Safe standard remnant liver volume after hepatectomy in HCC patients in different stages of hepatic fibrosis.

BACKGROUND: To determine the standard remnant liver volume (SRLV) threshold to avoid postoperative hepatic insufficiency inpatients in different stages of hepatic fibrosis who undergo right hemi-hepatectomy. METHODS: Data for 85 patients at our single medical center were analysed prospectively to examine whether the following factors differed significantly between those who experienced postoperative hepatic insufficiency and those who did not: height, prothrombin time, remnant liver volume, SRLV or hepatic fibrosis stage. RESULTS: Logistic regression showed SRLV and hepatic fibrosis stage to be independent risk factors for postoperative hepatic insufficiency. The threshold SRLV for predicting insufficiency was 203.2 ml/m2 across all patients [area under receiver operating characteristic curve (AUC) 0.778, sensitivity 66.67%, specificity 83.64%, p<0.0001), 193.8 ml/m2 for patients with severe hepatic fibrosis (AUC 0.938, sensitivity 91.30%, specificity 85.71%, p<0.0001), and 224.3 ml/m2 for patients with cirrhosis (AUC 0.888, sensitivity 100%, specificity 64.29%, p<0.0001). CONCLUSIONS: Right hemi-hepatectomy may be safer in Chinese patients when the standard remnant liver volume is more than 203.2 ml/m2 in the absence of hepatic fibrosis or cirrhosis, 193.8 ml/m2 in the presence of severe hepatic fibrosis or 224.3 ml/m2 in the presence of cirrhosis.

CD133 + cell infusion in patients with colorectal liver metastases going to be submitted to a major liver resection (CELLCOL): A randomized open label clinical trial.

BACKGROUND: Treatment of liver metastases of colorectal carcinoma is surgical resection. However, only 10-15% of the patients in this context will be candidate for curative resection arising other 10-13% after response to neoadyuvant chemotherapy. In order to perform the liver metastases surgery, it is necessary to have a sufficient remnant liver volume (RLV) which allows maintaining an optimal liver function after resection. Studies on liver regeneration have determined that CD133 + stem cells are involved in liver hypertrophy developed after an hepatectomy with encouraging results. As presented in previous studies, CD133 + stem cells can be selected from peripheral blood after stimulation with G-CSF, being able to obtain a large number of them. We propose to treat patients who do not meet criteria for liver metastases surgery because of insufficient RLV (<40%) with CD133 + cells together with portal embolization, in order to achieve enough liver volume which avoids liver failure. METHODS: /Design: The aim of this study is to evaluate the effectiveness of preoperative PVE plus the administration of CD133 + mobilized from peripheral blood with G-CSF compared to PVE only. SECONDARY AIMS ARE: to compare the grade of hypertrophy, speed and changes in liver function, anatomopathological study of hypertrophied liver, to determine the safety of the treatment and analysis of postoperative morbidity and surveillance. STUDY DESIGN: Prospective randomized longitudinal phase IIb clinical trial, open, to evaluate the efficacy of portal embolization (PVE) together with the administration of CD133 + cells obtained from peripheral blood versus PVE alone, in patients with hepatic metastasis of colorectal carcinoma (CCRHM). DISCUSSION: The number of CD133 + obtained from peripheral blood after G -CSF stimulation will be far greater than the number obtained with direct puncture of bone marrow. This will allow a greater intrahepatic infusion, which could have a direct impact on achieving a larger and quicker hypertrophy. Consequently, it will permit the treatment of a larger number of patients with an increase on their survival. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03803241.

Intrahepatic cholangiocarcinoma: Limitations for resectability, current surgical concepts and future perspectives.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and its incidence has been shown to increase significantly during the past decades. Complete surgical resection is currently acknowledged as the only curative treatment option able to provide adequate long-term outcomes. We herein review technical, functional and oncologic limitations for resectability, discuss current surgical aspects as well as highlight the fields in which future research and practice should focus on in order to ameliorate long-term outcomes in patients with iCCA.

