has taken a central role. Therefore, several techniques of inflow modulation have been attempted in cases of portal hyperperfusion first in liver transplantation, such as portocaval shunt, mesocaval shunt, splenorenal shunt, splenectomy or ligation of the splenic artery. However, high portal flow is not the only factor responsible, and before major liver resections, preoperative assessment of the residual liver function is necessary. Techniques such as portal vein embolization or portal vein ligation can be adopted to increase the future liver volume, preventing post-hepatectomy liver failure. More recently, a new surgical procedure, that combines in situ splitting of the liver and portal vein ligation, has gradually come to light, inducing remarkable hypertrophy of the healthy liver in just a few days. Further studies are needed to confirm this hypothesis and overcome one of the biggest issues in the field of liver surgery.

Splenomegaly Is a Risk Factor for Biliary and Artery Complications in Living Donor Liver Transplantation

Blood flow to the liver is maintained by hepatic arterial buffer response (HABR), which is an essential autoregulatory mechanism. Portal hyperperfusion impairs hepatic artery flow (HAF) due to the HABR, probably resulting in high incidence of biliary and artery complications in liver transplantation. The previous studies have reported that portal vein flow is directly correlated to the splenic volume. The aim of this study is to investigate the impact of preoperative splenomegaly, and assess the efficacy of portal modulation such as preoperative splenic artery embolization (SAE) or intraoperative splenic artery ligation (SAL) on biliary and artery complications after living donor liver transplantation (LDLT). From 2004 to 2011, 160 consecutive LDLT were retrospectively analyzed. Patients were divided into group 1 with splenomegaly (n= 128) and group 2 without splenomegaly (n=32). The overall biliary and artery complication rate was 43% (n=68) and 11% (n=17) respectively. The biliary complication rate was 48% (n=61) in group 1 and 22% (n=7) in group 2 (P=0.008). Biliary anastomotic stricture was seen in 54 patients(42%) in group 1, and 7 patients(22%) in group 2 (P=0.034), whereas biliary non anastomotic stricture was seen in 4 patients(3%) in group 1, and 0 patient in group 2 (P=0.311). 27 patients(20%) in group 1 and one patient(3%) in group 2 had early biliary stricture (≤90 days after LDLT) (P=0.024), on the other side, 33 patients(26%) in group 1 and six patients(19%) had late biliary stricture (>90 days after LDLT) (P=0.41). The artery complication rate was 13% in group 1 and 0% in group 2 (P=0.03). Hepatic arterial thrombosis (HAT) occurred in three (18%), and hepatic arterial stenosis (HAS) in four (23%), and splenic artery syndrome (SAS) in 10 patients (59%) each. The incidence of biliary complication, especially early biliary anastomotic stricture in group 1 was greater than in group 2. Similarly the incidence of artery complication was greater in group 1, and SAS was the most common artery complication in group 1. In a multivariate analysis, preoperative splenomegaly was an independent risk factor for both biliary and artery complications in LDLT. Of the 160 LDLT recipients, portal modulation such as preoperative SAE or intraoperative SAL was performed in 81. There was no significant difference in the incidence of biliary and artery complications between the patients who underwent portal modulation and those who didn‘t undergo portal modulation despite the rate of patients with splenomegaly was significantly higher in the patients who underwent portal modulation. In conclusion, preoperative splenomegaly is important to predict the risk of biliary and artery complication after LDLT. Recipient with Splenomegaly may have impaired HAF due to the HABR, resulting in high incidence of biliary and artery complications after liver transplantation. Portal modulation through preoperative SAE or intraoperative SAL may be effective in prevention of biliary and artery complications after LDLT through a decrease in portal hyperperfusion.

Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine.

To study the effect of H2 gas on liver injury in massive hepatectomy using the intermittent Pringle maneuver in swine. Male Bama pigs (n = 14) treated with ketamine hydrochloride and Sumianxin II as induction drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups: Hydrogen-group (n = 7), the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; contrast-group (n = 7), underwent 70% hepatotectomy without inhalation of hydrogen. Hemodynamic changes and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) in liver tissue were measured at pre-operation, post-hepatotectomy (PH) 1 h and 3 h. The apoptosis and proliferating cell nuclear antigen (PCNA) expression in liver remnant were evaluated at PH 3 h. Then we compared the two groups by these marks to evaluate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine. There were no significant differences in body weight, blood loss and removal liver weight between the two groups. There was no significant difference in changes of portal vein pressure between two groups at pre-operation, PH 30 min, but in hydrogen gas treated-group it slightly decrease and lower than its in contrast-group at PH 3 h, although there were no significant difference (P = 0.655). ALT and AST in Hydrogen-group was significantly lower comparing to contrast-group (P = 0.036, P = 0.011, vs. P = 0.032, P = 0.013) at PH 1 h and 3 h, although the two groups all increased. The MDA level increased between the two group at PH 1 h and 3 h. In the hydrogen gas treated-group, the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to Contrast-group (P = 0.0005, P = 0.0004). In Hydrogen-group, the HA level was also significantly low to contrast-group (P = 0.0005, P = 0.0005) although the two groups all increased at PH 1 h and 3 h. The expression of cluster of differentiation molecule 31 molecules Hydrogen-group was low to Contrast-group. However, PCNA index (%) was not statistically significant between the two groups (P = 0.802). Microphotometric evaluation of apoptotic index (AI) in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-stained tissue after hepatotectomy for 3h, the AI% level in the hydrogen was significantly low to contrast-group (P = 0.012). There were no significant difference between Hydrogen-group and contrast-group at pre-operation (P = 0.653, P = 0.423), but after massive hepatotectomy, the TNF-α and IL-6 levels increase, and its in Hydrogen-group was significantly low compared with contrast-group (P = 0.022, P = 0.013, vs. P = 0.016, P = 0.012), respectively. Hydrogen-gas inhalation reduce levels of these markers and relieved morphological liver injury and apoptosis. H2 gas attenuates markedly ischemia and portal hyperperfusion injury in pigs with massive hepatotectomy, possibly by the reduction of inflammation and oxidative stress, maybe a potential agent for treatment in clinic.

Small-for-size syndrome after living donor liver transplantation: Successful treatment with a transjugular intrahepatic portosystemic shunt

Small-for-size syndrome (SFSS) is a serious complication after living donor liver transplantation (LDLT) that can disrupt liver regeneration and result in hepatic dysfunction. Until now, the treatment options for SFSS after LDLT have been very limited. Here we describe a patient with SFSS after LDLT who was successfully treated with a transjugular intrahepatic portosystemic shunt (TIPS). A 56-year-old man who had undergone adult-to-adult LDLT because of decompensated liver cirrhosis started displaying signs of acute jaundice and ascites within 72 hours of the operation. The patient was diagnosed with SFSS, and because he had already undergone splenectomy before the transplant, partial splenic embolization was not feasible. Consequently, the TIPS procedure was chosen in an attempt to reduce portal hyperperfusion. After the procedure, the patient's symptoms were gradually ameliorated and were eventually resolved. In conclusion, when partial splenic embolization is not feasible, TIPS placement may be a feasible option for the treatment of SFSS after LDLT.