Increased mortality from acute liver failure in Mexico

Transcription

1 Acute liver filure in Mexico., 2; 11 (2): ORIGINAL ARTICLE Mrch-April, Vol. 11 No.2, 2: Incresed mortlity from cute liver filure in Mexico Norberto C. Chávez-Tpi,* Tontiuh Brrientos-Gutiérrez,**, *** Crlos Mnuel Guerrero-López,*** Jen Josue Sntigo-Hernández,* Nhum Méndez-Sánchez,* Misel Uribe* * Obesity nd Digestive Diseses Unit, Medic Sur Clinic nd Foundtion, Mexico City, Mexico. ** Center for Integrtive Approches to Helth Disprities, University of Michign. *** Ntionl Institute of Public Helth, Mexico City, Mexico. ABSTRACT Introduction. There is significnt geogrphic vrition in the etiology nd prognosis of cute liver filure (ALF). Since, little informtion is vilble for Ltin Americ. We nlyzed ALF mortlity trends in Mexico. Mteril nd methods. The rtes of mortlity ttributble to ALF were obtined for 1998 to 29 from the Ntionl System of Helth Informtion in Mexico nd nlyzed ccording to dte, etiology, sex, ge nd geogrphic chrcteristics through grphicl ssessment nd joinpoint regression. Results. From 1998 to 29, 2,193 ALF-relted deths were reported. A threefold increse in ALF mortlity ws observed during the period from 1998 to 29 (the globl mortlity rte incresed from 13.1 to 4.2 deths per 1,, inhbitnts). The most significnt increse ws observed for virl etiologies fter 26, ffecting people 45 yers old nd over. Conclusion. ALF-relted deths hve incresed since 26. Although we cnnot speculte on the specific cuses of this increse, it my reflect improvements in the ccess of vulnerble popultions to helth cre. Key words. Fulminnt liver filure. Heptitis. Epidemiology. INTRODUCTION Acute liver filure (ALF) is n uncommon but life-thretening liver disese, chrcterized by the presence of cute liver dmge, encephlopthy, cogulopthy nd jundice. ALF cn be divided in hypercute (less thn seven dys from the onset of encephlopthy), cute (more thn eight dys, but less thn four weeks from the onset of encephlopthy) nd subcute (more thn four weeks from the onset of encephlopthy). 1 The epidemiology of ALF is heterogeneous, being geogrphic vritions nd ge the most relevnt fctors in the pttern of disese etiology. This etiologicl vrition could ffect the prognosis nd therpeutic options. 2 ALF is considered rre disese, with n incidence rte of 1-6 cses per 1,, inhbitnts in developed countries. 3,4 The ALF mortlity rte fluctutes depending on its Correspondence nd reprint request: Norberto C. Chávez-Tpi M.D. Obesity nd Digestive Diseses Unit. Medic Sur Clinic & Foundtion Puente de Piedr No. 15. Col. Toriello Guerr, Del. Tllpn. C.P. 5, Mexico City, Mexico E mil: nchvezt@medicsur.org.mx Mnuscript received: November 4, 211. Mnuscript ccepted: December 5, 211. severity nd on ccess to liver trnsplnttion, nd rnges from 13 to 33%. 5,6 ALF hs significnt impct on liver trnsplnttion progrms, ccounting for 9-11% of trnsplnts. Liver trnsplnttion significntly reduces ALF mortlity, but ccess to it is still limited. 6 In developed countries, the consumption of cetminophen nd other drugs hs overtken virl infection s the primry cuse of ALF, ccounting for t lest 5% of cses. 2,7 However, in developing countries, informtion regrding the epidemiology of ALF is scrce. The im of this study ws to nlyze the dt for ALF from the ntionwide sttistics registry of Mexico. MATERIAL AND METHODS The mortlity dtbses were obtined from the Ntionl System of Helth Informtion (vilble t index.html; ccessed September 2, 211) for every yer from 1998 to 29. The dtbses contined ll deths registered in Mexico, coded under the Interntionl Clssifiction of Diseses version 1 (ICD- 1) for the generl cuse of deth, specific cuse of deth, plce of deth, ge, sex nd other socioeconomic vribles. Census dt from the Ntionl Popultion Council were used to estimte the Mexicn

