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Tm (generation narrow band imaging compared)Tj 9 0 0 9 106.3693 100.701 Tm 10.85838 -1.222 Td ( )Tj 0.286 Tw -18.01038 -1.222 Td [(to white light imaging on detecting early)-27.2 ( )]TJ 0.063 Tw T* [(gastric )0.5 (cancer )0.6 (in )0.5 (high-)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 106.3693 100.701 Tm 1.83558 -3.666 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 122.8843 67.707 Tm (risk )Tj 9 0 0 9 106.3693 100.701 Tm 3.60854 -3.666 Td [(patients. )0.6 (The )0.5 (trial)-26.9 ( )]TJ 0.19099 Tw -10.76054 -1.222 Td [(was expertly designed with a large patient)-27 ( )]TJ 0.517 Tw T* [(population and, although superiority of)-26.9 ( )]TJ 0.114 Tw 19.399 77.018 Td [(narrow )0.6 (band )0.6 (imaging )0.6 (could )0.6 (not )0.6 (be )0.6 (proven,)-26.8 ( )]TJ 0.679 Tw T* [(has )0.7 (important )0.7 (implications )0.7 (for )0.8 (further)-27.1 ( )]TJ -0.01801 Tw T* [(research on this topic. However)54.5 (, a significant)-27.1 ( )]TJ 0.183 Tw T* [(issue concerning the analyses attracted our)-27.2 ( )]TJ -0.019 Tw T* (interest and we would like to comment on it.)Tj 0.215 Tw 1 -1.222 Td [(The primary outcome, the difference in)-27.1 ( )]TJ 0.026 Tw -1 -1.222 Td [(proportion of patients )0.5 (in whom early gastric)-26.9 ( )]TJ 0.09 Tw T* (cancer was diagnosed, failed to reach statis)Tj 0 Tc 0 Tw (-)Tj -0.02699 Tc 0.08501 Tw T* [(tical significance \(p=0.412\). This difference)-26.8 ( )]TJ 0.291 Tw T* [(in proportions was tested for significance)-26.9 ( )]TJ 0.34399 Tw T* [(using F)17.3 (isher)-36.8 (\222s exact test. This might not)-27 ( )]TJ 0.00301 Tw T* [(have been the proper method for analysis, as)-27.1 ( )]TJ 0.054 Tw T* [(patients )0.7 (in )0.7 (the )0.7 (study )0.7 (were )0.7 (randomised )0.7 (using)-27.2 ( )]TJ 0.354 Tw T* [(minimisation )0.7 (with )0.7 (a )0.7 (random )0.7 (component,)-26.8 ( )]TJ -0.013 Tw T* [(stratified by institution, age and indication of)-27 ( )]TJ 0.02699 Tw T* [(endoscopy)114.6 (.)]TJ -0.022 Tc 0.183 Tw 1 -1.222 Td [(I)0.6 (mb)0.7 (a)0.7 (l)0.7 (a)0.7 (nc)0.7 (e)0.6 ( of)0.5 ( ri)0.7 (sk)0.7 ( f)0.6 (a)0.7 (c)0.6 (tors b)0.7 (e)0.6 (tw)0.6 (e)0.6 (e)0.6 (n tre)0.7 (a)0.7 (t)]TJ 0 Tc 0 Tw (-)Tj -0.022 Tc 0.036 Tw -1 -1.222 Td [(me)0.6 (nt a)0.7 (nd c)0.6 (ontrol)0.6 ( a)0.7 (rms c)0.7 (a)0.7 (n oc)0.7 (c)0.6 (u)0.6 (r b)0.7 (y c)0.7 (ha)0.7 (nc)0.6 (e)-21.9 ( )]TJ 0.83 Tw T* [(u)0.6 (nde)0.6 (r )0.7 (norma)0.8 (l)0.6 ( )0.6 (ra)0.7 (ndomi)0.6 (sa)0.7 (ti)0.7 (on,)0.7 ( )0.6 (possi)0.7 (b)0.6 (l)0.7 (y)-22.2 ( )]TJ 0.09801 Tw T* [(l)0.7 (e)0.6 (a)0.7 (di)0.7 (ng to c)0.6 (onf)0.5 (ou)0.6 (nde)0.7 (d tre)0.6 (a)0.7 (tme)0.7 (nt e)0.7 (sti)0.7 (ma)0.8 (te)0.5 (s.)-21.8 ( )]TJ 0.312 Tw T* [(S)0.5 (tra)0.8 (ti)0.7 (f)0.5 (i)0.7 (c)0.6 (a)0.8 (ti)0.6 (on a)0.8 (nd mi)0.7 (ni)0.7 (mi)0.7 (sa)0.7 (ti)0.7 (on a)0.7 (re)0.6 ( u)0.6 (se)0.6 (f)0.5 (u)0.6 (l)-21.9 ( )]TJ 0.22701 Tw T* [(me)0.6 (thods )0.6 (to )0.5 (e)0.6 (nsu)0.6 (re)0.6 ( )0.5 (b)0.7 (a)0.7 (l)0.7 (a)0.7 (nc)0.7 (e)0.6 ( )0.5 (of)0.5 ( )0.5 (ri)0.6 (sk)0.7 ( )0.6 (f)0.5 (a)0.7 (c)0.6 (tors)-22.1 ( )]TJ 0.117 Tw T* [(b)0.7 (e)0.5 (t)0.5 (w)0.6 (e)0.6 (e)0.6 (n tre)0.6 (a)0.7 (tme)0.6 (nt a)0.7 (rms.)]TJ 0 0 1 rg /GS1 gs 0.022 Tw 5.967 0 0 5.967 309.4011 500.9131 Tm (2\2264)Tj 0 0 0 1 k /GS0 gs 0.117 Tw 9 0 0 9 318.619 496.8632 Tm [( T)0.5 (he)0.6 (se)0.6 ( me)0.6 (thods)-22.1 ( )]TJ -0.028 Tw -11.336 -1.222 Td [(c)0.6 (a)0.8 (n b)0.6 (e)0.6 ( b)0.7 (e)0.6 (ne)0.6 (f)0.5 (i)0.6 (c)0.7 (i)0.6 (a)0.8 (l)0.6 ( i)0.6 (n sma)0.8 (l)0.6 (l)0.7 ( a)0.8 (nd l)0.7 (a)0.7 (rge)0.6 ( tri)0.6 (a)0.8 (l)0.6 (s,)0.7 ( b)0.6 (u)0.6 (t)-22.1 ( )]TJ -0.073 Tw T* [(f)0.5 (or tri)0.7 (a)0.7 (l)0.7 (s l)0.7 (a)0.7 (rge)0.6 (r tha)0.7 (n 1000 pa)0.7 (ti)0.7 (e)0.6 (nts l)0.6 (i)0.7 (ttl)0.7 (e)0.6 ( e)0.6 (f)0.5 (f)0.5 (e)0.6 (c)0.7 (t)-22.2 ( )]TJ 0.05901 Tw T* [(of)0.6 ( mi)0.7 (ni)0.7 (mi)0.7 (sa)0.8 (ti)0.6 (on on i)0.7 (mb)0.7 (a)0.7 (l)0.7 (a)0.7 (nc)0.7 (e)0.6 ( w)0.6 (a)0.7 (s f)0.5 (ou)0.6 (nd a)0.7 (s)-22.1 ( )]TJ 0 Tw T* [(c)0.6 (ompa)0.7 (re)0.6 (d )0.6 (w)0.7 (i)0.6 (th )0.6 (si)0.7 (mpl)0.7 (e)0.6 ( )0.7 (ra)0.7 (ndomi)0.7 (sa)0.8 (ti)0.6 (on.)]TJ 0 0 1 rg /GS1 gs 0 Tc 5.967 0 0 5.967 355.7104 456.9131 Tm (4)Tj 0 0 0 1 k /GS0 gs 0.42599 Tw 9 0 0 9 225.5918 441.8632 Tm [(One of the assumptions )-0.7 (of F)17.4 (isher)-36.8 (\222s )]TJ 0.05901 Tw -1 -1.222 Td [(exact )1 (test is )0.5 (that samples are )0.6 (random and )]TJ 0.045 Tw T* (independent, which is not the case in this )Tj 0.007 Tw T* [(study)114.3 (. )0.8 (The )0.7 (problem )0.5 (that )0.5 (occurs )0.7 (with )0.7 (strat)]TJ 0 Tw (-)Tj 0.106 Tw T* (ified or minimised randomisation is clus)Tj 0 Tw (-)Tj 0.295 Tw T* (tering between treatment groups which )Tj 0.369 Tw T* (introduces positive correlation between )Tj 0.533 Tw T* [(observations. The )0.8 (correlation )0.6 (between )]TJ 0.444 Tw T* (observations violates the independence )Tj -0.097 Tw T* [(assumption )-0.7 (and will lead to standard )-0.6 (errors )]TJ 0.02 Tw T* [(\(SE\) that are biased upwards because )0.8 (tests )]TJ 0.15601 Tw T* [(for independent )-0.6 (samples do