闭合性肝损伤的早期诊断与治疗

为探讨闭合性肝损伤的早期诊断与治疗 ,笔者对 1 995年～ 2 0 0 2年 9月间收治 91例闭合性肝损伤临床资料进行回顾性分析。早期诊断性腹穿、B超和CT检查阳性率依次为 67.0 3 % (61 /91 ) ,94.83 % (55/58) ,96 .97% (32 /33)。非手术治疗 1 9例 ,治愈 1 8例 (中转手术 1例 )。手术治疗 73例(包括非手术治疗中转手术 1例 ) ,采用单纯缝合 2 9例、明胶海棉或大网膜填塞加褥式缝合 2 6例 ,填塞加肝动脉结扎 5例、碘仿纱条填塞 4例、肝叶切除 4例、手套温水囊压迫 3例 ,肝动脉栓塞 2例 ,治愈 70例 ,死亡 3例。全组治愈 88例 (96 .70 % )。笔者体会早期诊断及多种手段的有效治疗是减少死亡率的重要因素。

肝损伤28例诊断与治疗

目的 探讨肝损伤的临床诊断与治疗方法。方法对28例肝损伤进行分析。结果28例患者，Ⅰ～Ⅱ级损伤24例，Ⅲ级损伤4例。非手术治疗12例，手术治疗16例。治愈27例，死亡1例。结论腹腔穿刺、B超或腹部平片对肝损伤有较好的诊断作用。对于血液动力学稳定的Ⅰ～Ⅱ级患者可试行非手术治疗。名胶海绵填充后修补＋腹腔引流术为级肝损伤的最理想方案，选择性肝动脉结扎术及不规则性肝部分切除术可用于Ⅲ～Ⅳ级肝损伤患者。

严重肝外伤的诊断与治疗

目的 总结严重肝外伤临床诊断与治疗的经验。方法 对 94例严重肝外伤病人的临床诊断与治疗进行回顾性分析。结果 本组 94例均为外伤所致 ,入院时伴出血性休克 82例 (87 2 % ) ,明显腹膜炎 71例 (75 5% ) ,伴有合并伤者 72例 (76 6% )。肝外伤分级(按Moore氏分级法 ) ,Ⅲ级 52例 ,Ⅳ级 32例 ,Ⅴ级 1 0例。 94例均行手术治疗 ,治愈 78例(83 0 % ) ,死亡 1 6例 (1 7 0 % )。死亡原因 :严重失血性休克 5例 ,合并严重脑挫伤 4例。术后合并多器官功能衰竭 (MOF) 7例。结论 注重病人外伤史和外伤部位的询问 ,同时对生命体征及腹部情况进行认真检查 ,以及常规的腹腔穿刺和腹部B超检查 ,是早期诊断的关键。手术仍是治疗严重肝外伤的重要手段 ,但对术后重要器官功能的保护和并发症的防治也不容忽视。

损伤控制性复苏严重肝损伤86例

目的探讨损伤控制性复苏在严重肝损伤治疗中的作用。方法回顾性分析1998年～2008年86例严重肝损伤患者的临床资料。结果86例患者中10例死亡,76例治愈,治愈率为88.4%。结论损伤控制性复苏应贯穿严重肝损伤围手术期全过程,早期成功复苏是提高治愈率、减少病死率的关键。

Practical guidelines for diagnosis and early management of drug-induced liver injury

The spectrum of drug-induced liver injury （DILI） is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILl, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method （CIOMS/RUCAM） scale, may be helpful for the final diagnosis. Early management of DILl involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase （ALT）, alkaline phosphatase （ALP）, and total bilirubin （T-Bil）. However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.

Molecular therapy for hepatic injury and fibrosis:Where are we?

Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.

Gene expression profile analyses of mice livers injured by Leigongteng

AIM： To analyze the gene expression profiles of mice livers injured by Leigongteng and explore the relationship between the differentially expressed genes and liver damage. METHODS： The experimental mice were randomly divided into a control group and a liver-injured group in which the mice were administrated 33 μγ, of triptolide/ kg per day for 30 d. Liver mRNAs were extracted from animals in both groups and were reverse-transcribed to cDNA with dUTP labeled by different fluorescence （Cy3, Cy5） as hybridization probes. The mixed probes were hybridized with oligonucleotide microarray chips. The fluorescent signal results were acquired by scanner and analyzed with software. RESULTS： Among the 35852 target genes, 29 genes were found to be significantly differentially expressed, with 20 genes up-regulated and 9 genes down-regulated. The reliability of the differentially expressed genes was validated by RT-PCR experiments of 5 randomly selected differentially expressed genes. CONCLUSION： Based on the biological functions of the differentially expressed genes, it is obvious that the occurrence and development of liver damage induced by Leigongteng in mice are highly associated with immune response, metabolism, apoptosis and the cell skeleton of liver cells. This might be important for elucidating the regulatory network of gene expression associated with liver damage and it may also be important for discovering the pathogenic mechanisms of liver damage induced by Leigongteng.

