Changing epidemiology of hepatitis B in a U.S. Community: A preliminary report from the olmsted county hepatitis B registry

9

adenoviru was constructed with a N-terrninus it*st*dine tagNed recombinant IBP seqnence. In vito, inh'ctinn with our ader~oviral constrncl resnhed in the expression of a 60 kDa protein with I.BP biological activity In viva, adenovirus containing either a ccmtro] irrelevant protein (Adot~ga])or LgP (Adl BP) was green three days pnor to acetaminophen challenge in 1BP dehdent mice Liver injury was assessed by plasma traasaminase levels and histology at 6 m d 24 bnurs after acetaminophen Results: In viva imramuseular deliveU of Ad-LBP n'sul ed i~ plasma s levels sligh/y above that bund normal mouse serum Immunoblot confirmed b e presence o[ a 60 kDa protein in the Ad-LBP treated mice As expected, no detectable plasma ls was fPur,d in tha LBP deficient animals given Ad-13gal Plasma ALT and AST levels i.creased at 6 hams aud peaked at 24 hours alter acetanrinophen m kBP dehcient mice gwe* dlher Adts m Ad-~gaL However, signihcantly higher AST and AIT levels a 24 hours af'.er acetam ~mphen were bund in the Ad-LBP compared to Ad-,ggal neared race (~ = 5/gr(mp, p < 0001) }tistolog*caIanalysis at the fiver showed the classic ten lobnlar necrosis in both groups ot mice: however, quantitative' analysis revealed sign*itcarny mnre r:ectosis i r e A d I s treated mice (p= 00094 by ANOVA) Conclusion: Our restil5 shnw that leuans~ uriah of LBP in LBP deficieru mice resulted in increased hepa oloxici y fore acetanfirnphen These finding support the hypothesis that LBP is a critical meda or of acelantinopher nduced hepatotox/city

ls Obesity" a Risk Factol/ for Cirrhosis-Related Death or Hospitalization? A Population-Based Cohort Study George N loammu, Nod S Weiss, Kris V Kowdley Jason A Dominitz Context: Obesity has been associated wilh the presence of advanced fibrosis in patients with chronic liver disease Objective: To determine whether increased body mass index (BM[) in the general population is associated with cirrhosis-related death or hospitalization Design: Prospect*re cohort study. Setting: The first National Health and Nutrition Examination Survey and Epidemiologic Follow-up Study, a nationally representative survey" Participants: 11,465 persons aged 25-74 years witliout evidence of cirrhosis at entry into the study, or during the first 5 years of tallow-up, were subsequendy tbllowed tar a mean of 129 years Measurements: The BMI measured at baseline was used to categorize parlicipams into normal-weight (BMI < 25 kg/m~, N = 5,752), overweight (BM125 to < 30 k g / m N = 3,774) and obese (BMI > = 30 kg/m~ N = 1,939), Deaths and hospitalizations due to cirrhosis were identified from death certificates and hospitalization records. Results: Cirrhosis resulted in death or hospitalization of 89 participants during a total of 150,233 person-years of f011ow-np (059/1000 person-years) Cirrhosis-selated deaths or hospitalizations were more common in obese persons (0 81/1000 person-years, adjusted hazard ratio 169, 95% CI I0-3.0) and m overwdght persons (071/1000 person-years, actinsted hazard ratio 1.16, 95% C[ 0 7-1 9) compared to normal-weight persons (0 45/1000 person-years). Among persons who did not consume alcohol, them was a particularly strong association between obesity (adjusted hazard ratio 4 l, 95% Ct l 4-1 i 4) or overweight (adjusted hazard ratio 193.95% C107-53) and cirrhosis-related death or hospitalization. In contrast, this association was weaker among persons who cousnmed up to 03 alcoholic drinks per day (adjusted hazard ratio 248, 95% CI 0.7-8 4 for obesily, and adjusted hazard ratio 131, 95% CI 0442 thr ov'erweigbt) and no association was identified among those who consumed more than 03 alcoholic drinks/day (adjusted hazard ratio 080, 95% CI 0 3 - 2 1 tor obesity, and adjusted hazard ratio 097, 95% CI 05-1 8 for over weight). Conclusions: Obesity appears to be a risk tactor tar cirrhosis-related death or hospitalization among persons who consume fitde or no alcohol

