862 Poovorwn K, et l., 2015; 14 (6): 862-868 ORIGINAL ARTICLE November-December, Vol. 14 No. 6, 2015: 862-868 The burden of cirrhosis nd impct of universl coverge public helth cre system in Thilnd: Ntionwide study Kittiyod Poovorwn, Sombt Treeprsertsuk, Kewji Thepsuthmmrt, Polrt Wilirtn, Bubph Kitshwong, Kmthorn Phoswsdi Deprtment of Clinicl Tropicl Medicine, Fculty of Tropicl Medicine, Mhidol University, Bngkok, Thilnd. Deprtment of Medicine, Fculty of Medicine, Chullongkorn University nd King Chullongkorn Memoril Hospitl, Bngkok, Thilnd. Clinicl Epidemiology Unit, Fculty of Medicine, KhonKen University, Thilnd. Vichiyut Hospitl nd Medicl Center, Thilnd. ABSTRACT Bckground nd rtionle. Cirrhosis is responsible for significnt helth-cre costs nd morbidity. This study ims to evlute the burden of illness ssocited with cirrhosis, its impct on the universl coverge public helth cre system in Thilnd. Mteril nd methods. We used dt from the 2010 Ntionwide Hospitl Admission Dt, the Ntionl Helth Security Office (NHSO), Thilnd. Their bseline chrcteristics, hospitl costs, nd outcomes were nlyzed ccording to ntionl helth insurnce ctegories including medicl welfre scheme (MWFS), socil security scheme (SSS) nd civil servnt medicl benefit scheme (CSMBS). Results. 92,301 dmissions were eligible for nlysis. The men ge ws 55 ± 12.8 yers, nd 63.3% of ptients were bove 50 yers old. The mjority of ptients (79%) belonged to the MWFS group. The MWFS group incurred the lowest medicl expense nd hd the shortest hospitl sty compred to the SSS nd CSMBS groups. Overll in-hospitl mortlity ws 10.7%. Cirrhosis complictions include bleeding esophgel vrices, spontneous bcteril peritonitis, heptic encephlopthy, heptorenl syndrome, nd heptocellulr crcinom. These complictions significntly incresed mortlity rtes compred to ptients without complictions (26 vs. 8.9%, p < 0.001). In-hospitl mortlity of ptients with cirrhosis complictions did not differ mong the three ntionl helth insurnce groups. Respirtory filure nd septicemi were ssocited with the highest risk of deth (HR 5.4; 95% CI: 4.8-5.9 nd HR 5.2; 95% CI: 4.9-5.6 respectively; P < 0.001). Conclusions. Illness ssocited with cirrhosis is significnt public helth problem in Thilnd. Outcomes of cirrhosis complictions did not differ between universl public helth cre coverge systems in Thilnd. Key words. Liver-relted mortlity. Cirrhosis complictions. Helth cre reform. Popultion. Cost. INTRODUCTION Correspondence nd reprint request: Kittiyod Poovorwn, M.D., MSc. Division of Gstroenterology nd Liver Disese. Deprtment of Clinicl Tropicl Medicine, Fculty of Tropicl Medicine, Mhidol University, Bngkok, Thilnd. Fx: + 662-3549-168 E-mil: kittiyod.poo@mhidol.c.th Mnuscript received: Februry 23, 2015. Mnuscript ccepted: April 05, 2015. Cirrhosis is the end-stge of every chronic liver disese. Its nturl history is chrcterized by n symptomtic phse followed by rpidly progressive phse mrked by the development of complictions of portl hypertension nd/or liver dysfunction. 1 Vrious common chronic liver diseses such s lcohol consumption, metbolic syndromes relted to overweight nd obesity, virl heptitis B nd C hve end results of liver cirrhosis nd heptocellulr crcinom. 2 Reviewed dt in Europe demonstrted tht cirrhosis-ssocited mortlity is t lest comprble with other diseses tht re considered to be of mjor public helth concern, such s brest cncer, colon cncer, chronic lung disese nd renl diseses. 3 Liver-relted mortlity hs been underestimted during the pst two decdes in the United Sttes nd Brzil. 4,5 There re nerly s mny mortlity cses ttributed to complictions of cirrhosis s there re to dibetes, nd more thn re ttributble to kidney diseses. 6 Cirrhosis is lso responsible for significnt helth-cre costs nd morbidity, nd DOI:.10.5604/16652681.1171773
