Late Protective Effects of the Anticalmodulin Drug Fluphenazine on Carbon Tetrachloride-induced Liver Necrosis

Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature

Non-steroidal anti-inflammatory drugs:What is the actual risk of liver damage?

Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinfectious agents, list on the top for causes of DrugInduced Liver Injury (DILI). The incidence of liver disease induced by NSAIDs reported in clinical studies is fairly uniform ranging from 0.29/100 000 [95% confidence interval (CI): 0.17-051] to 9/100 000 (95% CI: 6-15). However, compared with these results, a higher risk of liver-related hospitalizations was reported (3-23 per 100 000 patients). NSAIDs exhibit a broad spectrum of liver damage ranging from asymptomatic, transient, hyper-transaminasemia to fulminant hepatic failure. However, under-reporting of asymptomatic, mild cases, as well as of those with transient liver-tests alteration, in conjunction with reports non-compliant with pharmacovigilance criteria to ascertain DILI and flawed epidemiological studies, jeopardize the chance to ascertain the actual risk of NSAIDs hepatotoxicity. Several NSAIDs, namely bromfenac, ibufenac and benoxaprofen, have been withdrawn from the market due to hepatotoxicity; others like nimesulide were never marketed in some countries and withdrawn in others. Indeed, the contro-versy concerning the actual risk of severe liver disease persists within NSAIDs research. The present work intends (1) to provide a critical analysis of the dissimilar results currently available in the literature concerning the epidemiology of NSAIDS hepatotoxicity; and (2) to review the risk of hepatotoxicity for each one of the most commonly employed compounds of the NSAIDs family, based on past and recently published data.

Glutamine:aprecursor of glutathione and its effect on liver

AIM To investigate the relationship between alanyl-glutamine (ALA-GLN) and glutathione (GSH) biosynthesis in hepatic protection.METHODS Twenty male Wistar rats were randomly divided into two groups: one receiving standard parenteral nutrition (STD) and the other supplemented with or without ALA-GLN for 7 days. The blood and liver tissue samples were examined after 5-fluorouracil (5-FU) was injected peritoneally.RESULTS The concentration measurements were significantly higher in ALA-GLN group than in STD group in serum GLN (687 μmol/ L±50 μmol/ L vs 505 μmol/ L±39 μmol/ L, P＜0.05), serum GSH (14 μmol/ L±5 μmol/ L vs 7 μmol/ L±3 μmol/ L, P＜0.01) and in liver GSH content (6.9 μmol/ g±2.5 μmol/ g vs 4.4 μmol/ g±1.6 μmol/ g liver tissue, P＜0.05). Rats in ALA-GLN group had lesser elevations in hepatic enzymes after 5-FU administration.CONCLUSION The supplemented nutrition ALA-GLN can protect the liver function through increasing the glutathione biosynthesis and preserving the glutathione stores in hepatic tissue.

Biochemical mechanisms in drug-induced liver injury:Certainties and doubts

Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development. Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites. Aging, preexisting liver disease, enzyme induction or inhibition, genetic variances, local 02 supply and, above all, the intrinsic molecular properties of the drug may affect this process. Necrotic death follows antioxidant consumption and oxidation of intracellular proteins, which determine increased permeability of mitochondrial membranes, loss of potential, decreased ATP synthesis, inhibition of Ca^2＋-dependent ATPase, reduced capability to sequester Ca^2＋ within mitochondria, and membrane bleb formation. Conversely, activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage. Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis, in which different HLA genotypes might play a major role. This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage. Future perspectives including new frontiers for research are discussed.

