第十章 乙型肝炎重症化和重型肝炎(肝衰竭)的治疗

内容提要

1.目前乙型肝炎重症化和重型肝炎（肝衰竭）的内科治疗尚缺乏特效药物和手段，其治疗原则强调早期诊断、早期治疗，针对不同病因采取相应的病因治疗措施和综合治疗措施，并积极防治各种并发症。综合治疗包括一般支持治疗、病因治疗、特异性治疗、预防并发症、人工肝支持系统治疗以及肝移植。重型肝炎(肝衰竭)的防治策略研究仍然处于不断进步之中。

2.乙型肝炎重症化和重型肝炎（肝衰竭）除需要进行常规监护(症状、体征和重要实验室指标)外，还应对其颅内压、感染、血流动力学、呼吸功能、肾功能、凝血功能、营养状况和血液净化过程等进行监护。护理工作应常规护理、心理护理和特殊护理(并发症)并重。

3.乙型肝炎重症化和重型肝炎（肝衰竭）除针对病因的药物治疗外，一般支持治疗、营养支持和护理等综合治疗措施在乙型重型肝炎的治疗中有着非常重要的作用，也是治疗成功的关键。

4.乙型肝炎重症化和重型肝炎（肝衰竭）的营养治疗贯穿整个治疗过程，常用的营养状态评价方法包括直接人体测量法、肌酐身高指数(CHI)和主观综合性营养评估(SGA)。营养不良时应分析原因，通过肠内营养和肠外营养支持进行积极干预。

5.乙型肝炎重症化和重型肝炎（肝衰竭）免疫治疗包括促进肝细胞再生、糖皮质激素抑制治疗、胸腺肽免疫调节、关键发病机制的靶向分子干预治疗等。近年在Toll样受体、NK细胞/NK受体、巨噬细胞/免疫凝血系统、CTLA-4基因转染重组、PD-1等分子靶向治疗研究方面均有进展。

6.人工肝能改善患者肝功能，清除内毒素、血氨等有毒物质，纠正氨基酸代谢紊乱、凝血功能障碍和内环境平衡失调。非生物型人工肝适用于重型肝炎的早、中期和晚期患者肝移植术前的等待期、肝移植术后排斥反应及移植后肝无功能期。应根据病情和治疗目的选择人工肝类型并规范操作流程，观察和处理其不良反应和并发症。生物型和混合型人工肝目前还处于开发阶段。

7.肝细胞移植和干细胞(主要是骨髓干细胞和脐血干细胞)移植在治疗肝衰竭中已进行了大量的动物实验，也开展了临床研究，显示出良好的前景。免疫细胞治疗研究较多的有细胞因子诱导的杀伤细胞(CIK)治疗及树突状细胞过继治疗，目前尚处于起步阶段。对移植细胞进行基因修饰是目前的研究热点。

8.MELD评分是目前选择肝移植的国际通用标准。肝移植的供肝来源分活体肝和尸体肝。手术方式主要有原位经典式和背驮式两种，移植术中分无肝前期、无肝期和新肝期。术前准备、术中和术后并发症的处理和术后长期治疗是成功的关键。

9.乙型肝炎重症化和重型肝炎（肝衰竭）的治疗应积极防治感染、肝性脑病、凝血功能障碍、肝肾综合征、酸碱失衡和电解质紊乱、肝肺综合征等并发症。

10.乙型肝炎重症化和重型肝炎（肝衰竭）属于中医的“急黄”“瘟黄”“肝瘟”等范畴，应注意辨证施治。治疗方法包括服用中药、针灸、穴位注射、穴位敷药、敷脐疗法、静脉滴注、吹鼻疗法、耳针、灌肠等。饮食调护也是中医治疗的重要组成部分。

11.随着对乙型肝炎重症化和重型肝炎（肝衰竭）分子病理机制的了解，未来开发更为有效的治疗措施成为可能，包括抑制肝细胞的凋亡、控制炎症反应、促进肝脏的修复与再生、阻止线粒体损伤和氧化应激、调节内质网应激反应、诱导细胞自噬和改善微循环等系列干预靶点。

12.重型肝炎合并甲亢的治疗除常规应用抗甲状腺药物、放射碘外，还可考虑激素和人工肝治疗；妊娠期重型肝炎需积极预防性治疗胎儿生长受限，及时、合理地选择终止妊娠时机和分娩方式；重型肝炎合并糖尿病除控制饮食外，还应选择胰岛素控制血糖；重型肝炎合并SLE、RA和干燥综合征等结缔组织疾病时，应注意激素和免疫抑制剂的肝毒性，应在免疫抑制治疗前进行核苷(酸)类似物抗病毒治疗。

13.乙型肝炎重症化和重型肝炎（肝衰竭）肝外器官功能衰竭包括脑、肾、凝血、循环、呼吸等功能衰竭。已有多项研究提示，肝外器官功能衰竭的发生与患者的近期预后相关，预防或缓解肝外器官功能衰竭的发生或发展，可以显著提高患者短期生存率。(https://www.daowen.com)

Abstract 10

1.Currently, the medical treatment of exacerbation ofhepatitis B and severehepatitis (liver failure)still lacks specific drugs.In principle, the treatment emphasizes early diagnosis and early treatment.Corresponding etiological treatment and comprehensive treatment measures should be taken for different causes, and various complications should be actively prevented.Comprehensive treatment includes general supportive treatment, etiological treatment, specific treatment, prevention of complications, artificial liver support treatment and liver transplantation.Innovative research on prevention and treatment strategies for severehepatitis (liver failure)is still in continuous progress.

