Reduction in albumin binding function following liver resection in patients with and without cirrhosis

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1 Originl Artile Redution in lumin inding funtion following liver resetion in ptients with nd without irrhosis Penglei Ge 1,2, Wenjun Lio 1, Huyu Yng 1, Jingfen Lu 3, Wei Xu 1, Dndn Hu 1, Shund Du 1, Hifeng Xu 1, Hito Zho 1, Xin Lu 1, Xinting Sng 1, Shouxin Zhong 1, Jiefu Hung 1, Yilei Mo 1 1 Deprtment of Liver Surgery, Peking Union Medil College (PUMC) Hospitl, Chinese Ademy of Medil Sienes nd PUMC, Beijing , Chin; 2 Deprtment of Heptopnretoiliry Surgery, the First Affilited Hospitl of Zhengzhou University, Zhengzhou , Chin; 3 Stte Key Lortory of Nturl nd Biomimeti Drugs, Shool of Phrmeutil Sienes, Peking University, Beijing , Chin Contriutions: (I) Coneption nd design: P Ge, Y Mo; (II) Administrtive support: None; (III) Provision of study mterils or ptients: None; (IV) Colletion nd ssemly of dt: S Du, H Xu, H Zho, X Lu, X Sng, S Zhong, J Hung; (V) Dt nlysis nd interprettion: W Lio, H Yng, J Lu, W Xu, D Hu; (VI) Mnusript writing: All uthors; (VII) Finl pprovl of mnusript: All uthors. Correspondene to: Yilei Mo. Deprtment of Liver Surgery, Peking Union Medil College (PUMC) Hospitl, 1# Shui-Fu-Yun, Wng-Fu-Jing, Beijing , Chin. Emil: pumh-liver@hotmil.om. Bkground: The im of this study is to investigte effets of liver resetion on lumin inding funtion in ptients with nd without irrhosis. Methods: An oservtionl study ws performed on 42 ptients with irrhosis nd heptoellulr rinom (HCC), nd 17 ptients without irrhosis dignosed with hepti vernous hemngiom, ll of whom underwent tumor resetion. Control group onsisted of 50 helthy volunteers. Alumin metl ion inding pity ws ssyed s ishemi-modified lumin trnsformed (IMAT, equl to 1-IMA), nd lumin ftty id inding strength ws lso tested. All inditors were mesured 1 dy efore nd 1, 3, 7 dys fter surgery. Results: Preopertive IMAT ws signifintly higher in helthy volunteers thn irrhoti ptients (P=0.02), ut not thn non-irrhoti ptients (P=0.79). Following surgery, prolonged nd shrp redution ws oserved in irrhoti ptients; wheres, in non-irrhoti ptients, the result rose sooner nd fster. Alumin ftty id inding strength in oth operted groups deresed for the first 3 dys fter heptetomy, then oth inresed to preopertive levels y dy 7. Alumin ftty id inding strength ws higher in nonirrhoti thn irrhoti ptients t ll time points. Conlusions: This is the first study to show tht lumin inding funtion dereses following liver resetion in ptients with nd without irrhosis. It is more ojetive thn lumin onentrtion nd less ffeted y lumin infusion. It my e n importnt inditor of liver funtion. Keywords: Alumin inding funtion; lumin onentrtion; irrhosis; liver resetion; ishemi-modified lumin (IMA) Sumitted Sep 06, Aepted for pulition Ot 19, doi: /tr View this rtile t: Introdution Assessing liver funtion in ptients undergoing liver resetion is ruil. As lumin onentrtion is regrded s n importnt mrker of liver funtion (1,2), serum lumin onentrtion rther thn its inding funtion is usully determined. Alumin onentrtion, however, is not n urte determinnt of lumin inding tivity, s irulting lumin my hve lost its inding funtion. The three-dimensionl struture of lumin is ltered when liver funtion is impired, reduing the ility of lumin to ind to its lignds. This my result in the filure to remove metoli produts, inluding iliruin, nd drugs from

