肝硬化
By Howard J. Worman, MD霍華德學者沃曼，醫學博士
What is Cirrhosis?什麼是肝硬化？
Cirrhosis is characterized anatomically by widespread nodules in the liver combined with fibrosis.肝硬化的特點受到廣泛結節解剖肝纖維化結合。 The fibrosis and nodule formation causes distortion of the normal liver architecture which interferes with blood flow through the liver.纖維化及結節形成原因歪曲正常肝架構干擾血流通過肝臟。 Cirrhosis can also lead to an inability of the liver to perform its biochemical functions.肝硬化患者還可以導致無法履行其肝臟生化功能。 To understand the pathophysiology of cirrhosis, the normal anatomy and physiology of the liver must first be briefly reviewed.了解肝硬化的病理生理的正常解剖與生理肝必須首先簡要回顧。
Liver Blood Flow肝血流
Oxygenated blood that has returned from the lungs to the left ventricle of the heart is pumped to all of the tissues of the body.氧合血已經回國，肺部左心室心臟泵的所有組織的機構。 This is called the systemic circulation.這就是所謂的體循環。 After reaching the tissues, blood is returned to the right side of the heart, from where it is pumped to the lungs and then returned to the left side of the heart after taking up oxygen and giving off carbon dioxide.組織後，血液又回到右邊的心臟，從那裡抽水到肺部，然後返回到左側的心臟，在巨大的壓力給了氧氣和二氧化碳。 This is called the pulmonary circulation. Blood from the gut and spleen flow to and through the liver before returning to the right side of the heart.這就是所謂的肺循環。血液腸和脾臟流向，並通過肝臟，然後再返回右邊的心。 This is called the portal circulation and the large vein through which blood is brought to the liver is called the portal vein.這就是所謂的門戶網站的大型流通和通過靜脈血液帶到肝臟被稱為門靜脈。 After passing through the liver, blood flows into the hepatic vein, which leads into the inferior vena cava to the right side of the heart.經過肝臟，血液流入肝靜脈，從而進入下腔靜脈至右側心。 The liver also receives some blood directly from the heart via the hepatic artery.肝臟還收到一些血液直接從心臟通過肝動脈。 In the esophagus, stomach, small intestine and rectum, the portal circulation and veins of the systemic circulation are connected.在食道，胃，小腸和直腸，門戶流通和靜脈循環連接。 Under normal conditions, there is little to no back flow from the portal circulation into the systemic circulation.在正常情況下，很少有不回流流通的門戶進入體循環。
Bilirubin Secretion膽紅素分泌
The liver is the site of bile formation.肝臟是網站膽汁的形成。 Bile contains bile salts, fatty acids, cholesterol, bilirubin and other compounds.膽汁中膽鹽，脂肪酸，膽固醇，膽紅素和其他化合物。 The components of bile are synthesized and modified in hepatocytes (the predominant cell type in the liver) and secreted into small bile ducts within the liver itself.各組成部分的膽汁合成和修改肝（主要的細胞類型的肝臟）和分泌到小膽管內的肝本身。 These small bile ducts form a branching network of progressively larger ducts that ultimately become the common bile duct that takes bile to the small intestine.這些小膽管形成一個分支網絡的逐步較大導管最終成為膽總管考慮膽汁的小腸。 Bilirubin is a yellow pigment that derives primarily from old red blood cells.膽紅素是一種黃色素的主要來自舊的紅血細胞。 Bilirubin is taken up by hepatocytes from the blood, modified in the hepatocytes to a water soluble form and secreted into the bile.膽紅素是採取由肝細胞從血液，修改中的肝細胞，以水溶性形式分泌到膽汁。
Biochemical Functions生化功能
The liver performs many biochemical functions.肝臟進行許多生化功能。 Blood clotting factors are synthesized in the liver.凝血因子是肝臟中合成。 Albumin, the major protein in the blood, is also synthesized in and secreted from the liver.白蛋白，主要蛋白在血液中，也合成和分泌的肝臟。 The modification and/or synthesis of bile components also takes place in the liver.修改和/或合成膽汁成分也發生在肝臟。 Many of the body's metabolic functions occur primarily in the liver including the metabolism of cholesterol and the conversion of proteins and fats into glucose.許多機構的代謝功能主要發生在肝臟代謝，包括膽固醇和蛋白質的轉化成糖和脂肪。 The liver is also where most drugs and toxins, including alcohol, are metabolized.肝臟也是最藥物和毒素，包括酒精，是代謝。
What Goes Wrong in Cirrhosis?什麼錯在哪裡肝硬化？
Cirrhosis results from damage to liver cells from toxins, inflammation, metabolic derangements and other causes.結果肝硬化肝細胞損害的毒素，炎症，代謝derangements和其他原因造成的。 Damaged and dead liver cells are replaced by fibrous tissue which leads to fibrosis (scarring).損壞和死亡的肝細胞所取代的纖維組織，導致纖維化（疤痕） 。 Liver cells regenerate in an abnormal pattern primarily forming nodules that are surrounded by fibrous tissue.肝細胞再生異常格局形成結節，主要是周圍纖維組織。 Grossly abnormal liver architecture eventually ensues that can lead to decreased blood flow to and through the liver.嚴重肝架構最終隨後，可導致血流量減少，並通過肝臟。