Cirrhosis nd public helth cre system in Thilnd., 2015; 14 (6): 862-868 863 the incidence of hospitliztions due to cirrhosis complictions is incresing. 7-9 Besides cirrhosis complictions, vrious co-morbidities such s dibetes, crdiovsculr disese, nd chronic kidney disese lso ffect the prognosis of cirrhosis ptients. 10 A study in chronic heptitis B ptients in Thilnd showed tht the yerly cost of tretment for ptients with end-stge liver disese including cirrhosis ws five times higher thn chronic liver disese without cirrhosis. 11 Previous reports of popultionbsed prevlence rtes of cirrhosis in Nkhon Nyok Province showed tht stndrdized prevlence rtes re 75.3 per 100,000, nd prevlence is higher mong mles thn femles, prticulrly for lcoholic cirrhosis. 12 Helth-finncing reforms in Southest Asi hve sought to reduce dependence on out-of-pocket pyments, increse pooled helth finnce, nd expnd service use s steps towrds universl coverge. 13 Thilnd developed universl coverge public helth cre system in 2002. 14,15 All citizens received individulized ntionl insurnce depending on work nd public helth clssifiction to ensure bsic helth cre services. Outcomes, economic burden, nd the effect of the public helth cre system of cirrhosis in Thilnd hve not been well reserched. We im to evlute the burden of illness ssocited with cirrhosis in Thilnd nd its effect on the ntionl helth insurnce systems. MATERIAL AND METHODS Dt sources We nlyzed cirrhosis dt mong hospitlized ptients in Thilnd from the 2010 Ntionwide Hospitl Admission Dt, the Ntionl Helth Security Office (NHSO), Thilnd. Dt consisted of inptient informtion from three helth insurnce coverge schemes (Medicl Welfre Scheme, MWFS, Socil Security Scheme, SSS, nd Civil Servnt Medicl Benefit Scheme, CSMBS), which covered 77% (MWFS), 10% (SSS), nd 13% (CSMBS) of ll dmissions. All ptients with cirrhosis dignosis (ICD10-K74) ged t lest 19 yers old were included. Their bseline chrcteristics, hospitl costs, nd outcomes were nlyzed ccording to ntionl helth insurnce ctegory. Universl coverge public helth cre system Thilnd dopted universl public helth cre system in 2002, which is comprised of three ntionl helth insurnce ctegories Civil Servnt Medicl Benefit Scheme (CSMBS), Socil Security Scheme (SSS), nd Medicl Welfre Scheme (MWFS). CSMBS includes ll civil servnt officers with close fmily which individully reimburses medicl expenses from the Controller Generl s Deprtment. SSS includes ll Thi employees who re registered to the Ntionl Socil Security Fund. MWFS includes ll the remining Thi citizens in the ntionl dtbse, which cn ccess public helth services from public hospitls nd privte hospitl registered with The Ntionl Helth Security Office. All ntionl helth insurnces cover bsic helthcre services, however there re some differences between them. CSMBS covers some medictions tht re prt of the Ntionl List of Essentil Medicines, nd liver trnsplnt, wheres other schemes do not cover this. There re lso some differences in hospitl room fee reimbursement rules mong these insurnces. In Thilnd, government hospitls re clssified into three levels, primry hospitl is community hospitl for primry helthcre, secondry hospitl is hospitl for generl helthcre, nd tertiry hospitl is referrl hospitl for complicted diseses nd specilized helthcre. Sttisticl nlysis All sttisticl nlyses were performed using SPSS version 13 (SPSS Inc., Chicgo, IL). Continuous vribles were compred between groups using unpired t-test nd one-wy ANOVA. Ctegoricl vribles were compred between groups using χ 2 /Fisher s exct test. Multiple logistic regression nlysis ws used to djust the odds rtio for the fctors influencing mortlity rte. The odds rtio nd 95% CI of ech fctor re presented. P < 0.05 ws considered sttisticlly significnt. Ethicl considertion This study ws done with pprovl from The Gstroenterologicl Assocition of Thilnd in collbortion with The Ntionl Helth Security Office, Thilnd. The reserch protocol ws pproved by the Institutionl Review Bord, Fculty of Tropicl Medicine, Mhidol University (MUTM 2014-056-01). RESULTS In the yer 2010, Thilnd s over 19-yer-old popultion ws 47.97 million, which ccounted for 74%