2 258 Chávez-Tpi NC, et l., 2; 11 (2): popultion on July 1 in ech yer of the period exmined, overll nd by ge groups, sex nd region (vilble t ccessed July 13, 211). The ALF-relted deths were clssified into two generl types bsed on the ICD-1 descriptors: B-codes. Including deths cused by B15 (heptitis A, with heptic com). B, cute heptitis B with delt gent, with heptic com. B2, cute heptitis B without delt gent, with heptic com; nd B19, unspecified virl heptitis, with heptic com; nd K-codes. Including deths cused by K72 (cute nd subcute heptic filure), K76 (ftty chnge in the liver, not otherwise clssified), K762 (centrl hemorrhgic necrosis of the liver) nd K763 (infrction of the liver). The mortlity rtes were clculted s the number of deths per 1 million inhbitnts per yer. The clculted mortlity rtes were regressed over the clendr yer using joinpoint regression to test for chnges in mortlity trends over time. Briefly, joinpoint regression uses n lgorithm tht tests whether multisegmented line is significntly better fit thn stright or less-segmented line, thus identifying brek points in the trend, clled joinpoints. Ech joinpoint denotes sttisticlly significnt (P =.5) chnge in the trend. 8 In our nlysis, mximum of three joinpoints (four line segments) were llowed for ech model. The dt were nlyzed using PASW (PASW Sttistics Version..9, 29; IBM, Chicgo, IL, USA) nd the Joinpoint Regression Progrm, Version Geogrphic differences in the ALF mortlity rtes were ssessed using the regionl divisions of the country proposed by the Ntionl Institute of Sttistics, Geogrphy nd Informtics, s follows: Zone 1. Guerrero, Oxc nd Chips. Zone 2. Cmpeche, Tbsco, Vercruz, Puebl, Hidlgo nd Sn Luis Potosí. Zone 3. Michocán, Gunjuto, Zctecs, Durngo nd Tlxcl. Zone 4. Morelos, Estdo de México, Querétro, Nyrit, Colim, Sinlo, Yuctán nd Quintn Roo. Zone 5. Tmulips, Chihuhu, Sonor, Bj Cliforni nd Bj Cliforni Sur. Zone 6. Nuevo León, Cohuil, Jlisco nd Agusclientes; nd Zone 7. Mexico City. A seprte liner regression line ws fitted for ech zone for the nd periods to identify differences in the slopes of the ALF mortlity rtes between periods nd regions. RESULTS From 1998 to 29, 2,193 deths ttributble to ALF were reported. From 1998 to 26, the number of ALF-relted deths remined stble, verging Totl deths ttributble to cute liver filure B-codes Codes K76 Code K Yers The ICD codes included re: K72 (cute nd subcute heptic filure), K76 (ftty chnge of the liver, not otherwise clssified), K762 (centrl hemorrhgic necrosis of the liver), K763 (infrction of the liver), B15 (heptitis A, with heptic com), B (cute heptitis B with delt gent, with heptic com), B2 (cute heptitis B without delt gent, with heptic com) nd B19 (unspecified virl heptitis, with heptic com). Figure 1. Totl deths ttributble to cute liver filure in the period ccording to the ntionl registry in Mexico.

3 Acute liver filure in Mexico., 2; 11 (2): Mortlity rte due to cute liver filure (deths/1,, hbitnts) Code K72 Codes K76 B-codes Yers The ICD codes included re: K72 (cute nd subcute heptic filure), K76 (ftty chnge of the liver, not otherwise clssified), K762 (centrl hemorrhgic necrosis of the liver), K763 (infrction of the liver), B15 (heptitis A, with heptic com), B (cute heptitis B with delt gent, with heptic com), B2 (cute heptitis B without delt gent, with heptic com) nd B19 (unspecified virl heptitis, with heptic com). Figure 2. Mortlity rte from cute liver filure (per 1,, hbitnts) ccording to the ICD etiology groups. Mortlity rte due to cute liver filure (deths/1,, hbitnts) Age (yers) The ICD codes included re: K72 (cute nd subcute heptic filure), K76 (ftty chnge of the liver, not otherwise clssified), K762 (centrl hemorrhgic necrosis of the liver), K763 (infrction of the liver), B15 (heptitis A, with heptic com), B (cute heptitis B with delt gent, with heptic com), B2 (cute heptitis B without delt gent, with heptic com) nd B19 (unspecified virl heptitis, with heptic com). Figure 3. Mortlity rte from cute liver filure (per 1,, hbitnts) clssified by ge. Tble 1. Geogrphic nlysis of the mortlity rte slopes for nd B-codes K-codes Slope Slope Zone First Second Δ Joinpoint First Second Δ Joinpoint segment segment segment segment ND *.5 - ND ND ND ND ND: not detected. *Second nd third segments presented. First segment from 1998 to 26 (slope, -.98).