[Meta-analysis of the outcomes of associating liver partition and portal vein ligation for staged hepatectomy versus portal vein embolization for the treatment of liver cancer with insufficient future liver remnant].

Objective: To explore the feasibility, safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) for the treatment of liver cancer with insufficient future liver remnant (FLR) . Methods: The data regarding the clinical controlled trials in comparison of ALPPS and PVE in liver surgery were collected from the both domestic and international publications searched through the datebases of PubMed, Cochrane Library, Embase, CNKI, and VIP.Meta analysis was performed by RevMan 5.3 software. Results: Total 10 studies with clinical control were analyzed (9 cohort studies and 1 randomized controlled study) .A total of 620 patients were included, with 165 cases in ALPPS group, 455 cases in PVE group.Results of Meta-analysis showed that there was statistically significant difference (P<0.05) between the two groups in the completion rate of two-steps surgery (OR=6.04, 95%CI: 2.97-12.31, Z=4.96) , FLR growth rate (MD=19.91, 95% CI: 8.64-31.18, Z=3.46) , two-steps surgical interval (MD=-30.48, 95%CI: -37.87--23.09, Z=8.09) , and R0 resection rate (OR=2.29, 95%CI=1.07-4.90, Z=2.13) .While there was no significant differences between the two groups in the mortality rate of postoperative within 90-days, postoperative the total complication rates, postoperative liver failure, and total hospital stay (all P>0.05) . Conclusions: Compared to the PVE procedures, ALPPS appears an effective treatment method for liver tumor with insufficient FLR.Therefore, the applications of ALPPS and PVE are limited and depending on further investigation.

A novel liver retraction method in laparoscopic gastrectomy for gastric cancer.

BACKGROUND: Retracting the lateral liver segment during laparoscopic distal gastrectomy is important for achieving an optimal surgical field. However, excessive force may injure the liver, causing temporary abnormalities of liver function tests after laparoscopic surgery. We developed a new liver retraction method and assessed its safety and utility. PATIENTS AND METHODS: We retrospectively analyzed records in our surgical database of consecutive surgical patients who underwent laparoscopic distal gastrectomy for early gastric cancer. We divided the 229 patients into two groups based on the liver retraction method used, either flexible liver retraction with clipping and suturing (FLICS) or the Nathanson retractor (NR). One-to-one propensity score matching was performed to match patients, resulting in the records of 53 pairs of cases extracted from the database. Operative and postoperative outcomes were assessed, including following the values of serum liver enzymes, total bilirubin, and C-reactive protein until postoperative day 30. RESULTS: There were no significant differences in patient characteristics or preoperative data in the two groups. The retraction method was not changed intraoperatively for any patients. The operative time was significantly shorter in the FLICS group, but the amount of bleeding did not differ. Liver injury was not observed as a result of liver retraction during surgery. In both groups, serum liver enzymes temporarily increased after surgery but improved rapidly thereafter. The postoperative increases in aspartate transaminase, alanine transaminase, and C-reactive protein levels were significantly lower in the FLICS than in the NR group. No serious complications associated with liver retraction were observed in either group. CONCLUSIONS: Our new liver retraction technique provided an optimal surgical field without inducing liver dysfunction. It is a simple, safe, and effective liver retraction technique.

[Aspects of the importance of postoperative hepatoprotector therapy in urgent surgery]. / Aspekty znachimosti posleoperatsionnoi gepatoprotektornoi terapii v urgentnoi khirurgii.

