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ABSTRACT: Monoclonal gammopathy of undetermined significance of the immunoglobulin M class was diagnosed in 213 patients at the Mayo Clinic, 29 (14%) of whom developed lymphoma, Waldenström macroglobulinemia, or a related disorder over 1567 person-years of follow-up. The cumulative probability of progression was 10% at 5 years, 18% at 10 years, and 24% at 15 years, or approximately 1.5% per year. The concentration of serum monoclonal protein at diagnosis and the initial serum albumin value were the only independent predictors of progression with multivariate analysis. By contrast, during 285 person-years of follow-up, 34 (71%) of 48 patients with smoldering Waldenström macroglobulinemia (SWM) progressed to Waldenström macroglobulinemia (WM), which required therapy, along with amyloid light chain (AL) amyloidosis (1) and lymphoma (1). The cumulative probability of progression was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 65% at 10 years. The percentage of lymphoplasmacytic cells in the bone marrow, size of the serum monoclonal (M) spike, and hemoglobin value were significant independent risk factors for progression.
Clinical lymphoma, myeloma & leukemia 03/2013;
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ABSTRACT: Patients with perihilar cholangiocarcinoma (CCA) undergoing neoadjuvant chemoradiation followed by liver transplantation (LTx) have excellent survival. However, little is known about their quality of life (QOL). We assess the QOL of these patients and compare this to patients transplanted for other liver diseases.Between 1993 and 2010, 129 CCA patients underwent LTx of whom 93 (73%) were alive as of November 2010. All recipients were sent a previously validated QOL questionnaire, composed of disease-specific (Liver Disease Symptoms, Karnofsky score, Health Perception and Index of Well-being) and generic (SF-36 and EuroQol) QOL metrics. These were compared to 110 transplant recipients with other (exclusive of hepatitis C) liver diseases.Among CCA recipients, the response rate was 85% (N=79). Patients with CCA scored significantly better on Liver Disease Symptoms (3.3 vs. 3.2; P=.05), Karnofsky score (90.8 vs. 86.6; P=.03), SF-36 physical function (52.0 vs. 46.3; P<.001) and EuroQol mobility (10% vs.33%; P<.01); and rated their overall health better (85.9 vs. 80.7; P=.02) than non-CCA patients. CCA patients scored consistently higher on all other domains, albeit without significant differences. The observed differences in QOL remained unchanged when adjusted for demographic factors, including level of education.In conclusion, patients who underwent neoadjuvant chemoradiation followed by LTx for perihilar CCA report excellent quality of life, which is equal to or better than recipients with other liver diseases. These results are important in light of the continued debate about the feasibility of this aggressive treatment in patients with perihilar CCA. © 2013 American Association for the Study of Liver Diseases.
Liver Transplantation 02/2013; · 3.39 Impact Factor
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Terry M Therneau,
Robert A Kyle,
L Joseph Melton,
Dirk R Larson, Joanne T Benson,
Colin L Colby,
Angela Dispenzieri,
Shaji Kumar,
Jerry A Katzmann,
James R Cerhan,
S Vincent Rajkumar
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ABSTRACT: OBJECTIVES: To determine the incidence of monoclonal gammopathy of undetermined significance (MGUS) in the general population and to estimate the duration of occult MGUS before first diagnosis. METHODS: To estimate incidence we used innovative methods to exploit the Olmsted County, Minnesota, MGUS prevalence data, along with follow-up from a large cohort of patients with clinically detected MGUS. The prevalence cohort consisted of 21,463 persons systematically screened for the presence or absence of MGUS. The clinical cohort consisted of 7472 patients with MGUS diagnosed at Mayo Clinic from January 1, 1990, to May 13, 2010. The incidence of MGUS was estimated using the prevalence estimates, the rate of MGUS progression, and the death rates from MGUS using Markov chain methods. RESULTS: We estimate that the annual incidence of MGUS in men is 120 per 100,000 population at the age of 50 years and increases to 530 per 100,000 population at the age of 90 years. The rates for women are 60 per 100,000 population at the age of 50 years and 370 per 100,000 population at the age of 90 years. We estimate that 56% of women 70 years of age diagnosed as having MGUS have had the condition for more than 10 years, including 28% for more than 20 years. Corresponding values for men are 55% and 31%, respectively. At 60 years of age, the proportion of prevalent cases that are clinically recognized is 13%. This rate increases to 33% at the age of 80 years. CONCLUSION: In addition to an accumulation of cases, the age-related increase in prevalence of MGUS is related to a true increase in incidence with age. When first clinically recognized, MGUS has likely been present in an undetected state for a median duration of more than 10 years.