2 Trnsltionl Cner Reserh, Vol 5, No 6 Deemer Tle 1 Inlusion nd exlusion riteri for ptients in the irrhoti group Cirrhoti group Inlusion riteri Preopertive dignosis of irrhosis y ultrsound, omputed tomogrphy, or mgneti resonne imging, nd onfirmtion y intropertive explortion nd/or pthologil tests; Lprotomi liver segment resetion, omined liver segment resetion, or hemiheptetomy performed; Postopertive pthology onfirmed for heptoellulr rinom Exlusion riteri Dignosis of non-irrhosis y intropertive explortion nd/or pthologil testing; Pthology onfirmed for intrhepti holngiorinom or metstti hepti rinom; Lprosopi resetion of the tumor; Tretment with immunosuppressnt within 1 month preopertively; Preopertive trnshepti rteril hemoemoliztion or rdiofrequeny ltion the ody (3,4). Mesuring oth lumin onentrtion nd inding funtion n etter indite tul liver funtion, thus guiding linil prtie. The most ommonly used inditors of lumin inding funtion re ishemi-modified lumin (IMA) nd lumin ftty id inding strength, whih reflet the inding of lumin to metl ions nd ftty ids, respetively (3,5,6). These tivities were found to e lower in ptients with liver irrhosis, espeilly those with liver filure, thn in norml sujets (7). Although lumin dilysis using moleulr dsorent reirulting system removed lumin-ound metolites from lood, it did not improve lumin inding funtion. Alumin inding funtion my e more ojetive inditor of liver sttus, nd IMA ould e used to predit prognosis. We previously showed tht the pities of lumin to ind metl ions nd ftty ids provided erlier nd more sensitive indition thn lumin onentrtion of liver dmge in ptients with nonloholi ftty liver disese, virl heptitis nd irrhosis. (Ge PL, Yng HY, Lu JF, et l. Alumin inding funtion: The potentil erliest inditor for liver funtion dmge. Gstroent Res Prt. In Press.) To our knowledge, however, there hve een no reports on periopertive hnges of lumin inding funtion in ptients with nd without irrhosis undergoing liver resetion. This oservtionl study therefore ssessed the effets of liver surgery on lumin inding funtion in ptients with liver tumors due to irrhosis nd in nonirrhoti ptients with hepti vernous hemngioms. Its findings suggest tht lumin inding funtion my e good inditor of liver funtion. Methods Ptients Ptients who underwent liver surgery from Jnury 2014 to Mrh 2015 t the Deprtment of Liver Surgery, Peking Union Medil College Hospitl, were eligile. The study inluded 42 irrhoti ptients who underwent liver resetion for heptoellulr rinom (HCC), nd 17 nonirrhoti ptients who underwent resetion for hepti vernous hemngiom. The ontrol group inluded 50 helthy volunteers (Tles 1,2). All sujets provided written informed onsent. The study ws performed ording to the priniples of the Delrtion of Helsinki nd the study protool ws pproved y the Ethis Committee of Peking Union Medil College Hospitl. Serum smple olletion Peripherl venous lood ws drwn from ll ptients undergoing surgery on preopertive dy 1 nd on postopertive dys (POD) 1, 3, nd 7. Only one smple ws otined from the sujets in the ontrol group. Blood smples were olleted into dditive-free vuum tues fter t lest 12 h of fsting, llowed to ogulte for min, nd entrifuged t 3000 rpm for 10 min. Serum smples were stored t 80 efore nlysis. Routine serologil tests Routine tests inluded totl iliruin, lnine