4 26 Chávez-Tpi NC, et l., 2; 11 (2): deths per yer. After 26, ALF-relted deths from ll cuses incresed stedily, lthough virl etiologies showed steeper increse, ccounting for the highest number of deths in 29 (Figure 1). The mortlity rtes behved in similr mnner. Deths clssified s K72 showed twofold increse from 1998 to 29 (from 9.1 to.3 deths per 1,, inhbitnts). Similrly, K76 showed 2.3-fold increse for the sme period (from 1.67 to 3.81 deths per 1,, inhbitnts) (Figure 2). A 1-fold increse in deths ws observed from 1998 to 29 for the B-code etiologies (from 1.8 to.1 deths per 1,, inhbitnts). Overll, ALF-relted mortlity experienced three- A Observed Slope =.65 B C Totl RATE per 1 million B relted cuses RATE per 1 million K relted cuses RATE per 1 million Slope 1 = -.8 Slope 1 =.23 Slope =.65 Slope 2 = 5.71 Slope 2 = Yers The ICD codes included re K72, K76, K762, K763 (A); B15, B, B2, B19 (B); nd ll cuses (C). Observed Slope 1 = -.8 Slope 2 = 5.71 Observed Slope 1 =.23 Slope 2 = 7.71 Figure 4. Mortlity rte from cute liver filure (per 1,, hbitnts) nd trends using joinpoint nlysis.

5 Acute liver filure in Mexico., 2; 11 (2): fold increse from 1998 to 29 (from 13.1 to 4.2 deths per 1,, hbitnts). Higher mortlity rtes, s well s incresed rtes over time, were concentrted in the group of ptients over 45 yers old, prticulrly fter 26 (Figure 3). No differences by sex were observed. The trends in ALF-relted mortlity displyed importnt increses fter 26 (Tble 1). Joinpoint nlysis reveled tht cross ll regions of Mexico, deths ttributble to virl cuses (B-codes) showed n verge increse of six deths per yer fter 26 compred with previous yers (Figure 4); the increses were remrkbly high for Mexico City (zone 7). For the K-code deths, n increse of nine deths per yer ws observed fter 27 in zones 1 (Guerrero, Oxc nd Chips) nd 6 (Nuevo León, Cohuil, Jlisco nd Agusclientes); the other zones mintined the sme slopes over time. DISCUSSION ALF is rre but lethl disese with importnt geogrphic vritions in its etiology nd prognosis. To the best of our knowledge, this is the first ntionl nlysis of ALF in Ltin Americ. Some reports hve previously been published involving peditric popultions. 1,11 nd infectious etiologies of ALF. We nlyzed the records of ALF-relted mortlity in Mexico for 11 yers. The most striking finding ws the increse in the number of deths in the lst three yers of the period. Mortlity incresed for ll etiologies, but heptitis-relted ALF cused by heptitis A nd B viruses nd undetermined viruses showed the lrgest increses. Becuse of the secondry nd ecologicl nture of the present study, we re unble to provide cusl explntion for the increse in ALF mortlity. However, some considertions cn be exmined to help interpret these findings. The incidence of heptitis infections showed its lst pek in Mexico in 1997, 13 nd hs remined stedy since then. An increse in heptitis-relted ALF mortlity with stble incidence of heptitis could suggest n increse in lethlity. However, the ssessment of lethlity in this sitution is difficult becuse no informtion on the time lg between heptitis onset nd ALF development exists, precluding ny meningful sttements bout lethlity. Therefore, the current cses of ALF could reflect the 1-yer lg since the 1997 heptitis pek well s present concurrent development of heptitis nd ALF. We relied on ntionl records to ssess these trends, which re subject to reporting bis nd chnges in the probbility of disese detection rising from chnges in ccess to helth cre. The simultneous