Liver injury associated with drug intake during pregnancy

Drug use during pregnancy is not common.Drug-induced liver injury(DILI)is a potential complication that is rare but can adversely affect both the mother and the fetus.Although many drugs can directly cause hepatotoxicity,idiosyncratic liver injury is common in pregnancy.Underreporting of adverse drug reactions,lack of adequate literature regarding drug safety in pregnancy,and the inherent difficulty in diagnosing DILI during pregnancy make the management of this condition challenging.This review attempts to describe the existing literature regarding DILI in pregnancy,which is mainly in the form of case reports;several studies have looked at the safety of antithyroid drugs,antiretroviral drugs,and paracetamol,which have an indication for use in pregnancy;the relevant data from these studies with regard to DILI has been presented.In addition,the review describes the diagnosis of DILI,grading the disease severity,assessment of causality linking the drug to the adverse event,regulatory guidelines for evaluating the potential of drugs to cause liver injury,efforts to ensure better participation of women in clinical trials and studies in pregnant women population in particular,and the challenges involved in generating adequate research evidence.The establishment of DILI registries in various countries is an encouraging development;however,there is a need for promoting active,spontaneous reporting of adverse events during pregnancy to ensure rapid generation of evidence regarding the safety of a drug in pregnant women.

Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes

AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.

Effects of combined use of diallyl disulfide and N-acetyl-cysteine on acetaminophen hepatotoxicity in β-naphthoflavone-pretreated mice

AIMS To assess the protective effect of diallyl disulfide (DADS) and its combined use with N-acetyl-cysteine (NAC) on acetaminophen (APAP) hepatotoxicity in C57BL/6N (B6) mice pretreated with β naphthoflavone (BNF). METHODS B6 mice were divided into six groups and all compounds used were injected intraperitoneally. Except for control and APAP group (receiving APAP only), the other groups received an injection of APAP (350mg/kg) 48 hours after BNF (200mg/kg) and either of DADS (200mg/kg), or NAC (500mg/kg) or both DADS and NAC. DADS was given 2 hours before APAP and NAC was injected with APAP. The mean survival time was recorded and livers were examined histologically. Hepatic glutathione (GSH) levels and plasma ALT were also determined at different time points. To evaluate the effect of DADS or NAC on hepatic P450 induction by BNF, liver microsomes were prepared and 7 ethoxyresorufin O dealkylase (ERD) activity was determined using spectrofluorometrical methods. In vitro effect of DADS or NAC on ERD activity was assayed by directly incubating microsomal suspension with DADS or NAC of different concentrations. RESULTS APAP was not toxic to mice without BNF pretreatment, but caused severe liver necrosis and death of all BNF treated mice in 4 hours. A sharp depletion of GSH (approximately 62% of its initial content at 2 hours and 67% at 4 hours) and a linear elevation of ALT levels (536 8±29 5 Sigma units at 2 hours and 1302 5±74 9 at 4 hours) were observed. DADS and NAC given individually produced mild protection, resulting in prolonged survival, a slower decline of GSH level and a less steeper elevation of ALT level. All mice died eventually. Co administration of DADS and NAC completely protected mice. GSH level in this group lowered by about 35% and 30% at 2 and 4 hours, and ALT was 126±18 and 157 5±36 6 Sigma units at 2 and 4 hours. ERD activity in BNF treated mice was about 5 times that of the constitutive level determined in normal mice. Neither DADS nor NAC inhibited P450 1A1/1A2 induction as determined by their effect on the induction of ERD activity. In vitro assay indicates that DADS, but not NAC, was a potent inhibitor of ERD activity (IC 50 =4 6μM). CONCLUSIONS A combined use of both DADS and NAC produced full protection in BNF treated mice against APAP hepatotoxicity. The mechanism is that DADS inhibits P450 1A1/1A2 activity, but not induction, which substantially reduces production of NAPQI, while NAC enhances liver detoxifying capability via serving as a precursor of GSH and stimulating GSH synthesis.

