Text B Liver Transplantation

Liver transplantation—the replacement of the native，diseased liver by a normal organ（allograft）—has matured from an experimental procedure reserved for desperately ill patients to an accepted，lifesaving operation applied more optimally in the natural history of end－stage liver disease．The preferred and technically most advanced approach is orthotopic transplantation，in which the native organ is removed and the donor organ is inserted in the same anatomic location．Pioneered in the 1960s by Starzl at the University of Colorado and， later，at the University of Pittsburgh and by Calne in Cambridge，England， liver transplantation is now performed routinely worldwide．Success measured as 1－year survival has improved from30％in the 1970s to about 90％today． These improved prospects for prolonged survival，dating back to the early 1980s，resulted from refinements in operative technique，improvements in organ procurement and preservation，advances in immunosuppressive therapy， and，perhaps most influentially，more enlightened patient selection and timing．

Despite the perioperative morbidity and mortality，the technical and management challenges of the procedure，and its costs，liver transplantation has become the approach of choice for selected patients whose chronic or acute liver disease is progressive，life－threatening，and unresponsive to medical therapy．1 Based on the current level of success，the number of liver transplants has continued to grow each year；in 2005，approximately 6，000patients received liver allografts in the United States．Still，the demand for new livers continues to outpace availability；in the same period，＞17，000patients in the United States were on a waiting list for a donor liver．In response to this drastic shortage of donor organs，many transplantation centers have begun to supplement cadaver－organ liver transplantation with living－donor transplantation．

Indications

Potential candidates for liver transplantation are children and adults who， in the absence of contraindications，suffer from severe，irreversible liver disease for which alternative medical or surgical treatments have been exhausted or are unavailable．Timing of the operation is of critical importance． Indeed，improved timing and better patient selection are felt to have contributed more to the increased success of liver transplantation in the 1980s and beyond than all the impressive technical and immunologic advances combined．Although the disease should be advanced，and although opportunities for spontaneous or medically induced stabilization or recovery should be allowed，the procedure should be done sufficiently early to give the surgical procedure a fair chance for success．

Ideally，transplantation should be considered in patients with end－stage liver disease who are experiencing or have experienced a life－threatening complication of hepatic decompensation or whose quality of life has deteriorated to unacceptable levels．2 Although patients with well－compensated cirrhosis can survive for many years，many patients with quasi－stable chronic liver disease have much more advanced disease than may be apparent．3 As discussed below，the better the status of the patient prior to transplantation， the higher will be the anticipated success rate of transplantation．The decision about when to transplant is complex and requires the combined judgment of an experienced team of hepatologists，transplant surgeons，anesthesiologists，and specialists in support services，not to mention the well－informed consent of the patient and the patient's family．

Contraindications

Absolute contraindications for transplantation include life－threatening systemic diseases，uncontrolled extrahepatic bacterial or fungal infections， preexisting advanced cardiovascular or pulmonary disease，multiple uncorrectable life－threatening congenital anomalies，metastatic malignancy，active drug or alcohol abuse．Because carefully selected patients in their sixties and even seventies have undergone transplantation successfully，advanced age per se is no longer considered an absolute contraindication；however，in older patients a more thorough preoperative evaluation should be undertaken to exclude ischemic cardiac disease and other comorbid conditions．Advanced age（＞70 years），however，should be considered a relative contraindication—that is，a factor to be taken into account with other relative contraindications．

Other relative contraindications include portal vein thrombosis，HIV infection，preexisting renal disease not associated with liver disease，intrahepatic or biliary sepsis，severe hypoxemia［Pa O2（动脉血氧分压）＜50 mm Hg］resulting from right－to－left intrapulmonary shunts，portopulmonary hypertension with high mean pulmonary artery pressures（＞35 mm Hg），previous extensive hepatobiliary surgery，any uncontrolled serious psychiatric disorder，and lack of sufficient social supports．Any one of these relative contraindications is insufficient in and of itself to preclude transplantation．For example，the problem of portal vein thrombosis can be overcome by constructing agraft from the donor liver portal vein to the recipient's superior mesenteric vein．Now that highly active antiretroviral therapy has dramatically improved the survival of persons with HIV infection，and because end－stage liver disease caused by chronic hepatitis C and chronic hepatitis B has emerged as a serious source of morbidity and mortality in the HIV－infected population，liver transplantation has now been performed successfully in selected HIV－positive persons who have excellent control of HIV infection．4