Risk factors for alcohol-related liver injury in the island population of China: A population-based case-control study

AIM:To investigate the association of alcohol dose, duration of drinking and obesity with abnormal alcohol-related liver injury indicators, the prevalence of alcohol-related liver injury in the island population of China.METHODS:Randomized multistage stratified cluster sampling from the island population of China was used in the population-based case-control study. Then interview, physical examination, laboratory assessments and ultrasonography were done. RESULTS:Daily alcohol intake ≥ 20 g, duration of drinking ≥ 5 years and obesity were closely related to alcohol-related liver injury (P < 0.05). The odds-ratio (OR) (95% CI) was 1.965 (1.122-3.442), 3.412 (1.789-6.507) and 1.887 (1.261-2.824), respectively. The prevalence rate of alcohol-related liver injury in ≥ 20 g daily alcohol intake group and < 20 g daily alcohol intake group was 37.14% and 12.06%, respectively. The prevalence rate of alcohol-related liver injury in ≥ 5 years drinking group and < 5 years drinking group was 34.44% and 8.53%, respectively. No significant dose-response relation was found between daily alcohol intake and abnormal alcohol-related liver injury indicators as well as between duration of drinking and abnormal alcohol-related liver injury indicators. There was no significant difference in the prevalence of alcohol-related liver injury between beer drinking group and yellow rice wine drinking group, hard liquor drinking group, multiple drinking group.CONCLUSION:The risk threshold of daily alcohol intake is 20 g and duration of drinking inducing alcohol-related liver injury 5 years in the island population of China. Liver injury induced by obesity should be concerned.

Surgical management in biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury

AIM: To discuss the surgical method and skill of biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury. METHODS: From November 2005 to December 2006, eight patients with biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury were admitted to our hospital. Their clinical data were analyzed retrospectively. RESULTS: Bile duct injury was caused by cholecys- tectomy in the eight cases, including seven cases with laparoscopic cholecystectomy and one with mini- incision choleystectomy. According to the classification of Strasberg, type E1 injury was found in one patient, type E2 injury in three, type E3 injury in two and type E4 injury in two patients. Both of the type E4 injury patients also had a vascular lesion of the hepatic artery. Six patients received Roux-en-Y hepaticojejunostomy for the second time, and one of them who had type E4 injury with the right hepatic artery disruption received right hepatectomy afterward. One patient who had type E4 injury with the proper hepatic artery lesion underwent liver transplantation, and the remaining one with type E3 injury received external biliary drainage. All the patients recovered fairly well postoperatively. CONCLUSION: Roux-en-Y hepaticojejunostomy is still the main approach for such failed surgical cases with bile duct injury. Special attention should be paid to concomitant vascular injury in these cases. The optimal timing and meticulous and excellent skills are essential to the success in this surgery.

Cell cycle and radiosensitivity of progeny of irradiated primary cultured human hepatocarcinoma cells

AIM： To evaluate the change of growth characteristics and radiosensitivity of irradiated primary cultured human hepatocarcinoma cells. METHODS： All tumor tissue samples were obtained from 39 hepatocarcinoma patients with a mean age of 49.6 years （range 22-76 years）. We divided the samples into irradiated group and non-irradiated group and measured their plating efficiency （PE）, population doubling time （PDT）, radiosensitivity index SF2 and cell RESULTS： The PDT of primary culture of hepatocardnoma cells was 91.0±6.6 h, PE was 12.0±1.4%, SF2 was 0.41±0.05%. The PDT of their inadiated progeny was 124.8±5.8 h, PE was 5.0±0.7%, SF2 was 0.65±0.09%. The pdmary cultured human hepatocarcinoma cells showed significant S reduction and G^2 arrest in a dose-dependent manner. The progeny of irradiated primary cultured hepatocarcinoma cells grew more slowly and its radiosensitivity increased. CONCLUSION： The progeny of irradiated primary cultured human hepatocarcinoma cells grows more slowly and its radiosensitivity increases.