7

Non-transterrin Bound Iron Uptake By ttepatocytes Is Increased In a Hie Knockout Mouse Model Of ttereditary Hemochromatosis A:ua C (hua, John K Ol nyk, Deborah 7rinder Hereditary hemochmmatosis (HH) i~ a~ antosnmal recessive disorder of iron metabolism b a ca *sesran ore and lu runs HH patients, the genetic deft:el is due to a C282Y mutation m the fqFE gene HI} knoc~..o ~t mice have rnany c)aracteristics of the human disease, accumulating e,~cess iou i~ h e live, as a res*r increased i o n absorption by the duoden u m [~ Htf. pasma non- ransk~r n bonnd iron (NTB[) levels ate increased and NTBI is /amnd mainly by ci rate ghe a m o ths study was to examine the importance of iron citrate r) fie pa hog,'nesis ul bepa ic n e loading in the Hfi"knockout mouse Hepatocytes were iso/aled tom ~fi~ knock(n and control (57BL/6] mice and
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Changing Epidemiology of Hepatitis B in a U.S. Community.: A Preliminary Report from the Olmsted County Hepatitis B Registry Kiran Bambha, Joanne T Benson, W Ray Kim Background: Recent data indicate that mortality related to hepatitis B (HBV) Juliet*ion increased in the past 20 years predominantI? among non-white, non-black men (Hepatology 2002;222A) Aims:el)To estatafish a population-based registry of commumty residents with HBV and (2)To describe demographic and serologm characteristics of the registry members Method: Population-based epidemiologic research can be conducted in Olmsted CounV, MN, because medical care is virtually sell-contained and heakhcare delivered by the by, providers in the community is tracked by the Rochester Epidemiology Proiect(REP). The REP database has been used to study the epidemiology of diseases such as primary biliab cirrhosis (Gastro 2000;I631) All Olmsted County residents diagnosed with I-fBV were identified using the REP database Complete in- and out-patient medical records were revsewed to verily residency slants and HBV diagnosis and to extract demographic, clinical and laboratory' data Results: To date, 172 community residents diagnosed with hepatitis B or had positive HBsAg dunng 1999 and 2000 have been included in the registry. O[ those 27, including 18 who had a clinical diagnosis of acute hepatitis B, had a subsequent negative HBsAg, while in the remaining 145 patients the most recent HBsAg was positive The mean age of the 145 patients as of 1/1/2000 was 38 years. Asian/Pacitlc Islander accounted thr 51%, followed by' African (31%) and Caucasian (I4%) races in the table, the vast majont} of subjects of non-white race were immigrants The most common origin elf the immigrants were Somailia(n = 36) and Cambodia(n = 23) Race-specific prevalence was much higher for not>whites than whites. There was a substantial difference m the proportions of replicative disease and transaminase activity by race Conclusions An initial cohort of a communibbased hepantis B reSiStU suggests that patients with chronic HBV intection in a Midwestem US comnmnity are mostly- immigrants lrom endemic countries Seroiogm and biochemical characteristics in these individuals were distinct from Caucasians. The registry will fie instrumental in studying the natural histou, virologic profile and treatment response in this population.

