Poor prognosis for hepatocellular carcinoma with transarterial chemoembolization pre-transplantation:Retrospective analysis

AIM: To investigate whether transarterial chemoembolization(TACE) before liver transplantation(LT) improves long-term survival in hepatocellular carcinoma(HCC) patients.METHODS: A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA General Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein(AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-TurcottePugh(Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the logrank and χ2 tests were used for comparisons.RESULTS: In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo(χ2 = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo(χ2 = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of metastasis of the primary tumor in the group with TACE was significantly higher than that of the group without TACE.CONCLUSION: TACE pre-LT for HCC patients increased the chances of pulmonary or distant metastasis of the primary tumor, thus reducing the long-term survival rate.     

Factors influencing the short-term and long-term survival of hepatocellular carcinoma patients with portal vein tumor thrombosis who underwent chemoembolization

BACKGROUNDThe factors affecting the short-term and long-term prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) receiving transarterial chemoembolization (TACE) are still unclear.AIMTo clarify the predictors correlated with the short-term and long-term survival of HCC patients with PVTT who underwent TACE.METHODSThe medical records of 181 HCC patients with PVTT who underwent TACE at the Second Affiliated Hospital of Chongqing Medical University from January 2015 to July 2019 were retrospectively analyzed. We explored the short-term and long-term prognostic factors by comparing the preoperative indicators of patients who died and survived within 3 mo and 12 mo after TACE. Multivariate analyses were conducted using logistic regression. The area under the receiver operating characteristic curve (area under curve) was used to evaluate the predictive ability of the factors related to the short-term and long-term prognosis.RESULTSThe median survival time was 4.8 mo (range: 2.5-8.85 mo). The 3 mo, 6 mo, and 12 mo survival rates were 68.5%, 38.7%, and 15.5%, respectively. In multivariable analysis, total bilirubin, sex, and aspartate aminotransferase (AST) were closely linked to short-term survival. When AST ≥ 87 U/L and total bilirubin ≥ 16.15 µmol/L, the 3-mo survival rate after TACE was reduced significantly (P < 0.05). AST had the best predictive ability, followed by total bilirubin, while sex had the worst predictive ability for short-term survival area under curve: 0.763 (AST) vs 0.707 (total bilirubin) vs 0.554 (sex)]. The long-term survival outcome was significantly better in patients with a single lesion than in those with ≥ three lesions (P = 0.009). Patients with massive block HCC had a worse long-term survival than patients with nodular and diffuse HCC (P = 0.001).CONCLUSIONAST, total bilirubin, and sex are independent factors associated with short-term survival. The number of tumors and the gross pathological type of tumor are related to the long-term outcome.     

Regulatory effect and mechanisms of carbon monoxidereleasing molecule Ⅱ on hepatic energy metabolism in septic mice

AIM:To investigate the possible mechanisms of exogenous carbon monoxide-releasing moleculeⅡ(CORM-2)intervention on hepatic energy metabolism in experimental sepsis.METHODS:Forty-eight C57BL/6 mice were randomly divided into four groups(n=12):sham group;cecal ligation and puncture(CLP)group;CLP+CORM-2group and CLP+iCORM-2(inactive CORM-2)group.Survival rates were determined after 72 h.Twenty-four similarly treated mice(n=6 in each group)were assayed for post-operative continuous blood glucose in the first 36 h.Thirty-six similarly treated mice(n=9in each group)underwent micro-positron emission tomography(PET)scanning after tail vein injection of18Ffluorodeoxyglucose(FDG)24 h after operation.Plasma and liver specimens were collected for assay of liver pathology,alanine transaminase(ALT)and aspartate transaminase(AST)activities.Hepatic glucokinase activity,lactic acid levels and mitochondrial swelling were also determined.RESULTS:Improved survival was observed in CORM-2treated mice.Both the CLP and CLP+CORM-2 groups had sustained low blood glucose levels within the first post-operative 36 h.18F-FDG micro-PET images showed abnormally high levels of hepatic glucose metabolism(standardized uptake value)in the CLP group(2.76±0.39 vs 0.84±0.14,P<0.01),which declined to normal levels after CORM-2 intervention(1.29±0.32 vs2.76±0.39,P<0.05).glucokinase activity was markedly increased in the CLP group(6.38±0.56 U/g vs 4.60±0.21 U/g,P<0.01),but was normal after CORM-2intervention(4.74±0.14 U/g vs 6.38±0.56 U/g,P<0.05).CORM-2 suppressed plasma lactic acid levels(4.02±0.02 mmol/L vs 7.72±2.37 mmol/L,P<0.05)and protected hepatic mitochondria in CLP mice.CORM-2 intervention also reduced elevated plasma AST(199.67±11.08 U/L vs 379.67±16.34 U/L,P<0.05)and ALT(63.67±12.23 U/L vs 112.67±9.74 U/L,P<0.05)activities in CLP mice.CONCLUSION:The release of CO molecules by CORM-2 protects mitochondria and maintains a stable level of hepatic glucose metabolism.Thus,CORM-2 improves liver function and survival in septic mice.     