Mayo Clinic Proceedings 08/2012; · 5.70 Impact Factor
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ABSTRACT: The purpose of this study was to define the risk of progression and survival of patients with smoldering Waldenström macroglobulinemia (SWM). SWM is defined clinically as having a serum monoclonal IgM protein≥3 g/dL and/or≥10% bone marrow lymphoplasmacytic infiltration but no evidence of end-organ damage (anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly). We searched a computerized database and reviewed the medical records of all patients at Mayo Clinic who fulfilled the criteria of SWM between 1974 and 1995. During 285 cumulative person-years of follow-up of the 48 patients with SWM (median, 15.4 years), 34 (71%) progressed to symptomatic Waldenström macroglobulinemia (WM) requiring treatment, one to primary amyloidosis, and one to lymphoma (total, 75%). The cumulative probability of progression to symptomatic WM, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 68% at 10 years. The major risk factors for progression were percentage of lymphoplasmacytic cells in the bone marrow, size of the serum M-spike, and the hemoglobin value. Patients with SWM should be followed and not treated until symptomatic WM develops. Treatment on a clinical trial for those at greatest risk of progression should be considered.
Blood 03/2012; 119(19):4462-6. · 9.90 Impact Factor
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The American Journal of Gastroenterology 12/2011; 106(12):2209. · 7.28 Impact Factor
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ABSTRACT: We analyzed serial data in patients with clinically stable monoclonal gammopathy to determine the total variation of serum M-spikes [measured with serum protein electrophoresis (SPEP)], urine M-spikes [measured with urine protein electrophoresis (UPEP)], and monoclonal serum free light chain (FLC) concentrations measured with immunoassay.
Patients to be studied were identified by (a) no treatment during the study interval, (b) no change in diagnosis and <5 g/L change in serum M-spike over the course of observation; (c) performance of all 3 tests (SPEP, UPEP, FLC immunoassay) in at least 3 serial samples that were obtained 9 months to 5 years apart; (d) serum M-spike ≥10 g/L, urine M-spike ≥200 mg/24 h, or clonal FLC ≥100 mg/L. The total CV was calculated for each method.
Among the cohort of 158 patients, 90 had measurable serum M-spikes, 25 had urine M-spikes, and 52 had measurable serum FLC abnormalities. The CVs were calculated for serial SPEP M-spikes (8.1%), UPEP M-spikes (35.8%), and serum FLC concentrations (28.4%). Combining these CVs and the interassay analytical CVs, we calculated the biological CV for the serum M-spike (7.8%), urine M-spike (35.5%), and serum FLC concentration (27.8%).
The variations in urine M-spike and serum FLC measurements during patient monitoring are similar and are larger than those for serum M-spikes. In addition, in this group of stable patients, a measurable serum FLC concentration was available twice as often as a measurable urine M-spike.
Clinical Chemistry 12/2011; 57(12):1687-92. · 7.91 Impact Factor
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ABSTRACT: Population-based data on chronic pancreatitis (CP) in the United States are scarce. We determined incidence, prevalence, and survival of CP in Olmsted County, MN.
Using Mayo Clinic Rochester's Medical Diagnostic Index followed by a detailed chart review, we identified 106 incident CP cases from 1977 to 2006 (89 clinical cases, 17 diagnosed only at autopsy); CP was defined by previously published Mayo Clinic criteria. We calculated age- and sex-adjusted incidence (for each decade) and prevalence rate (1 January 2006) per 100,000 population (adjusted to 2000 US White population). We compared the observed survival rate for patients with expected survival for age- and sex-matched Minnesota White population.
Median age at diagnosis of CP was 58 years, 56% were male, and 51% had alcoholic CP. The overall (clinical cases or diagnosed only at autopsy) age- and sex-adjusted incidence was 4.05/100,000 person-years (95% confidence interval (CI) 3.27-4.83). The incidence rate for clinical cases increased significantly from 2.94/100,000 during 1977-1986 to 4.35/100,000 person-years during 1997-2006 (P<0.05) because of an increase in the incidence of alcoholic CP. There were 51 prevalent CP cases on 1 January 2006 (57% male, 53% alcoholic). The age- and sex-adjusted prevalence rate per 100,000 population was 41.76 (95% CI 30.21-53.32). At last follow-up, 50 patients were alive. Survival among CP patients was significantly lower than age- and sex-specific expected survival in Minnesota White population (P<0.001).
Incidence and prevalence of CP are low, and ∼50% are alcohol related. The incidence of CP cases diagnosed during life is increasing. Survival of CP patients is lower than in the Minnesota White population.
The American Journal of Gastroenterology 09/2011; 106(12):2192-9. · 7.28 Impact Factor
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ABSTRACT: The Model for End Stage Liver Disease (MELD) was originally developed based on data from patients who underwent the transjugular intrahepatic portosystemic shunt procedure. An updated MELD based on data from patients awaiting liver transplantation should improve mortality prediction and allocation efficiency.
Wait-list data from adult primary liver transplantation candidates from the Organ Procurement and Transplantation Network were divided into a model derivation set (2005-2006; n=14,214) and validation set (2007-2008; n=13,945). Cox regression analysis was used to derive and validate an optimized model that updated coefficients and upper and lower bounds for MELD components and included serum levels of sodium. Main outcomes measure was ability to predict 90-day mortality of patients on the liver transplantation wait list.