Immune-mediated liver injury following COVID-19 vaccination

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

贝达喹啉联合背景方案治疗耐药肺结核的疗效

目的:探讨贝达喹啉联合背景方案治疗耐药肺结核的疗效。方法:回顾性选择2022年1月至2023年1月广东省广州市胸科医院收治的159例耐药肺结核患者,按随机对照原则分组。对照组(80例)接受常规背景方案治疗,研究组(79例)在其基础上联合贝达喹啉治疗。于6个月后评估两组病灶吸收率、痰菌转阴率及空洞闭合率,对比两组治疗前后血清肝功能指标、心电图QTc变化,统计两组不良反应发生率。结果:研究组病灶吸收率、痰菌转阴率及空洞闭合率均较对照组高(P<0.05)。两组治疗后丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平升高(P<0.05);研究组治疗后ALT、AST水平与对照组相比,差异无统计学意义(P>0.05)。两组治疗后QTcF值升高,心率降低(P<0.05)。且研究组治疗后QTcF值比对照组高,心率比对照组低(P<0.05)。两组转氨酶升高、白细胞减少及胃肠道反应发生率对比,差异无统计学意义(P>0.05);研究组QT间期延长发生率显著高于对照组(P<0.05)。结论:贝达喹啉联合背景方案治疗耐药肺结核的疗效较佳,未引起肝功能指标异常,但QT间期延长发生率较高。

人常见肝UGTs活性与抑制体外评价体系的建立与验证

目的 本研究旨在建立一种可靠的体外评价体系,用于评估人肝UDP-葡萄糖醛酸转移酶活性及药物对人肝UGTs的抑制作用,并验证该体系的准确性和稳定性。方法 选择了人肝微粒体UGTs酶6种主要亚型的6个探针底物,在优化的温孵条件下通过测定其代谢产物生成反映人肝微粒体UGTs酶的活性,代谢产物浓度测定利用经过确证的液相色谱-质谱法(LC-MS/MS)进行。同时应用已知抑制剂对所建立的温孵体系进行验证。结果 建立的LC-MS/MS分析方法符合生物分析要求;在本实验温孵体系下,已知的UGT抑制剂均表现出明显的抑制作用。结论 该研究成功建立了一种准确可靠的体外评价体系,该方法可应用于评估药物对UGTs酶的体外抑制作用,该研究可为药物研发和临床合理用药提供重要指导。

探讨益肝灵联合甘草酸二铵治疗抗结核药物性肝损伤的疗效

目的 探讨益肝灵联合甘草酸二铵治疗抗结核药物性肝损伤(ATB-DILI)的疗效,并分析其对肝功能、炎性因子水平、免疫功能的影响。方法 选取2021年6月至2023年6月鹿邑县疾病预防控制中心收治的80例ATB-DILI患者为研究对象,随机分为单一组40例、联合组40例。单一组予以甘草酸二铵治疗,联合组予以益肝灵联合甘草酸二铵治疗。统计对比两组临床疗效、不良反应、临床症状积分及治疗前后肝功能[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、γ-谷氨酰转肽酶(γ-GT)]、炎性因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)]、外周血T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+))水平变化。结果 联合组治疗有效率高于单一组,差异有统计学意义(P <0.05);治疗后,联合组临床症状积分低于单一组,差异有统计学意义(P <0.05);治疗后,联合组血清ALT、AST、TBIL、γ-GT、IL-6、TNF-α、IL-1β水平低于单一组,差异均有统计学意义(P <0.05);治疗后,联合组CD3^(+)、CD4^(+)高于单一组,CD8^(+)低于单一组,差异均有统计学意义(P <0.05);联合组不良反应发生率与单一组比较差异无统计学意义(P> 0.05)。结论 益肝灵联合甘草酸二铵治疗ATB-DILI的疗效确切且具有一定安全性,可改善临床症状,促进免疫功能、肝功能恢复,抑制炎性反应。