8 "lhc Incidence of ttepatocellular Carcinoma in the Umted States; Is It Still Rising? tiashe n B El-Scrag jessca Davtla, Nancy Petersen P,ackgm nn~: Increasing incidence rares [or fiepatocellutar carcinoma (HCC) were previously inputted in the U ~ited States possibly due o chronic HCV inti'ction However, ahernate ~'xplanations were diag ~ostic and,'or reclassification bias, and changes in the demographics ~f the general popn/ation {he purpose l this study is to ~*pdate recenl trends in HCC incide ~ce hnmgh 9 9 8 and to exarrine t mporal changes in incidence while adjusting for changes in age, gender e hnicty wthin g~'ograpbic regions Methods: Using inti,rmation )am ~e S)rvei/lance, pidemiol gb and laud Results (SEER) program, we identified all histologically c n[ *~ ed cases of primary HCC dining 1975-98 Age-adinsted incidence rates (AIR) were calculated k~r consecutive 3-yer per ads during 1975-98 We used Hierarchical ?nisson mnlt valia e regress*or: o examine temporal trends in HCC commI/ing for changes m age ger;der arat race a m n g h(Xi cases and in the underlying population at risk, while acc(ml ~g ha po ential cIustering ot persons with similar characteristics within geographic ~egions Resuts: Ifhe ovetall AIR ncreased from 14/100000 in 1975-77 to 3W100,000 n 1996-98:114% overall increase There was a 25% increase over the last 3 years of the study T~e pl >par o~s of patie ~ts with liver cancer undergoing m~croscnpic confirnmtion remained relative y sta)le over i m e Phe in*re'ase in HCC afiected most age groups above '40, wth tie grea est increase between ages 45 and 49 For instance, there was a striking 110% i~ crease dv~ri~:gtie [990s ~ wtim men (including Hispanic) between 45-49 The AIRs were 2 tnlds greater in blacks than whites and 2-folds greater in Asians than blacks However, w-fi~e ~:e~ and black women had the g~eatest percentage increase (31%) in the last ime period (996-98) as compared to 1993-95 Tha Poisson hierehichal regression model conhrmed an almost two thld increase in HCC incidence between 1975 and 1998. A signiheant ~ teraction between line of diagnosis and race such as that a greater increase iu H(C c i d e n c e ace.fred n whites compared to blacks and !Mians during more recent nine periods ( onclusio ~s T~e incidence of HCC continues to rapidly increase in the United States Axhough lis increase has atiected most age, gender, ethnic groups the [fastestrising rates have been obselved n whir* men between the ages at 45 and 55. "lhese findings are cons strut wit* a ~ue increase in HCC and could be explained by consequences of HCV acquired earlier n lde duing the 1960s and 1970s

AASLD Abstracts

Race

n

Age

Male

A~an African Whites OL~/Llnknown

74 ~5 20 5

38 35 44 3?

53% 53% 65% 100%

~ 99% 91% 15% I0(~%

P,ac~ HBe~ Abnom'~ Treabne~ Npciflc or DNAr Te'~msam~eeee ~revaleece 13% 35% ~% 12% 3.6% 10% 26% 2% 0.02% 25% 50% 5% 0.2% 25% 80% 0%

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Model tor End Stage Liver Disease (MELD) Scores Predict Mortality Across a Broad Spectrum of Liver Disease in a Us Tertiary"Care-Setting Adnan Said, Jeremy P. Holden, John B Williams, A.lexandru Musat, Rafael C, Botero, Michael R. Lucey Background: Although MELD scores are proposed as a predictor of 3-month mortality m severe liver disease, their accuracy have been tested intYequent/y among patients referred to a US tertiary care liver center We studied risk factors for mortality in 1611 consecutwe chronic liver disease patients presenting to a university-based hepatology service (1994 2001) and esmnated the predictive ability of MELD for 3 and 12-month mortality, Methods: 75 % were seen in the ompatlent clinic, 25% as inpatients, Survival data were censored at transplant and median survival fi'om ~terral was calculated for each diagnosis Cox proportional hazards were' used to model risk factors for mortality'. MELD scores were compared with observed 3- and 12-month sut'vival for the cohort and ROC curves analyzed to evaluate model validity (concordance and c-statistic) Next, we analyzed MELD in predicting 1-year

A-690