Hepatoprotective effects of baicalein against liver ischemia-reperfusion injury and partial hepatectomy in a rat model.

BACKGROUND: Baicalein is the main active flavonoid in Scutellariae Radix and is included in shosaikoto, a Kampo formula used for treating hepatitis and jaundice. However, little is known about its hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI), a severe clinical condition directly caused by interventional procedures. We aimed to investigate the hepatoprotective effects of baicalein against HIRI and partial hepatectomy (HIRI + PH) and its potential underlying mechanisms. METHODS AND RESULTS: Male Sprague-Dawley rats received either baicalein (5 mg/kg) or saline intraperitoneally and underwent a 70% hepatectomy 15 min after hepatic ischemia. After reperfusion, liver and blood samples were collected. Survival was monitored 30 min after hepatic ischemia and hepatectomy. In interleukin 1ß (IL-1ß)-treated primary cultured rat hepatocytes, the influence of baicalein on inflammatory mediator production and the associated signaling pathway was analyzed. Baicalein suppressed apoptosis and neutrophil infiltration, which are the features of HIRI + PH treatment-induced histological injury. Baicalein also reduced the mRNA expression of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). In addition, HIRI + PH treatment induced liver enzyme deviations in the serum and hypertrophy of the remnant liver, which were suppressed by baicalein. In the lethal HIRI + PH treatment group, baicalein significantly reduced mortality. In IL-1ß-treated rat hepatocytes, baicalein suppressed TNF-α and chemokine mRNA expression as well as the activation of nuclear factor-kappa B (NF-κB) and Akt. CONCLUSIONS: Baicalein treatment attenuates HIRI + PH-induced liver injury and may promote survival. This potential hepatoprotection may be partly related to suppressing inflammatory gene induction through the inhibition of NF-κB activity and Akt signaling in hepatocytes.

Sulforaphane Is Protective against Warm Ischemia/Reperfusion Injury and Partial Hepatectomy in Rats.

Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1ß (IL-1ß)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1ß-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.

[A Case of Adenocarcinoma of Duct of Luschka].

A 75-year-old man was transferred to our hospital with a diagnosis of acute cholecystitis. On next day, a laparoscopic cholecystectomy was performed. Histologic examination confirmed an adenocarcinoma arising from duct of Luschka. Patient underwent additional resection of the liver bed. No residual adenocarcinoma was seen in the surgical specimen. Adenocarcinoma of duct of Luschka is rare, but it is important during cholecystectomy to consider the presence of duct of Luschka, possibility of malignant disease and careful dissection of the gallbladder from its fossa staying close to the gallbladder wall.

The Impact of Sorafenib in Combination with Intermittent Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma with Major Vascular Invasion.

The aim of the current study was to investigate the efficacy and safety of sorafenib and intermittent hepatic arterial infusion chemotherapy with cisplatin for unresectable hepatocellular carcinoma (HCC) with severe portal vein invasion. The antitumor effect was a complete response in 1 of 38 patients, a partial response in 12 patients, stable disease in 16 patients, and progressive disease in 9 patients, for a 34.2% response rate and a 76.3% disease control rate. This regimen had favorable efficacy and acceptable safety and may be feasible for unresectable HCC with severe portal vein invasion.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a multi-centre propensity score-based analysis.

BACKGROUND: The frequency of liver resection in elderly patients has been increasing. However, data are limited regarding the safety of laparoscopic liver resection (LLR) compared with that of open liver resection (OLR) for hepatocellular carcinoma (HCC) in elderly patients. The present study aimed to compare short-term outcomes between LLR and OLR in elderly patients with HCC using propensity score matching. METHODS: The study included 630 patients (age, ≥ 75 years) who underwent liver resection for HCC at nine liver centres between April 2010 and December 2017. Patients were divided into LLR and OLR groups, and perioperative outcomes were compared between the groups. In addition, subgroup analysis was performed according to age (75-79 and ≥ 80 years). RESULTS: Of the 630 patients, 221 and 409 were included in the LLR and OLR groups, respectively. After propensity score matching, 155 patients were included in each group. Intraoperative blood loss and the transfusion, post-operative overall complication and major complication rates were lower in the matched LLR than the matched OLR group (P < 0.001, P = 0.004, P < 0.001 and P < 0.001, respectively). Moreover, post-operative pulmonary and cardiovascular complications were less frequent in the matched LLR group (P = 0.008 and P = 0.014, respectively). In subgroup analysis, among octogenarians, the post-operative major complication rate was lower and hospital stay was shorter in the matched LLR than the matched OLR group (P < 0.001 and P < 0.001, respectively). CONCLUSION: LLR for HCC is associated with good short-term outcomes in patients aged ≥ 75 years compared with OLR. LLR is safe and feasible in selected octogenarians with HCC.