The purpose of this study was to determine the effect on the effectiveness of the correction of enteric insufficiency syndrome in patients with urgent surgical pathology included in the scheme of complex therapy Remaxol. The results of complex therapy of 227 patients (98 people with common peritonitis and 129 patients with acute intestinal obstruction) were analyzed. 128 patients of the main group in the postoperative period were included in the therapy scheme Remaxol: intravenously drip in a daily dose of 400 ml at a rate of 40 drops per minute, a course of -5 days. Patients of the control group (99 people) received standard treatment. The study is devoted to the role of postoperative hepatoprotective therapy in the treatment of patients with urgent surgical pathology. The main attention is paid to the hepatoenteric link of the pathogenesis of polyorganism insufficiency. This approach gives hope for a reduction in the risk of abdominal sepsis and a reduction in mortality among patients with acute abdominal pathology. The study found that in patients with acute abdominal pathology, an increase in the severity of enteric insufficiency syndrome due to toxic aggression and bacterial translocation can lead to hepatic dysfunction. Consequently, the implementation of hepatoprotective therapy is a pathogenetic link in the complex treatment of urgent surgical patients. The obtained results allowed to draw a number of conclusions. In particular, it has been established that the use of hepatoprotective therapy in the complex medical treatment of patients with acute abdominal pathology makes it possible to stop hepatorenal syndrome by the 5th day, and the syndrome of enteric insufficiency by the 7th day. Earlier relief of hepatic dysfunction and enteral insufficiency syndrome due to hepatoprotective therapy allowed to reduce the incidence of infectious complications to 9.7%, to reduce the lethality to 9.4% and to shorten hospitalization from 17.29 to 1.734 to 12.14±1.385 bed/day.

[Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) in focal liver diseases management]. / Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) v lechenii ochagovykh obrazovanii pecheni.

AIM: To determine ALPPS advisability in small future remnant liver. MATERIAL AND METHODS: 22 ALPPS procedures were performed at the Center for Surgery and Transplantology for the period from 2011 to 2016. Indications were both tumoral and non-tumoral unresectable liver diseases. Postoperative complications were classified according to Clavien-Dindo, ISGLS. RESULTS: According to CT-volumetry future remnant liver before the 1st stage of ALPPS was from 17 to 25%, before the 2nd stage - from 28 to 49%. Both stages were carried out in all patients with R0-resection in 100%. Postoperative complications were diagnosed in 40.9%, 1 death was caused by severe pulmonary embolism. Follow-up varied from 3 to 48 months (median 17.5), 86% of patients are alive at present. CONCLUSION: ALPPS provides rapid and effective FLR growth and can be used for both tumoral and non-tumoral unresectable liver diseases. However, ALPPS should be performed strictly according to indications and only in specialized centers with extensive experience of advanced liver resection and transplantation after previous comprehensive selection of patients.

Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na+), potassium (K+), chloride (Cl-), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Inhibition of Toll-like receptor 4 ameliorates experimental postischemic injury in the cholestatic liver through inhibition of high-mobility group box protein b1 (HMGB1) signaling.

BACKGROUND: The objective of this study was to elucidate whether the inhibition of Toll-like receptor 4 attenuates liver injury ischemia/reperfusion in the cholestatic liver. METHOD: Rats were assigned into sham, bile duct ligation, sham ischemia/reperfusion (ischemia/reperfusion after laparotomy), and bile duct ligation ischemia/reperfusion (ischemia/reperfusion after bile duct ligation) groups. In some rats, TAK-242, an inhibitor of Toll-like receptor 4, was administered 15 minutes before ischemia/reperfusion. We measured intrahepatic Toll-like receptor 4 expression, serum hepatic marker expression, liver necrosis, gene expression of inflammation-associated factors, and serum high-mobility group box protein b1 levels. RESULTS: Intrahepatic Toll-like receptor 4 expression was significantly greater in the bile duct ligation group than in the sham group. Toll-like receptor 4 expression was further increased after ischemia/reperfusion in bile duct ligation ischemia/reperfusion groups. The levels of serum hepatic markers were significantly greater in both the sham ischemia/reperfusion and bile duct ligation ischemia/reperfusion groups than in the groups without ischemia/reperfusion. Liver necrosis was greater in the bile duct ligation group than in the sham group and was further increased in the bile duct ligation ischemia/reperfusion group. Genomic expression of inflammation-associated factors was also significantly greater in the bile duct ligation ischemia/reperfusion group than in the sham group. Serum high-mobility groups box protein b1 levels were greater in the bile duct ligation ischemia/reperfusion group than in the sham group (28.1 ng/ml versus 9.2 ng/ml, P = .011) and the bile duct ligation group (28.1 ng/ml versus 10.6 ng/ml, P = .017). These changes in the bile duct ligation ischemia/reperfusion group were significantly attenuated by preconditioning with TAK242. CONCLUSIONS: Toll-like receptor 4 inhibition has a potential to minimize severe injury after ischemia/reperfusion in the cholestatic liver through inhibition of high-mobility groups box protein b1.