increse in ll etiologies nd cross sexes suggests n improvement in the registrtion of ALF ptients, probbly resulting from improved ccess to helth cre. ALF is n expensive disese, requiring reltively dvnced technologicl resources to estblish n etiologicl dignosis. Mexico hs recently undergone n extensive reform in helth-cre ccess through Seguro Populr, subsidized governmentl system creted to provide ccess to helth cre for the previously uninsured popultion. From 24 to June 211, 48.5 million people becme ffilited with Seguro Populr, mny of whom belong to vulnerble groups (Informe de resultdos 211, vilble t: contenidos/informes_resultdos/ informe_resultdos_1sem_211.pdf). Becuse Seguro Populr provides coverge for ctstrophic expenses nd fcilittes ccess to helth cre, it is resonble to expect tht previously untreted cses of ALF will now be properly dignosed nd followed up. This could explin the increse in ALF mortlity, prticulrly mong the elderly. Another likely explntion is n increse in the vulnerbility of the popultion infected with heptitis. It is well known tht mny popultions with formerly high prevlence of heptitis A virl infections re moving towrd medium prevlence in response to improved snittion. At the sme time, heptitis infections in dulthood hve incresed s result of intrvenous drug use nd sexul trnsmission, which re lso importnt risk fctors for HIV infection, which is still incresing in Mexico. 15 Recently, some reports hve shown tht lrge proportion of the dult popultion infected with heptitis is lso infected with HIV. The comorbidity of HIV nd heptitis hs been linked to worse helth outcomes, including mortlity.,17 Finlly, locl conditions, such s the rre but still prevlent prctice of pying plsm donors, could lso contribute to the increse in ALF. It is importnt to note tht there re sociogeogrphic vritions in the min cuses of ALF. This joint nlysis showed slight temporl nd geogrphic vritions. Probbly the most relevnt is the generl increse in B-code disese, but the increse in K-code disese in only zones 1 nd 6 is lso remrkble. This should encourge locl reserchers to identify the regionl epidemiologicl chrcteristics nd to develop preventive nd therpeutic strtegies. Regrdless of the specific cuses of the increse, 1,1 ALF-relted deths occurred from 26 to

6 262 Chávez-Tpi NC, et l., 2; 11 (2): During the sme period, only 383 ptients underwent orthotopic liver trnsplnttion for ll cuses (vilble t interior/trsplnte_estdistics.html; ccessed October 1, 211). This mismtch highlights the drmtic shortge of orgns required to ccommodte t lest the ptients who most urgently require liver trnsplnttion. In the current scenrio, the vst mjority of ptients ffected by ALF will succumb to the ominous nturl history of the disese. This should encourge the development of lterntive strtgems to promote living-donor liver trnsplnttion, 19 to improve the mngement of these ptients in criticl cre units, nd to promote reserch into prognostic 2,21 nd therpeutic options. This study ws bsed on dministrtive dt, nd some limittions re intrinsic to this methodology. Moreover, other cuses of cute liver filure were not included (e.g., cetminophen, utoimmune disese, Amnit phlloides consumption). CONCLUSION In conclusion, in this study, we hve shown n increse in the mortlity ttributble to ALF in Mexico, which ws greter in people older thn 45 yers, with slight geogrphic vritions. These findings wrrnt further reserch to determine the rel cuse of this increse in ALF-relted mortlity. ABBREVIATIONS ALF: Acute