The Proton Pump Inhibitor Lansoprazole Has Hepatoprotective Effects in In Vitro and In Vivo Rat Models of Acute Liver Injury.

BACKGROUND/AIMS: The proton pump inhibitor lansoprazole (LPZ) is clinically used to reduce gastric acid secretion, but little is known about its possible hepatoprotective effects. This study aimed to investigate the hepatoprotective effects of LPZ and its potential mechanisms using in vitro and in vivo rat models of liver injury. METHODS: For the in vitro model of liver injury, primary cultured rat hepatocytes were treated with interleukin-1ß in the presence or absence of LPZ. The influence of LPZ on inducible nitric oxide synthase (iNOS) induction and nitric oxide (NO) production and on the associated signaling pathways was analyzed. For the in vivo model, rats were treated with D-galactosamine (GalN) and lipopolysaccharide (LPS). The effects of LPZ on survival and proinflammatory mediator expression (including iNOS and tumor necrosis factor-α) in these rats were examined. RESULTS: LPZ inhibited iNOS induction partially through suppression of the nuclear factor-kappa B signaling pathway in hepatocytes, thereby reducing potential liver injury from excessive NO levels. Additionally, LPZ increased survival by 50% and decreased iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 mRNA expression in the livers of GalN/LPS-treated rats. LPZ also inhibited nuclear factor-kappa B activation by GalN/LPS. CONCLUSIONS: LPZ inhibits the induction of several inflammatory mediators (including cytokines, chemokines, and NO) partially through suppression of nuclear factor-kappa B, resulting in the prevention of fulminant liver failure. The therapeutic potential of LPZ for liver injuries warrants further investigation.

Loss of skeletal muscle mass in patients with chronic liver disease is related to decrease in bone mineral density and exercise tolerance.

AIM: This study aimed to identify the relationship between loss of skeletal muscle mass and clinical factors such as osteoporosis in patients with chronic liver disease. METHODS: The subjects were 112 patients (85 men and 27 women) with hepatocellular carcinoma who were scheduled to undergo hepatectomy. Skeletal muscle reduction was diagnosed according to the cut-off level of the skeletal mass index (SMI) for Asians (men <7.0 kg/m2 , women <5.4 kg/m2 ). Osteoporosis was diagnosed according to T-score ≤-2.5 standard deviation. The SMI and T-score were assessed using the results of dual-energy X-ray absorption. Peak oxygen consumption (PeakVO2 ), an index of exercise tolerance, was evaluated using the cardiopulmonary exercise test. The characteristics of patients with low SMI (low SMI group) were compared with those of patients whose SMI was not low (control group). Outcomes are presented as median (interquartile range). RESULTS: The T-score was significantly lower in the low SMI group (control vs. low SMI -1.1 [1.8] vs. -1.6 [1.9], P = 0.049). T-score positively correlated with SMI (r = 0.409, P < 0.0001). PeakVO2 was significantly decreased in the low SMI group (17.7 [6.3] vs. 14.4 [4.5], P = 0.006). In multivariate logistic regression analysis, T-score (odds ratio [OR], 3.508; 95% confidence interval [CI], 1.074-11.456; P = 0.038) and PeakVO2 (OR, 3.512; 95% CI, 1.114-11.066; P = 0.032) were significantly related to SMI, independent of age and sex. CONCLUSIONS: Skeletal muscle reduction in chronic liver disease is closely related to exercise tolerance and osteoporosis, and these factors are believed to be associated with physical inactivity in daily life.

Perioperative allogenic blood transfusion is a poor prognostic factor after hepatocellular carcinoma surgery: a multi-center analysis.

PURPOSE: The influence of allogenic blood transfusion on the postoperative outcomes of hepatocellular carcinoma (HCC) surgery remains controversial. This study aims to clarify the clinical impacts of perioperative allogenic blood transfusion on liver resection outcome in HCC patients. METHODS: We analyzed data collected over 5 years for 642 patients who underwent hepatectomy for HCC at one of the five university hospitals. We investigated the impact of allogenic blood transfusion on postoperative outcome after surgery in all patients and in 74 matched pairs, using a propensity score. RESULTS: Of the 642 patients, 198 (30.8%) received perioperative allogenic blood transfusion (AT group) and 444 (69.2%) did not (non-AT group). Overall survival was lower in the AT group than in the non-AT group in univariate (P < 0.001) and multivariate analyses (risk ratio 1.521, P = 0.011). After matching the different distributions using propensity scores, perioperative blood transfusion was found to be a poor prognostic factor for HCC patients. CONCLUSIONS: In this multi-center study, perioperative blood transfusion was an independent factor for poor prognosis after curative surgery for primary HCC in the patient group and in pairs matched by propensity scores.