Surgical Technique

Removal of the recipient's native liver is technically difficult，particularly in the presence of portal hypertension with its associated collateral circulation and extensive varices．Further complicating removal is the presence of scarring from previous abdominal operations．The combination of portal hypertension and coagulopathy（elevated prothrombin time and thrombocytopenia）may translate into large blood product transfusion requirements．After the portal vein and infrahepatic and suprahepatic inferior vena cavae are dissected，the hepatic artery and common bile duct are dissected．Then the native liver is removed and the donor organ inserted．During the anhepatic phase，coagulopathy， hypoglycemia，hypocalcemia，and hypothermia are encountered and must be managed by the anesthesiology team．Caval，portal vein，hepatic artery，and bile duct anastomoses are performed in succession，the last by end－to－end suturing of the donor and recipient common bile ducts or by choledochojejunostomy to a Roux－en－Y loop if the recipient common bile duct cannot be used for reconstruction（e．g．in sclerosing cholangitis）．A typical transplant operation lasts 8 h，with a range of 6—18 h．Because of excessive bleeding，large volumes of blood，blood products，and volume expanders may be required during surgery；however，blood requirements have fallen sharply with improvements in surgical technique and experience．

Postoperative Complications

Complications of liver transplantation can be divided into hepatic and nonhepatic categories．In addition，both immediately postoperative and late complications are encountered．Patients who undergo liver transplantation as a rule have been chronically ill for protracted periods and may be malnourished and wasted．The impact of such chronic illness and the multisystem failure that accompanies liver failure continue to require attention in the postoperative period．Because of the massive fluid losses and fluid shifts that occur during the operation，patients may remain fluid－overloaded during the immediate postoperative period，straining cardiovascular reserve；this effect can be amplified in the face of transient renal dysfunction and pulmonary capillary vascular permeability．Continuous monitoring of cardiovascular and pulmonary function，measures to maintain the integrity of the intravascular compartment and to treat extravascular volume overload，and scrupulous attention to potential sources and sites of infection are of paramount importance． Cardiovascular instability may also result from the electrolyte imbalance that may accompany reperfusion of the donor liver as well as from restoration of systemic vascular resistance following implantation．Pulmonary function may be compromised further by paralysis of the right hemidiaphragm associated with phrenic nerve injury．The hyperdynamic state with increased cardiac output that is characteristic of patients with liver failure reverses rapidly after successful liver transplantation．

Transplant Rejection

Despite the use of immunosuppressive drugs，rejection of the transplanted liver still occurs in a proportion of patients，beginning 1—2 weeks after surgery．Clinical signs suggesting rejection are fever，right upper quadrant pain，and reduced bile pigment and volume．Leukocytosis may occur，but the most reliable indicators are increases in serum bilirubin and aminotransferase levels．Because these tests lack specificity，distinguishing among rejection and biliary obstruction，primary graft nonfunction，vascular compromise，viral hepatitis，CMV infection，drug hepatotoxicity，and recurrent primary disease may be difficult．Radiographic visualization of the biliary tree and／or percutaneous liver biopsy often helps to establish the correct diagnosis．Morphologic features of acute rejection include a mixed portal cellular infiltrate，bile duct injury， and／or endothelial inflammation；some of these findings are reminiscent of graft－versus－host disease（GVHD），primary biliary cirrhosis，or recurrent allograft hepatitis C．

As soon as transplant rejection is suspected，treatment consists of intravenous methylprednisolone in repeated boluses；if this fails to abort rejection，many centers use antibodies to lymphocytes，such as OKT35（注射用抗人T细胞CD3鼠单克隆抗体），or polyclonal antilymphocyte globulin．Caution should be exercised when managing acute rejection with pulse glucocorticoids in patients with hepatitis C virus（HCV）infection，because of the high risk of triggering recurrent allograft hepatitis C．6 Chronic rejection is a relatively rare outcome that can follow repeated bouts of acute rejection or that occurs unrelated to preceding rejection episodes．Morphologically，chronic rejection is characterized by progressive cholestasis，focal parenchymal necrosis，mononuclear infiltration， vascular lesions，and fibrosis．This process may be reflected as ductopenia—the vanishing bile duct syndrome．Reversibility of chronic rejection is limited；in patients with therapy－resistant chronic rejection，retransplantation has yielded encouraging results．