Decreased blood flow to the liver and blood back up in the portal vein and portal circulation leads to some of the serious complications of cirrhosis.減少血流到肝臟和血液回在門靜脈和門靜脈循環導致一些嚴重的並發症，肝硬化。 Blood can back up in the spleen causing it to enlarge and sequester blood cells.血液可以備份脾造成放大和螯合血細胞。 Most often, the platelet count falls because of splenic sequestration leading to abnormal bleeding.多數情況下，血小板計數下降，因為脾隔離導致異常出血。 If the pressure in the portal circulation increases because of cirrhosis and blood back up (note: this can also sometimes occur in severe cases of acute hepatitis and liver damage), blood can flow backwards from the portal circulation to the systemic circulation where they are connected.如果壓力門戶流通增加，因為肝硬化和血液備份（注：這也可以，有時會發生嚴重例急性肝炎和肝功能損害） ，血可流向後從門戶流通的體循環相連的地方。 This can lead to varicose veins in the stomach and esophagus (gastric and esophageal varices) and rectum (hemorrhoids).這會導致靜脈曲張在胃和食管（胃和食管靜脈曲張）和直腸（痔） 。 Gastric and esophageal varices can rupture, bleed massively and even cause death.胃和食管靜脈曲張可以破裂，大量出血，甚至造成死亡。 Hypertension in the portal circulation, along with other hormonal, metabolic and kidney abnormalities in cirrhosis, can also lead to fluid accumulation the abdomen (ascites) and the peripheral tissue (peripheral edema).高血壓門戶流通，與其他激素，代謝和腎臟異常肝硬化，也可能導致腹部積液（腹水）和外週組織（周圍水腫） 。

Decreased bilirubin secretion from hepatocytes in cirrhosis leads to the back up of bilirubin in the blood.降低膽紅素分泌肝細胞肝硬化導致備份膽紅素在血液中。 This leads to jaundice, the yellow discoloration of the skin and eyes.這導致黃疸，黃色變色的皮膚和眼睛。 As the water-soluble form of bilirubin also backs up in the blood, bilirubin can also spill into the urine giving it a bright yellow to dark brown color.至於水溶性形式的膽紅素也支持了血液中，膽紅素也可以蔓延到尿給它一個光明的黃色深棕色顏色。

Abnormal biochemical function of the liver in cirrhosis can lead to several complications.生化功能異常的肝臟纖維化可導致一些並發症。 The serum albumin concentration falls which can lead to aggravation of ascites and edema.血清白蛋白濃度的下降可能會導致嚴重腹水和水腫。 The metabolism of drugs can change requiring dose adjustments.藥物代謝的改變，需要調整劑量。 In men, breast enlargement (gynecomastia) sometimes occurs because metabolism of estrogen in the liver is decreased.在男子，隆乳（乳房）有時發生原因，是因為雌激素代謝的肝臟下降。 Decreased production of blood clotting factors can lead to bleeding complications.降低生產凝血因子可導致出血並發症。 Derangements in the metabolism of triglycerides, cholesterol and sugar can occur. Derangements在代謝的甘油三酯，膽固醇和糖，就可能發生。 In earlier stages, cirrhosis frequently can cause insulin resistance and diabetes mellitus. In later stages or in severe liver failure, blood glucose may be low because it cannot be synthesized from fats or proteins.在早期階段，往往會導致肝硬化胰島素抵抗和糖尿病。在稍後階段或嚴重肝功能衰竭，血糖可能較低，因為它不能合成油脂或蛋白質。