Correlation between anti-fibrotic effect of baicalin and serum cytokines in rat hepatic fibrosis

AIM： To investigate the correlation between the antifibrotic effect of baicalin and serum cytokine production in rat hepatic fibrosis, METHODS： Forty male Sprague-Dawley rats were divided randomly into four groups： normal control group, model group, baicalin-treated group, and colchicine-treated group. Except for the normal control group, all rats in the other groups were administered with carbon tetrachloride to induce hepatic fibrosis. At the same time, the last two groups were also treated with baicalin or colchicine. At the end of the 8 wk, all animals were sacrificed. Serum alanine aminotransferase （ALl＇）, aspartate aminotransferase （AST）, transforming growth factor （TGF）-β1, tumor necrosis factor （TNF）-α, interleukin （IL）-6 and IL-10 were measured. Liver index, hepatic hydroxyproline content and the degree of liver fibrosis were also evaluated. RESULTS： The levels of ALT, AST and liver index in the baicalin-treated group were markedly lower than those in the model group （ALT： 143.88 ± 14.55 U/L vs 193.58± 24.35 U/L; AST： 263.66 ± 44.23 U/L vs 404.37± 68.29 U/L; liver index： 0.033 ± 0.005 vs 0.049± 0.009, P 〈 0.01）. Baicalin therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percentage in liver tissue （P 〈 0.01）. Furthermore, the levels of serum TGF-β1, TNF-α and IL-6 were strikingly reduced in the baicalin-treated group compared with the model group, while the production of IL-10 was up-regulated： （TGF-β1：260.21 ± 31.01 pg/mL vs 375.49 ± 57.47 pg/mL; TNF-α： 193.40±15.18 pg/mL vs 260.04 ± 37.70 pg/mL; IL-α：339.87 ± 72.95 pg/mL vs 606.47 ± 130.73 pg/mL; IL-10：506.22 ± 112.07 pg/mL vs 316.95 ± 62.74 pg/mL, P 〈 0.01）. CONCLUSION： Baicalin shows certain therapeutic effects on hepatic fibrosis, probably by immunoregulating the imbalance between profibrotic and antifibrotic cytokines.     

Role of surgical resection for multiple hepatocellular carcinomas

AIM:To clarify the role of surgical resection for multiple hepatocellular carcinomas(HCCs)compared to transarterial chemoembolization(TACE)and liver transplantation(LT). METHODS:Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008,160 patients who met the following criteria were retrospectively enrolled:(1) two or three radiologically diagnosed HCCs;(2)no radiologic vascular invasion;(3)Child-Pugh class A;(4) main tumor smaller than 5 cm in diameter;and(5) platelet count greater than 50 000/mm3.Long-term outcomes were compared among the following three treatment modalities:surgical resection or combined radiofrequency ablation(RFA)(n=36),TACE(n=107), and LT(n=17).The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test.To identify the patients who gained a survival benefit from surgical resection,we also investigated prognostic factors for survival following surgical resection.Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model. RESULTS:The overall survival(OS)rate was significantly higher in the surgical resection group than in the TACE group(48.1%vs 28.9%at 5 years,P<0.005). LT had the best OS rate,which was better than that of the surgical resection group,although the difference was not statistically significant(80.2%vs 48.1%at 5 years,P=0.447).The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group(88.2%vs 11.2%at 5 years, P<0.001).Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6%(20/36)in the resection group and 93.5%(100/107)in the TACE group.There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients,multisite resection was performed in 5 patients,and combined resection with RFA was performed in 8 patients. In the TACE group,only 34 patients(31.8%)were record     