健脾散结方联合载药微球栓塞治疗中晚期肝癌的临床疗效

目的观察健脾散结方联合载药微球栓塞治疗中晚期肝癌的临床疗效。方法纳入医院2021年8月—2022年12月住院的中晚期肝癌患者60例,按照随机数字表法分为两组,对照组30例进行载药微球栓塞治疗,观察组30例采用健脾散结方联合载药微球栓塞治疗。比较分析两组患者的实体瘤客观疗效,症状改善率,体质量变化和卡诺夫斯基健康状况量表(Karnofsky performance scores, KPS)评分,肿瘤标志物甲胎蛋白(alpha-fetoprotein, AFP)、糖类抗原199(carbohydrate antigen 199,CA199)、糖类抗原125(carbohydrate antigen 125,CA125)的变化以及不良反应发生情况。结果两组患者实体瘤客观疗效比较,观察组、对照组有效率分别为83.33%(25/30)、66.67%(22/30),差异无统计学意义(P>0.05),观察组、对照组稳定率分别为96.67%(29/30)、73.33%(22/30),观察组显著高于对照组,差异有统计学意义(P<0.05)。观察组、对照组症状改善率分别为93.33%(28/30)、70.00%(21/30),观察组显著高于对照组,差异有统计学意义(P<0.05)。观察组和对照组体质量变化情况比较,差异无统计学意义(P>0.05)。治疗后两组患者KPS评分均显著增高(P<0.05),并且观察组显著高于对照组[(71.31±9.22)分vs (64.54±7.26)分](P<0.05)。观察组患者肿瘤标志物AFP、CA199、CA125水平降低更显著,与对照组比较差异有统计学意义[(29.72±6.34)μg/L、(34.08±3.10)U/mL、(127.71±29.65)kU/L vs (34.08±5.26)μg/L、(37.67±4.35)U/mL、(156.83±27.54)kU/L](P<0.05)。观察组不良反应发生情况优于对照组,差异有统计学意义(P<0.05)。结论健脾散结方联合载药微球栓塞治疗中晚期肝癌能够更好地抑制肿瘤病灶的生长、改善患者的临床症状、提高疗效,并且安全性良好,为中西医结合治疗中晚期肝癌提供了可行的思路、方法及指导依据。

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents

Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.

Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice

AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.

Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma

INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.

Heat shock protein 72 normothermic ischemia,and the impact of congested portal blood reperfusion on rat liver

INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .

COVID-19 impact on the liver

The coronavirus disease 2019(COVID-19)pandemic imposed arestructuring of global health systems by rethinking spaces used for the care of these patients and the additions of intensive care,infectious diseases and pneumology departments.This paper provides evidence on the presence of severe acute respiratory syndrome coronavirus 2 in hepatocytes and its direct cytopathic activity,as well as the degree of liver damage due to drug toxicity,inflammation and hypoxia in COVID-19.A review of clinical trials has quantified liver damage through both pathology and biochemistry studies.Additionally,we briefly present the results of a study conducted in our clinic on 849 patients admitted for COVID-19 treatment,of which 31 patients had pre-existing chronic liver disease and 388 patients had values above the normal limit for alanine aminotransferase,aspartate aminotransferase,and total bilirubin.It was observed that patients with abnormal liver tests were significantly statistically older,had more comorbidities and had a higher percentage of unfavourable evolution(death or transfer to intensive care).The conclusion of this paper is that the main causes of liver damage are direct viral aggression,coagulation dysfunction and endothelial damage,and patients with impaired liver function develop more severe forms of COVID-19 which requires special care by a multidisciplinary team that includes a hepatologist.

异甘草酸镁防治结肠癌化疗药物致肝损伤的药物经济学评价

目的评价异甘草酸镁防治结肠癌化疗药物致肝损伤的疗效和药物经济学,为临床合理选用保肝药提供参考依据。方法回顾性分析2016年1月—2019年12月东南大学附属中大医院120例符合入选标准进行保肝治疗的结肠癌患者,分为A组(异甘草酸镁组,61例)及B组(还原型谷胱甘肽组,59例)。比较2组防治肝损伤的临床效果(总有效率),采用成本—效果分析法进行经济学评价,同时进行敏感性分析。结果A组患者治疗总有效率为83.61%,高于B组的67.80%(χ^(2)=4.091,P=0.043);A组的成本效果比(C/E)明显大于B组,增量成本效果比(ΔC/ΔE)为3158.29;调整后A组成本效果比(C′/E′)小于B组,增量成本效果比(ΔC′/ΔE′)为1792.03。结论两种保肝方案均可有效预防化疗所致肝损伤,异甘草酸镁保肝治疗效果优于还原型谷胱甘肽,但成本—效果分析显示还原型谷胱甘肽在经济性上具有优势,敏感性分析显示异甘草酸镁更具优势。