3 758 Ge et l. Redued lumin inding funtion fter heptetomy Tle 2 Inlusion nd exlusion riteri for ptients in the non-irrhoti groups Non-irrhoti group Inlusion riteri Preopertive dignosis of non-irrhosis y ultrsound, omputed tomogrphy, or mgneti resonne imging, nd onfirmtion y intropertive explortion nd/or pthologil testing Lprotomi liver segment resetion, omined liver segments resetion, hemiheptetomy, or hepti hemngiom stripping Postopertive pthology onfirmed for hepti vernous hemngiom Exlusion riteri Dignosis of irrhosis y intropertive explortion nd/or pthologil testing Only liver hemngiom nding performed Lprosopi resetion of the tumor Tretment with immunosuppressnt within 1 month preopertively minotrnsferse (ALT), retinine, prothromin time (PT), nd interntionl normlized rtio (INR). Child-Pugh sore nd model for end-stge liver disese (MELD) sore were lso determined of irrhoti ptients (1). Periopertive serum lumin onentrtions were mesured in smples from ptients in the irrhoti nd non-irrhoti groups. Alumin olt inding pity Alumin olt inding pity ws mesured essentilly s desried (6). Briefly, 100 µl of serum were mixed with 25 µl olt hloride (CoCl2, 1 mg/ml) (Sigm-Aldrih, USA) in eh well of 96-well plte nd inuted t room temperture for 10 min. To eh well ws dded 25 µl dithiothreitol (DTT, 1.5 mg/ml) (Sigm-Aldrih, USA). After inution for 2 min, 150 µl sline were dded to terminte the retion, nd sorne ws mesured spetrophotometrilly t 470 nm (Synergy H1; BioTek, USA). IMA ws defined s the sorne of the tested smple minus tht of the ontrol (no DTT dded). High sorne vlue indited more free olt reted with DTT, with less ound to lumin. To e more strightforwrd, results re presented s IMA trnsformed (IMAT), defined s 1-IMA, with higher IMAT inditing higher metl ion inding pity. To ssess metl ion inding funtion per unit of lumin, IMAT ws lso normlized to lumin onentrtion nd reported s the IMAT/lumin rtio. Alumin ftty id inding strength To mesure lumin ftty id inding strength, 100 µl serum nd 20 µl spin lel 3.0 mmol/l 16-doxyl steri id (Sigm-Aldrih, USA) were dded to 0.5-mL Eppendorf tue. Eh mixture ws stirred with glss rod for 3 min t 4. The tues were seled nd inuted in 37 wter th for 20 min. A 10-µL liquot of eh smple ws trnsferred to n eletron prmgneti resonne instrument (Bruker EMX A200, Bruker BioSpin GmH, Germny), operted with enter field G, sweep width 100 G, mirowve frequeny 9.6 GHz, mirowve power 6.5 MW, nd modultion frequeny 100 KHz with modultion mplitude 2.5 G. Dt were nlyzed with Origin 8 imge proessing softwre (OriginL, USA), nd spetrl digrm of the spin lel nd lumin omplex ws onstruted (Figure 1). The rtio of the numer of high-ffinity to low-ffinity ftty id inding sites (H/L) ould e lulted from the spetrum. H/L refleted not only the inding strength of lumin to ftty id, ut lso its onformtionl ltertion. Sttistil nlysis Continuous vriles were expressed s men ± stndrd devition. Sttistil nlyses were performed with SPSS 13.0 sttistil softwre (SPSS In., USA). The dt onformed to norml distriution nd homogeneity of vrine. The differene etween preopertive tumor sizes ws nlyzed y independent smple t-tests, nd the differenes in other preopertive prmeters mong the three groups were nlyzed y one-wy nlysis of vrine. The differenes etween the irrhoti nd non-irrhoti ptient groups t eh preopertive nd postopertive time

4 Trnsltionl Cner Reserh, Vol 5, No 6 Deemer H L point were nlyzed y two ftor repeted mesurements nlysis of vrine, wheres within-group differenes mong time points were nlyzed y pired t tests. Multivrite nlysis of vrine ws used to test differenes t the sme time point etween the two operted groups. Two-wy tests were used for ll nlyses. A P vlue <0.05 ws onsidered sttistilly signifint. Results Figure 1 Eletron prmgneti resonne spetrum of ll 16-doxyl steri ids (16-DS) ound to lumin. H nd L represent the numer of 16-DS ound to high- nd low-ffinity ftty id inding sites on lumin, respetively. The H/L rtio reflets the inding strength of lumin to ftty ids nd the hnges in lumin onformtion. Tumor size ws