Hyperoxygenated hydrogen-rich solution suppresses shock- and resuscitation-induced liver injury.

BACKGROUND: It is not known whether simultaneous delivery of hydrogen and oxygen can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver injury. MATERIALS AND METHODS: Rats (n = 60) were randomly divided into 5 groups (n = 6 per group at each time point). One group underwent sham operation, and the others were subjected to severe hemorrhagic shock and then treated with lactated Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from the femoral artery and serum concentrations of alanine aminotransferase and aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and histopathological changes in the liver were evaluated by quantifying the percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by assessing malondialdehyde content and tumor necrosis factor-α, and interleukin (IL)-6 expression. RESULTS: Compared to lactated Ringer's solution, hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine aminotransferase levels and IL-6, tumor necrosis factor-α, and malondialdehyde expression in liver tissue were decreased by HHOS treatment. The number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h after resuscitation. CONCLUSIONS: HHOS has protective effects against liver injury in a rat model of HSR.

Parenteral fish oil and liver function tests in hospitalized adult patients receiving parenteral nutrition: A propensity score-matched analysis.

BACKGROUND & AIMS: Intravenous fat emulsions are associated with liver disease and there is some evidence that the administration of intravenous fish oil (FO) may be useful in reversing it. The aim of our study was to assess whether there are differences in the changes of liver function tests (LFTs) in hospitalized adult patients with parenteral nutrition (PN) with FO and vegetal lipids vs patients without FO. The secondary aim was to study the relationship between impaired LFT and FO. METHODS: This was a 4-year, propensity score-matched analysis including patients aged ≥18 years treated with PN for ≥10 days. The exclusion criteria were previous liver disease, biliary disorders or pancreatic cancer, and altered initial LFT values. Patients were classified into 2 groups: FO cohort (patients who received FO - in addition to vegetal oil - after the first week of PN) and the vegetal oil cohort (patients who received only vegetal oil). A propensity score matched cohort design was developed. Univariate analyses were used to study the changes in LFTs. To evaluate whether LFT alterations vary with FO administration, four stepwise multiple linear regression models were conducted. RESULTS: 52 patients were included, 52% men, median 66 (55-75) years and 69 kg (61.7-78.8), with 18.5 (14-31.8) days of PN treatment. Maximum FO supplementation was 23%. During the first week with PN (none of the groups receiving FO), gammaglutamyl transferase (GGT), alkaline phosphatase (AP) and total bilirubin (BIL) increased significantly. Comparing LFT values at seven days of PN with at the end of PN treatment, the univariate analysis showed a better response for the FO group. The group without FO showed a significant increase for GGT and AP. In multivariate models, the percentage of FO administered was associated with a decrease in GGT, B = -0.33 [CI 95% = -0.54/-0.12], in AP, B = -0.12 [CI 95% = -0.20/-0.03] and ALT, B = -0.12 [CI 95% = -0.21/-0.024]. CONCLUSIONS: Lipid composition plays a significant role in LFT alteration associated with PN, and FO intravenous lipid emulsions (ILEs) minimize disturbance of LFTs in hospitalized adult patients.

N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion.