Hydrogen-rich water protects against acetaminopheninduced hepatotoxicity in mice

AIM: To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water(HRW) in acetaminophen(APAP)-induced liver injury in mice.METHODS: Male mice were randomly divided into the following four groups: normal saline(NS) control group, mice received equivalent volumes of NS intraperitoneally(ip); HRW control group, mice were given HRW(same volume as the NS group); APAP + NS group, mice received NS ip for 3 d(5 mL /kg body weight, twice a day at 8 am and 5 pm) after APAP injection; APAP + HRW group, mice received HRW for 3 d(same as NS treatment) after APAP challenge.In the first experiment, mice were injected ip with a lethal dose of 750 mg/kg APAP to determine the 5-d survival rates.In the second experiment, mice were injected ip with a sub-lethal dose of 500 mg/kg.Blood and liver samples were collected at 24, 48, and 72 h after APAP injection to determine the degree of liver injury.RESULTS :Treatment with HRW resulted ina significant increase in the 5-d survival rate compared with the APAP + NS treatment group(60% vs 26.67%, P 0.05).HRW could significantly decrease the serum alanine aminotransferase level(24 h: 4442 ± 714.3 U/L vs 6909 ± 304.8 U/L, P 0.01; 48 h: 3782 ± 557.5 U/L vs 5111 ± 404 U/L, P 0.01; and3255 ± 337.4 U/L vs 3814 ± 250.2 U/L, P 0.05, respectively) and aspartate aminotransferase level(24 h: 4683 ± 443.4 U/L vs 5307 ± 408.4 U/L, P 0.05; 48 h: 3392 ± 377.6 U/L vs 4458 ± 423.6 U/L, P 0.01; and 3354 ± 399.4 U/L vs 3778 ± 358 U/L, respectively) compared with the APAP treatment group.The alkaline phosphatase, total bilirubin and lactate dehydrogenase levels had the same result.Seventy-two hours after APAP administration, liver samples were collected for pathological examination and serum was collected to detect the cytokine levels.The liver index(5.16% ± 0.26% vs 5.88% ± 0.073%, P 0.05) and percentage of liver necrosis area(27.73% ± 0.58% vs 36.87% ± 0.49%, P 0.01) were significantly lower in the HRW-treated animals.The malonyldialdehyde(MDA) contents were significantly reduced in the HRW pretreatment group, but they were increased in the APAP-treated group(10.44 ± 1.339 nmol/mg protein vs 16.70 ± 1.646 nmol/mg protein, P 0.05).A decrease in superoxide dismutase(SOD) activity in the APAP treatment group and an increase of SOD in the HRW treatment group were also detected(9.74 ± 0.46 U/mg protein vs 12.1 ± 0.67 U/mg protein, P 0.05).Furthermore, HRW could significantly increase the glutathione(GSH) contents(878.7 ± 76.73 mg/g protein vs 499.2 ± 48.87 mg/g protein) compared with the APAP treatment group.Meanwhile, HRW could reduce the inflammation level(serum TNF-α: 399.3 ± 45.50 pg/L vs 542.8 ± 22.38 pg/L, P 0.05; and serum IL-6: 1056 ± 77.01 pg/L vs 1565 ± 42.11 pg/L, P 0.01, respectively).In addition, HRW could inhibit 4-HNE, nitrotyrosine formation, JNK phosphorylation, connexin 32 and cytochrome P4502 E expression.Simultaneously, HRW could facilitate hepatocyte mitosis to promote liver regeneration.CONCLUSION: HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.     

Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma

AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, re-currence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P<0.05 and I 2>50%, the assumption of homogeneity was deemed invalid, and the random-effects model wasused; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted us-ing Review manager (version 4.2.2.) from the Cochrane collaboration. RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a sig-nificantly higher overall survival rate (OR 1-year=2.96, 95%CI: 1.84-7.74, P<0.001; OR 2-year=3.72, 95%CI: 1.24-11.16, P=0.02; OR 3-year=2.65, 95%CI: 1.81-3.86, P<0.001) and recurrence-free survival rate (OR 3-year=3.00, 95%CI: 1.75-5.13, P<0.001; OR 5-year=2.26, 95%CI: 1.43-3.57, P=0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR=0.60, 95%CI: 0.42-0.88, P=0.008) and there was no significant difference on major complications between two different kinds of treatment (OR=1.20, 95%CI: 0.31-4.62, P=0.79). Additionally, the meta-analysis data of subgroups revealed that the     

Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients tha     

Radiofrequency ablation of hepatocellular carcinoma in difficult locations:Strategies and long-term outcomes

AIM:To investigate the treatment strategies and longterm outcomes of radiofrequency ablation(RFA) of hepatocellular carcinoma(HCC) in difficult locations and to compare the results with non-difficult HCC.METHODS:From 2004 to 2012,a total of 470 HCC patients underwent ultrasound-guided percutaneous RFA.Among these HCC patients,382 with tumors located ≤ 5 mm from a major vessel/bile duct(n = 87),from peripheral important structures(n = 232) or from the liver capsule(n = 63) were regarded as difficult cases.There were 331 male patients and 51 female patients,with an average age of 55.3 ± 10.1 years old.A total of 235 and 147 patients had ChildPugh class A and class B liver function,respectively.The average tumor size was 3.4 ± 1.2 cm.Individual treatment strategies were developed to treat these difficult cases.During the same period,88 HCC patients with tumors that were not in difficult locations served as the control group.In the control group,74 patients were male,and 14 patients were female,with an average age of 57.4 ± 11.8 years old.Of these,62 patients and 26 patients had Child-Pugh class A and class B liver function,respectively.Regular follow-up after RFA was performed to assess treatment efficacy.Survival results were generated from Kaplan-Meier estimates,and multivariate analysis was performed using the Cox regression model.RESULTS:Early tumor necrosis rate in the difficult group was similar to that in the control group(97.6% vs 94.3%,P = 0.080).The complication rate in the difficult group was significantly higher than that in thecontrol group(4.9% vs 0.8%,P = 0.041).The followup period ranged from 6 to 116 mo,with an average of 28 ± 22.4 mo.Local progression rate in the difficult group was significantly higher than that in the control group(12.7% vs 7.1%,P = 0.046).However,the 1-,3-,5-,and 7-year overall survival rates in the difficult group were not significantly different from those in the control group(84.3%,54.4%,41.2%,and 29.9% vs 92.5%,60.3%,43.2%,and 32.8%,respectively,P = 0.371).Additionally,a multivariate analysis revealed that tumor location was not a significant risk factor for survival.CONCLUSION:There was no significant difference in long-term overall survival between the two groups even though the local progression rate was higher in the difficult group.     

Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients

AIM:To clarify the utility of using des-γ-carboxy prothrombin(DCP)andα-fetoprotein(AFP)levels to predict the prognosis of hepatocellular carcinoma(HCC)in patients with hepatitis B virus(HBV)and the hepatitis C virus(HCV)infections.METHODS:A total of 205 patients with HCC(105patients with HBV infection 100 patients with HCV infection)who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively.Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy,and cutoff levels were calculated.Patients in the HBV and HCV groups were classified into three groups:a group with low AFP and DCP levels(LL group),a group in which one of the two parameters was high and the other was low(HL group),and a group with high AFP and DCP levels(HH group).Liver function parameters,the postoperative recurrence-free survival rate,and postoperative overall survival were compared between groups.The survival curves were compared by logrank test using the Kaplan-Meier method.Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis.RESULTS:The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/m L and 60 m AU/m L,respectively;for preoperative DCP levels,the cutoff levels were 21.0 ng/m L in the HBV group and 67 m AU/m L in the HCV group.The HBV group was significantly different from the other groups in terms of vascular invasion,major hepatectomy,volume of intraoperative blood loss,and surgical duration.Significant differences were found between the LL group,the HL group,and the HH group in terms of both mean disease-free survival time(MDFST)and mean overall survival time(MOST):64.81±7.47 vs 36.63±7.62 vs 18.98±6.17mo(P=0.001)and 85.30±6.55 vs 59.44±7.87 vs46.57±11.20 mo(P=0.018).In contrast,the HCV group exhibited a significant difference in tumor size,vascular invasion,volume of intraoperative blood loss,and surgical duration;however,no significant difference was observed between the three groups in liver function parameters except for albumin levels.In the LL group,the HL group,and the HH group,the MDFST was 50.09±5.90,31.01±7.21,and 14.81±3.08 mo(log-rank test,P0.001),respectively,and the MOST was 79.45±8.30,58.82±7.56,and 32.87±6.31 mo(log-rank test,P0.001),respectively.CONCLUSION:In the HBV group,the prognosis was poor when either AFP or DCP levels were high.In the HCV group,the prognosis was good when either or both levels were low;however,the prognosis was poor when both levels were high.High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups.The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.     

Investigation of genome instability in patients with non-alcoholic steatohepatitis

AIM:To evaluate the occurrence of micronucleus(MN),nucleoplasmic bridges(NPBs)and nuclear buds(NBUDs)in the mitogen-stimulated lymphocytes of patients with non-alcoholic steatohepatitis(NASH).METHODS:The study was performed in 25(9 females,16 males)patients newly diagnosed with NASH,and 25healthy subjects of similar ages and genders were used as a control group.None of the controls was known to be receiving any drugs for medical or other reasons or using alcohol.Hepatosteatosis was further excluded by abdominal ultrasound imaging in the control group.The numbers of MN,NPBs and NBUDs scored in binucleated(BN)cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects.Statistical comparisons of the numbers of BN cells with MN,NPBs and NBUDs and ages between the patients with NASH and control subjects were performed.RESULTS:The mean ages of the patients and the control group were 41.92±13.33 and 41.80±13.09 years(P>0.05),respectively.The values of the mean body mass index(BMI),HOMA-IR,hemoglobin,creatinin,aspartate aminotransferase,alanine aminotransferase,triglyceride,high density lipoprotein,and low density lipoprotein were 31.19±4.62 kg/m2vs 25.07±4.14 kg/m2,6.71±4.68 vs 1.40±0.53,14.73±1.49 g/dL vs 14.64±1.30 g/dL,0.74±0.15 mg/dL vs 0.80±0.13 mg/dL,56.08±29.11 U/L vs 16.88±3.33 U/L,92.2±41.43U/L vs 15.88±5.88 U/L,219.21±141.68 mg/dL vs102.56±57.98 mg/dL,16.37±9.65 mg/dL vs 48.72±15.31 mg/dL,and 136.75±30.14 mg/dL vs 114.63±34.13 mg/dL in the patients and control groups,respectively.The total numbers and frequencies of BN cells with MN,NPBs and NBUDs,which were scored using the CBMN cytome assay on PHA-stimulated lymphocytes,were evaluated in the patients with NASH and control group.We found significantly higher numbers of MN,NPBs and NBUDs in the BN cells of patients with NASH than in those of the control subjects(21.60±9.32vs 6.88±3.91;29.28±13.31 vs 7.84±3.96;15.60±5.55 vs 4.20±1.63,respectively,P<0.0001).CONCLUSION:The increased numbers of MN,N     

Photodynamic therapy vs radiofrequency ablation for Barrett’s dysplasia: Efficacy,safety and cost-comparison