signifintly smller in the irrhoti thn in the non-irrhoti group (5.94±3.46 vs ±5.64 m, P<0.001). Ptients in oth groups underwent lprotomy for resetion of one or more liver segments or hemiheptetomy, wheres some ptients in the non-irrhoti group underwent hepti hemngiom stripping (Tle 3). Tle 3 Demogrphi nd linil hrteristis of irrhoti nd non-irrhoti ptients undergoing liver resetion nd of helthy volunteers Prmeters Control (n=50) Cirrhoti (n=42) Non-irrhoti (n=17) P vlue Age (yers) 49.20± ± ± Sex (M/F) 27/23 39/3 6/11 <0.001 Virl heptitis HBV <0.001 HCV NA None <0.001 Tumor size (m) NA 5.94± ±5.64 <0.001 Alumin (g/l) 46.64± ± ±3.43 <0.001 Biliruin (µmol/l) 11.51± ± ±3.32 <0.001 ALT (U/L) 18.56± ± ±38.93 <0.001 Cretinine (µmol/l) 68.94± ± ± PT (s) 11.58± ± ±0.61 <0.001 INR 0.98± ± ±0.06 <0.001 Child-Pugh sore NA 5.62±0.73 NA NA MELD sore NA 7.95±1.56 NA NA IMAT 0.57± ± ± IMAT/lumin 1.23± ± ± H/L 0.76± ± ±0.09 <0.001 Dt re expressed s mens±stndrd devition or numer. M, mle; F, femle; HBV, heptitis B virus; HCV, heptitis C virus; n.., not ville; ALT, lnine minotrnsferse; PT, prothromin time; INR, interntionl normlized rtio; MELD, model for end-stge liver disese; IMAT, ishemi modified lumin trnsformed; H/L, high-ffinity/low-ffinity ftty id-inding sites; NA, not pplile.

5 760 Ge et l. Redued lumin inding funtion fter heptetomy Following surgery, ll ptients in the irrhoti nd nonirrhoti groups reeived prophylti ntiiotis for 1 3 dys nd nutritionl support. Ptients in the irrhoti group who underwent resetion of severl liver segments or hemiheptetomy reeived infusions of 20 g/dy ommeril lumin (200 g/l, Huln Bio, Chin) for 3 5 dys. Alumin infusions were not dministered to ptients in the irrhoti group who underwent resetion of single liver segment or to ptients in the non-irrhoti group. All ptients reovered well nd were dishrged from the hospitl 7 10 dys fter surgery. No ptients died within 30 dys postopertion. Cirrhoti Non-irrhoti Alumin onentrtion Alumin (g/l) Preopertive lumin onentrtion ws signifintly higher in helthy volunteers thn in irrhoti ptients (P<0.001). Alumin onentrtions shrply deresed in oth the irrhoti nd non-irrhoti groups fter surgery (P<0.001), grdully inresing long with improvements in liver funtion. Alumin onentrtion rose fster nd higher in the irrhoti thn in the non-irrhoti group, nd ws higher in the former on POD 7 (P=0.03) (Figure 2, Tle 4). 25 Pre-opertion POD1 POD3 POD7 Figure 2 Serum lumin onentrtions in ptients in the irrhoti nd non-irrhoti groups t different timepoints. The lk dshed line represents the men lumin onentrtion in 50 helthy volunteers. P<0.05 versus preopertive onentrtion in the irrhoti group; P<0.05 versus POD 1 in the irrhoti group; P<0.05 versus preopertive onentrtion in the non-irrhoti group. POD, post-opertive dy. Alumin olt inding pity IMAT IMAT in oth operted groups ws signifintly lower on POD 1 thn preopertively (P=0.01). Minimum IMAT ws oserved on POD 1 in the non-irrhoti group nd on POD 3 in the irrhoti group. On POD 7, IMAT hd returned to preopertive onentrtion in oth the non- Tle 4 Periopertive lumin inding funtion of irrhoti nd non-irrhoti ptients undergoing liver resetion Prmeters groups Pre-opertion POD1 POD3 POD7 P* vlue IMAT Cirrhoti 0.52± ± ± ±0.13 <0.001 Non-irrhoti 0.55± ± ± ± P** vlue IMAT/lumin Cirrhoti 1.25± ± ± ± Non-irrhoti 1.26± ± ± ± P** vlue <0.001 H/L Cirrhoti 0.66± ± ± ± Non-irrhoti 0.75± ± ± ± P** vlue <0.001 < <0.001 Dt re expressed s mens ± stndrd devition. P*, intr-group omprison mong different time points efore nd fter surgery; P**, omprison etween different groups; POD, post-opertive dy.