BACKGROUND: N-acetylcysteine (NAC) is an antioxidant with direct and indirect antioxidant actions used in the clinical setting. Oxidative stress is known to play a pivotal role in the intestinal ischemia reperfusion (IIR). Therefore, we studied the effect of different pretreatment regimens with NAC on the IIR injury in rats. MATERIALS AND METHODS: Thirty-five male Wistar rats were randomly assigned to five groups. In group sham, only laparotomy was performed. Group control underwent IIR without NAC. In the other groups, NAC was administered intraperitoneally with different regimens: 150 mg/kg before ischemia (NAC 150), 300 mg/kg before ischemia (NAC 300), and 150 mg/kg before ischemia plus 150 mg/kg 5 min before reperfusion (NAC 150 + 150). Measurements in tissues and blood were conducted at 4 h of reperfusion following exsanguination. RESULTS: Histological score of the liver was significantly improved in NAC 300 compared with control (1.7 ± 0.5 versus 2.9 ± 1.1, respectively, P = 0.05). In addition, NAC treatment significantly reduced liver transaminases in all groups of treatment, mostly in group NAC 300. Plasma malondialdehyde levels were lower with NAC treatment, although not statistically significant. Lung glutathione peroxidase was significantly increased in group NAC 300 (P = 0.04), while the other oxidation biomarkers showed no significant differences. CONCLUSIONS: NAC exerts a significant protective role in liver injury following IIR, which seems to be independent of an intestinal protective effect. Additional administration of NAC before reperfusion was of no further benefit. The most effective regimen among the compared regimens was that of 300 mg/kg before ischemia.

Effects of Myrtus communis extract treatment in bile duct ligated rats.

BACKGROUND: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. MATERIALS AND METHODS: The rats were randomized into four groups (n = 8). Control group (C), MC-administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-α, and interleukin-1ß measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. RESULTS: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, and interleukin-1ß levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. CONCLUSIONS: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.

Construction of local gene network for revealing different liver function of rats fed deep-fried oil with or without resistant starch.

To study the mechanism underlying the liver damage induced by deep-fried oil (DO) consumption and the beneficial effects from resistant starch (RS) supplement, differential gene expression and pathway network were analyzed based on RNA sequencing data from rats. The up/down regulated genes and corresponding signaling pathways were used to construct a novel local gene network (LGN). The topology of the network showed characteristics of small-world network, with some pathways demonstrating a high degree. Some changes in genes led to a larger probability occurrence of disease or infection with DO intake. More importantly, the main pathways were found to be almost the same between the two LGNs (30 pathways overlapped in total 48) with gene expression profile. This finding may indicate that RS supplement in DO-containing diet may mainly regulate the genes that related to DO damage, and RS in the diet may provide direct signals to the liver cells and modulate its effect through a network involving complex gene regulatory events. It is the first attempt to reveal the mechanism of the attenuation of liver dysfunction from RS supplement in the DO-containing diet using differential gene expression and pathway network.

Postponing the Hypoglycemic Response to Partial Hepatectomy Delays Mouse Liver Regeneration.

All serious liver injuries alter metabolism and initiate hepatic regeneration. Recent studies using partial hepatectomy (PH) and other experimental models of liver regeneration implicate the metabolic response to hepatic insufficiency as an important source of signals that promote regeneration. Based on these considerations, the analyses reported here were undertaken to assess the impact of interrupting the hypoglycemic response to PH on liver regeneration in mice. A regimen of parenteral dextrose infusion that delays PH-induced hypoglycemia for 14 hours after surgery was identified, and the hepatic regenerative response to PH was compared between dextrose-treated and control mice. The results showed that regenerative recovery of the liver was postponed in dextrose-infused mice (versus vehicle control) by an interval of time comparable to the delay in onset of PH-induced hypoglycemia. The regulation of specific liver regeneration-promoting signals, including hepatic induction of cyclin D1 and S-phase kinase-associated protein 2 expression and suppression of peroxisome proliferator-activated receptor γ and p27 expression, was also disrupted by dextrose infusion. These data support the hypothesis that alterations in metabolism that occur in response to hepatic insufficiency promote liver regeneration, and they define specific pro- and antiregenerative molecular targets whose regenerative regulation is postponed when PH-induced hypoglycemia is delayed.

Inhibition of lipogenesis reduces inflammation and organ injury in sepsis.

