Answer to the editorial letter from E. Harrison

First of all I would like to thank the comment of E. M. Harrison to our study, because there are a few interesting questions affecting previous and future ischemic preconditioning (IP) and intermittent portal clamping (IPC) studies, which should be discussed. In terms of statistical analysis you may have right; continuous variables are expressed as mean SEM and some of the statistics as median, as appropriate. Our variation is very low indeed, but I do not think it is unexpected. The explanations are as follows: The severity of ischemia‐reperfusion (I‐R) injury of the liver (and so the transaminase elevations after I‐R) is predominantly depending on the duration of the ischemia, although several further factors, like “temperature” (warm or cold ischemia), energetic condition of the liver (glycogen content, ATP content) play a role also [1]. In our study, the liver ischemia time was not only shorter, than for example in the Clavien [2] or in the Azoulay [3] or Scatton [4] study, but the length of liver ischemia was very similar in the groups (34 vs. 33min, 22 vs. 21min) and the variation between the individual patients was low (ischemia time (min): Hahn study: normal liver IPC: 34 3.2, normal liver IP: 33 2.1; cirrhosis IPC: 22 2.2, cirrhosis IP: 21 1.8; Clavien study normal liver IP: 37.7 1.5, normal liver IPC: 40.0 2.1; Azoulay: without IP: 47.7 8.3, with IP 44.5 9.2; Table I). In our study, resected liver volume and remnant liver volume were very similar between the groups resected liver volume/total liver volume (%): IPC normal liver: 45 22, IP normal liver: 42 26; IPC cirrhosis: 29 21, IP cirrhosis: 27 23; remnant liver volume/total liver volume (%) IPC normal liver 42 11, IP normal liver 39 9; IPC cirrhosis: 62 21, IP cirrhosis: 67 26; Table II). We could not find any data about resected liver volume and/or remnant liver volumes in the studies mentioned above. If the resected volumes are relatively large and the remnant volumes are small, the postoperative peak liver enzyme values can be markedly elevated, and gross difference in volume ratios of IP and IPC groups may result marked variation. This was not the case in our study. Analysing the variations of the data in the studies cited in the letter to the author, it is obvious, that there is a huge difference between the results (e.g., compare the preoperative AST variations of the Li [5] or the Clavien study with the variation of the Petrowsky [6] study, or the postoperative AST variation of the Clavien [2] or Arkadopoulos [7] study with the Heizmann [8]. In one of the IP studies [2] in 12 of 37 (32%) patients with IC, parenchymal transsection was interrupted due to significant bleeding during the 5‐min reperfusion cycles, while this did not occur in the IP group, in an other study [3] resections from the remnant liver were also performed in some patients. Such actions can lead to higher variations. In our study such actions, which can lead to higher variations did not occur. Studies on ischemic preconditioning report partially contradictory results [2–8]. This is probably due to diverse energy status of livers which is essentially influencing severity of I‐R injury. ATP content, glycogen level, nutritional status, etc. are well known parameters affecting tolerance of the liver to different injuries. All of these factors are hardly or not at all measurable. Effectiveness of preconditioning can be questionable if relevant differences between patients, or groups occur. In this regard, patient groups are most likely homogenous in our study, which might be accindental, however. The variance we have found is indeed minimal. It is obvious that we had very homogenous groups in terms of preoperative liver function (as it can be seen on ICG clearence values, low variation of preoperative bilirubin, prothrombin and liver enzymes) after randomization. Because of the constant operative technique (shorter ischemia, similar ischemia time in the groups and in the individual patients) the variations of the postoperative values were also lower, than in other studies.We think,that standardized surgical technique is essential to achieve reproducible results. In our practice,