6 Trnsltionl Cner Reserh, Vol 5, No 6 Deemer IMAT Cirrhoti Non-irrhoti 0.65 d Pre-opertion POD1 POD3 POD7 Figure 3 Alumin olt inding pity in ptients in the irrhoti nd non-irrhoti groups t different timepoints. A higher IMAT vlue represents greter lumin olt inding pity. The lk dshed line presents the men IMAT in 50 helthy volunteers., P<0.05 versus preopertive onentrtion in the irrhoti group;, P<0.05 versus POD 3 in the irrhoti group;, P<0.05 versus preopertive onentrtion in the non-irrhoti group; d, P<0.05 versus POD 1 in the non-irrhoti group. IMAT, ishemi modified lumin trnsformed; POD, post-opertive dy. H/L Cirrhoti Non-irrhoti Pre-opertion POD1 POD3 POD7 Figure 5 Alumin ftty id inding strength in the irrhoti nd non-irrhoti groups t different timepoints. Higher H/L indites stronger inding to ftty ids. The lk dshed line represents the men H/L rtio in helthy volunteers., P<0.05 versus POD 3 in the irrhoti group;, P<0.05 versus POD 3 in the non-irrhoti group. H/L, lumin high-ffinity/low-ffinity ftty id inding sites; POD, post-opertive dy. IMAT/Alumin Pre-opertion Cirrhoti Non-irrhoti POD1 POD3 POD7 Figure 4 Alumin olt inding funtion per unit lumin in the irrhoti nd non-irrhoti groups t different time points. The lk dshed line represents the men IMAT/lumin vlue in helthy volunteers., P<0.05 versus preopertive onentrtion in the non-irrhoti group;, P<0.05 versus POD 1 in the nonirrhoti group;, P<0.05 versus POD 3 in the non-irrhoti group. POD, post-opertive dy. irrhoti (P=0.65) nd irrhoti (P=0.28) groups, ut there were no signifint etween group differenes t ny time point (P=0.07) (Figure 3, Tle 4). IMAT/lumin Preopertive IMAT/lumin in the irrhoti nd nonirrhoti groups ws similr to tht in helthy volunteers (P=0.83). IMAT/lumin in the irrhoti group slightly flututed fter surgery (P=0.23). In the non-irrhoti group, IMAT/lumin on POD 1 ws similr to tht preopertively (P=0.89). IMAT/lumin in this group inresed susequently, peking on POD 7 (P<0.001), t whih time it ws signifintly higher thn in the irrhoti group (P<0.001). (Figure 4, Tle 4). Alumin ftty id inding strength Preopertive H/L rtio ws signifintly lower in the irrhoti group thn in the non-irrhoti group nd in helthy volunteers, ut did not differ signifintly in the ltter two groups. H/L rtios in oth the irrhoti nd nonirrhoti groups delined for 3 dys fter heptetomy, eing signifintly lower on dy 3 thn preopertively in the irrhoti (P=0.01) nd non-irrhoti (P=0.03) groups. Susequently, these rtios egn to rise, rehing preopertive onentrtions in the irrhoti (P=0.17) nd non-irrhoti (P=0.24) groups. H/L rtios were higher in the non-irrhoti thn in the irrhoti group t ll time points (P<0.001 preopertively nd on PODs 1 nd 7; P=0.01 on POD 3) (Figure 5, Tle 4). Disussion Alumin onentrtion hs een used more frequently thn

7 762 Ge et l. Redued lumin inding funtion fter heptetomy lumin inding tivity to ssess liver funtion in ptients with liver disese (8). Alumin tivity my etter reflet hnges in liver funtion, deresing when liver funtion is impired, lumin onformtion hnges, or metoli urden inreses (9). Our previous study found tht lumin inding tivity ws signifintly lower in ptients with virl heptitis thn in norml individuls, lthough lumin onentrtions in the two groups did not differ. Furthermore, lumin onentrtions nd inding tivities in ptients with vrious degrees of irrhosis differed from eh other. (Ge PL, Yng HY, Lu JF, et l. Alumin inding funtion: The potentil erliest inditor for liver funtion dmge. Gstroent Res Prt. In Press.) Alumin metl ion inding pity ws found to derese in ptients with oth hroni heptitis nd irrhosis (10). As these results were less ffeted y lumin infusion, lumin inding pity ws regrded s more ojetive. To ssess whether lumin inding tivity orrelted with lumin