864 Poovorwn K, et l., 2015; 14 (6): 862-868 of the country s popultion (64.7 million). The totl number of dult inptients ws 3.87 million, who were dmitted 4.86 million times, ccounting for 71% of ll inptients. The diseses of digestive system were the third leding cuse of hospitliztion, which ccounted for 379,532 dmissions, or 10% of ll dmissions. Among dmissions of digestive system, 92,301 dmissions for cirrhosis (24.3%) were eligible for nlysis. The men ge of ptients dmitted with cirrhosis ws 55 ± 12.8 yers nd 63.3% of ptients were bove 50 yers old. The mle to femle rtio ws 2:1, most ptients were hospitlized in primry level hospitls, nd in the centrl prt of Thilnd. The mjority of ptients (79%) belonged to the group of MWFS (Tble 1). The overll in-hospitl mortlity ws 10.7%. Cirrhotic ptients with complictions including bleeding esophgel vrices, spontneous bcteril peritonitis, heptic encephlopthy, heptorenl syndrome, nd heptocellulr crcinom-relted complictions hd significntly higher mortlity rte thn those ptients without complictions (26 vs. 8.9%, p < 0.001). The overll men length of hospitl sty ws 5.8 dys in cirrhosis ptients. Longer durtions, up to 8.6 dys, were observed in ptients with cirrhosis complictions. Heptorenl syndrome ws the compliction tht cused the longest dmission period, up to 10.2 dys, nd the highest mortlity rte, up to 42.6% (Tble 2). Cirrhosis ptients in the group of MWFS incurred the lest medicl expense compred to those in the SSS nd CSMBS groups both for ptients with nd without complictions. After ctegorizing ccording to cirrhosis complictions including bleeding esophgel vrices, spontneous bcteril peritonitis, heptic encephlopthy, heptorenl syndrome nd heptocellulr crcinom-relted complictions, the MWFS group still incurred significntly lower medicl expense (Tble 3). Cirrhosis ptients in the MWFS group hd significntly shorter dmission durtions compred to the SSS nd CSMBS groups, despite cirrhosis complictions (Figure 1). In-hospitl mortlity of ptients with cirrhosis complictions did not differ mong the three groups (Figure 2). Comorbidities nd cirrhosis complictions were significntly correlted with ptient survivl. Respirtory filure requiring continuous invsive mechnicl ventiltion for 96 consecutive hours or more, nd septicemi were ssocited with the highest risk of deth (HR 5.4; 95% CI: 4.8-5.9 nd HR 5.2; 95% CI: 4.9-5.6 respectively; P<0.001) (Tble 4). The etiology of liver cirrhosis ws identified in 31,423/92,301 (34%) of cses. Out of these, the cuses were identified s lcoholic liver disese in 73%, chronic heptitis B in 14%, chronic heptitis C in 12.6%, nd non-lcoholic stetoheptitis (NASH) in < 1%. DISCUSSION In 2010, cirrhosis ccounted for 1.3 million deths round the world, bout 2% of globl deths. 16 Tble 1. Bseline chrcteristics, hospitl level nd geogrphic distribution of cses were clssified ccording to their ntionl helth insurnce. Totl Medicl Welfre Scheme Civil Servnt Medicl Socil Security Scheme P vlue (n = 92,301) (MWFS) Benefit Scheme (SSS) (n = 6,637) (n = 72,985) (CSMBS) (n = 12,679) Age(yers) 55.4 ± 12.8 54.9 ± 12.7 61.9 ± 12.5 47.4 ± 8.8 < 0.001 Mle gender (%) 68.0 66.1 69.3 86.8 < 0.001 Hospitl level (%) Primry 34.1 39.0 22.8 2.2 < 0.001 Secondry 25.0 25.9 23.4 18.6 < 0.001 Tertiry 32.9 29.8 53.7 27.0 < 0.001 Privte 8.0 5.3 0.2 52.2 < 0.001 Region (%) Northern 24.0 25.5 19.5 15.9 < 0.001 Northest 29.8 31.9 28.4 10.0 < 0.001 Centrl 38.2 34.7 42.0 69.9 < 0.001 Southern 7.9 7.9 10.1 4.3 < 0.001 Plus-minus vlues re men ± SD for ll comprisons.