Phase I Study of Sorafenib in Combination with Intermittent Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma.

OBJECTIVES: We conducted a phase I study of sorafenib and intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable hepatocellular carcinoma. METHODS: Sorafenib was administered continuously, whereas cisplatin was administered once every 3 weeks. We estimated the safety and efficacy. RESULTS: Fifteen patients were enrolled into this study. The dose-limiting toxicities occurred at sorafenib 800 mg and cisplatin 20 mg/m2. The recommended dose was at sorafenib 400 mg and cisplatin 30 mg/m2. The disease control rate was 73.3%. CONCLUSIONS: This treatment is feasible for unresectable hepatocellular carcinoma. Further evaluation of the regimen in a randomized controlled trial is warranted.

Effects of implementing an "enhanced recovery after surgery" program on patients undergoing resection of hepatocellular carcinoma.

PURPOSE: To evaluate the effects of implementing an "enhanced recovery after surgery" (ERAS) program on the feasibility, safety, and effectiveness of extensive and potentially curative liver resection for hepatocellular carcinoma (HCC). METHODS: We compared clinicopathologic factors, surgical factors, and outcomes of patients who underwent extended hepatectomy (defined as resection of more than two sections) for HCC, before and after the introduction of an ERAS program. RESULTS: Operating times and postoperative hospital stay were significantly shorter, and total volume infused during surgery was significantly lower, for the ERAS group than for the control group. Although the ERAS group had a significantly lower percentage of patients with retention of abdominal drainage, this group had a higher frequency of abdominal paracentesis in patients without intraoperative abdominal drainage. Oral dietary intake and the ability to walk steadily resumed significantly earlier in the ERAS group. Postoperative serum concentrations of albumin and cholinesterase were significantly higher in the ERAS group than in the control group. CONCLUSIONS: The ERAS program was feasible and effective for patients with chronic liver disease undergoing extended liver resection for HCC, because it allowed earlier oral dietary intake and promoted faster postoperative recovery.

Geriatric assessment as a predictor of postoperative complications in elderly patients with hepatocellular carcinoma.

BACKGROUND: Older patients are considered to have increased risk for complications after major surgery, but age alone is not a reliable predictor of postoperative complications. However, no universal screening test adequately predicts postoperative complications in older patients. This prospective study recorded pertinent baseline geriatric assessment variables to identify risk factors for postoperative complications in hepatocellular carcinoma (HCC) for patients aged ≥70 years who undergo hepatectomy. METHODS: We retrospectively analyzed 71 consecutive patients ≥70 years of age. Patients had geriatric assessments of baseline and later cognition, nutritional and functional status, and burden of comorbidities, completed preoperatively and at 1, 3, and 6 months postoperatively. Postoperative morbidities were recorded. RESULTS: Postoperative morbidities developed in 18 patients (25 %). Univariate analysis identified serum albumin, operating time and blood loss, cirrhosis, geriatric 8 (G8), and Mini Nutritional Assessment as possible risk factors for postoperative complications, but only G8 < 14 survived multivariate analysis as an independent predictor of complications. CONCLUSIONS: Our findings indicate that the G8 score, based on patients' nutritional assessments, is a useful screening method for older HCC patients who qualify for elective liver resection. Preoperative G8 scores can help forecast postoperative complications in older HCC patients. Future studies with larger numbers of patients, limited to HCC and liver resections, are needed to verify our results.

Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma.

BACKGROUND: Aberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC. METHODS: We studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RT-PCR, immunohistochemistry and Western blotting. RESULTS/CONCLUSION: High ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.

[Two Patients with Recurrence of Hepatocellular Carcinoma after Liver Resection Who Achieved Long-Term Stable Disease with Small Doses of Sorafenib Therapy].

Case 1: A6 4-year-old man with hepatocellular carcinoma (HCC) had received local therapy repeatedly for 20 years. In 2012, he underwent hepatic right lobectomy for recurrence of HCC. Multiple recurrences were found in the hepatic remnant, and transcatheter arterial chemoembolization (TACE) was performed. Considering his condition, a small dose of sorafenib (200 mg per day) was administered. He complained of general fatigue, so we prolonged the administration interval (200 mg every other day). Thereafter, compliance improved and long-term stable disease (long SD), for more than 6 months, long SD was achieved. Case 2: A7 5-year-old man with HCC was treated by TACE repeatedly for multiple recurrences after liver resection (segment 6). In 2008, metastases to the thoracic vertebra and left rib were treated by radiation therapy and radiofrequency ablation, respectively. Subsequently, sorafenib (400 mg per day) was administered. We reduced the dose of sorafenib to less than 400 mg per day because of diarrhea, hypertension, and general fatigue. Thereafter, long SD was achieved despite the small dose of sorafenib. We report here 2 cases of HCC where we achieved long SD in spite of treating with a small dose of sorafenib.

