肝脏测试解释 - 肝病患者的方法：常用肝脏检查指南

StephenW

www.natap.org
Liver Test Interpretation - Approach to the Patient with Liver Disease: A Guide to Commonly Used Liver TestsPublished: April 2014

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/guide-to-common-liver-tests/#table01
Isolated Abnormalities in Liver Test Results A common clinical scenario is the unanticipated discovery of an abnormal liver test result, obtained when a bundle of tests has been done for other reasons. Most clinical laboratories offer bundled blood tests, which often contain all or most of the following:
        

• Bilirubin
• Aspartate transaminase (AST, formerly referred to as serum glutamic-oxaloacetic transaminase, SGOT)
• Alanine transaminase (ALT, formerly called serum glutamic-pyruvic transaminase, SGPT)
• Gamma-glutamyl-transpeptidase (GGTP)
• Alkaline phosphatase
• Lactate dehydrogenase (LDH)
  

Of these tests only the GGTP is liver specific. An isolated elevation of just one of the other test values should raise suspicion that a source other than the liver is the cause (Table 1). When several liver test results are simultaneously out of the normal range, consideration of non-hepatic sources becomes irrelevant.


Table 1: Nonhepatic Sources of Abnormalities for Select Laboratory Tests




Evaluation of Liver Disease Based on Enzyme LevelsIt is customary and useful to categorize liver diseases into three broad categories: Hepatocellular, in which primary injury is to the hepatocytes; cholestatic, in which primary injury is to the bile ducts; and infiltrative, in which the liver is invaded or replaced by non-hepatic substances, such as neoplasm or amyloid. Although there is a great deal of overlap in liver test result abnormalities seen in these three categories, particularly in cholestatic and infiltrative disorders, an attempt to characterize an otherwise undifferentiated clinical case as hepatocellular, cholestatic, or infiltrative often makes subsequent evaluation faster and more efficient. The AST, ALT, and alkaline phosphatase tests are most useful to make the distinction between hepatocellular and cholestatic disease.
The normal range for aminotransferase levels in most clinical laboratories is much lower than that for the alkaline phosphatase level. Accordingly, when considering levels of elevations, it is necessary to consider them relative to the respective upper limit of normal for each test compared. Consider a patient with an AST level of 120 IU/mL (normal, ≤40 IU/mL) and an alkaline phosphatase of 130 IU/mL (normal, ≤120 IU/mL). This represents a hepatocellular pattern of liver injury because the AST level is three times the upper limit of normal, whereas the alkaline phosphatase level is only marginally higher than its upper limit of normal.
Serum aminotransferase levels—ALT and AST—are two of the most useful measures of liver cell injury, although the AST is less liver specific than is ALT level. Elevations of the AST level may also be seen in acute injury to cardiac or skeletal muscle. Lesser degrees of ALT level elevation may occasionally be seen in skeletal muscle injury or even after vigorous exercise. Thus in clinical practice, it is not uncommon to see elevations of AST, ALT or both in common non-hepatic conditions such as myocardial infarction and rhabdomyolysis. Diseases that primarily affect hepatocytes, such as viral hepatitis, will cause disproportionate elevations of the AST and ALT levels compared with the alkaline phosphatase level. The ratio of AST/ALT is of little benefit in sorting out the cause of liver injury except in acute alcoholic hepatitis, in which the ratio is usually greater than 2.
The current upper limit of serum ALT, though varied among laboratories, is generally around 40 IU/L. However, recent studies have shown that the upper limit threshold of ALT level should be lowered because people who have slightly raised ALT levels that are within the upper limit of normal (35-40 IU/L) are at an increased risk of mortality from liver disease.4 In addition, it has been suggested that gender-specific thresholds be applied because women have slightly lower normal ALT levels than men. One such study conducted in the U.S. identified an ALT upper limit of 29 IU/L for men and 22 IU/L for women.5 In asymptomatic patients with minimal elevations of aminotransferases, it is reasonable to repeat the test in a few weeks to confirm elevation. Common causes of mild increases in AST and ALT levels include non-alcoholic fatty liver disease (NAFLD), hepatitis C, alcoholic fatty liver disease, and medication effect (e.g., due to statins).
Serum alkaline phosphatase comprises a heterogeneous group of enzymes. Hepatic alkaline phosphatase is most densely represented near the canalicular membrane of the hepatocyte. Accordingly, diseases that predominately affect hepatocyte secretion (e.g., obstructive diseases) will be accompanied by elevations of alkaline phosphatase levels. Bile-duct obstruction, primary sclerosing cholangitis, and primary biliary cirrhosis (PBC) are some examples of diseases in which elevated alkaline phosphatase levels are often predominant over transaminase level elevations (Table 2).