2.Important factors to monitor in patients with exacerbation ofhepatitis B and severehepatitis (liver failure)include intracranial pressure，infection，blood dynamics，respiratory function，renal function，blood coagulation function，nutritional status and blood purification process.Nursing care should include not only routine care，but also psychological and special care (complications).

3.In addition to drug treatment for the cause of exacerbation ofhepatitis B and severehepatitis (liver failure), comprehensive treatment measures such as general supportive treatment, nutritional support and nursing care also play a very important role.

4.Nutritional support and nursing care should be maintained throughout the treatment for exacerbation ofhepatitis B and severehepatitis(liver failure).Common methods of evaluating nutritional status include directhuman body measurement，creatinine-height index (CHI)and subject global assessment of nutrition (SGA).Malnourished patients should receive enteral or parenteral nutrition support.

5.Immune therapies for exacerbation ofhepatitis B and severehepatitis(liver failure)include promotinghepatocyte regeneration (e.g. with glucagon，hepatocyte growth factors,and prostaglandin E1)，glucocorticoid suppressive therapy，thymosin immune regulation，and targeting molecular blocking.Treatments being investigated currently are those targeting Toll-like receptors，NK cell/NK cell receptors，macrophage/immune coagulation system，CTLA-4 and PD-1.

6.An artificial liver can improve patients’ liver function；remove endotoxins，blood ammonia and other toxins；correct amino acid metabolism and coagulation disorders；and reverse internal environment imbalances.Non-bioartificial livers are suitable for patients with early and middle stage severehepatitis；for late-stage patients waiting for liver transplantation；and for transplanted patients with rejection reaction or transplant failure.The type of artificial liver should be determined by each patient’s condition and previous treatment purpose，and patients should be closely monitored for adverse reactions and complications.Bio- andhybrid artificial livers are still under development.

7.Hepatocyte and stem cells (mainly bone marrow stem cells and umbilical cord stem cells)transplantationhave been widely utilized to treat liver failure in animals andhave shown promising results inhumans.Researches about immune cell therapy，including cytokine induced killer cells (CIK)and dendritic cells，are still in their initial stage.Gene modification of transplanting cells is ahot research topic at present.

8.MELD score is the international standard for choosing liver transplantation.Organ sources include living donor and cadaveric livers.Surgical methods mainly include the in situ classic type and the piggyback type.Transplantation includes no liver prophase，no liver phase or new liver phase.Preoperative preparation，management of intraoperative and postoperative complications and postoperative long-term treatment are keys to success.

9.Infection，hepatic encephalopathy，blood coagulation disorders，hepatorenal syndrome，acid-base imbalances and electrolyte disorders，hepatopulmonary syndrome and other complications of exacerbation ofhepatitis B and severehepatitis(liver failure)should be actively prevented and treated.

10.Exacerbation ofhepatitis B and severehepatitis(liver failure)belongs to the categories of “fulminant jaundice”“scourge jaundice” and “hot liver” in traditional Chinese medicine.Treatment methods include Chinese traditional medicine，acupuncture and acupoint injection，external application of drugs，umbilical compress therapy，drip，blow nose therapy，earpins，and clysis.Dietary care is also an important part of traditional Chinese medicine treatment.

11.With the understanding of the molecular pathology of severehepatitis B and severehepatitis (liver failure), it is possible to develop more effective treatments in the future, including inhibiting apoptosis of liver cell, controlling inflammation, and promoting repair and regeneration of liver, preventing mitochondrial damage and oxidative stress, regulating of endoplasmic reticulum stress response, inducting autophagy and improving microcirculation.

12.In addition to conventional drugs and radioiodine，corticosteroids and artificial liver treatment can also be considered for severehepatitis patients withhyperthyroidism.Patients with gestational severehepatitis require preventive therapy for fetal growth restriction，and it is necessary to choose the timing and method of fetal delivery.For patients with both diabetes and severehepatitis，insulin is preferred to oral antidiabetic agents to control blood glucose concentration.Liver toxicity of corticosteroids and immune suppressors should be monitored during treatment for severehepatitis in patients with connective tissue diseases including SLE，RA and sicca syndrome.Treatment for connective tissue diseases should preferably be started after the antiviral treatment with nucleos(t)ide analogues.

13.Extrahepatic organ failure of exacerbation ofhepatitis B and severehepatitis (liver failure)includes brain failure,kidney injury, blood coagulation failure, circulation failure and breathing failure.Multiple studieshave suggested that the occurrence of extrahepatic organ failure is related to the patient’s short-term prognosis.Preventing or alleviating the occurrence or development of extrahepatic organ failure can significantly improve the short-term survival of patients.