Transplantation in Adults

Liver transplantation is indicated for end－stage cirrhosis of all causes．In sclerosing cholangitis and Caroli disease（multiple cystic dilatations of the intrahepatic biliary tree），recurrent infections and sepsis associated with inflammatory and fibrotic obstruction of the biliary tree may be an indication for transplantation．Because prior biliary surgery complicates，and is a relative contraindication for，liver transplantation，surgical diversion of the biliary tree has been all but abandoned for patients with sclerosing cholangitis．In patients who undergo transplantation for hepatic vein thrombosis，postoperative anticoagulation is essential；underlying myeloproliferative disorders may have to be treated but are not a contraindication to liver transplantation．If a donor organ can be located quickly，before life－threatening complications—including cerebral edema—set in，patients with acute liver failure are candidates for liver transplantation．Routine candidates for liver transplantation are patients with alcoholic cirrhosis，chronic viral hepatitis，and primary hepatocellular malignancies．Although all three of these categories are considered to be high risk，liver transplantation can be offered to carefully selected patients． Currently，chronic hepatitis C and alcoholic liver disease are the most common indications for liver transplantation，accounting for over 40％of all adult candidates who undergo the procedure．

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New Words and Phrases

procurement［prəʊ'kjʊəmənt］n． 取得；实现

anesthesiologist［,ænəs,θiːzɪ'ɔːlədʒɪst］n． 麻醉学家，麻醉医师

congenital［kən'dʒenɪtəl］a． 先天的，天生的

metastatic［metə'stætɪk］a． 转移性的，迁徙的

shunt［ʃʌnt］v．＆n． 分流；转向一边

portopulmonary［pɔːtə'pʌlmənərɪ］a． 肺门静脉的

psychiatric［,saɪkɪ'ætrɪk］a． 精神病的；治疗精神病的

antiretroviral［'antɪ,retro'vaɪrəl］a． 抗反转录病毒的

thrombocytopenia［'θrɒmbəʊ,saɪtə'piːnɪə］n． 血小板减少（症）

vena cava（［复］venae cavae） 腔静脉

hypocalcemia［,haɪpəʊkæl'siːmɪə］n． 低钙血症，低血钙

hypothermia［haɪpəʊ'θзːmɪə］n． 低温；低体温

choledochojejunostomy 胆总管空肠吻合术

Roux－en－Y loop 胆管空肠襻式吻合术

cholangitis［kɒlən'dʒaɪtɪs］n． 胆管炎

protract［prəʊ'trækt］v． 延长，伸出；绘制

scrupulous［'skruːpjʊləs］a． 谨慎的，细心的

paramount［'pærəmaʊnt］a． 最重要的；最高的

reperfusion［rɪpзː'fjuːʒən］n． 再灌注

compromise［'kɔmprəmaɪz］n．＆v． 和解，妥协；危及

paralysis［pə'ræləsɪs］n． 麻痹（症）；瘫痪（症）

hemidiaphragm［,hemiː'daɪəfræm］n． 偏侧膈

phrenic［'frenɪk］a． 膈的

reminiscent［remɪ'nɪsənt］a． 怀旧的，回忆往事的；暗示的

methylprednisolone［,meθɪlpred'nɪsələʊn］n． 甲泼尼龙

cholestasis［kɒʊliː'steɪsɪs］n． 胆汁淤积；胆汁阻塞

parenchymal［pə'reŋkɪməl］a． 实质的；主质的

myeloproliferative［,maɪələʊprə'lɪfəreɪtɪv］a． 骨髓及外骨髓增殖的

Notes

1．Despite the perioperative morbidity and mortality，the technical and management challenges of the procedure，and its costs，liver transplantation has become the approach of choice for selected patients whose chronic or acute liver disease is progressive，life－threatening，and unresponsive to medical therapy．

参考译文：尽管手术引起的发病率和死亡率比较高，手术技术和术后护理要求严格，手术费用昂贵，但肝移植业已成为适应证患者的一种选择，因其所患肝病为进行性，危及生命，且药物治疗无效的急慢性肝病。

Despite the perioperative morbidity and mortality，the technical and management challenges of the procedure，and its costs为介词短语。despite意为“不管，尽管”；whose引导限定定语从句，修饰patients。

2．Ideally，transplantation should be considered in patients with end－stage liver disease who are experiencing or have experienced a life－threatening complication of hepatic decompensation or whose quality of life has deteriorated to unacceptable levels．