Bilirubin Level ElevationsBilirubin is produced by the normal breakdown of pigment-containing proteins, especially hemoglobin from senescent red blood cells and myoglobin from muscle breakdown. Bilirubin released from such sources, tightly albumin bound, is delivered to the liver, where it is efficiently extracted and conjugated by hepatic glucuronidation and sulfation. Conjugated bilirubin is rapidly excreted into bile and removed from the body through the gut. Therefore, the amount of conjugated bilirubin present in serum in healthy subjects is trivial (<10% of measured total bilirubin). An elevated level of conjugated serum bilirubin implies liver disease. Also, it is important to note that only conjugated bilirubin appears in urine (unconjugated bilirubin is albumin bound and water insoluble). The presence of bilirubin in urine almost always implies liver disease.
Many laboratories report only the total bilirubin level, the sum of the conjugated and unconjugated portions. It is sometimes useful to determine the fraction of total serum bilirubin that is unconjugated versus that which is conjugated, usually referred to as fractionation of bilirubin. This is most useful when all the standard liver test results are normal, except the total bilirubin. To make matters more confusing, the conjugated bilirubin is sometimes referred to as the direct-reacting bilirubin and the unconjugated as the indirect-reacting bilirubin (Table 3).
                Table 3: Bilirubin Fractions Present in Blood and Urine               
Normally, 90% or more of measured serum bilirubin is unconjugated (indirect-reacting). When the total bilirubin level is elevated and fractionation shows that the major portion (≥90%) is unconjugated, liver disease is never the explanation. Instead, the clinician should suspect one of two explanations: Gilbert disease or hemolysis. If the patient is young and healthy, an inherited decrease in the inability to conjugate bilirubin is likely and is referred to as Gilbert syndrome. It is seen in about 5% of the general population and causes only mild hyperbilirubinemia without symptoms. It is not associated with liver disease. Interestingly, fasting and intercurrent illnesses such as influenza often make the level of unconjugated bilirubin even higher in those with Gilbert syndrome. This syndrome is easily diagnosed when all standard liver-test results are normal and 90% or more of the total bilirubin is unconjugated. There is no need for an imaging study or liver biopsy in cases of suspected Gilbert syndrome.
Elevations of the unconjugated bilirubin level when the conjugated bilirubin level remains normal may also indicate an increased load of bilirubin caused by hemolysis. Anemia and an elevated reticulocyte count are usually present in such cases (Table 4).
                Table 4: Common Causes of Isolated Bilirubin Elevation
               

Cause	Direct-Reacting Bilirubin	Indirect-Reacting Bilirubin	Associated Features
Liver disease (many types)	Elevated	Elevated or normal	Liver enzyme levels often elevated
Hemolysis	Normal	Elevation represents more than 90% of total bilirubin	Anemia usual; increased reticulocyte count; normal liver enzyme levels (although LDH may be elevated)
Gilbert's syndrome	Normal	Elevation represents more than 90% of total bilirubin (common)	No abnormal liver tests; no anemia; onset in late adolescence; fasting makes bilirubin rise

LDH, lactate dehydrogenase.