not account )]TJ 0.10201 Tw T* [(for this correlation and will )1 (overestimate )]TJ 0 Tw T* (the variance of the treatment effect.)Tj -0.022 Tc 0.17101 Tw 1 -1.222 Td [(A)0.5 (s a)0.7 ( S)0.5 (E)0.7 ( tha)0.7 (t i)0.7 (s b)0.6 (i)0.7 (a)0.7 (se)0.6 (d u)0.6 (pw)0.6 (a)0.7 (rds l)0.7 (e)0.6 (a)0.8 (ds to)-22.2 ( )]TJ 0.16701 Tw -1 -1.222 Td [(i)0.7 (nf)0.5 (l)0.7 (a)0.7 (te)0.6 (d p va)0.7 (l)0.6 (u)0.6 (e)0.6 (s,)0.7 ( not a)0.8 (c)0.6 (c)0.7 (ou)0.6 (nti)0.7 (ng f)0.6 (or the)0.6 (se)-21.9 ( )]TJ 0.08299 Tw T* [(b)0.6 (a)0.8 (l)0.6 (a)0.8 (nc)0.6 (i)0.7 (ng va)0.7 (ri)0.6 (a)0.7 (b)0.7 (l)0.6 (e)0.7 (s i)0.7 (n the)0.6 ( a)0.7 (na)0.8 (l)0.6 (ysi)0.7 (s ma)0.7 (y l)0.6 (e)0.6 (a)0.8 (d)-22.2 ( )]TJ 0.043 Tw T* [(to )0.7 (w)0.6 (rongf)0.5 (u)0.6 (l)0.7 (l)0.6 (y )0.7 (not )0.6 (re)0.6 (j)0.5 (e)0.6 (c)0.6 (ti)0.7 (ng )0.7 (the)0.6 ( )0.7 (nu)0.6 (l)0.7 (l)0.6 ( )0.7 (hypoth)]TJ 0 Tc 0 Tw (-)Tj -0.022 Tc 0.23199 Tw T* [(e)0.6 (si)0.7 (s.)0.7 ( )0.5 (T)0.5 (hi)0.7 (s )0.5 (e)0.6 (f)0.5 (f)0.5 (e)0.6 (c)0.7 (t )0.5 (c)0.6 (a)0.7 (n )0.5 (b)0.6 (e)0.6 ( )0.5 (c)0.7 (onsi)0.7 (de)0.6 (ra)0.7 (b)0.7 (l)0.6 (e)0.6 (,)0.7 ( )0.5 (a)0.7 (s )0.5 (a)-21.8 ( )]TJ 0.032 Tw T* [(re)0.6 (a)0.8 (na)0.7 (l)0.7 (ysi)0.6 (s of)0.5 ( a)0.7 ( l)0.7 (a)0.7 (rge)0.6 ( tri)0.7 (a)0.7 (l)0.7 ( show)0.6 (e)0.6 (d tw)0.6 (of)0.5 (ol)0.7 (d to)-22.2 ( )]TJ 0.075 Tw T* [(f)0.5 (ou)0.6 (rf)0.5 (ol)0.6 (d i)0.7 (nc)0.6 (re)0.6 (a)0.8 (se)0.6 (s i)0.7 (n p va)0.8 (l)0.6 (u)0.6 (e)0.6 (s a)0.7 (nd a)0.7 ( si)0.6 (mu)0.6 (l)0.6 (a)]TJ 0 Tc 0 Tw 17.677 0 Td (-)Tj -0.022 Tc 0.17 Tw -17.677 -1.222 Td [(ti)0.7 (on stu)0.6 (dy show)0.6 (e)0.6 (d re)0.6 (du)0.6 (c)0.6 (ti)0.7 (ons i)0.6 (n pow)0.6 (e)0.6 (r of)-22 ( )]TJ 0.095 Tw T* [(u)0.6 (p to 30)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 225.5918 441.8632 Tm 2.66838 -26.884 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 250.5128 199.9072 Tm (pe)Tj 9 0 0 9 225.5918 441.8632 Tm 3.74339 -26.884 Td [(rc)0.6 (e)0.6 (nta)0.7 (ge)0.6 ( poi)0.7 (nts.)]TJ 0 0 1 rg /GS1 gs 5.967 0 0 5.967 318.1669 203.9132 Tm (5 6)Tj 0 0 0 1 k /GS0 gs 9 0 0 9 326.6302 199.8632 Tm [( T)0.5 (hu)0.6 (s,)0.6 ( stu)0.7 (di)0.7 (e)0.6 (s)-22.1 ( )]TJ -0.03999 Tw -12.226 -1.222 Td [(u)0.6 (si)0.7 (ng e)0.6 (i)0.7 (the)0.6 (r of)0.5 ( the)0.6 ( b)0.6 (a)0.8 (l)0.6 (a)0.7 (nc)0.6 (i)0.7 (ng me)0.6 (thods shou)0.6 (l)0.7 (d)-22.2 ( )]TJ 0.144 Tw T* [(a)0.7 (dju)0.7 (st the)0.6 (i)0.7 (r a)0.7 (na)0.7 (l)0.6 (ysi)0.7 (s f)0.5 (or the)0.6 ( b)0.6 (a)0.7 (l)0.7 (a)0.7 (nc)0.6 (i)0.7 (ng va)0.7 (ri)]TJ 0 Tc 0 Tw 17.677 0 Td (-)Tj -0.022 Tc -17.677 -1.222 Td [(a)0.7 (b)0.7 (l)0.6 (e)0.6 (s )0.7 (u)0.6 (se)0.6 (d )0.7 (i)0.6 (n )0.7 (the)0.6 ( )0.7 (ra)0.7 (ndomi)0.7 (sa)0.7 (ti)0.7 (on )0.7 (proc)0.6 (e)0.6 (du)0.6 (re)0.6 (.)]TJ 0 0 1 rg /GS1 gs 0 Tc 5.967 0 0 5.967 374.0331 170.9132 Tm (5)Tj 0 0 0 1 k /GS0 gs 0.015 Tw 9 0 0 9 225.5918 155.8632 Tm [(Considering the report of Y)123.7 (oshida )]TJ /TT1 1 Tf (et al)Tj /TT0 1 Tf 0 Tw (, )Tj 0.061 Tw -1 -1.222 Td [(this could )0.6 (mean )0.6 (that )0.5 (they may have )0.5 (erro)]TJ 0 Tw (-)Tj 0.002 Tw T* [(neously concluded that )0.5 (second-)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 225.5918 155.8632 Tm 12.4585 -2.444 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 337.7138 133.8672 Tm (generation )Tj 0.285 Tw -13.458 -1.222 Td (narrow band imaging was not superior )Tj 0.12 Tw T* (to white light imaging. W)Tj 9 0 0 9 225.5918 155.8632 Tm 10.34628 -4.888 Td (e cannot deter)Tj 0 Tw 6.33072 0 Td (-)Tj 0.08701 Tw -17.677 -1.222 Td [(mine the precise effect adjustment )-0.6 (would )]TJ 0.23801 Tw T* [(have )0.7 (had )0.6 (in )0.7 (the )0.7 (study by )0.7 (Y)123.6 (oshida )]TJ /TT1 1 Tf [(et )0.5 (al)]TJ /TT0 1 Tf 0 Tw ( )Tj 0.422 Tw T* [(as )0.7 (a )0.6 (reanalysis )0.8 (requires )0.7 (the individual )]TJ 0.04601 Tw T* [(patient data. )0.6 (While )0.5 (adjustment is possible )]TJ 0.327 Tw T* [(using F)17.4 (isher)-36.8 (\222s exact test,)]TJ 0 0 1 rg /GS1 gs 5.967 0 0 5.967 318.9829 60.9132 Tm (7 8)Tj 0 0 0 1 k /GS0 gs 9 0 0 9 329.2315 56.8632 Tm ( we suggest )Tj 0.146 Tw -12.516 -1.222 Td [(performing )-0.9 (logistic regression )-0.7 (analysis as )]TJ 0.117 Tw 19.399 77 Td [(this allow)0.5 (s adjustment )-0.6 (for multiple mini)]TJ 0 Tw (-)Tj 0.101 Tw 0 -1.226 TD [(misation variables, )0.8 (does not rely on inef)]TJ 0 Tw 17.677 0 Td (-)Tj 0.125 Tw -17.677 -1.226 Td (ficient stratification,)Tj 0 0 1 rg /GS1 gs 0 Tw 5.967 0 0 5.967 470.0983 720.8531 Tm (8)Tj 0 0 0 1 k /GS0 gs 0.125 Tw 9 0 0 9 473.4169 716.8032 Tm ( and can be used to )Tj 0.064 Tw -9.137 -1.226 Td [(determine the )0.5 (confidence )0.6 (interval )0.8 (around )]TJ 0 Tw T* (the treatment effect estimate.)Tj 1.10699 Tw 1 -1.226 Td [(Unadjusted )-0.6 (analyses in balanced )]TJ 0.37 Tw -1 -1.226 Td [(randomised trials seem to be a )0.5 (recur)]TJ 0 Tw 17.677 0 Td (-)Tj 0.14999 Tw -17.677 -1.226 Td [(ring phenomeno)-0.9 (n. )0.5 (In 2012, a )0.7 (systematic )]TJ 0.27901 Tw T* [(review )0.6 (showed that only 26% of trials )]TJ 0.132 Tw T* [(published )0.7 (in )0.6 (leading journals )0.5 (that )0.5 (used )0.5 (a )]TJ 0.23599 Tw T* [(balancing )0.7 (method correctly adjusted for )]TJ 0.198 Tw T* [(all )0.8 (balan)0.6 (cing factors.)]TJ 0 0 1 rg /GS1 gs 0 Tw 5.967 0 0 5.967 474.0847 621.5831 Tm (6)Tj 0 0 0 1 k /GS0 gs 0.198 Tw 9 0 0 9 477.4033 617.5331 Tm ( But even in more )Tj -0.069 Tw -9.58 -1.226 Td [(recent trials )0.5 (analyses are often not adjusted )]TJ 0.30499 Tw T* [(for bala)0.7 (ncing factors, as shown by the )]TJ 0.138 Tw T* [(study of Y)123.6 (oshida )]TJ /TT1 1 Tf (et al)Tj /TT0 1 Tf (, but also by other )Tj 0.286 Tw T* [(trials )0.6 (in the lea)0.5 (ding journals of gastro)]TJ 0 Tw (-)Tj 0.39101 Tw T* [(enterology )-0.6 (and hepatology)114.2 (.)]TJ 0 0 1 rg /GS1 gs 5.967 0 0 5.967 502.8217 566.4332 Tm (1 9 10)Tj 0 0 0 1 k /GS0 gs 9 0 0 9 524.0787 562.3832 Tm ( When )Tj 0.37601 Tw -14.766 -1.226 Td (used correctly minimisation and strati)Tj 0 Tw (-)Tj 0.149 Tw T* [(fication )0.6 (are powerful tools for balancing )]TJ 0.604 Tw T* [(randomised trials )0.5 (and improv)-0.6 (ing the )]TJ 0.452 Tw T* [(validity of studies. )0.6 (However)54.3 (, )0.5 (this has )]TJ 0.04401 Tw T* [(important )-0.8 (consequences for )-0.6 (data analysis. )]TJ 0.183 Tw T* (As such, we urge trialists to include the )Tj 0.17 Tw T* [(balancing )1.1 (variables )1.1 (as )0.6 (adjustment factors )]TJ 0 Tw T* (in their statistical analyses.)Tj /T1_2 1 Tf 8 0 0 8 391.1837 458.1432 Tm [(Reinier Cornelis )55.1 (Anthonius van Linschoten )]TJ ET BT /Span <>BDC /T1_2 1 Tf 8 0 0 8 533.6549 458.1432 Tm ( )Tj EMC ET /PlacedGraphic /MC0 BDC q 533.654 458.143 5.6 5.598 re W n 1 0 0 1 537.3625 461.6358 cm 0.293 0.015 1 0 k /GS1 gs 0 0 m 0.04 -0.019 0.08 -0.041 0.115 -0.065 c 0.151 -0.089 0.184 -0.116 0.214 -0.144 c 0.299 -0.222 0.361 -0.313 0.404 -0.415 c 0.445 -0.516 0.466 -0.629 0.466 -0.753 c 0.466 -0.88 0.445 -0.997 0.405 -1.102 c 0.364 -1.207 0.302 -1.301 0.22 -1.384 c 0.195 -1.41 0.168 -1.432 0.141 -1.454 c 0.112 -1.475 0.083 -1.494 0.051 -1.512 c 0.021 -1.528 -0.013 -1.544 -0.05 -1.559 c -0.09 -1.574 -0.132 -1.587 -0.178 -1.598 c -0.223 -1.608 -0.279 -1.617 -0.342 -1.623 c -0.409 -1.63 -0.481 -1.633 -0.564 -1.633 c -0.989 -1.633 l -0.989 0.093 l -0.574 0.093 l -0.496 0.093 -0.427 0.091 -0.368 0.088 c -0.31 0.084 -0.263 0.08 -0.226 0.074 c -0.19 0.069 -0.154 0.061 -0.117 0.048 c 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-6.295 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 176.1139 404.8232 Tm (kr and)Tj 8 0 0 8 44.5459 455.1832 Tm 18.80997 -6.295 Td ( )Tj -19.12797 -1.134 Td (Dr\037Eun-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 2.49196 -7.429 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 64.4819 395.7512 Tm (Hee Nah,)Tj 8 0 0 8 44.5459 455.1832 Tm 5.92296 -7.429 Td [( Department of Labor)18 (atory Medicine)37 (,)47 ( )]TJ -6.24096 -1.134 Td [(Health Promotion Research Institute)37 (,)37 ( Gangseo-)]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 17.11675 -8.563 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 181.4819 386.6792 Tm (gu,)Tj 8 0 0 8 44.5459 455.1832 Tm 18.26598 -8.563 Td ( )Tj -18.58398 -1.134 Td [(Seoul 07572,)37 ( Republic of K)37 (orea;)37 ( )]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 11.88182 -9.697 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 139.6019 377.6072 Tm (cellonah@)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 15.80995 -9.697 Td ( )Tj EMC ET BT 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-4.88799 -1.134 Td [(of the manuscript:)37 ( HP)128 (.)37 ( Supervision:)37 ( DWJ)37 (,)36.9 ( E-)]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 15.61186 -15.867 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 169.4419 328.2472 Tm (HN)Tj 8 0 0 8 44.5459 455.1832 Tm 16.74399 -15.867 Td [(.)47 ( )]TJ -17.06199 -1.134 Td [(All authors have approved the \036nal version of the)10 ( )]TJ -0.00999 Tw T* (manuscript.)Tj /T1_2 1 Tf 0 Tc 0 Tw 0 -1.634 TD (Funding)Tj ET BT /Span <>BDC /T1_2 1 Tf 8 0 0 8 44.5459 455.1832 Tm 3.036 -19.769 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 72.8339 297.0312 Tm (T)Tj 8 0 0 8 44.5459 455.1832 Tm 3.925 -19.769 Td (he authors have not declared a speci\036c )Tj -4.243 -1.134 Td [(gr)18 (ant for this research from any funding agency in the )]TJ 0 -1.134 TD [(public,)37 ( commercial or not-)]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 9.147 -22.037 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 117.7219 278.8872 Tm (for)Tj 8 0 0 8 44.5459 455.1832 Tm 10.103 -22.037 Td (-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 10.399 -22.037 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 127.7379 278.8872 Tm (pro\036t sectors)Tj 8 0 0 8 44.5459 455.1832 Tm 15.0679 -22.037 Td (.)Tj /T1_2 1 Tf -15.3859 -1.634 Td [(Competing inter)10.1 (ests)]TJ ET BT /Span <>BDC /T1_2 1 Tf 8 0 0 8 44.5459 455.1832 Tm 8.1569 -23.671 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 113.8019 265.8152 Tm (None declared.)Tj /T1_2 1 Tf -8.975 -1.634 Td (P)Tj 8 0 0 8 44.5459 455.1832 Tm 0.146 -25.305 Td (atient consent for publication)Tj ET BT /Span <>BDC /T1_2 1 Tf 8 0 0 8 44.5459 455.1832 Tm 12.598 -25.305 