BACKGROUND: Sepsis is a life-threatening acute inflammatory condition associated with metabolic complications. Accumulation of free fatty acids (FFAs) induces inflammation and causes lipotoxic effects in the liver. Because fatty acid metabolism plays a role in the inflammatory response, we hypothesized that the administration of C75, a fatty acid synthase inhibitor, could alleviate the injury caused by sepsis. METHODS: Male mice were subjected to sepsis by cecal ligation and puncture (CLP). At 4 h after CLP, different doses of C75 (1- or 5-mg/kg body weight) or vehicle (20% dimethyl sulfoxide in saline) were injected intraperitoneally. Blood and liver tissues were collected at 24 h after CLP. RESULTS: C75 treatment with 1- and 5-mg/kg body weight significantly lowered FFA levels in the liver after CLP by 28% and 53%, respectively. Administration of C75 dose dependently reduced serum indexes of organ injury (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase) and serum levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). In the liver, C75 treatment reduced inflammation (TNF-α and IL-6) and oxidative stress (inducible nitric oxide synthase and cyclooxygenase 2) in a dose-dependent manner. The 5-mg dose improved the 10-d survival rate to 85% from that of 55% in the vehicle. In the presence of C75, TNF-α release in RAW 246.7 cells with 4-h lipopolysaccharide stimulation was also significantly reduced. CONCLUSIONS: C75 effectively lowered FFA accumulation in the liver, which was associated with inhibition of inflammation and organ injury as well as improvement in survival rate after CLP. Thus, inhibition of FFA by C75 could ameliorate the hepatic dysfunction seen in sepsis.

Perioperative antiviral therapy improves safety in patients with hepatitis B related HCC following hepatectomy.

INTRODUCTION: Hepatectomies may exacerbate chronic hepatitis B in patients with high hepatitis B viral (HBV) DNA levels, and could result in hepatic insufficiency. Antiviral treatment is effective for suppressing HBV virus loads. This study investigated whether perioperative antiviral therapy is warranted for resection of hepatocellular carcinoma (HCC) with concurrent HBV infections. METHODS: Patients with HBV-related HCC (n = 112) who underwent major liver resection were retrospectively divided into two groups based on treatment with perioperative antiviral therapy (antiviral group) (n = 72) or absence of antiviral treatment (control group) (n = 40). RESULTS: Exacerbation of chronic hepatitis B occurred in 6 patients of the control group (15.0%). The prevalence of hepatic insufficiency in the antiviral group and control group were 1.4% (1/72) and 12.5% (5/40), respectively (p < 0.05). Five of them (4.5%) developed hepatic encephalopathy and 3 of them (2.7%) developed hepatorenal syndrome. The control group had significantly higher morbidity (75.0% vs. 34.7%, p < 0.01) than the antiviral group. The control group had significantly higher levels of postoperative alanine aminotransferase (ALT) and serum bilirubin than the antiviral group. CONCLUSION: Perioperative antiviral treatment improves patient safety by decreasing morbidity and speeding recovery of postoperative liver function for HBV-related major HCC resection.

Synergistic effect of black tea and curcumin in improving the hepatotoxicity induced by aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is a toxic compound commonly found as a contaminant in human food. It is carcinogenic due its potential in inducing the oxidative stress and distortion of the most antioxidant enzymes. Since black tea possesses strong antioxidant activity, it protects cells and tissues against oxidative stress. Curcumin (CMN), a naturally occurring agent, has a combination of biological and pharmacological properties that include antioxidant activity. Therefore, the present study was carried out to investigate the possible role of separate and mixed supplementation of black tea extract and CMN in the hepatotoxicity induced by AFB1 in rats. A total of 48: adult male Sprague Dawley rats were randomly divided into eight groups with six rats in each group. Group 1 (normal control) includes rats that received no treatment. Groups 2, 3, and 4 (positive control) include rats that received olive oil, black tea extract, and CMN, respectively. Group 5 includes rats that received AFB1 at a dose of 750 µg/kg body weight (b.w.) dissolved in olive oil. Groups 6, 7, and 8 include rats that received AFB1 along with 2% black tea extract, CMN at a dose of 200 mg/kg b.w., and both black tea extract and CMN at the same previous doses, respectively. After 90 days, biochemical and histopathological examination was carried out for the blood samples and liver tissues. A significant decrease in the antioxidant enzymes and a significant increase in the lipid peroxidation and hydrogen peroxide in the rats treated with AFB1 were observed. Moreover, there were dramatic changes in the liver function biomarkers, lipid profile, and liver architecture. Supplementation of black tea extract or CMN showed an efficient role in repairing the distortion of the biochemical and histological changes induced by AFB1 in liver. This improvement was more pronounced when both CMN and black tea were used together.