        
Many clinicians mistakenly interpret elevations of direct-reacting bilirubin to indicate that cholestatic (obstructive) liver disease is present. It is apparent from Table 2 that the serum bilirubin level plays no useful role in categorizing a case as hepatocellular, cholestatic, or infiltrative. The bilirubin level may be normal or elevated in each type of disorder. Viral hepatitis A, a prototypic hepatocellular disease, may frequently be associated with bilirubin levels that are high, whereas PBC, a prototypic cholestatic disorder, is associated with a normal serum bilirubin level except in later stage disease. Serum bilirubin levels should be disregarded when trying to decide whether the liver-test pattern is more suggestive of hepatocellular or cholestatic disease.

StephenW

肝脏测试解释 - 肝病患者的方法：常用肝脏检查指南
发布时间：2014年4月

Http://www.clevelandclinicmeded. ... iver-tests/#table01
肝脏测试结果的孤立异常

常见的临床情况是当出于其他原因进行一系列测试时获得的异常肝脏测试结果的意外发现。大多数临床实验室提供捆绑血液检查，通常包含以下全部或大部分：

胆红素
天冬氨酸转氨酶（AST，以前称为血清谷草转氨酶，SGOT）
丙氨酸转氨酶（ALT，以前称为血清谷丙转氨酶，SGPT）
γ-谷氨酰转肽酶（GGTP）
碱性磷酸酶
乳酸脱氢酶（LDH）

在这些测试中，仅GGTP是肝特异性的。只有一个其他测试值的升高应该引起怀疑，肝脏以外的来源是其原因（表1）。当几个肝脏测试结果同时超出正常范围时，考虑非肝源变得无关紧要。

表1：选择实验室检查的非肝脏异常来源



基于酶水平的肝病评价

将肝脏疾病分为三大类是常规和有用的：肝细胞，其中原发性损伤是肝细胞;胆汁淤积，其中原发性损伤是胆管;和浸润性的，其中肝脏被侵入或被非置换。尽管在这三个类别中看到的肝脏试验结果异常中存在大量重叠，特别是在胆汁淤积性和浸润性疾病中，试图将另外未分化的临床病例表征为肝细胞，胆汁郁积，例如肿瘤或淀粉样蛋白。 AST，ALT和碱性磷酸酶测试是最有用的，以区分肝细胞和胆汁淤积性疾病。

大多数临床实验室中氨基转移酶水平的正常范围比碱性磷酸酶水平低得多。然而，当考虑海拔高度时，需要考虑它们相对于相应的每个测试的相应正常上限。考虑（IU / mL）和130 IU / mL（正常，≤120IU / mL）的碱性磷酸酶。这代表肝脏损伤的肝细胞模式，因为AST水平（正常，≤40IU/ mL）是正常上限的三倍，因为碱性磷酸酶水平仅略高于其正常上限。

血清转氨酶水平-ALT和AST是肝细胞损伤的两个最有用的测量，尽管AST比ALT水平更少肝特异性。在心脏或骨骼肌的急性损伤中也可见AST水平的升高。 ALT在常见和非肝脏条件下，例如心肌梗死和横纹肌溶解，在常见的非肝病状例如心肌梗死和横纹肌溶解症中看到AST，ALT或两者的升高并不罕见。 AST / ALT的比例在排除肝损伤的原因（除了急性（AMSC））方面没有什么益处。酒精性肝炎，其比例通常大于2。

然而，最近的研究表明，ALT水平的上限阈值应该降低，因为已经升高的ALT水平升高在40IU / L以内的人。血清ALT的当前上限，正常上限（35-40 IU / L）患肝病死亡的风险增加.4此外，有人建议应用性别特异性阈值，因为妇女的正常ALT水平略低于男性。在美国进行的这样的研究确定了ALT上限为男性29IU / L和女性22IU / L。在具有最小氨基转移酶升高的无症状患者中，在几周内重复该试验是合理的。 AST和ALT水平轻度增加的常见原因包括非酒精性脂肪肝病（NAFLD），丙型肝炎，酒精性脂肪肝病和药物效应（例如，由于他汀类药物）。