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 149.3299 252.7432 Tm (Not required.)Tj /T1_2 1 Tf -13.416 -1.634 Td (Ethics appr)Tj 8 0 0 8 44.5459 455.1832 Tm 4.3219 -26.939 Td (oval)Tj ET BT /Span <>BDC /T1_2 1 Tf 8 0 0 8 44.5459 455.1832 Tm 6.0999 -26.939 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 97.3459 239.6712 Tm (T)Tj 8 0 0 8 44.5459 455.1832 Tm 6.989 -26.939 Td [(his study w)18 (as approved by the )]TJ -7.307 -1.134 Td [(Hany)18 (ang University Hospital Institutional Review Board )]TJ -0.24001 Tw T* [(\(IRB )-240 (no)37 (.)37 ( )-240 (HY)111 (-)]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 3.97699 -29.207 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 3.97698 -29.207 Td (2021-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 6.19298 -29.207 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 6.19298 -29.207 Td (04-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 7.44898 -29.207 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 7.44897 -29.207 Td (001\).)Tj /T1_2 1 Tf 0 Tw -7.76697 -1.634 Td [(Pr)10 (ovenance and peer r)10.1 (eview)]TJ ET BT /Span <>BDC /T1_2 1 Tf 8 0 0 8 44.5459 455.1832 Tm 11.5739 -30.841 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 141.1379 208.4552 Tm (Not commissioned;)Tj 8 0 0 8 44.5459 455.1832 Tm 18.9859 -30.841 Td ( )Tj -19.3039 -1.134 Td (externally peer reviewed.)Tj /T1_2 1 Tf 0 -1.634 TD (Supplemental material)Tj ET BT /Span <>BDC /T1_2 1 Tf 8 0 0 8 44.5459 455.1832 Tm 9.206 -33.609 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 122.1939 186.3112 Tm (T)Tj 8 0 0 8 44.5459 455.1832 Tm 10.095 -33.609 Td (his content has been )Tj -10.413 -1.134 Td [(supplied by the author\(s\).)37.1 ( It has not been vetted by )]TJ 0 -1.134 TD (BMJ Publishing Group Limited \(BMJ\) and may not have )Tj T* [(been peer)45 (-)]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 3.544 -37.011 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 72.8979 159.0952 Tm (reviewed.)Tj 8 0 0 8 44.5459 455.1832 Tm 7.008 -37.011 Td [( )55 (Any opinions or recommendations )]TJ -7.326 -1.134 Td (discussed are solely those of the author\(s\) and are )Tj T* [(not endorsed by BMJ)37.1 (.)37 ( BMJ disclaims all liability and )]TJ T* (responsibility arising from any reliance placed on the )Tj T* [(content.)37 ( )55 (Where the content includes any tr)18.2 (anslated )]TJ T* [(material)70.1 (,)37 ( BMJ does not w)18.1 (arr)17.9 (ant the accur)18.1 (acy and )]TJ T* [(reliability of the tr)18.1 (anslations \(including but not limited )]TJ T* [(to local regulations)37.1 (,)37 ( clinical guidelines)37.1 (,)37 ( terminology,)37.1 ( )]TJ T* [(drug names and drug dosages\),)37.2 ( and is not responsible )]TJ T* [(for any error and/or omissions arising from tr)18.3 (anslation )]TJ T* [(and adaptation or otherwise)37.2 (.)]TJ 0 -1.634 TD [(\251 )55 (Author\(s\) \(or their employer\(s\)\) 2022.)37.3 ( No commercial )]TJ 0 -1.134 TD (re-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 0.682 -51.119 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 50.0019 46.2312 Tm (use)Tj 8 0 0 8 44.5459 455.1832 Tm 1.886 -51.119 Td [(.)37 ( See rights and permissions)37.2 (.)37 ( Published by BMJ)37 (.)]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 224.5139 739.6152 Tm ( )Tj EMC ET BT /C2_0 1 Tf 8 0 0 8 216.5939 739.6152 Tm <0179>Tj /T1_0 1 Tf 1.5 0 Td (Additional supplemental material is published )Tj -1.5 -1.141 Td (online only.)Tj 8 0 0 8 44.5459 455.1832 Tm 25.6739 34.413 Td [( )55 (T)37 (o view,)37 ( please visit the journal online )]TJ -0.24001 Tw -4.1679 -1.141 Td (\(http://)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 24.005 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 24.00499 33.272 Td (dx.)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 25.09699 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 25.09699 33.272 Td [(doi)70 (.)]TJ ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 26.39799 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 26.39798 33.272 Td (org/)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 27.86198 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 27.86198 33.272 Td (10.)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 29.06198 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 29.06197 33.272 Td (1136/)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 31.24097 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 31.24097 33.272 Td (gutjnl-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 33.61197 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 33.61196 33.272 Td (2021-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 35.82796 33.272 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 35.82796 33.272 Td (325102\).)Tj 0 Tw -14.32196 -1.641 Td [(HP and EL)111.1 (Y contributed equally.)]TJ 0 -1.141 TD (DWJ and E-)Tj ET BT /Span <>BDC /T1_0 1 Tf 8 0 0 8 44.5459 455.1832 Tm 25.726 30.49 Td ( )Tj EMC ET BT /T1_0 1 Tf 8 0 0 8 250.3539 699.1032 Tm (HN contributed equally.)Tj -4.22 -1.641 Td (HP and EL)Tj 8 0 0 8 44.5459 455.1832 Tm 25.0969 28.849 Td [(Y are joint \036rst authors)37.1 (.)]TJ ET /PlacedGraphic /MC1 BDC q 252.915 677.876 m 252.463 677.876 252.094 677.509 252.094 677.056 c 252.094 677.056 l 252.094 661.465 l 252.094 661.011 252.463 660.643 252.915 660.643 c 252.915 660.643 l 342.36 660.643 l 342.814 660.643 343.181 661.011 343.181 661.465 c 343.181 661.465 l 343.181 677.056 l 343.181 677.509 342.814 677.876 342.36 677.876 c 342.36 677.876 l h W n q 0 g /GS1 gs -0.0000007 -15.2309999 15.2309999 -0.0000007 297.6377563 675.9277954 cm BX /Sh0 sh EX Q Q q 251.72 660.269 91.836 17.982 re W n 1 0 0 1 252.9151 677.876 cm 0.44099 0.39101 0.383 0.02499 K 0.75 w /GS1 gs 0 0 m 89.445 0 l 89.898 0 90.266 -0.367 90.266 -0.82 c 90.266 -16.411 l 90.266 -16.864 89.898 -17.232 89.445 -17.232 c 0 -17.232 l -0.453 -17.232 -0.82 -16.864 -0.82 -16.411 c -0.82 -0.82 l -0.82 -0.367 -0.453 0 0 0 c h S 1 0 0 1 24.8438 -6.9263 cm 0.642 0.563 0.558 0.32401 k 0 0 m -0.039 0.155 -0.097 0.303 -0.172 0.443 c -0.243 0.578 -0.337 0.697 -0.451 0.796 c -0.572 0.898 -0.712 0.977 -0.861 1.026 c -1.033 1.084 -1.214 1.112 -1.395 1.108 c -1.662 1.115 -1.926 1.053 -2.162 0.928 c -2.373 0.814 -2.553 0.65 -2.688 0.452 c -2.826 0.244 -2.927 0.013 -2.987 -0.229 c -3.117 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m -5.58 3.718 l -5.58 8.182 l 0 8.182 l h f 1 0 0 1 -2.7901 -1.6483 cm 0.68401 0.09801 0.18401 0 k 0 0 m -2.568 0 -4.649 2.081 -4.649 4.648 c -4.649 7.216 -2.568 9.297 0 9.297 c 2.567 9.297 4.648 7.216 4.648 4.648 c 4.648 2.081 2.567 0 0 0 c 0 10.803 m -3.399 10.803 -6.154 8.047 -6.154 4.648 c -6.154 1.25 -3.399 -1.506 0 -1.506 c 3.399 -1.506 6.154 1.25 6.154 4.648 c 6.154 8.047 3.399 10.803 0 10.803 c f 1 0 0 1 3.4092 1.5018 cm 0 0.22 0.914 0 k 0 0 m -1.733 -1.889 -4.668 -2.014 -6.556 -0.28 c -7.98 1.027 -8.445 3.081 -7.721 4.874 c -9.01 5.694 l -10.406 2.595 -9.025 -1.049 -5.926 -2.444 c -3.426 -3.57 -0.482 -2.907 1.293 -0.817 c h f EMC Q BT /T1_2 1 Tf 8 0 0 8 216.5919 647.1385 Tm [(T)85 (o cite )]TJ /T1_0 1 Tf -0.05499 Tw [(P)37 (ark\037H,)37.1 ( Y)74 (oon\037EL,)37 ( )-55 (Cho\037S)37.1 (,)37 ( )]TJ /T1_1 1 Tf 0 Tw 11.618 0 Td (et\037al)Tj /T1_0 1 Tf -0.037 Tc 0.037 Tw (. )Tj /T1_1 1 Tf 0 Tc 0 Tw (Gut)Tj /T1_0 1 Tf ( )Tj -11.618 -1.141 Td (2022;)Tj /T1_2 1 Tf (71)Tj /T1_0 1 Tf (:1035\2261036.)Tj /T1_3 1 Tf 0 -1.641 TD (Received 5 May 2021)Tj /T1_0 1 Tf 0 -1.141 TD (Accepted 5 June 2021)Tj T* (Published Online First 14\037June\0372021)Tj /T1_1 1 Tf 0 -2.141 TD (Gut)Tj /T1_0 1 Tf ( 2022;)Tj /T1_2 1 Tf (71)Tj /T1_0 1 Tf [(:1035\2261036.)37 ( doi:10.1136/)]TJ 0 -1.141 TD (gutjnl-2021-325102)Tj /T1_2 1 Tf 0 -2.141 TD (ORCID iD)Tj /T1_0 1 Tf -0.05499 Tw 0 -1.141 TD [(Dae W)18 (on\037Jun )]TJ 0 0 1 rg /GS1 gs 0 Tw 5 0 Td (http://orcid.org/0000-0002-2875-6139)Tj 0 0 0 1 k /GS0 gs /T1_4 1 Tf 9.5 0 0 9.5 216.5919 530.4686 Tm (REFERENCES)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm (1)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 220.1919 521.3386 Tm ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 225.5919 521.3386 Tm (F)Tj 7.5 0 0 7.5 216.5919 521.3386 Tm [-1570 (r)18 (ancque S)37 (,)37 ( )55 (W)18 (ong )55 (VW-)]TJ ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm 9.404 0 Td ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 287.1219 521.3386 Tm (S)Tj 7.5 0 0 7.5 216.5919 521.3386 Tm 9.793 0 Td [(.)37 ( Na\035d in lean individuals:)37 ( not a )]TJ -8.593 -1.217 Td [(benign disease)37 (.)37 ( )]TJ 0 0 1 rg /GS1 gs /T1_1 1 Tf (Gut)Tj 0 0 0 1 k /GS0 gs /T1_0 1 Tf ( 2022;71:234\2266.)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 503.0836 Tm ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 216.5919 503.0836 Tm (2)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm 0.48 -2.434 Td ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 225.5919 503.0836 Tm (Alberti KGMM,)Tj 7.5 0 0 7.5 216.5919 521.3386 Tm 6.6249 -2.434 Td [( Eck)37 (el RH,)37 ( Grundy SM,)37.1 ( )]TJ /T1_1 1 Tf (et\037al)Tj /T1_0 1 Tf [(.)37 ( Harmonizing )]TJ -5.4249 -1.217 Td [(the metabolic syndrome:)37 ( a joint interim statement of )]TJ 0 -1.217 TD [(the International diabetes F)37.1 (eder)18 (ation )55 (T)74 (ask force on )]TJ T* [(epidemiology and prevention;)37 ( National heart,)37 ( lung,)37 ( )]TJ T* [(and blood Institute;)37 ( )55 (American heart association;)37 ( world )]TJ T* [(heart F)37 (eder)18 (ation;)37 ( international atherosclerosis Society;)37 ( )]TJ T* [(and international association for the study of obesity.)37 ( )]TJ 0 0 1 rg /GS1 gs /T1_1 1 Tf T* (Circulation)Tj 0 0 0 1 k /GS0 gs /T1_0 1 Tf ( 2009;120:1640\2265.)