Cirrhosis nd public helth cre system in Thilnd., 2015; 14 (6): 862-868 865 Tble 2. Bseline chrcteristic, durtion of hospitl sty, cost of hospitliztion, nd mortlity rte clssified ccording to complictions directly relted with cirrhosis. Cirrhosis complictions Without With cirrhosis Bleeding Spontneous Heptic Heptorenl HCC relted P vlue compliction complictions esophgel bcteril encephlopthy syndrome complictions (n = 82,652) (n = 9,649) vrices peritonitis (n = 5,292) (n = 458) (n = 1,407) (n = 868) (n = 2,406) Age (yers) 55.3 ± 12.9 55.6 ± 12.3 53.5 ± 11.5 54.9 ± 12.4 55.5 ± 12.3 56.8 ± 12.1 58.5 ± 11.6 0.073 Length of 5.8 ± 7.7 8.6 ± 10.2 8.4±9.9 8.6 ± 10.3 9.1 ± 10.9 10.2 ± 10.3 7.7 ± 8.9 < 0.001 sty (dys) Hospitl 22,677 ± 65,990 41,937 ± 69,050 58,310 ± 87,746 35,310 ± 60,896 44,606 ± 71,001 58,134 ± 79,763 40,056 ± 65,453 < 0.001 chrge (bths) In-hospitl 8.9% 26% 19.7% 21.9% 32% 42.6% 17.1% < 0.001 mortlity rte Plus-minus vlues re men ± SD for ll comprisons. 1 US dollr = 32 bths (currency exchnge). Some ptients hd more thn 1 compliction. HCC: heptocellulr crcinom. Tble 3. Medicl expenses clssified by cirrhosis complictions nd ntionl helth insurnce. Medicl expense Totl Medicl Welfre Scheme Civil Servnt Medicl Benefit Socil Security Scheme P vlue (n = 92,301) (MWFS) (n = 72,985) Scheme (CSMBS) (n = 12,679) (SSS) (n = 6,637) Overll 24,691 ± 66,577 20,845 ± 62,781 38,795 ± 82,604 40,036 ± 66,998 < 0.001 (n = 92,301) With cirrhosis 41,937 ± 69,050 35,119.3 ± 54,256.3 64,550.2 ± 107,373.8 67,661.0 ± 89,028.0 < 0.001 complictions (n = 9,649) Bleeding esophgel 58,310 ± 87,746 52,104.7 ± 76,134.1 74,916.3 ± 117,425.2 76,644.3 ± 105,558.6 0.013 vrices (n = 868) Spontneous bcteril 35,310 ± 60,896 29,034.7 ± 46,720.9 62,209.5 ± 104,787.0 55,747.9 ± 67,326.2 < 0.001 peritonitis (n = 2,406) Heptic 58,134 ± 79,763 37,787.1 ± 55,215.3 68,692.7 ± 114,138.6 75,349.4 ± 94,665.9 < 0.001 encephlopthy (n = 5,292) Heptorenl 58,134 ± 79,763 36,429.4 ± 49,981.1 104,787.2 ± 102,096.5 129,973.2 ± 129,182.8 < 0.001 syndrome (n = 458) HCC relted 40,056 ± 65,453 31,508.8 ± 51,778.7 62,101.0 ± 94,105.0 49,806.3 ± 60,332.4 < 0.001 complictions (n= 1,407) Plus-minus vlues re men ± SD for ll comprisons. Some ptients hd more thn 1 compliction. HCC: heptocellulr crcinom.