Medium-chain TAG attenuate hepatic oxidative damage in intra-uterine growth-retarded weanling piglets by improving the metabolic efficiency of the glutathione redox cycle.

The present study investigated the effects of medium-chain TAG (MCT) on hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). At weaning (mean 21 (SD 1·06) d of age), twenty-four IUGR piglets and twenty-four normal-birth weight (NBW) piglets were selected according to their birth weight (BW; IUGR: mean 0·95 (SD 0·04) kg; NBW: mean 1·58 (SD 0·04) kg) and weight at the time of weaning (IUGR: mean 5·26 (SD 0·15) kg; NBW: mean 6·98 (SD 0·19) kg) and fed either a soyabean oil (SO) diet (containing 5% SO) or a MCT diet (containing 1% SO and 4% MCT) for 28 d. IUGR piglets exhibited poor (P<0·05) growth performance, lower (P<0·05) metabolic efficiency of hepatic glutathione (GSH) redox cycle, and increased (P<0·05) levels of reactive oxygen species, apoptosis and necrosis in hepatocytes compared with NBW piglets. The MCT diet increased (P<0·05) the average daily gain and feed efficiency of piglets during the first 4 weeks after weaning. Furthermore, MCT diet-fed piglets had a higher (P<0·05) GSH:oxidised glutathione ratio and increased (P<0·05) activities of glucose-6-phosphate dehydrogenase (G6PD) and GSH reductase. The expression of G6PD was up-regulated (P<0·05) by the MCT diet irrespective of BW. Moreover, malondialdehyde concentrations in the liver and apoptosis and necrosis levels in hepatocytes were decreased (P<0·05) by the MCT diet irrespective of BW. These results indicate that MCT might have auxiliary therapeutic potential to attenuate hepatic oxidative damage in IUGR offspring during early life, thus leading to an improvement in the metabolic efficiency of the hepatic GSH redox cycle.

Benefits of exenatide on obesity and non-alcoholic fatty liver disease with elevated liver enzymes in patients with type 2 diabetes.

BACKGROUND: The purpose of this study was to evaluate the advantages of exenatide treatment on obesity and non-alcoholic fatty liver disease (NAFLD) with elevated liver enzymes in patients with type 2 diabetes (T2D). METHODS: A total of 60 newly diagnosed patients with obesity, NAFLD with elevated liver enzymes and T2D were included in the study. The patients were randomly divided into two groups. The exenatide treatment group (n = 30) were treated with exenatide and insulin glargine, and the intensive insulin therapy group (n = 30) were treated with insulin aspart and insulin glargine for 12 weeks. Selected clinical characteristics were determined, and ultrasonography was performed at both baseline and 12 weeks following treatment. RESULTS: At baseline, the clinical characteristics were matched between the two groups. After 12 weeks, fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG) and total bilirubin levels were significantly decreased in the two groups (p < 0.001). Body weight and waist circumference were significantly decreased in the exenatide group but increased in the intensive insulin group (p < 0.001). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGGT) in the exenatide group were significantly lower than in the intensive insulin group (p < 0.001). The mean body weight change correlated with the levels of ALT, AST and γGGT change (ALT, r = 0.761; AST, r = 0.733; γGGT, r = 0.752; p < 0.001). Moreover, the reversal rate of fatty liver was significantly higher in the exenatide group (93.3%) than the intensive insulin group (66.7%) (p < 0.01). CONCLUSIONS: Exenatide has a better hepatic-protective effect than intensive insulin therapy and perhaps represents a unique option for adjunctive therapy for patients with obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D.