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 430.0636 Tm ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 216.5919 430.0636 Tm (3)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm 0.48 -12.17 Td ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 225.5919 430.0636 Tm (J)Tj 7.5 0 0 7.5 216.5919 521.3386 Tm 1.486 -12.17 Td [(arvis H,)37 ( Cr)18.1 (aig D)37 (,)37 ( Bark)37 (er R,)37 ( )]TJ /T1_1 1 Tf (et\037al)Tj /T1_0 1 Tf [(.)37 ( Metabolic risk factors )]TJ -0.286 -1.217 Td [(and incident adv)18 (anced liver disease in non-)]TJ ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm 16.848 -13.387 Td ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 342.9519 420.9361 Tm (alcoholic )Tj -15.648 -1.217 Td (fatty liver disease \(NAFLD\):)Tj 7.5 0 0 7.5 216.5919 521.3386 Tm 10.94 -14.604 Td ( a systematic review and )Tj -9.74 -1.217 Td (meta-)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm 3.33 -15.821 Td ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 241.5669 402.6811 Tm (analysis of population-)Tj ET BT /Span <>BDC /T1_0 1 Tf 7.5 0 0 7.5 216.5919 521.3386 Tm 11.572 -15.821 Td ( )Tj EMC ET BT /T1_0 1 Tf 7.5 0 0 7.5 303.3819 402.6811 Tm (based observ)Tj 7.5 0 0 7.5 216.5919 521.3386 Tm 16.315 -15.821 Td (ational )Tj -15.115 -1.217 Td [(studies)37 (.)37 ( )]TJ 0 0 1 rg /GS1 gs /T1_1 1 Tf (PLoS Med)Tj 0 0 0 1 k /GS0 gs /T1_0 1 Tf ( 2020;17:e1003100.)Tj /T1_5 1 Tf -0.24001 Tw 13.5 0 0 13.5 216.5919 368.0185 Tm (Acute-)Tj ET BT /Span <>BDC /T1_5 1 Tf 13.5 0 0 13.5 250.0854 368.0185 Tm ( )Tj EMC ET BT /T1_5 1 Tf 13.5 0 0 13.5 250.08533 368.0185 Tm (on-)Tj ET BT /Span <>BDC /T1_5 1 Tf 13.5 0 0 13.5 267.09533 368.0185 Tm ( )Tj EMC ET BT /T1_5 1 Tf 13.5 0 0 13.5 267.09525 368.0185 Tm [(chronic )-240 (liver )-240 (failure )]TJ 0 Tw -3.74099 -1.111 Td (\(A)Tj 13.5 0 0 13.5 216.5919 368.0185 Tm 0.834 -1.111 Td (CLF\) precipitated by severe )Tj -0.834 -1.111 Td [(alcoholic hepatitis:)37.1 ( another )]TJ 0 -1.111 TD (collateral damage of the )Tj -0.24001 Tw T* [(CO)18 (VID-)]TJ ET BT /Span <>BDC /T1_5 1 Tf 13.5 0 0 13.5 216.5919 368.0185 Tm 2.78 -4.444 Td ( )Tj EMC ET BT /T1_5 1 Tf 13.5 0 0 13.5 216.5919 368.0185 Tm 2.77999 -4.444 Td (19\035pandemic?)Tj /TT0 1 Tf 0.015 Tc 0.314 Tw 9 0 0 9 216.5919 279.8885 Tm [(W)118.6 (e have read with interest the study)14.7 ( )]TJ 1.06599 Tw 0 -1.237 TD [(recently published by Bajaj and)14.8 ( )]TJ -0.015 Tw T* (colleagues.)Tj 0 0 1 rg /GS1 gs 0 Tc 0 Tw 5.967 0 0 5.967 259.8117 261.6785 Tm (1)Tj 0 0 0 1 k /GS0 gs 0.015 Tc 0.438 Tw 9 0 0 9 263.2198 257.6285 Tm [( )0.5 (The )0.5 (authors convincingly)14.8 ( )]TJ 0.476 Tw -5.181 -1.237 Td [(demonstrate that underlying cirr)17.4 (hosis)14.9 ( )]TJ 0.924 Tw T* (should be considered a high-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 263.2198 257.6285 Tm 11.21497 -2.474 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 364.1638 235.3625 Tm (risk)Tj 9 0 0 9 263.2198 257.6285 Tm 12.8288 -2.474 Td ( )Tj 0.735 Tw -18.0098 -1.237 Td [(comorbid condition among patients)14.9 ( )]TJ 0.39799 Tw T* [(with CO)27 (VID)-36.5 (-)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 263.2198 257.6285 Tm 1.27649 -4.948 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 274.7038 213.0965 Tm (19. However)Tj 9 0 0 9 263.2198 257.6285 Tm 7.41449 -4.948 Td [(, increasing)14.9 ( )]TJ 0.74899 Tw -12.59549 -1.237 Td [(evidence )0.6 (demonstrates )0.6 (that )0.6 (patients)14.8 ( )]TJ 0.162 Tw T* (not infected with SARS-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 263.2198 257.6285 Tm 5.95999 -7.422 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 316.8508 190.8305 Tm (CoV)Tj 9 0 0 9 263.2198 257.6285 Tm 7.9183 -7.422 Td (-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 263.2198 257.6285 Tm 8.2663 -7.422 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 337.6228 190.8305 Tm (2 are also)Tj 9 0 0 9 263.2198 257.6285 Tm 12.8301 -7.422 Td ( )Tj 0.726 Tw -18.0111 -1.237 Td (highly affected by pandemic-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 263.2198 257.6285 Tm 9.79298 -8.659 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 351.3568 179.6975 Tm (related)Tj 9 0 0 9 263.2198 257.6285 Tm 12.8292 -8.659 Td ( )Tj 0.586 Tw -18.0102 -1.237 Td [(circumstances. While the CO)27.1 (VID)-36.6 (-)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 263.2198 257.6285 Tm 11.70248 -9.896 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 368.5378 168.5645 Tm (19)Tj 9 0 0 9 263.2198 257.6285 Tm 12.8291 -9.896 Td ( )Tj 0.28799 Tw -18.0101 -1.237 Td [(pandemic led to a significant drop in)14.8 ( )]TJ 0.26601 Tw T* [(medical emergencies with low priority)14.8 ( )]TJ 0.252 Tw T* [(presenting to )0.5 (emergency departments,)]TJ 0 0 1 rg /GS1 gs 0 Tc 0 Tw 5.967 0 0 5.967 375.3651 139.2486 Tm (2)Tj 0 0 0 1 k /GS0 gs 9 0 0 9 378.6837 135.1985 Tm ( )Tj 0.015 Tc 0.519 Tw -18.01 -1.237 Td [(presentations of medical emergencies)14.9 ( )]TJ 0.168 Tw T* [(requiring urgent treatment appeared to)14.9 ( )]TJ -0.052 Tw T* [(be significantly delayed. F)49.6 (or example, De)15.1 ( )]TJ -0.015 Tw T* [(R)30.9 (osa )]TJ /TT1 1 Tf -0.06799 Tw 2.342 0 Td (et al)Tj 0 0 1 rg /GS1 gs /TT0 1 Tf 0 Tc 0 Tw 5.967 0 0 5.967 254.3462 94.7286 Tm (3)Tj 0 0 0 1 k /GS0 gs 0.015 Tc -0.06799 Tw 9 0 0 9 257.7543 90.6786 Tm [( observed a reduction of nearly)14.8 ( )]TJ 0.062 Tw -4.574 -1.237 Td [(50% in admissions for acute myocardial)15.1 ( )]TJ 0.03 Tw T* [(infarctions, but the case fatality rate and)14.9 ( )]TJ 0.271 Tw T* [(associated )0.5 (complications )0.5 (were )0.5 (substan)]TJ 0 Tc 0 Tw (-)Tj 0.015 Tc 0.57201 Tw T* [(tially )0.5 (increased. )0.5 (In )0.5 (addition, )0.5 (several)15.2 ( )]TJ 0.367 Tw 19.399 