Induction of ischemic tolerance in rat liver via reduced nicotinamide adenine dinucleotide phosphate oxidase in Kupffer cells

AIM: To elucidate the mechanisms of hepatocyte preconditioning by H2O2 to better understand the pathophysiology of ischemic preconditioning. METHODS: The in vitro effect of H2O2 pretreatment was investigated in rat isolated hepatocytes subjected to anoxia/reoxygenation. Cell viability was assessed with propidium iodide fluorometry. In other experiments, rat livers were excised and subjected to warm ischemia/ reperfusion in an isolated perfused liver system to determine leakage of liver enzymes. Preconditioning was performed by H2O2 perfusion, or by stopping the perfusion for 10 min followed by 10 min of reperfusion. To inhibit Kupffer cell function or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gadolinium chloride was injected prior to liver excision, or diphenyleneiodonium, an inhibitor of NADPH oxidase, was added to the perfusate, respectively. Histological detection of oxygen radical formation in Kupffer cells was performed by perfusion with nitro blue tetrazolium. RESULTS: Anoxia/reoxygenation decreased hepatocyte viability compared to the controls. Pretreatment with H2O2 did not improve such hepatocyte injury. In liver perfusion experiments, however, H2O2 preconditioning reduced warm ischemia/reperfusion injury, which wasreversed by inhibition of Kupffer cell function or NADPH oxidase. Histological examination revealed that H2O2 preconditioning induced oxygen radical formation in Kupffer cells. NADPH oxidase inhibition also reversed hepatoprotection by ischemic preconditioning. CONCLUSION: H2O2 preconditioning protects hepato- cytes against warm ischemia/reperfusion injury via NADPH oxidase in Kupffer cells, and not directly. NADPH oxidase also mediates hepatoprotection by ischemic preconditioning.

Fenofibrate-induced liver injury

Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently observed after the administration of fenofibrate and this phenomenon is considered to be non-pathological because fenofibrate activates the gene expression of the aminotransferases. Recently, fenofibrate has been used not only for hypercholesterolemia but also for primary biliary cirrhosis （PBC）. However, the occurrence of liver injury induced by fenofibrate has not yet been reported written in the English literature. We herein report a rare case of liver injury due to the oral use of this drug.

Effects of Wy14643 on hepatic ischemia reperfusion injury in rats

AIM: To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemia-reperfusion (I/R) injury in rats.METHODS: Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups: sham group (G1, n = 6): a sham operation was performed (except for liver I/R); I/R-untreated group (G2, n = 6): rats underwent liver ischemia for 90 min followed by reperfusion for 4 h; and I/R + Wy14643 groups (G3, G4, G5; n = 6): after the same surgical procedure as in group 2, animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively. Hepatic ischemia-reperfusion (I/R) was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST), myeloperoxidase (MPO), serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α), as well as activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the hepatic tissue homogenate. RESULTS: Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-α, IL-1β and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced bypretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment. In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups, respectively.CONCLUSION: Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation response.

Hepatorenal syndrome: Update on diagnosis and treatment

Acute kidney injury(AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome(HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.

Liver transplantation for severe hepatic trauma:Experience from a single center

Liver transplantation has been reported in the literature as an extreme intervention in cases of severe and complicated hepatic trauma.The main indications for liver transplant in such cases were uncontrollable bleeding and postoperative hepatic insufficiency.We here describe four cases of orthotopic liver transplantation after penetrating or blunt liver trauma.The indications were liver failure,extended liver necrosis,liver gangrene and multiple episodes of gastrointestinal bleeding related to portal hypertension,respectively.One patient died due to postoperative cerebral edema.The other three patients recovered well and remain on immunosuppression.Liver transplantation should be considered as a saving procedure in severe hepatic trauma,when all other treatment modalities fail.

Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

AIM： TO investigate the effects of ursodeoxycholic acid （UDCA） on chenodeoxycholic acid （CDCA）-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS： Liver injury was induced in hamsters by administration of 0.5% （w/w） CDCA in their feed for 7 d. UDCA （50 mg/kg and 150 mg/kg） was administered for the last 3 d of the experiment.RESULTS： At the end of the experiment, serum alanine aminotransferase （ALl） increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid （LCA）. UDCA （50 mg/kg and 150 mg/kg） improved liver histology, with a significant decrease （679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ±35.5 U/ L, respectively, P 〈 0.01） in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION： The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.

Study on protecting effects of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.

Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl_4-induced chronic liver damage in rats

AIM： To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan （GB34） on CCl4-induced chronic liver damage in rats. METHODS： Rats were injected intraperitoneally with CCh （1 mL/kg） and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 （Yanglingquan） 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS： Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION： Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCh-intoxicated rats.