866 Poovorwn K, et l., 2015; 14 (6): 862-868 Whitout compliction (n = 82,652) With cirrhosis complictions (n = 9,649) Bleeding esophgel vrices (n = 868) Spontneous bcteril peritonitis (n = 2,406) Heptic encephlopthy (n = 5,292) Heptorenl syndrome (n = 458) Heptocellulr crcinom (n = 1,407) relted complictions 0 2 4 6 8 10 12 14 16 18 Dys Medicl Welfre Scheme (MWFS) Socil Security Scheme (SSS) Civil Servnt Medicl Benefit Scheme (CSMBS) Figure 1. Length of hospitliztion (dys) clssified by cirrhosis complictions nd ntionl helth insurnce. Sttisticlly significnce difference. 60 Mortlity rte (%) 50 40 30 20 10 0 Bleeding esophgel vrices (n = 868) Spontneous bcteril peritonitis (n = 2,406) Heptic encephlopthy (n = 5,292) Heptorenl syndrome (n = 458) Heptocellulr crcinom relted complictions (n = 1,407) Cirrhosis complictions Civil Servnt Medicl Benefit Scheme (CSMBS) Socil Security Scheme (SSS) Medicl Welfre Scheme (MWFS) Figure 2. Mortlity rte of cirrhosis complictions clssified ccording to ntionl helth insurnce. No sttisticlly significnce difference. According to the Ntionl Center for Helth Sttistics (NCHS), chronic liver disese nd cirrhosis is the 12th leding cuse of deth in the United Sttes. The highest risk groups consist of persons ged 45 to 54 yers nd 55 to 64 yers, where chronic liver disese nd cirrhosis re the 4th nd 7th leding cuse of deth. 4,17 Our dt supports tht liver cirrhosis is public helth problem in ll res nd t every hospitl level in Thilnd. Mortlity rte of hospitlized liver cirrhosis ptients in Thilnd 2010 ws 10.7%, compred to the overll mortlity rte of inptients of 4.4, 1.4 nd 3.3% in CSMBS, SSS, nd MWFS groups ccordingly. In nlysis of dt from the Ntionl Helth Security Office (NHSO), Thilnd (2010), cirrhosis-relted deths ws 20.5/100,000 persons which is comprble to estimted liverrelted deths in United Stte (25.7/100,000 persons
Cirrhosis nd public helth cre system in Thilnd., 2015; 14 (6): 862-868 867 Tble 4. Cirrhosis complictions nd co-morbidities ssocited with in-hospitl mortlity in ptients hospitlized with liver cirrhosis. Risk fctors Hzrd rtio 95% CI P vlue Cirrhosis complictions Bleeding esophgel vrices 2.0 1.7, 2.4 < 0.001 Spontneous bcteril peritonitis 1.8 1.6, 2.0 < 0.001 Heptic encephlopthy 2.9 2.7, 3.1 < 0.001 Heptorenl syndrome 4.1 3.3, 5.2 < 0.001 Heptocellulr crcinom relted complictions 1.8 1.6, 2.1 < 0.001 Septicemi 5.2 4.9, 5.6 < 0.001 Dibetes mellitus 0.7 0.7, 0.8 < 0.001 Renl filure 2.9 2.7, 3.0 < 0.001 Ischemic hert diseses 1.4 1.2, 1.6 < 0.001 Continuous invsive mechnicl ventiltion for 96 consecutive hours or more 5.4 4.8, 5.9 < 0.001 Hemodilysis 1.8 1.5, 2.2 < 0.001 in 2008). 4 Mortlity rtes of hospitlized cirrhosis ptients rnge from 3.3 to 40% depended on severity of cirrhosis, complictions, nd co-morbidities. 5,18,19 Cirrhosis complictions significntly increse risk of deth. According to our dt, heptorenl syndrome ws the most ftl compliction of cirrhosis, which might be due to decompensted liver disese nd insufficient liver trnsplnttion. We found tht only 19 liver trnsplnts hve been done in this registry dt, compre with more thn 2,500 endoscopic interventions for bleeding esophgel vrices. Our dt were consistent with previous dt, nd show tht infectious nd renl complictions in persons with cirrhosis directly impct clinicl outcomes. 20,21 These dt support tht morbidity nd mortlity due to cirrhosis nd its complictions re significnt public helth problems in Thilnd. Length of hospitl sty nd hospitl expenses incurred were higher in SSS nd CSMBS groups, compred with MWFS, however no sttisticlly significnt differences were found in mortlity rtes from the vrious cirrhosis complictions. Acute-on chronic liver filure (ACLF) is distinct from cute decompenstion nd hs been significntly relted to deth in ptients with cirrhosis. 