AIM:To compare effectiveness,safety,and cost of photodynamic therapy(PDT)and radiofrequency ablation(RFA)in treatment of Barrett’s dysplasia(BD).METHODS:Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared.Thirty-three patients with high-grade dysplasia(HGD)had treatment with porfimer sodium photosensitzer and 630 nm laser(130 J/cm),with maximum of 3 treatment sessions.Fifty-three patients with BD(47 with low-grade dysplasia-LGD,6 with HGD)had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions.Both groups received proton pump inhibitors twice daily.Endoscopic biopsies were acquired at 2 and 12 mo after enrollment,with 4-quadrant biopsies every 1 cm of the original BE extent.A complete histological resolution response of BD(CR-D)was defined as all biopsies at the last endoscopy session negative for BD.Fisher’s exact test was used to assess differences between the two study groups for primary outcomes.For all outcomes,a two-sided P value of less than 0.05 was considered to indicate statistical significance.RESULTS:Thirty(91%)PDT patients and 39(74%)RFA were men(P=0.05).The mean age was 70.7±12.2 and 65.4±12.7(P=0.10)year and mean length of BE was 5.4±3.2 cm and 5.7±3.2 cm(P=0.53)for PDT and RFA patients,respectively.The CR-D was(18/33)54.5%with PDT vs(47/53)88.7%with RFA(P=0.001).One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA.PDT was five times more costly than RFA at our institution.The two groups were not randomized and had different BD grading are the limitations of the study.CONCLUSION:In our experience,RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.     

Biliary fistula after treatment for hydatid disease of the liver:When to intervene

AIM:To determine the outcome of patients with biliary fistula(BF)after treatment for hydatid disease of the liver. METHODS:Between January 2000 and December 2010,out of 301 patients with a diagnosis of hydatid cyst of the liver,282 patients who underwent treatment [either surgery or puncture,aspiration,injection and reaspiration(PAIR)procedure]were analysed.Patients were grouped according to the presence or absence of postoperative biliary fistula(PBF)(PBF vs no-PBF groups,respectively).Preoperative clinical,radiological and laboratory characteristics,operative characteristics including type of surgery,peroperative detection of BF,postoperative drain output,morbidity,mortality and length of hospital stays of patients were compared amongst groups.Multivariate analysis was performed to detect factors predictive of PBF.Receiver operative characteristics(ROC)curve analysis were used to determine ideal cutoff values for those variables found to be significant.A comparison was also made between patients whose fistula closed spontaneously(CS)and those with intervention in order to find predictive fac-tors associated with spontaneous closure. RESULTS:Among 282 patients[median(range)age, 23(16-78)years;77.0%male];210(74.5%)were treated with conservative surgery,33(11.7%)radical surgery and 39(13.8%)underwent percutaneous drainage with PAIR procedure A PBF developed in 46(16.3%) patients,all within 5 d after operation.The maximum cyst diameter and preoperative alkaline phosphatase levels(U/L)were significantly higher in the PBF group than in the no-PBF group[10.5±3.7 U/L vs 8.4±3.5 U/L(P<0.001)and 40.0±235.1 U/Lvs 190.0±167.3 U/L(P=0.02),respectively].Hospitalization time was also significantly longer in the PBF group than in the no-PBF group[37.4±18.0 d vs 22.4±17.9 d(P< 0.001)].A preoperative high alanine aminotransferase level(>40 U/L)and a peroperative attempt for fistula closure were significant predictors of PBF development (P=0.02,95%CI:-0.03-0.5 and P=0.001,95%CI:0.1-0.4),respectively.Comparison of     

经导管肝动脉化疗栓塞联合射频消融治疗原发性肝癌患者临床疗效评价*

目的 评价经导管肝动脉化疗栓塞（TACE）与射频消融（RFA）联合治疗原发性肝癌患者的临床疗效。方法 采用随机数字表法将60例原发性肝癌患者分为联合组30例和TACE组30例,分别给予TACE联合RFA或TACE治疗,对比分析两组患者的近期和远期临床疗效。结果 联合组完全缓解和部分缓解率分别为26.7%和50.0%,显著高于TACE组的6.7%和23.3%,差异均具有统计学意义（P<0.05）;联合组患者生存时间为（2.86±0.48）年,显著长于TACE组的（0.93±0.27） 年,差异具有统计学意义（P<0.05）;联合组患者治疗后1年、2年、3年血清AFP水平分别为（475.4±200.7） μg/L、（416.4±229.0） μg/L、（320.4±243.5） μg/L,显著低于TACE组的（639.1±190.9） μg/L、（623.4±234.6） μg/L、（674.4±300.2） μg/L,差异均具有统计学意义（P<0.05）;联合组患者1 a、2 a、3 a生存率分别为86.7%、66.7%、56.7%,显著高于TACE组的46.7%、26.7%、10.0%,差异均具有统计学意义（P<0.05）。结论 TACE与RFA联合治疗原发性肝癌患者,临床疗效显著。     

Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

AIM:To investigate the protective effects of ethyl pyruvate(EP) on acute-on-chronic liver failure(ACLF) in rats.METHODS:An ACLF model was established in rats,and animals were randomly divided into normal,model and EP treatment groups.The rats in EP treatment group received EP(40 mg/kg) at 3 h,6 h,12 h and 24 h after induction of ACLF.Serum endotoxin,high mobility group box-1(HMGB1),alanine transaminase(ALT),tumor necrosis factor-(TNF-),interferon-(IFN-),interleukin(IL)-10 and IL-18 levels,changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF.The effects of EP on the survival of ACLF rats were also observed.RESULTS:Serum levels of endotoxin(0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL,P 0.001),HMGB1(35.42 ± 10.86 g/L vs 2.14 ± 0.27 g/L,P 0.001),ALT(8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L,P 0.001),TNF-(190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L,P 0.001),IFN-(715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L,P 0.001),IL-10(6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L,P 0.001) and IL-18(85.19 ± 3.49 ng/L vs 55.38 ± 1.25 ng/L,P 0.001) were significantly increased,and liver tissues presented severe pathological injury in the model group compared with the normal group.However,EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin(0.155 ± 0.045 EU/mL vs 0.394 ± 0.066 EU/mL,P 0.001) and inflammatory cytokines(11.13 ± 2.58 g/L vs 35.42 ± 10.86 g/L for HMGB1,3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT,128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-,438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-,3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10,and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18,respectively,P 0.001),and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF.EP treatment at the four time points prolonged the median survival time of ACLF rats(60 h) to 162 h,120 h,102 h and 78 h,respectively(2 = 41.17,P 0.0001).CONCLUSION:EP administration can protect against ACLF in rats,and is a potential and novel therapeutic agent for severe liver injury.     

Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice

AIM: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS: C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg. The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP. Twenty-four hours after APAP administration, blood samples of mice were analyzed for serum enzyme alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) levels, and malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS: Compared with the vehicle control group, the serum levels (IU/L) of ALT, AST and LDH were all increased significantly in APAP group (8355 ± 3940 vs 30 ± 21, P < 0.05; 6482 ± 4018 vs 146 ± 58, P < 0.05; 24627 ± 10975 vs 1504 ± 410, P < 0.05). Compared with APAP group, the serum ALT levels (IU/L) (1674 ± 1810 vs 8355 ± 3940, P < 0.05; 54 ± 39 vs 8355 ± 3940, P < 0.05; 19 ± 9 vs 8355 ± 3940, P < 0.05), AST levels (IU/L) (729 ± 685 vs 6482 ± 4108, P < 0.05; 187 ± 149 vs 6482 ± 4108, P < 0.05; 141 ± 12 vs 6482 ± 4108, P < 0.05) and LDH levels (IU/L) (7220 ± 6317 vs 24 627 ± 10 975, P < 0.05; 1618 ± 719 vs 24 627 ± 10 975, P < 0.05; 1394 ± 469 vs 24 627 ± 10 975, P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups. Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP, including hepatocellular necrosis and infiltration of inflammatory cells, and the effect was dose-dependent. MDA levels (nmol/mg) were decreased by 5-MOP in a dose-dependent manner (0.98 ± 0.45 vs 2.15 ± 1.07, P > 0.05; 0.59 ± 0.07 vs 2.15 ± 1.07, P < 0.05; 0.47 ± 0.06 vs 2.15 ± 1.07, P < 0.05). The pretreatment of 5-MOP could also increase the GSH/GSSG ratio (3.834 ± 0.340 vs 3.306 ± 0.282, P > 0.05; 5.330 ± 0.421 vs 3.306 ± 0.282, P < 0.05; 6.180 ± 0.212 vs 3.306 ± 0.282, P < 0.05). In the group treated with 5-MOP but without APAP, the serum enzyme levels, the liver histopathologic manifestation, and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION: 5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity, and does not cause liver injury at the protective doses.     