[OBJECTIVE ASSESSMENT OF POSTOPERATIVE PAIN AFTER DIGESTIVE TRACT SURGERY].

Pain is a sensation associated with subjective factors, making it difficult to measure and assess. Currently, there is no widely accepted method of objectively assessing pain, and therefore subjective assessments such as the Visual Analogue Scale (VAS) are generally used. The PainVision system has been developed for the quantitative analysis of pain and comparison of postoperative pain intensity. In this study, we investigated whether postoperative pain could be objectively assessed using this system in digestive tract surgery patients. Pain scores were measured with the VAS, the PainVision system, and the short-form McGill Pain Questionnaire in patients undergoing open or laparoscopic hepatectomy, open or laparoscopic gastrectomy, and laparoscopic cholecystectomy. As measured using the PainVision system, postoperative pain intensity was lower in patients who underwent laparoscopic surgery compared with open hepatectomy. In open hepatectomy patients, pain intensity measured by the PainVision system was significantly lower on postoperative days (POD) 7 and 10 than on POD 1. Preemptive use of nonsteroidal antiinflammatory drugs significantly reduced postoperative pain in open hepatectomy patients. The results showed that PainVision effectively quantifies pain intensity after digestive tract surgery. Objective assessment of postoperative pain may lead to earlier mobility and improved quality of life.

Bone marrow cells enhance liver regeneration after massive hepatectomy in mice.

BACKGROUND: Recent evidence indicates that transplanted autologous bone marrow cells (BMCs) can be converted into functional liver cells. BMC therapy can improve hepatic function and increase the potential for liver regeneration in patients with serious liver damage. We investigated whether BMC therapy influenced liver regeneration after massive hepatectomy in mice. METHODS: Male C57/BL6 mice underwent 70 % hepatectomy, followed by injection of BMCs via the portal vein (PV group), BMCs via the tail vein (IV group), or saline via the portal vein (control group). Analysis of serum enzyme levels and liver histology was performed on postoperative days (POD) 1, 3, and 5. RESULTS: Compared with the control group, the rate of liver regeneration on POD 3 and 5 was significantly higher in the PV group, but not in the IV group. Examination of the mitotic index and Ki-67 labeling index revealed that the increased liver regeneration resulted from stimulation of DNA synthesis. On POD 3, the serum levels of interleukin (IL)-6 and hepatocyte growth factor (HGF) were significantly higher and the expression of IL-6 and HGF mRNA in the remnant liver tended to be higher in the PV group than in the control group. Histological examination showed BMCs in the liver of the PV group, as well as conversion of BMCs into liver cells. CONCLUSIONS: Our findings indicate that the injection of BMCs via the portal vein, but not the injection of BMCs via the tail, enhances liver regeneration after massive hepatectomy in mice.

Detection of Portal Vein Stenosis by Technetium-99m-Diethylenetriaminepentaacetic Acid-Galactosyl Human Serum Albumin Liver Scintigraphy after Living-Donor Liver Transplantation.

BACKGROUND/AIM: To investigate portal vein stenosis after living-donor liver transplantation by liver scintigraphy. METHODOLOGY: A 63-year-old woman with hepatic cirrhosis due to autoimmune hepatitis underwent living-donor liver transplantation using a graft donated by her daughter. Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (Tc-99m-GSA) scintigraphy was used to determine the maximum rate of Tc-99m-GSA removal (GSA-Rmax) by hepatocytes, as a parameter of hepatic functional reserve. RESULTS: Conventional liver function parameters on laboratory tests and graft volume on computed tomography (CT) were almost unchanged at postoperative month (POM) 12. GSA-Rmax was 0.11 mg/min before surgery and increased 5-fold to approximately 0.5 mg/min at POM 1 and 3, followed by a decrease to 0.25 mg/min at POM 6 and 12. Enhanced CT did not detect blood flow in the intra- or extrahepatic portions of the portal vein at POM 12. The portal vein stenosis was dilated with a balloon catheter, followed by deployment of a self-expanding stent across the stenotic segment via the transileocolic vein. GSA-Rmax recovered to 0.5 mg/min at POM 15, and subsequently remained high. CONCLUSIONS: Decreased GSA-Rmax at POM 6 indicated that the portal vein stenosis was affecting graft function. Tc-99m-GSA liver scintigraphy may be a useful noninvasive method for evaluation of graft functional reserve.