22 This study hs limittions, since it is relted to retrospective survey, nd non-specilized doctors re more prone to describe ll morbid events in cirrhosis s decompenstion. The bsence of dt description on ACLF does not men tht these cses re rre. Etiology of cirrhosis could only be determined in 34% of cses, nd better method to define etiology of cirrhosis in Thilnd should be developed, since its tretment nd prevention is essentil for better ptient cre. Bse on this limited dt, lcoholic liver disese might be one of the significnt cuses of liver cirrhosis consistent with previous report, 23 however out-ptient dt from the liver clinic in King Chullongkorn Memoril hospitl, Thilnd, showed tht chronic heptitis B ws the most common etiology (44.7%), followed by chronic heptitis C (29.7%), lcoholic liver disese (14.8%), NASH (6.7%), nd utoimmune heptitis(4.1%) (unpublished dt). These dt suggest tht most lcoholic ptients did not ccess helthcre before dmission from cirrhosis-relted illness. Alcohol consumption, virl heptitis B nd C, nd metbolic syndromes relted to overweight nd obesity re the leding cuses of cirrhosis nd primry liver cncer. 24-26 Prevention nd tretment interventions in those conditions nd risk fctors re necessry to control further morbidities, mortlity, nd economic burden relted to cirrhosis. In conclusion, illness ssocited with cirrhosis is significnt public helth problem in Thilnd, with mortlity rte of up to 26% in hospitlized ptients with decompensted forms of cirrhosis. Preventive mesures re very importnt to reduce the burden of the disese in the future. Although differences mong the three helth cre systems were found regrding medicl expenses nd dmission periods, the outcomes of cirrhosis complictions were similr for ll of them. ABBREVIATIONS CI: confidence intervl. CSMBS: civil servnt medicl benefit scheme. HCC: heptocellulr crcinom. HR: hzrd rtio.
868 Poovorwn K, et l., 2015; 14 (6): 862-868 MWFS: medicl welfre scheme. NASH: non-lcoholic stetoheptitis. NCHS: Ntionl Center for Helth Sttistics. NHSO: Ntionl Helth Security Office. SSS: socil security scheme. CONFLICTS OF INTEREST No potentil conflict of interest relevnt to this rticle ws reported. FINANCIAL SUPPORT This work ws supported by the Gstroenterologicl Assocition of Thilnd, The ICTM Grnt of the Fculty of Tropicl Medicine, Mhidol University, Thilnd. ACKNOWLEDGEMENTS We would like to express our grtitude to the stff of the Office of Reserch Services nd stffs t the Fculty of Tropicl Medicine, Mhidol University, Fculty of Medicine, Chullongkorn University, Clinicl Epidemiology Unit, Fculty of Medicine, KhonKen University, Vichiyut Medicl Center, nd The Ntionl Helth Security Office, Thilnd. REFERENCES 1. D mico G, Grci-Tso G, Pgliro L. Nturl history nd prognostic indictors of survivl in cirrhosis: systemtic review of 118 studies. J Heptol 2006; 44: 217-31. 2. Fttovich G, Stroffolini T, Zgni I, Donto F. Heptocellulr crcinom in cirrhosis: incidence nd risk fctors. Gstroenterology 2004; 127: S35-S50. 3. Blchier M, Leleu H, Peck-Rdosvljevic M, Vll DC, Roudot- Thorvl F. The burden of liver disese in Europe: review of vilble epidemiologicl dt. J Heptol 2013; 58: 593-608. 4. Asrni SK, Lrson JJ, Ywn B, Therneu TM, Kim WR. Underestimtion of liver-relted mortlity in the United Sttes. Gstroenterology 2013; 145: 375-82. 5. Nder LA, De Mttos AA, Bstos GA. Burden of liver disese in Brzil. Liver Int 2014; 34: 844-9. 6. Kim WR, Brown RS, Jr., Terrult NA, El-Serg H. Burden of liver disese in the United Sttes: summry of workshop. Heptology 2002; 36: 227-42. 