参考译文：晚期肝病患者开始出现或已经出现了肝脏失去代偿能力而危及生命的并发症时，其生活质量已下降到难以接受的水平，这样的患者理论上说应考虑肝移植。

with end－stage liver disease是介词短语，修饰patients。who和whose是关系代词，分别引导两个并列的限定定语从句，也修饰patients。

3．Although patients with well－compensated cirrhosis can survive for many years，many patients with quasi－stable chronic liver disease have much more advanced disease than may be apparent．

参考译文：尽管代偿能力尚好的肝硬化患者可存活多年，但许多半稳定慢性肝病患者的病程进展要比明显稳定慢性肝病患者的病程进展快得多。

Although引导让步状语从句“虽然，尽管……”。than may be apparent是比较状语从句，than在从句中做主语，等于than chronic liver disease that may be apparent。e．g．The numbers were smaller than had been expected （＝than the numbers that had been expected）．

4．Now that highly active antiretroviral therapy has dramatically improved the survival of persons with HIV infection，and because end－stage liver disease caused by chronic hepatitis C and chronic hepatitis B has emerged as a serious source of morbidity and mortality in the HIV－infected population，liver transplantation has now been performed successfully in selected HIV－positive persons who have excellent control of HIV infection．参考译文：由于高度活性抗反转录病毒疗法已极大地提高了HIV感染者的存活率，加之慢性丙肝、乙肝引发的晚期肝病在HIV感染人群中已成为发病率和死亡率的主要起因，肝移植已成功地在选择性HIV阳性且很好地控制住HIV感染的患者身上实施。

Now that引导的原因状语从句，表示由于新情况的出现，而促成某事的发生。e．g．Now that you mention it，I do remember the incident．

5．OKT3ː是抗排斥药，莫罗单抗－CD3（muromonadb－CD3）的商品名。它是美国Ortho公司生产的OKT（Ortho Kung T cell）系列中的一种抗人体T淋巴细胞分化抗原CD3的单克隆抗体，CD3抗原是成熟T细胞的共同分化抗原，在全部外周血T细胞和胸腺、淋巴结内接近成熟的T细胞上表达。作为一种免疫抑制剂，OKT3主要用于预防和治疗同种异体肾移植等器官移植后的急性排斥反应。OKT3主要通过细胞清除、不育性激活、功能性受体封阻、免疫调变、刺激抑制细胞增殖以及直接作用于效应细胞等途径杀伤成熟T细胞或阻断机体细胞免疫反应达到抗排斥目的。

6．Caution should be exercised when managing acute rejection with pulse glucocorticoids in patients with hepatitis C virus（HCV）infection，because of the high risk of triggering recurrent allograft hepatitis C．

参考译文：由于引起同种异体移植性丙肝复发的危险极高，故诊治处理伴有糖肾上腺皮质激素急性排斥反应的丙型肝炎病毒感染患者应极为慎重。

when managing acute rejection with pulse glucocorticoids in patients with hepatitis C virus（HCV）infection是带有从属连词when的现在分词短语做状语，相当于一个when引导的时间状语从句。现在分词作时间状语，如强调分词动作与谓语动作同时发生，分词前可用从属连词when或while。

e．g．While flying over the Channel，the pilot saw what he thought to be a meteorite．

Exercises

Ⅰ．Answer the following questions．

1．What is the critical importance of the operation for liver transplantation？

2．What are the contradictions for liver transplantation？

3．What measures can be taken to manage the postoperative complications？

4．How should surgeons deal with the rejections after the transplantation？

5．Talk about the significance of liver transplantation briefly．

Ⅱ．Decide whether the following statements are True or False．

1．The preferred and technically most advanced approach is orthotopic transplantation，in which the native organ is removed and the donor organ is inserted in the same anatomic location．

2．The decision about when to transplant is not complex and requires the combined judgment of an experienced team of hepatologists，transplant surgeons，anesthesiologists，and specialists in support services，not to mention the well－informed consent of the patient and the patient's family．

3．Advanced age should be considered an absolute contraindication．

4．Removal of the recipient's native liver is not technically easy，particularly in the presence of portal hypertension with its associated collateral circulation and extensive varices．

5．Despite the use of immunosuppressive drugs，rejection of the transplanted liver still occurs in the great majority of patients，beginning 1—2 weeks after surgery．