Higher complication rate in hepatocellular carcinoma patients undergoing prophylactic cholecystectomy with curative hepatic resection.

AIMS: We performed a retrospective analysis to evaluate the short and long-term impact of simultaneous prophylactic cholecystectomy with hepatectomy in these patients. METHODS: We identified 642 patients who underwent curative hepatocellular carcinoma resection between 2001 and 2005 at five university hospitals. One hundred and twenty-five hepatocellular carcinoma patients who received left lateral sectionectomy or partial resection in the left lateral and Spiegel lobes were identified and followed. They were divided into two groups, 74 with and 51 without simultaneous cholecystectomy. None of these patients had gallbladder stones or polyps at preoperative diagnosis. RESULTS: Although not statistically significant, the operating time was longer and blood loss was greater in the cholecystectomy group. Patients in the cholecystectomy group had a significantly higher postoperative morbidity rate. Surgical complications according to the Clavien classification differed significantly between the two groups. Variables significantly associated with complications in the univariate and multivariate analyses were simultaneous cholecystectomy and operative blood loss ≥ 1000 ml. CONCLUSION: Simultaneous cholecystectomy of the asymptomatic gallbladder with curative resection of hepatocellular carcinoma in the left lateral section or Spiegel lobe resulted in higher postoperative complications. Consequently, the gallbladder should be preserved except in cases of gallbladder stones or polyps.

[A novel technique of laparoscopic hepatectomy].

We report a novel technique of laparoscopic hepatectomy (lap-HT) performed at our hospital and the outcomes.Lap -HT was performed in 90 cases at our hospital, including 38 cases of anatomical resection of the liver.After mobilization of the right lobe with the patient in the half-lateral position, we resected the liver tissue using cavitron ultrasonic surgical aspirator (CUSA) and AquamantysTM Bipolar®.This surgical instrument is useful for laparoscopic anatomical resection of the liver because it is based on vessel sealing technology.In the 90 cases in which lap-HT was performed, the mean duration of surgery and mean blood loss were 332.9 minutes and 381 mL, respectively. The mean duration of hospitalization after surgery was 12.1 days, and postoperative complications were noted in 5 cases(5.6%). Comparison of the clinical factors and short-term performance of the surgery between liver cirrhosis patients who underwent open hepatectomy and lap-HT revealed that blood loss was significantly lower and the hospital stay duration was significantly shorter in patients who underwent lap-HT. Our findings suggest that laparoscopic anatomical resection of the liver can be safely performed using this novel technique and surgical instrument.

Hepatoprotection of a Standardized Extract of Cultured Lentinula edodes Mycelia against Liver Injury Induced by Ischemia-Reperfusion and Partial Hepatectomy.

A standardized extract of cultured Lentinula edodes mycelia (ECLM, AHCC®) has been shown to have beneficial effects on organ metabolism. ECLM has been indicated to have liver protective properties by suppressing inflammatory responses. The pathogenesis of hepatic ischemia-reperfusion injury is thought to involve the induction of inflammatory mediators. However, whether ECLM affects inflammatory mediators caused by warm hepatic ischemia-reperfusion injury and partial hepatectomy (HIRI+PH) has not been clarified. In this study, we evaluated the protective effects of ECLM against liver damage caused by HIRI+PH. Rats were fed a normal diet (HIRI+PH) or a normal diet with 2% ECLM (HIRI+PH and ECLM) for ten days, then the liver and duodenal ligament were clamped and subjected to 15 min of hepatic ischemia. After 70% hepatectomy, the inflow occlusion was released, and liver and blood samples were collected at 3, 6, and 24 h. The effect of ECLM on mortality induced by 30 min of ischemia and hepatectomy was evaluated. The results showed that ECLM attenuated pathological liver damage, including apoptosis, in the rats treated with HIRI+PH, and decreased serum aminotransferase activity; ECLM decreased mRNA levels of the inflammation-related genes inducible nitric oxide synthase and C-X-C motif chemokine ligand 1, and increased mRNA levels of interleukin 10, an anti-inflammatory cytokine; ECLM increased hepatocyte growth factor mRNA levels and Ki-67 labeled nuclei in the liver at 24 h; ECLM significantly reduced HIRI+PH-induced mortality. In conclusion, ECLM may prevent HIRI+PH-induced liver injury in part by suppressing various inflammatory responses and promoting liver regeneration.