血清碱性磷酸酶包括异质的酶组。肝碱性磷酸酶在肝细胞的小管膜附近最密集。因此，主要影响肝细胞分泌的疾病（例如阻塞性疾病）将伴随碱性磷酸酶水平的升高。胆管阻塞，原发性硬化性胆管炎和原发性胆汁性肝硬化（PBC）是其中升高的碱性磷酸酶水平通常超过转氨酶水平升高的疾病的一些实例（表2）。

胆红素水平升高

胆红素是通过含颜料的蛋白质，特别是来自衰老红细胞的血红蛋白和来自肌肉分解的肌红蛋白的正常分解产生的。从这些来源释放的胆红素，紧密结合的白蛋白，被递送到肝脏，在那里通过肝葡萄糖醛酸化和硫酸化有效地提取和缀合。缀合的胆红素快速排泄到胆汁中并通过肠道从身体中除去。因此，健康受试者血清中存在的结合胆红素的量是微不足道的（<测量的总胆红素的10％）。升高的结合血清胆红素水平意味着肝脏疾病。此外，重要的是要注意，只有共轭胆红素出现在尿液中（未结合的胆红素是白蛋白结合的和水不溶性的）。尿中胆红素的存在几乎总是意味着肝脏疾病。

许多实验室只报告总胆红素水平，即共轭和非共轭部分的总和。有时有用的是确定未缀合的总血清胆红素与缀合的血清胆红素的比例，通常称为胆红素的分级。这是最有用的，当所有的标准肝脏测试结果是正常的，除了总胆红素。为了使事情更加混乱，结合的胆红素有时被称为直接反应胆红素和未结合的作为间接反应胆红素（表3）。
表3：存在于血液和尿液中的胆红素部分

通常，90％或更多的测量血清胆红素是非共轭的（间接反应）。当总胆红素水平升高并且分级分离显示大部分（≥90％）未结合时，肝脏疾病绝不是解释。相反，临床医生应该怀疑两个解释之一：吉尔伯特病或溶血。如果患者是年轻和健康的，则不能结合胆红素的遗传性降低可能，并且被称为吉尔伯特综合征。它在约5％的一般人群中可见，并且仅引起轻度高胆红素血症而无症状。它与肝脏疾病无关。有趣的是，空腹和流行性疾病如流感常常使吉尔伯特综合征患者的非结合胆红素水平更高。当所有标准肝脏测试结果正常且总胆红素的90％或更多未偶联时，该综合征容易诊断。在怀疑是吉尔伯特综合征的情况下，没有必要进行成像研究或肝活检。

当结合胆红素水平保持正常时，未缀合的胆红素水平的升高也可以指示由溶血引起的胆红素的负荷增加。贫血和升高的网织红细胞计数通常存在于这种情况下（表4）。
表4：分离的胆红素升高的常见原因

因为直接反应胆红素间接反应胆红素相关特征
肝病（许多类型）升高升高或正常肝酶水平经常升高
溶血正常升高代表超过90％的总胆红素贫血通常;增加网织红细胞计数;正常肝酶水平（尽管LDH可能升高）
吉尔伯特综合征正常升高代表超过总胆红素的90％（常见）无异常肝脏检查;无贫血;发病晚期青春期禁食使胆红素上升

LDH，乳酸脱氢酶。

许多临床医生错误地解释了直接反应性胆红素的升高，表明存在胆汁淤积性（阻塞性）肝病。从表2显而易见，血清胆红素水平在将病例分类为肝细胞，胆汁郁积或浸润性方面没有作用。在每种类型的病症中，胆红素水平可以是正常的或升高的。病毒性甲型肝炎（一种原型肝细胞疾病）可能常常与高胆红素水平相关，而原型性胆汁淤积性疾病PBC与正常血清胆红素水平相关，除了晚期疾病。当试图确定肝脏测试模式是否更多地提示肝细胞或胆汁淤积性疾病时，应当忽略血清胆红素水平。