76.967 Td (studies report an increase of psycho)Tj 0 Tc 0 Tw (-)Tj 0.015 Tc 0.19 Tw 0 -1.222 TD [(logical symptoms, such as anxiety)114.5 (, fear)14.9 ( )]TJ 0.147 Tw T* [(and stress, during the pandemic, which)14.9 ( )]TJ 0.60201 Tw T* [(correlated )0.6 (significantly )0.6 (to )0.6 (a )0.6 (general)15.2 ( )]TJ 0.785 Tw T* (increase in alcohol consumption.)Tj 0 0 1 rg /GS1 gs -0.015 Tw 5.967 0 0 5.967 543.476 698.9131 Tm (4\2266)Tj 0 0 0 1 k /GS0 gs 0 Tc 0 Tw 9 0 0 9 553.2756 694.8632 Tm ( )Tj 0.015 Tc 0.16701 Tw -18.01 -1.222 Td [(Another study could show that alcohol)15.2 ( )]TJ 0.239 Tw T* (consumption of heavy drinkers signifi)Tj 0 Tc 0 Tw (-)Tj 0.015 Tc 0.173 Tw T* (cantly increased.)Tj 0 0 1 rg /GS1 gs 0 Tc 0 Tw 5.967 0 0 5.967 459.0106 665.9131 Tm (7)Tj 0 0 0 1 k /GS0 gs 0.015 Tc 0.173 Tw 9 0 0 9 462.4187 661.8632 Tm [( Alcohol consumption)14.9 ( )]TJ 0.19 Tw -7.915 -1.222 Td (is the main trigger of acute-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 462.4187 661.8632 Tm 5.29299 -1.222 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 510.0467 650.8652 Tm (on-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 462.4187 661.8632 Tm 6.782 -1.222 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 523.4567 650.8652 Tm (chronic)Tj 9 0 0 9 462.4187 661.8632 Tm 10.0948 -1.222 Td ( )Tj -0.017 Tw -18.0098 -1.222 Td [(liver failure \(A)17.5 (CLF\),)]TJ 0 0 1 rg /GS1 gs 0 Tc 0 Tw 5.967 0 0 5.967 471.9419 643.9131 Tm (8)Tj 0 0 0 1 k /GS0 gs 0.015 Tc -0.017 Tw 9 0 0 9 475.35 639.8632 Tm [( which is a frequent)14.9 ( )]TJ 0.364 Tw -9.352 -1.222 Td [(syndrome in patients with underlying)14.9 ( )]TJ 0.33501 Tw T* [(liver cirr)17.4 (hosis and is characterised by)14.8 ( )]TJ -0.039 Tw T* [(acute )0.5 (decompensation )0.5 (of )0.5 (cirr)17.5 (hosis, )0.5 (organ)14.9 ( )]TJ 0.00301 Tw T* (failure\(s\) and high short-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 475.35 639.8632 Tm 1.67 -4.888 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 490.371 595.8712 Tm (term mortality)Tj 9 0 0 9 475.35 639.8632 Tm 7.9965 -4.888 Td (.)Tj 0 0 1 rg /GS1 gs 0 Tc 0 Tw 5.967 0 0 5.967 549.957 599.9131 Tm (9)Tj 0 0 0 1 k /GS0 gs 9 0 0 9 553.2756 595.8632 Tm ( )Tj 0.015 Tc 0.25301 Tw -18.01 -1.222 Td [(W)118.6 (e retrospectively analysed the preva)]TJ 0 Tc 0 Tw (-)Tj 0.015 Tc -0.071 Tw T* [(lence and outcome of patients with A)17.6 (CLF)14.8 ( )]TJ 0.008 Tw T* [(precipitated by severe alcoholic hepatitis)14.8 ( )]TJ 0.142 Tw T* (in a non-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 553.2756 595.8632 Tm -13.73201 -4.888 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 429.6876 551.8712 Tm (CO)Tj 9 0 0 9 553.2756 595.8632 Tm -12.188 -4.888 Td [(VID)-36.5 (-)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 553.2756 595.8632 Tm -9.9435 -4.888 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 463.7886 551.8712 Tm (19 intensive care unit)Tj 9 0 0 9 553.2756 595.8632 Tm 0.00108 -4.888 Td ( )Tj 0.131 Tw -18.01108 -1.222 Td [(\(ICU\) of the University Liver Center in)14.8 ( )]TJ 0.33 Tw T* [(F)35.4 (rankfurt am Main \(Hesse, Germany\))15 ( )]TJ 0.44299 Tw T* (during the SARS-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 553.2756 595.8632 Tm -9.46702 -8.554 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 468.0726 518.8772 Tm (CoV)Tj 9 0 0 9 553.2756 595.8632 Tm -7.5077 -8.554 Td (-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 553.2756 595.8632 Tm -7.1597 -8.554 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 488.8446 518.8772 Tm (2 pandemic in)Tj 9 0 0 9 553.2756 595.8632 Tm 0.00008 -8.554 Td ( )Tj 0.50301 Tw -18.01008 -1.222 Td [(2020 )0.6 (in )0.6 (comparison )0.6 (with )0.6 (equivalent)14.9 ( )]TJ 0.237 Tw T* [(time periods between 2017 and 2019.)15.2 ( )]TJ 0.22701 Tw T* [(All )0.7 (patients )0.7 (admitted )0.7 (to )0.6 (the )0.7 (ICU )0.7 (were)15.1 ( )]TJ 0.399 Tw T* [(screened )0.5 (for )0.5 (A)17.6 (CLF)100.4 (, )0.6 (according )0.5 (to )0.5 (the)15.1 ( )]TJ 0.22501 Tw T* [(European Association for the Study of)15 ( )]TJ 0 Tw T* [(the )0.5 (Liver \226 Chronic Liver )0.5 (F)49.5 (ailure \(EASL-)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 553.2756 452.8892 Tm ( )Tj EMC ET BT /TT0 1 Tf -0.00101 Tw 9 0 0 9 391.1856 441.8912 Tm (CLIF\) )Tj 9 0 0 9 553.2756 595.8632 Tm -15.08371 -17.108 Td (criteria,)Tj 0 0 1 rg /GS1 gs -0.015 Tw 5.967 0 0 5.967 448.5755 445.9131 Tm (10)Tj 0 0 0 1 k /GS0 gs -0.00101 Tw 9 0 0 9 455.3916 441.8632 Tm [( )0.6 (via )0.6 (patient )0.6 (charts. )0.7 (Diag)]TJ 0 Tc 0 Tw (-)Tj 0.015 Tc 0.364 Tw -7.134 -1.222 Td [(nosis )0.5 (of )0.5 (liver )0.5 (cirr)17.5 (hosis )0.5 (was )0.5 (based )0.5 (on)14.9 ( )]TJ 0.209 Tw T* (clinical data, laboratory results, sonog)Tj 0 Tc 0 Tw (-)Tj 0.015 Tc 0.13499 Tw T* [(raphy )0.5 (and/or )0.5 (other )0.6 (imaging, )0.5 (liver )0.5 (biop)]TJ 0 Tc 0 Tw (-)Tj /C2_1 1 Tf 0.015 Tc -0.015 Tw T* <0056004C00480056>Tj ET BT /Span <>BDC /C2_1 1 Tf 9 0 0 9 455.3916 441.8632 Tm -5.593 -4.888 Td <0003>Tj EMC ET BT /C2_1 1 Tf 9 0 0 9 408.6276 397.8712 Tm <004400510047>Tj ET BT /Span <>BDC /C2_1 1 Tf 9 0 0 9 455.3916 441.8632 