liver filure. ICD-1: Interntionl Clssifiction of Diseses version 1. FINANCIAL SUPPORT Prtilly supported by Medic Sur Clinic & Foundtion. REFERENCES 1. O Grdy JG, Schlm SW, Willims R. Acute liver filure: redefining the syndromes. Lncet 1993: 342: Nguyen NT, Vierling JM. Acute liver filure. Current opinion in orgn trnsplnttion 211: : Doi: 1.197/MOT.b13e328346c8ee. 3. Bretherick AD, Crig DG, Msterton G, et l. Acute liver filure in Scotlnd between 1992 nd 29; incidence, etiology nd outcome. QJM: monthly journl of the Assocition of Physicins 211. Doi: 1.193/qjmed/hcr Bernl W, Auzinger G, Dhwn A, Wendon J. Acute liver filure. Lncet 21: 376: Doi: 1.1/S- 6736(1) Nemes B, Zdori G, Gorog D, Fehervri I, Kobori L, Lnger RM. Liver trnsplnttion for cute liver filure: the Hungrin experience. Trnsplnttion proceedings 211: 43: Doi: 1.1/j.trnsproceed Shkil AO, Krmer D, Mzriegos GV, Fung JJ, Rkel J. Acute liver filure: clinicl fetures, outcome nlysis, nd pplicbility of prognostic criteri. Liver trnsplnttion 2: 6: 3-9. Doi: 1./lt Pthikond M, Munoz SJ. Acute liver filure. Ann Heptl 21: 9: Kim HJ, Fy MP, Feuer EJ, Midthune DN. Permuttion tests for joinpoint regression with pplictions to cncer rtes. Sttistics in medicine 2: 19: Dentovsky SV, Anisimov AP, Kondkov AN, et l. Functionl Chrcteriztion nd Biologicl Significnce of Yersini pestis Lipopolyscchride Biosynthesis Genes. Biochemistry. Biokhimii 211: 76: Doi: / S Moreir-Silv SF, Fruches DO, Almeid AL, Mendonc HF, Pereir FE. Acute liver filure in children: observtions in Vitori, Espirito Snto Stte, Brzil. Revist d Sociedde Brsileir de Medicin Tropicl 22: 35: Sntos DC, Mrtinho JM, Pcheco-Moreir LF, et l. Fulminnt heptitis filure in dults nd children from Public Hospitl in Rio de Jneiro, Brzil. Brzilin J Infect Dis 29: 13: Doi: 1.159/S Ciocc M, Moreir-Silv SF, Alegri S, et l. Heptitis A s n etiologic gent of cute liver filure in Ltin Americ. Peditric Infect Dis J 27: 26: Doi: 1.197/ INF.b13e3f6bed. 13. Perdigón-Villseñor G, Fernández-Cntón S. Evolución reciente del comportmiento de ls heptitis virles en México, Bol Med Hosp Infnt Mex 29: 66: Mendez-Snchez N, Grci-Villegs E, Merino-Zeferino B, et l. Liver diseses in Mexico nd their ssocited mortlity trends from 2 to 27: A retrospective study of the ntion nd the federl sttes. Ann Heptol 21: 9: Cse P, Rmos R, Brouwer KC, et l. At the borders, on the edge: use of injected methmphetmine in Tijun nd Ciudd Jurez, Mexico. J of Immigrnt nd minority helth/center for Minority Public Helth 28: 1: Doi: 1.17/s Girrdi E, Scognmiglio P, Scirrone MR, et l. High HIV prevlence in mle ptients with cute heptitis A in the Rome metropolitn re, Itly J Heptol 211: 54: 1-6. Doi: 1.1/j.jhep Brrientos-Gutierrez T, Brizuel-Alcntr D, Chvez-Tpi NC. Heptitis A virus infection in high-risk subjects. Ann Heptol 211: 1: Volkow P, Brouwer KC, Loz O, et l. Cross-border pid plsm dontion mong injection drug users in two Mexico-U.S. border cities. Inter J Drug Policy 29: 2: 49-. Doi: 1.1/j.drugpo Oketni M, Ido A, Tsubouchi H. Chnging etiologies nd outcomes of cute liver filure: A perspective from Jpn. J Gstroenterol nd Heptol 211: 26(Suppl. 1): Doi: /j x. 2. Ajmer V, Xi G, Vughn G, et l. Wht fctors determine the severity of heptitis A-relted cute liver filure? J Virl Heptitis 211: : e7-74. Doi: /j x. 21. Merle U, Sieg O, Stremmel W, Encke J, Eisenbch C. Sensitivity nd specificity of plsm disppernce rte of indocynine green s prognostic indictor in cute liver filure. BMC Gstroenterology 29: 9: 91. Doi: 1./ 71-23X-9-91.