PD-1抑制剂联合靶向药物治疗晚期原发性肝癌的安全性及临床疗效观察

目的:探讨PD-1抑制剂联合靶向药物治疗晚期原发性肝癌的安全性及有效性。方法:选取2020至2021年本院收治的70例晚期原发性肝癌患者作为研究对象,分为两组,分别予以单药PD-1抑制剂治疗(单药治疗组)、PD-1抑制剂联合靶向药物治疗(联合用药组),并对两组患者的相关病历资料及获取的有效性及安全性数据行回顾性分析。结果:安全性比较可知,单药治疗组发生不良事件的比率分别为皮肤及皮下组织类疾病占17.14%,肝功能异常占25.71%,血液学毒性占31.42%,全身性症状占8.57%,胃肠道占17.14%,呼吸系统、胸及纵隔疾病占11.43%,代谢及营养类疾病占20.00%,肾脏及泌尿系统疾病占5.71%,内分泌系统疾病占5.71%;联合用药组发生不良事件的比率分别为皮肤及皮下组织类疾病占22.85%,肝功能异常占28.57%,血液学毒性占25.71%,全身性症状占11.43%,胃肠道占20.00%,呼吸系统、胸及纵隔疾病占14.29%,代谢及营养类疾病占17.14%,肾脏及泌尿系统疾病占8.57%,内分泌系统疾病占2.86%,两组比较差异均无统计学意义(P> 0.05),联合用药并不会增加不良事件发生。有效性比较可知,单药治疗组患者的完全缓解率为8.57%、部分缓解率为31.43%、疾病稳定率为48.57%、疾病进展率为11.43%;联合治疗组患者的完全缓解率为14.29%、部分缓解率为54.29%、疾病稳定率为25.71%、疾病进展率为5.71%,差异具有统计学意义(P<0.05)。联合用药组对疾病更为有效。T淋巴细胞水平高于单药组(P<0.05)。结论:对晚期原发性肝癌患者行PD-1抑制剂联合靶向药物治疗比单药PD-1抑制剂提升T淋巴细胞水平,治疗能取得更好的临床效果,保证患者足够的安全性。

CalliSpheres载药栓塞微球加载表柔比星治疗不可切除原发性肝癌的疗效

目的 探讨CalliSpheres载药栓塞微球加载表柔比星在不可切除原发性肝癌(PLC)中的疗效。方法 选取2016年2月至2020年10月铜陵市人民医院收治的104例不可切除PLC患者为研究对象,以随机数字表法分为研究组、对照组,每组各52例。对照组采用常规动脉化疗栓塞(TACE)表柔比星,研究组采用CalliSpheres载药微球加载表柔比星的TACE。治疗后3个月观察效果,并随访12个月。记录患者抗肿瘤疗效、血液肿瘤标志物、肝功能、并发症情况,统计患者预后情况。结果 研究组客观缓解率、临床控制率高于对照组(P<0.05)。治疗后两组患者的甲胎蛋白(AFP)、碱性成纤维细胞生长因子(BFGF)、核因子κB(NF-κB)均低于治疗前(P<0.05),研究组治疗后的AFP、BFGF、NF-κB均低于对照组(P<0.05)。治疗前后两组患者的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、总胆红素(TBil)、白蛋白(Alb)水平对比差异均无统计学意义(均P>0.05)。两组总不良事件发生率对比差异无统计学意义(P>0.05)。研究组存活33例,对照组存活22例,差异有统计学意义(P<0.05)。结论 CalliSpheres载药栓塞微球加载表柔比星治疗不可切除PLC疗效显著,安全性及预后良好。