November 2, 2006 (波士顿) -- 目前可接受的血清丙氨酸转胺酵素(ALT)正常上限值是由美国肝脏疾病研究协会人为提高的，目前的正常范围排除了那些看似良好但却有
肝病风险者。
AASLD官方致力于“再校正”正常范围，部分原因系基于此周在波士顿所发表的 AASLD 57届年会的一些研究，这些研究指出升高的肝脏酵素是一般疾病和肝病的死亡危险因子。
根据梅约诊所医学院的副教授W. Ray Kim医师所述，升高的血清转胺酵素如 ALT 和天门冬安酸转胺酵素 (AST)，可预测一般人的死亡率。
Kim医师发表18,330 位社区居民于1995年的AST指数资料，有15,991位是正常结果，2339 位有升高的AST值；同样在1995年，有6792位检测 ALT 值，其中907位有升高现象。
Kim 医师报告指出，AST和ALT升高者的死亡率比标准值有显著升高，有正常 AST 或 ALT 值者的死亡风险则比预期低。
AST 值两倍于正常上限值的死亡比率是1.79倍，ALT 值两倍于正常上限值的死亡比率是1.63倍；Kim 医师表示，不论性别，AST与ALT数值和死亡风险之间有几近线性的关系。
他认为，AST 和 ALT 筛检应纳入病患的一般医疗评估中，他向AASLD之与会听众表示，[升高的] ALT值可以在病患肝病后初期即鉴别其死亡风险。
Kim医师的研究基金独立，Kim医师之报告没有相关财金关系。
另一个研究中，杜克大学医学中心胃肠肝胆科主任John McHutchison医师，和同事发表对研究中的慢性C型肝炎(HCV)感染
制剂PF-03491390 (Pfizer Ltd, Sandwich, UK)的资料。
此制剂是一种pancaspase 抑制剂，可藉由阻断肝细胞凋零而降低升高的ALT和 AST值。
此一剂量范围研究包括204位慢性活性HCV 感染与肝纤维化病患，随机分派使用安慰剂5 mg、25 mg或 50 mg 的 PF-03491390，每天口服两次，疗程12 周。
如果 ALT和 AST值在第十周时仍旧偏高，可以在最后两周将剂量加倍。
结果显示，可以在第一周治疗时即见到两种酵素值降低并且持续，这种降低情况是剂量相关的线性关系 。
副作用方面，一般轻微或中等，最多的是分别有24和22位民众被报告有
头痛和疲劳。
此一pancaspase 抑制剂不会影响HCV RNA 。
McHutchison医师的研究受Pfizer, Ltd, Sandwich, UK赞助部分资金，他也接受Vertex Pharmaceuticals, Inc, GlaxoSmithKline，和 Coley Pharmaceutical Group, Inc等公司对他其他研究的赞助。
AASLD公共政策主席、圣路易大学医学院肝胆科主任Adrian DiBisceglie医师向Medscape表示，该协会目前正进行ALTY值的“再校正”。
他指出，我们将设定比较低的上限值，以纳入那些有异常ALT值但却感觉良好而实际上却是有肝病风险者，这样的设定也许会降低准确度，但是可以增加敏感度。
正常上限值因不同实验技术而从30 IU/L到 60 IU/L；DiBisceglie医师表示， 我们要往下修正到30 IU/L，他指出，ALT 值反映出一般血管的状况，如果数值大于30，此人即可能有某些状况— 脂肪肝或者某些血管疾病，包括阻塞的冠状动脉疾病。
AASLD 57届年会：摘要95，发表于October 30, 2006；摘要1251，发表于October 31, 2006。
Elevated ALT Levels Predict Risk of Death From Liver Cancer
By Martha Kerr
Medscape Medical News
November 2, 2006 (Boston) — The currently accepted upper limit of normal for serum alanine aminotransferase (ALT) levels is "artificially high," officials from the American Association for the Study of Liver Diseases (AASLD) believe. The current normal range excludes a number of individuals who feel well but who are at increased risk for liver disease.
AASLD officials are working to "recalibrate" the normal range, based in part on a number of studies presented here this week at the AASLD 57th annual meeting, which show that elevated liver enzymes are a risk factor for mortality in general and liver disease, specifically.
Elevated serum aminotransferases, such as ALT and aspartate aminotransferase (AST), predict mortality in the general population, according to W. Ray Kim, MD, associate professor of medicine at the Mayo Clinic College of Medicine in Rochester, Minnesota.
Dr. Kim presented data on 18,330 community residents who had AST levels measured at least once in 1995. Of these, 15,991 had normal results and 2339 had elevated AST levels.
Also in 1995, 6792 residents had ALT levels measured, and of these, 907 had elevated values.
Dr. Kim reported "a significant increase in the standardized mortality ratio with increasing AST and ALT levels, whereas a normal AST or ALT level was associated with a risk of death lower than expected."
AST levels 2 times the upper limit of normal had a mortality ratio of 1.79 and ALT levels 2 times the upper limit of normal had a mortality ratio of 1.63. There was "a near-linear relationship between AST and ALT values and subsequent risk of death in both genders," Dr. Kim showed.
He suggested that AST and ALT screening be a part of the general medical evaluation of patients. " ALT may identify patients at risk of death from liver disease early in their disease," he told AASLD meeting attendees.
Dr. Kim's study was independently funded. Dr. Kim reported no relevant financial relationships.
In a separate study, John McHutchison, MD, director of gastroenterology and hepatology research at Duke University Medical Center in Durham, North Carolina, and colleagues presented data on an investigational agent, PF-03491390 (Pfizer Ltd, Sandwich, UK), used in chronic active hepatitis C virus (HCV) infection.
The agent, a pancaspase inhibitor, lowers elevated ALT and AST levels by blocking apoptosis of hepatocytes.
The dose-ranging study involved 204 patients with chronic active HCV infection and liver fibrosis, who were randomized to placebo, 5 mg, 25 mg, or 50 mg of PF-03491390 twice a day orally for 12 weeks.
If ALT and AST levels were still elevated at week 10, the dose was doubled for the remaining 2 weeks.
Reductions in both liver enzymes were seen within the first week of treatment and were sustained throughout. Reductions were dose-related in a linear fashion.
Adverse events were primarily mild or moderate, with headache and fatigue reported in 24 and 22 patients, respectively, the most common.
The pancaspase inhibitor did not affect HCV RNA levels.
Dr. McHutchison's study was funded in part by Pfizer, Ltd, Sandwich, UK. He has also received funding grants from Vertex Pharmaceuticals, Inc, GlaxoSmithKline, and Coley Pharmaceutical Group, Inc, for other research.
AASLD Chairman of Public Policy Adrian DiBisceglie, MD, chief of hepatology at St. Louis University School of Medicine in Missouri, told Medscape that the association is in the process of "recalibrating" the ALT normal range.
"We are setting limits lower than they have been to include people with abnormal ALT levels who feel well but who still have an increased risk of liver disease," he said. Setting the upper limit of normal lower will decrease the specificity some, but it will increase the sensitivity."
Upper limits of normal range from 30 IU/L to 60 IU/L, depending on the laboratory. "We want to reset it southward of 30 IU/L," Dr. DiBisceglie said.
"ALT levels are a reflection of the general vascular condition," he said. "If the level is above 30, then that person probably has a problem — fatty liver or some vascular disease, including occlusive coronary artery disease."
AASLD 57th Annual Meeting: Abstract 95, presented October 30, 2006; abstract 1251, presented October 31, 2006.
作者：
Martha Kerr 2007-6-20