Outcome of transarterial chemoembolization in patients with inoperable hepatocellular carcinoma eligible for radiofrequency ablation

AIM: To evaluate the outcome of transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC)<5 cm in diameter eligible for radiofrequency ablation (RFA). METHODS: The treatment-related mortality, morbidity, long-term survival, and prognostic factors of HCC patients who had TACE and fulfilled the present inclusion criteria for RFA were evaluated. RESULTS: Of the 748 patients treated with TACE between January 1990 and December 2002,114 patients were also eligible for RFA. The treatment-related mortality and morbidity were 1% and 19%, respectively. Survival at 1, 3, and 5 years was 80%, 43%, and 23%, respectively. Older age and a high albumin level were associated with a better survival, whereas a high a-fetoprotein level (AFP) and the size of the largest tumor >3 cm in diameter were adverse prognostic factors in multivariate analysis. CONCLUSION: The morbidity, mortality, and survival data after TACE for small HCCs eligible for RFA are comparable to those reported after RFA in the literature. Our data suggest the need for a randomized comparison of the two treatment modalities for small HCCs.     

Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver ischemia/reperfusion injury

AIM: To investigate the effect of diazoxide administration on liver ischemia/reperfusion injury.METHODS: Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from the medium and left anterior lateral segments for 1 h under mechanical ventilation. They were divided into 3 groups: Control Group, rats submitted to liver manipulation, Saline Group, rats received saline, and Diazoxide Group, rats received intravenous injection diazoxide (3.5 mg/kg) 15 min before liver reperfusion. 4 h and 24 h after reperfusion, blood was collected for determination of aspartate transaminase (AST), alanine transaminase (ALT), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), nitrite/nitrate, creatinine and tumor growth factor-β1 (TGF-β1). Liver tissues were assembled for mitochondrial oxidation and phosphorylation, malondialdehyde (MDA) content, and histologic analysis. Pulmonary vascular permeability and myeloperoxidase (MPO) were also determined.RESULTS: Four hours after reperfusion the diazoxide group presented with significant reduction of AST (2009 ± 257 U/L vs 3523 ± 424 U/L, P = 0.005); ALT (1794 ± 295 U/L vs 3316 ± 413 U/L, P = 0.005); TNF-α (17 ± 9 pg/mL vs 152 ± 43 pg/mL, P = 0.013; IL-6 (62 ± 18 pg/mL vs 281 ± 92 pg/mL); IL-10 (40 ± 9 pg/mL vs 78 ± 10 pg/mL P = 0.03), and nitrite/nitrate (3.8 ± 0.9 μmol/L vs 10.2 ± 2.4 μmol/L, P = 0.025) when compared to the saline group. A significant reduction in liver mitochondrial dysfunction was observed in the diazoxide group compared to the saline group (P < 0.05). No differences in liver MDA content, serum creatinine, pulmonary vascular permeability and MPO activity were observed between groups. Twenty four hours after reperfusion the diazoxide group showed a reduction of AST (495 ± 78 U/L vs 978 ± 192 U/L, P = 0.032); ALT (335 ± 59 U/L vs 742 ± 182 U/L, P = 0.048), and TGF-β1 (11 ± 1 ng/mL vs 17 ± 0.5 ng/mL, P = 0.004) serum levels when compared to the saline group. The control group did not present alterations when compared to the diazoxide and saline groups.CONCLUSION: Diazoxide maintains liver mitochondrial function, increases liver tolerance to ischemia/reperfusion injury, and reduces the systemic inflammatory response. These effects require further evaluation for using in a clinical setting.