Tm -3.571 -4.888 Td <0003>Tj EMC ET BT /C2_1 1 Tf 9 0 0 9 426.8346 397.8712 Tm <00480051004700520056004600520053005C>Tj 9 0 0 9 455.3916 441.8632 Tm 1.39549 -4.888 Td <0011>Tj ET BT /Span <>BDC /C2_1 1 Tf 9 0 0 9 455.3916 441.8632 Tm 1.68849 -4.888 Td <0003>Tj EMC ET BT /C2_1 1 Tf 9 0 0 9 474.1656 397.8712 Tm <0033>Tj 9 0 0 9 455.3916 441.8632 Tm 2.6215 -4.888 Td <00440057004C0048005100570056>Tj ET BT /Span <>BDC /C2_1 1 Tf 9 0 0 9 455.3916 441.8632 Tm 5.5195 -4.888 Td <0003>Tj EMC ET BT /C2_1 1 Tf 9 0 0 9 508.6446 397.8712 Tm <005A004C0057004B>Tj ET BT /Span <>BDC /C2_1 1 Tf 9 0 0 9 455.3916 441.8632 Tm 7.895 -4.888 Td <0003>Tj EMC ET BT /C2_1 1 Tf 9 0 0 9 530.0196 397.8712 Tm <0024>Tj 9 0 0 9 455.3916 441.8632 Tm 8.9564 -4.888 Td <0026002F0029>Tj ET BT /Span <>BDC /C2_1 1 Tf 9 0 0 9 553.2756 397.8712 Tm <0003>Tj EMC ET BT /TT0 1 Tf 0.27499 Tw 9 0 0 9 391.1856 386.8732 Tm (were categorised into two groups: \(1\))Tj 9 0 0 9 455.3916 441.8632 Tm 10.87605 -6.11 Td ( )Tj 0.336 Tw -18.01005 -1.222 Td (precipitated by severe alcoholic hepa)Tj 0 Tc 0 Tw (-)Tj 0.015 Tc -0.005 Tw T* [(titis )0.5 (and )0.5 (\(2\) )0.5 (precipitated )0.5 (by )0.5 (other )0.5 (causes.)15.1 ( )]TJ 0.043 Tw T* [(Severe )0.5 (alcoholic )0.6 (hepatitis )0.6 (was )0.5 (diagnosed)14.9 ( )]TJ 0 Tw T* (as recently described.)Tj 0 0 1 rg /GS1 gs 0 Tc 5.967 0 0 5.967 476.3271 346.9131 Tm (8)Tj 0 0 0 1 k /GS0 gs 0.015 Tc 0.01199 Tw 9 0 0 9 400.1837 331.8632 Tm [(Overall, 3649 admissions to ICU were)15.1 ( )]TJ 0.25301 Tw -1 -1.222 Td [(screened during 2017\2262020. Of these,)15.2 ( )]TJ 0.21899 Tw T* (820 were admitted for a gastroentero)Tj 0 Tc 0 Tw (-)Tj 0.015 Tc 0.071 Tw T* [(logical or hepatological disease and 237)14.9 ( )]TJ 0.317 Tw T* [(patients )0.7 (presented )0.7 (with )0.7 (A)17.6 (CLF)100.4 (. )0.7 (In )0.7 (our)14.9 ( )]TJ -0.026 Tw T* [(analysis, )0.5 (a )0.5 (moderate )0.5 (increase )0.5 (in )0.5 (all )0.5 (A)17.6 (CLF)14.8 ( )]TJ -0.10899 Tw T* [(cases )0.6 (was )0.7 (observed )0.7 (in )0.6 (2020 )0.7 (in )0.6 (comparison)14.8 ( )]TJ -0.008 Tw T* [(with 2017\2262019 \(15.9% of all ICU cases)14.9 ( )]TJ 0.158 Tw T* [(in 2020 vs 12.2%\22613% in 2017\2262019,)15.2 ( )]TJ 0.298 Tw T* [(respectively\). The majority of patients)14.9 ( )]TJ 0.07201 Tw T* [(suffered from A)17.5 (CLF grade 2 and 3, and)14.8 ( )]TJ 0.19299 Tw T* [(the median Model for )0.5 (End-)]TJ ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 400.1837 331.8632 Tm 11.92246 -13.442 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 507.4817 210.8852 Tm (Stage Liver)Tj 9 0 0 9 400.1837 331.8632 Tm 17.01119 -13.442 Td ( )Tj 0.08099 Tw -18.01119 -1.222 Td (Disease \(MELD\) score was 25 \()Tj 0 0 1 rg /GS1 gs (table)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 400.1837 331.8632 Tm 15.43895 -14.664 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 400.1837 331.8632 Tm 15.81294 -14.664 Td (1)Tj 0 0 0 1 k /GS0 gs 0 Tc 0 Tw [(\))-15 (. )]TJ 0.015 Tc 0.41701 Tw -16.81294 -1.222 Td [(Importantly)114.5 (, in 2020, 57% of A)17.6 (CLF)14.8 ( )]TJ 0.55099 Tw T* [(cases were precipitated by alcoholic)15.1 ( )]TJ 0.334 Tw T* [(hepatitis )0.7 (vs )0.6 (24%\22627% )0.7 (in )0.6 (2017\2262019,)15.2 ( )]TJ 0.08701 Tw T* [(an )0.6 (increase )0.6 (of )0.6 (111%\226137% )0.7 (\()]TJ 0 0 1 rg /GS1 gs (figure)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 400.1837 331.8632 Tm 14.7515 -19.552 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 536.3627 155.8952 Tm (1A)Tj 0 0 0 1 k /GS0 gs 0 Tc 0 Tw 9 0 0 9 400.1837 331.8632 Tm 16.384 -19.552 Td [(\))-15 (. )]TJ 0.015 Tc -0.043 Tw -17.384 -1.222 Td [(This increase was even more pronounced)14.9 ( )]TJ 0.49001 Tw T* [(over time during the pandemic and)14.8 ( )]TJ 0.118 Tw T* [(inversely correlated with reduced social)15.1 ( )]TJ 0.01199 Tw T* (activity due to pandemic-)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 400.1837 331.8632 Tm 10.28296 -24.44 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 492.7217 111.9032 Tm (related govern)Tj 0 Tc 0 Tw 9 0 0 9 400.1837 331.8632 Tm 16.67698 -24.44 Td (-)Tj 0.015 Tc 0.062 Tw -17.67698 -1.222 Td [(ment )0.7 (regulations )0.7 (\()]TJ 0 0 1 rg /GS1 gs (figure)Tj ET BT /Span <>BDC /TT0 1 Tf 9 0 0 9 400.1837 331.8632 Tm 9.77658 -25.662 Td ( )Tj EMC ET BT /TT0 1 Tf 9 0 0 9 491.3627 100.9052 Tm (1B)Tj 0 0 0 1 k /GS0 gs 9 0 0 9 400.1837 331.8632 Tm 11.328 -25.662 Td [(\). )0.6 (The )0.7 (group)14.9 ( )]TJ 0.64999 Tw -12.328 -1.222 Td [(of patients with A)17.5 (CLF precipitated)14.8 ( )]TJ 0.381 Tw T* [(by severe alcoholic hepatitis included)14.8 ( )]TJ 0.27499 Tw T* [(a higher percentage of A)17.6 (CLF grade 3)14.8 ( )]TJ 0.118 Tw T* [(patients \(53.7% )0.5 (vs )0.5 (36.1%, respectively\))14.9 ( )]TJ 0.22301 Tw T* [(and )0.7 (a )0.7 (slightly )0.7 (higher )0.7 (MELD )0.7 (score )0.7 (\(27)14.8 ( )]TJ ET q 1 0 0 1 30.047 41.151 cm 0 g 0 G 1 w /GS2 gs 0 Tc 0 Tw /Fm1 Do Q q 1 0 0 1 212.72 386.7 cm 0 g 0 G 1 w /GS2 gs 0 Tc 0 Tw /Fm2 Do Q BT 0 g /GS2 gs /T1_6 1 Tf 0 Tc 0 Tw 0 -9 9 0 578 299.70071 Tm ( on September 19, 2022 by guest. 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