onentrtion in ptients undergoing liver surgery nd whether these prmeters differed in ptients with nd without irrhosis, we ompred irrhoti ptients with HCC nd non-irrhoti ptients with hepti vernous hemngiom. To our knowledge, this study is the first to ompre lumin inding tivity in ptients with nd without irrhosis. IMA, originlly n inditor of myordil ishemi, n e mesured y testing the inding pity of the N-terminl metl ion inding sites of lumin to olt ions (6). Studies hve found tht IMA is higher in ptients with type 2 dietes mellitus, stroke, mesenteri ishemi, nd Alzheimer s disese thn in helthy individuls (11-14). IMA ws ltered erlier thn other inditors of oxidtive stress (15), perhps euse the impt of oxygen free rdils on lumin struture n e deteted erlier thn their impt on other prmeters (16). IMA is regrded s n inditor of liver dmge (7,9). Our study found tht lumin metl ion inding pity ould e used s prmeter to ssess the reovery stte of ptients following heptetomy. Our results showed tht preopertive metl ion inding pity nd lumin onentrtion were oth lower in ptients with irrhosis thn in helthy volunteers (P=0.02). Although preopertive lumin onentrtion ws lso lower in ptients without irrhosis thn in helthy volunteers, their lumin inding tivity ws similr (P=0.79). These findings indite tht irrhosis not only redues lumin onentrtion, ut lowers lumin inding pity. This tivity ws lso slightly lower in non-irrhoti ptients with huge hepti vernous hemngioms (tumor size 10.88±5.64 m). In non-irrhoti ptients, inding tivity ws lowest on POD 1 (P=0.01), rising to preopertive onentrtions on POD 3 (P=0.19), lthough no lumin ws infused. In irrhoti ptients, however, lumin inding pity ws lower on POD 1 (P=0.01). Despite infusion of exogenous lumin, inding tivity in this group remined low until POD 3. By POD 7, lumin inding tivity returned to preopertive onentrtions in oth the nonirrhoti (P=0.65) nd irrhoti (P=0.28) groups, wheres the lumin onentrtion in oth groups remined signifintly lower thn preopertively (oth P<0.001). Although surgery gretly ffeted lumin onentrtion nd inding funtion, these effets differed from eh other, s well s differing in irrhoti nd non-irrhoti ptients. Speifilly, surgil trum hd more profound nd prolonged impt on lumin inding funtion in ptients with liver irrhosis. The mehnism underlying the return of lumin inding funtion, ut not lumin onentrtion, to preopertive onentrtions y POD 7 remins unler, ut my e due to lumin ompenstion, whih helps the liver resist surgil stress. We therefore lulted the rtio of lumin inding to metl ion to unit lumin onentrtion (IMAT/lumin). Although preopertive lumin onentrtion nd inding funtion were oth lower in ptients with irrhosis thn in helthy volunteers, IMAT/lumin did not differ (P=0.83), suggesting tht lumin inding funtion in irrhoti ptients egn ompensting for liver injury efore heptetomy. Compenstory ility, however, did not inrese fter liver resetion (P=0.06), suggesting tht the ompenstory ility of inding funtion per unit of lumin is limited in irrhoti ptients. Furthermore, the metl ion inding pity of ommerilly infused lumin (200 g/l) ws 1.34 times tht of ntive serum lumin of helthy volunteers with the sme volume, nd 4.29 times for lumin onentrtion. Thus, the inding pity of ommeril lumin ws 31.24% tht of the sme onentrtion of ntive lumin, in greement with previous findings (17). Thus, lumin infusion ontriuted more to inresing onentrtion thn inding funtion. In ontrst, preopertive IMAT/lumin ws similr in non-irrhoti ptients with hepti vernous hemngiom nd in helthy volunteers (P=0.83), inditing tht these lesions hd no disernile effet on lumin inding funtion, nd therefore did not indue ompenstory inrese. Nevertheless, heptetomy ould dmge lumin inding funtion of ptients with non-irrhosis.

