In the March 6 issue of the Annals of Internal Medicine, there is an article entitled “Screening for Liver Acalabrutinib mw Cancer: A Rush to Judgment”.1 In it, the investigators criticize the AASLD recommendations on screening for HCC.2, 3 The basis for their criticism is that the only randomized, controlled trial (RCT) that showed a benefit4 to screening was statistically invalid. They imply that there is no reliable information on HCC screening, and that therefore AASLD should not be recommending screening to patients at risk for HCC. However, in addition to the AASLD, other organizations, such as the U.S. Veterans

Administration,5 the World Gastroenterology Association,6 European Association for Study of the Liver,7 Aloxistatin supplier and the liver disease societies of several Asian countries8, 9 consider the Chinese study to be valid and recommend screening for HCC. The National Comprehensive Cancer Network in the United Sstates also recommends HCC screening.10 All these recommendations recognize the presence of a well-defined at-risk population and the availability of effective treatment for early-stage disease. There have been two RCTs of HCC screening in China.4, 11 The first found no difference between the screened and unscreened group.11 However, the conduct of this trial made it impossible to show a difference.

Resection was to be used as the treatment of early-stage HCC, but a large proportion of those with screen-detected HCC did not undergo resection. Therefore, this trial failed for methodological reasons and not because screening was ineffective. The second trial, also in China,4 used a cluster randomization method, but then analyzed the results on an individual patient

basis. This is not statistically correct. The argument by the investigators of the Annals of Internal Medicine article is that if the study had been correctly analyzed, there would be no statistical difference between the screened and unscreened groups; and furthermore, even 上海皓元医药股份有限公司 if the study had shown a difference in mortality, the results would not be applicable in North America, because in North America, the dominant cause of HCC is hepatitis C, not hepatitis B. Therefore, they argue, HCC screening was not worthy of a high level of recommendation. There are two issues here: The first is the level of evidence, and the second is the recommendation and the strength of the recommendation. At the time of the initial guidelines, the AASLD was using a grading system that had broader categories with some overlap. A grade 1 level of evidence was defined as that based on RCTs and, to some extent, was to encompass the general consensus of experts in the field who treat these types of patients on a day-to-day basis.