Cirrhosis, especially in advanced cases, can cause profound abnormalities in the brain.肝硬化，尤其是在先進的情況下，可能會造成深遠的大腦中的異常。 In cirrhosis, some blood leaving the gut bypasses the liver as blood flow through the liver is decreased.肝硬化，一些血液離開腸繞過肝臟的血流通過肝臟下降。 Metabolism of components absorbed in the gut can also be decreased as liver cell function deteriorates.代謝的成分在腸道吸收也可降低肝細胞功能的惡化。 Both of these derangements can lead to hepatic encephalopathy as toxic metabolites, normally removed from the blood by the liver, can reach the brain.這兩個derangements可導致肝性腦病的有毒代謝產物，通常從血肝，可以到達大腦。 In its early stages, subtle mental changes such as poor concentration or the inability to construct simple objects occurs.在早期階段，微妙的心理變化，如窮人的濃度或無法構造簡單物體發生。 In severe cases, hepatic encephalopathy can lead to stupor, coma, brain swelling and death.在嚴重的情況下，肝性腦病可導致昏迷，昏迷，腦腫脹和死亡。

Cirrhosis of the liver can also cause abnormalities in other organ systems.肝硬化也可能導致其他器官的異常體系。 Cirrhosis can lead to immune system dysfunction causing an increased risk of infection.肝硬化可導致免疫系統功能障礙引起的感染風險增加。 Ascites fluid in the abdomen often becomes infected with bacteria normally present in the gut (spontaneous bacterial peritonitis).腹水的腹部往往成為感染細菌通常存在於腸道（自發性細菌性腹膜炎） 。 Cirrhosis can also lead to kidney dysfunction and failure.肝硬化也可導致腎功能損害和衰竭。 In end-stage cirrhosis, a type of kidney dysfunction called hepatorenal syndrome can occur.在終末期肝硬化，一種稱為腎功能不全，就會發生肝腎綜合徵。 Hepatorenal syndrome is almost always fatal unless liver transplantation is performed.肝腎綜合徵幾乎總是致命的，除非進行肝移植。
Clinical Symptoms and Diagnosis of Cirrhosis臨床症狀和診斷肝硬化
Cirrhosis is usually an easy diagnosis to make when any or all of the above abnormalities and complications are present.肝硬化通常是一個容易作出診斷時，任何或所有上述異常及並發症的存在。 This is especially true when the underlying liver disease can be identified.尤其是當潛在的肝臟疾病可確定。 The underlying liver disease (see below) is identified in most patients, however, sometimes it will not be discovered.基本肝病（見下文）所確定的大部分患者，但是，有時候也不會被發現。 Such cases are called "cryptogenic" cirrhosis.這種情況被稱為“隱”肝硬化。 Sometimes, other conditions such as metastatic cancer, hepatic or portal vein thrombosis, severe acute hepatitis or acute bile duct obstruction can cause some of the abnormalities seen in cirrhosis. A careful history combined with special diagnostic tests will usually identify these conditions.有時，其他條件，如轉移癌，肝或門靜脈血栓，急性重症肝炎或急性梗阻性黃疸可導致一些異常出現肝硬化。仔細歷史加上特殊的診斷測試通常會確定這些條件。

Some patients with cirrhosis, especially early in the course of the disease, will have no overt clinical signs or symptoms.一些肝硬化患者，尤其是早期過程中的疾病，不會有任何公開的臨床症狀或症狀。 Some may have only subtle physical changes such as red palms, red spots that blanch on their upper body (spider angiomata), hypertrophy of the parotid glands, gynecomastia or fibrosis of tendons in the palms.有些可能只有細微的物理變化，如紅的手掌，紅色景點灼其上身（蜘蛛angiomata ） ，肥大的腮腺，乳房或纖維化的肌腱在手心。 Some patients may only have subtle abnormalities on blood tests, and in some cases, all blood tests may be normal.有些病人可能只有細微的異常的血液測試，並在某些情況下，所有的血液測試，可能是正常的。 Radiological and nuclear medicine tests may give clues as to the presence of cirrhosis, but the diagnosis of cirrhosis must often be made by liver biopsy.放射性和核醫學檢測可能的線索的存在，肝硬化，但肝硬化的診斷必須經常作肝活檢。

Causes of Cirrhosis原因肝硬化
Although most often associated with alcohol abuse, cirrhosis of the liver can result from many causes.雖然大多數往往與酗酒，肝硬化可以產生多方面的原因。 Almost any chronic liver disease can lead to cirrhosis.幾乎所有的慢性肝病可導致肝硬化。 This list gives some of the many causes:這份清單提供一些原因很多：

* Alcoholic liver disease - most common cause in the USA 酒精性肝病 -最常見的原因在美國
* Chronic viral hepatitis B, C and D慢性病毒性肝炎B ， C和D
* Chronic autoimmune hepatitis慢性自身免疫性肝炎
* Inherited metabolic diseases (eg hemochromatosis, Wilson disease)遺傳性代謝病（如血色病，肝豆狀核變性）
* Chronic bile duct diseases (eg primary biliary cirrhosis )慢性膽道疾病（如原發性膽汁性肝硬化 ）
* Chronic congestive heart failure慢性充血性心力衰竭
* Parasitic infections (eg schistosomiasis)寄生蟲感染（如血吸蟲病）
* Nonalcoholic steatohepatitis (liver inflammation that can be caused by fatty liver )非酒精性脂肪性肝炎（肝臟發炎，可以引起脂肪肝 ）
* Long term exposure to toxins or drugs長期接觸有毒物質或藥物