7. Volk M L, Tocco R S, Bzick J, Rkoski M O, Lok A S. Hospitl redmissions mong ptients with decompensted cirrhosis. Am J Gstroenterol 2012; 107: 247-52. 8. Nguyen GC, Segev DL, Thuluvth PJ. Ntionwide increse in hospitliztions nd heptitis C mong inptients with cirrhosis nd sequele of portl hypertension. Clin Gstroenterol Heptol 2007; 5: 1092-9. 9. Dvlos Moscol M, Bustios Snchez C. The burden of heptic encephlopthy in Ltin Americ. Ann Heptol 2011; 10(Suppl. 2): S31-S35. 10. Jepsen P. Comorbidity in cirrhosis. World J Gstroenterol 2014; 20: 7223-30. 11. Yeekin C, Gertikornsupk N, Chumpongthong P, Tongsiri S, Dhitvt J, Phonrt B, Pitisuttithum P. Medicl nd economic burden of chronic heptitis B ptients t Queen Svng Vdhn Memoril Hospitl. J Med Assoc Thi 2014; 97: 447-55. 12. Rttnmongkolgul S, Wongjitrt C, Pupnkitchroen P. Prevlence of cirrhosis registered in Nkhon Nyok, Thilnd. J Med Assoc Thi 2010; 93(Suppl. 2): S87-S91. 13. Tngchroensthien V, Ptchrnrumol W, Ir P, Aljunid S M, Mukti A G, Akkhvong K, Bnzon E, et l. Helth-finncing reforms in southest Asi: chllenges in chieving universl coverge. Lncet 2011; 377: 863-73. 14. Limwttnnon S, Tngchroensthien V, Tisyticom K, Boonypisrnchroen T, Prkongsi P. Why hs the Universl Coverge Scheme in Thilnd chieved pro-poor public subsidy for helth cre? BMC Public Helth 2012; 12(Suppl. 1): S6. 15. Tngchroensthien V, Pityrngsrit S, Ptchrnrumol W, Prkongsi P, Sumlee H, Tosngun J, Mills A. Promoting universl finncil protection: how the Thi universl coverge scheme ws designed to ensure equity. Helth Res Policy Syst 2013; 11: 25. 16. Lozno R, Nghvi M, Foremn K, Lim S, Shibuy K, Aboyns V, Abrhm J, et l. Globl nd regionl mortlity from 235 cuses of deth for 20 ge groups in 1990 nd 2010: systemtic nlysis for the Globl Burden of Disese Study 2010. Lncet 2012; 380: 2095-128. 17. Heron M. Deths: leding cuses for 2009. Ntl Vitl Stt Rep 2012; 61: 1-94. 18. Wddinghm W, Cepkov M. PTU-139 Outcomes Of Ptients With Liver Cirrhosis In A Non Liver-specilist Intensive Cre Unit: Do Admission Lctte And Apche 2 Score Help Predict Successful Dischrge? Gut 2014; 63(Suppl. 1): A99-A100. 19. Rtib S, Fleming K M, Crooks C J, Aithl G P, West J. 1 nd 5 yer survivl estimtes for people with cirrhosis of the liver in Englnd, 1998-2009: lrge popultion study. J Heptol 2014; 60: 282-9. 20. Arvniti V, D mico G, Fede G, Mnousou P, Tsochtzis E, Pleguezuelo M, Burroughs AK. Infections in ptients with cirrhosis increse mortlity four-fold nd should be used in determining prognosis. Gstroenterology 2010; 139: 1246-56, 56 e1-5. 21. Fede G, D mico G, Arvniti V, Tsochtzis E, Germni G, Georgidis D, Morbito A, et l. Renl filure nd cirrhosis: systemtic review of mortlity nd prognosis. J Heptol 2012; 56: 810-8. 22. Moreu R, Jln R, Gines P, Pvesi M, Angeli P, Cordob J, Durnd F, et l. Acute-on-chronic liver filure is distinct syndrome tht develops in ptients with cute decompenstion of cirrhosis. Gstroenterology 2013; 144: 1426-37. 23. Mrinho RT, Durte H, Giri J, Nunes J, Ferreir A, Velos J. The burden of lcoholism in fifteen yers of cirrhosis hospitl dmissions in Portugl. Liver Int 2014. Doi: 10.1111/liv.12569. 24. Venook AP, Ppndreou C, Furuse J, De Guevr LL. The incidence nd epidemiology of heptocellulr crcinom: globl nd regionl perspective. Oncologist 2010; 15(Suppl. 4): 5-13. 25. Thong V D, Akkrthmrongsin S, Poovorwn K, Tngkijvnich P, Poovorwn Y. Heptitis C virus genotype 6: virology, epidemiology, genetic vrition nd clinicl impliction. World J Gstroenterol 2014; 20: 2927-40. 26. Younossi Z M, Stepnov M, Afendy M, Fng Y, Younossi Y, Mir H, Srishord M. Chnges in the prevlence of the most common cuses of chronic liver diseses in the United Sttes from 1988 to 2008. Clin Gstroenterol Heptol 2011; 9: 524-30.