8 Trnsltionl Cner Reserh, Vol 5, No 6 Deemer Per unit lumin inding funtion in these ptients grdully reovered fter surgery, peking on POD 7 (P<0.001). These findings indite the ompenstory ility of lumin inding funtion ws etter in nonirrhoti thn in irrhoti ptients, ounting for the differenes in reovery etween lumin onentrtion nd lumin inding funtion. Normlly funtioning inding sites re the struturl sis for the trnsport nd metoli roles of lumin. However, funtioning of these inding sites my e ffeted y mny ftors, inluding lumin struture, toxins, nd drugs in the lood. The three-dimensionl struture of lumin my e dmged in ptients with irrhosis, heptitis, nd liver ishemi. The inding to lignds hnged, resulting in hnges in the rtio of high- to lowffinity inding sites to ftty id (18). To explore the reson for these differenes, we ssessed lumin strutures in the three groups of sujets. H/L reflets the strength of lumin inding to ftty ids. This rtio ws similr in non-irrhoti ptients preopertively nd in helthy volunteers (P=0.96). In ontrst, the preopertive inding funtion of irrhoti ptients ws signifintly lower, whih indited tht insted of the size of tumor, irrhosis ws to lme. Following surgery, oth irrhoti nd non-irrhoti ptients showed redutions in inding pity, eing miniml in oth groups on POD 3 nd slowly returning to preopertive onentrtions on POD 7. Liver surgery my hve dmged the three-dimensionl struture of lumin, with these onformtionl hnges reduing lumin ftty id inding pity. The postopertive reovery of dmged lumin struture nd newly generted lumin grdully enhned ftty id inding pity to preopertive level. Although postopertive infusion of ommeril lumin into irrhoti ptients inresed their serum lumin onentrtions, mking it higher thn in non-irrhoti ptients, the ftty id inding pity of lumin remined lower in irrhoti thn in non-irrhoti ptients t ll time points. Alumin inding funtion reflets syntheti pity of liver. On the other side, linilly relevnt postopertive prognosis is minly ffeted y heterogenous periopertive tretment nd overll liver funtion, so orreltion nlysis etween them isn t done. One limittion of the study is the smll smple size. The heterogeneity of dt nd omplex effet of liver surgery to lumin onentrtion nd inding funtion limit us to get solid onlusion. Conlusions To our knowledge, this study is the first to show tht lumin inding funtion dereses following liver resetion in ptients with nd without irrhosis, espeilly the former. Binding pity is etter inditor of liver dmge thn lumin onentrtion, with the results less ffeted y lumin infusion. Alumin inding pity my e n importnt inditor of liver funtion. Aknowledgements The uthors thnk Y-Nn Wng for the vlule dvie on test tehnique, Zi-Xing Wng for the help on sttistil nlysis, nd Ednz Group Chin for the English lnguge revision. Funding: This work ws supported y Ntionl Nturl Siene Foundtion of Chin ( ) nd Ntionl Key Tehnology Reserh nd Development Progrm of Chin (2012BA I06B01). Footnote Conflits of Interest: The uthors hve no onflits of interest to delre. Ethil Sttement: The study ws performed ording to the priniples of the Delrtion of Helsinki nd the study protool ws pproved y the Ethis Committee of Peking Union Medil College Hospitl nd written informed onsent ws otined from ll ptients. Referenes 1. Ge PL, Du SD, Mo YL. Advnes in preopertive ssessment of liver funtion. Heptoiliry Pnret Dis Int 2014;13: Cheung TT, Lo CM. Lprosopi liver resetion for heptoellulr rinom in ptients with irrhosis. Heptoiliry Surg Nutr 2015;4: Gri-Mrtinez R, Creni P, Bernrdi M, et l. Alumin: pthophysiologi sis of its role in the tretment of irrhosis nd its omplitions. Heptology 2013;58: Ishizw T, Siur A, Kokudo N. Clinil pplition of indoynine green-fluoresene imging during heptetomy. Heptoiliry Surg Nutr 2016;5: Kzmierzk SC, Gurhevsky A, Mtthes G, et l.

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