Treatment治療
Cirrhosis of the liver is irreversible but treatment of the underlying liver disease may slow or stop the progression.肝硬化是不可逆轉的，但根本的治療肝臟疾病可能會放慢或停止發展。 Such treatment depends upon the underlying etiology.這種治療取決於基本的病因。 Termination of alcohol intake will stop the progression in alcoholic cirrhosis and for this reason, it is important to make the diagnosis early in a chronic alcohol abuser. Similarly, discontinuation of a hepatotoxic drug or removal of an environmental toxin will stop progression.終止酒精的攝入會停止進展酒精性肝硬化，並基於這個原因，重要的是使早期診斷慢性酗酒者。同樣，停止了肝臟藥物或清除環境毒素會停止發展。 Treatment of metabolic diseases, such as treatment of iron overload in hemochromatosis or copper overload in Wilson disease, are also effective therapies.治療代謝性疾病，如治療鐵超負荷血色病或銅超載的肝豆狀核變性，也有效的療法。 Chronic viral hepatitis B and C may respond to treatment with interferon and autoimmune hepatitis may improve with prednisone and azathioprine (Imuran).慢性病毒性肝炎乙型和丙型肝炎治療的反應可能與干擾素和自身免疫性肝炎可提高潑尼松和硫唑嘌呤（依木蘭） 。 Drugs such as ursodiol (Actigall) may slow the progression of primary biliary cirrhosis and possibly sclerosing cholangitis.藥物，如ursodiol （ Actigall ）可延緩原發性膽汁性肝硬化，並可能硬化性膽管炎。

In patients with cirrhosis of the liver, treatment must also be directed at the complications.肝硬化患者的肝，治療也必須針對並發症。 Bleeding esophageal varices can be treated with endoscopic sclerotherapy or rubber band ligation.食管靜脈曲張出血可以治療或內鏡下硬化橡膠帶結紮。 Ascites and edema are often responsive to a low sodium diet and such a diet must be emphasized in patients with these symptoms.腹水及水腫往往響應低鈉鹽飲食，這種飲食必須強調患者的這些症狀。 More advanced ascites and edema can respond to diuretic therapy.更先進的腹水及水腫能夠應付利尿劑治療。 A low protein diet and agents such as lactulose may help hepatic encephalopathy.低蛋白飲食和劑，如乳果糖可能有助於肝性腦病。 Infections such as spontaneous bacterial peritonitis must be rapidly treated with appropriate antibiotics.感染，如自發性細菌性腹膜炎，必須迅速適當的抗生素可治療。 Drugs metabolized in the liver must be given with caution.藥物在肝臟代謝，必須給予慎重。 Coagulation disorders will sometimes respond to vitamin K.凝血功能障礙，有時會回應維生素光

Liver transplantation is highly effective for the treatment of end-stage cirrhosis.肝移植是非常有效的治療終末期肝硬化。 Transplantation is usually needed when complications such as encephalopathy, ascites or bleeding varices are uncontrollable or when biochemical function is severely depressed.移植時，通常需要等並發症性腦病，腹水或出血靜脈曲張是不能控制的，或當生化功能是嚴重抑鬱。 In patients with primary biliary cirrhosis, a rising bilirubin indicates a poor prognosis and such patients should be considered for transplantation as the serum bilirubin concentration begins to rise.原發性膽汁性肝硬化，膽紅素上升表明預後不良等患者，應考慮用於移植的血清膽紅素濃度開始上升。 Active drug or alcohol abuse are contraindications to liver transplantation.積極吸毒或酗酒的禁忌，以肝移植。 However, alcoholics who have abstained from drinking for an extended period of time (usually more than six months), and have participated in rehabilitation programs and support groups such as Alcoholics Anonymous, can be considered as candidates and will often have a good prognosis.然而，酗酒誰投了棄權票從飲用水的一段較長的時間（通常為6個月以上） ，並參加了康復計劃和支持的群體，如戒酒，可被視為候選人往往有良好的預後。 Liver cancer is usually a contraindication to transplantation, except in experimental protocols. Liver transplantation is usually not performed in patients more than 70 years old.肝癌通常是一個禁忌移植，但在實驗議定書。肝移植通常是在患者沒有進行70歲以上。

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