Optimized MELD score updated coefficients and implemented new upper and lower bounds for creatinine (0.8 and 3.0 mg/dL, respectively) and international normalized ratio (1 and 3, respectively). Serum sodium concentrations significantly predicted mortality, even after adjusting for the updated MELD model. The final model, based on updated fit of the 4 variables (ie, bilirubin, creatinine, international normalized ratio, and sodium) had a modest yet statistically significant gain in discrimination (concordance: 0.878 vs 0.865; P<.01) in the validation dataset. Utilization of the new score could affect up to 12% of patients (based on changed score for 459 of 3981 transplants in the validation set).
Modification of MELD score to update coefficients, change upper and lower bounds, and incorporate serum sodium levels improved wait-list mortality prediction and should increase efficiency of allocation of donated livers.
Gastroenterology 02/2011; 140(7):1952-60. · 11.68 Impact Factor
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ABSTRACT: There are few data available about the prevalence or effects of cirrhosis in patients with hepatocellular carcinoma (HCC) from viral hepatitis. We compared patients with HCC and hepatitis B virus (HBV) or hepatitis C virus (HCV) infections to determine the proportions of cirrhosis in each group, virologic and tumor characteristics, and overall survival.
This analysis included patients with HBV (n = 64) or HCV (n = 118) infection who were diagnosed with HCC at the Mayo Clinic in Rochester, Minnesota from 1994-2008; groups were matched for age and sex. The diagnosis of cirrhosis was based on histology and, if histologic information was insufficient or unavailable, clinical indicators that included ascites or varices, thrombocytopenia or splenomegaly, and radiographic configuration of cirrhosis. Virologic characteristics, tumor stage, and patient survival were also assessed.
The prevalence of histologic cirrhosis was 88% among patients with HBV infection and 93% among those with HCV infection (P = .46). When the most inclusive criteria for cirrhosis were applied, cirrhosis was present in 94% of patients with HBV and 97% with HCV (P = .24). Among HCV patients, 5.2% were negative for HCV RNA after antiviral treatment; 63.4% of HBV patients had HBV DNA <2000 IU/mL with or without treatment. Patients with HBV tended to have less surveillance and more advanced stages of HCC, without differences in survival from those with HCV infection (P = .75).
Most patients with HCC and chronic viral hepatitis had evidence of cirrhosis, including those with HBV infection and those without active viral replication.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2011; 9(1):64-70. · 5.64 Impact Factor
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ABSTRACT: Serum creatinine, a component of the model for end-stage liver disease (MELD), is an important prognostic indicator in patients with end-stage liver disease (ESLD). In addition, serum sodium has recently been recognized as an important predictor of mortality in patients with ESLD. We investigate the role of serum creatinine and sodium, and glomerular filtration rate (GFR) as determinants of survival in patients with ESLD.
A prospective database was utilized to identify all adults listed for primary liver transplantation (LTx) at the Mayo Clinic, Rochester, between 1990 and 1999. GFR was measured by iothalamate clearance.
Among 837 patients listed for LTx, 660 had complete data including measured GFR. There was a significant association between GFR and survival after adjustment for MELD, with a linear rise in the risk of death as GFR decreased between 60 and 20ml/min/1.73m(2). Multivariable models showed that GFR is superior to creatinine in predicting mortality - a model consisting of total bilirubin (hazard ratio (HR)=2.17, p<0.01), INR (HR=3.26, p<0.01) and GFR (HR=0.42, p<0.01) was superior to MELD (chi-square 65.6 vs. 59.4, c-statistic 0.792 vs. 0.780). Serum sodium did not contribute to survival prediction when accurately measured GFR data were available.
Serum concentrations of creatinine and sodium in patients with end-stage liver disease reflect a reduction in renal function, the underlying event that decreases survival.
Journal of Hepatology 02/2010; 52(4):523-8. · 9.26 Impact Factor
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ABSTRACT: Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting orthotopic liver transplantation (OLT). However, data are sparse regarding the impact of hyponatremia on outcome following OLT. We investigated the effect of hyponatremia at the time of OLT on mortality and morbidity following the procedure. The study included 2,175 primary OLT recipients between 1990 and 2000. Serum sodium concentrations obtained immediately prior to OLT were correlated with subsequent survival using proportional hazards analysis. Morbidity associated with hyponatremia was assessed, including length of hospitalization, length of intensive care unit (ICU) admission, and occurrence of central pontine myelinolysis (CPM). Out of 2,175 subjects, 1,495 (68.7%) had normal serum sodium (>135 mEq/L) at OLT, whereas mild hyponatremia (125-134 mEq/L) was present in 615 (28.3%) and severe hyponatremia (<125 mEq/L) in 65 (3.0%). Serum sodium had no impact on survival up to 90 days after OLT (multivariate hazard ratio = 1.00, P = 0.99). Patients with severe hyponatremia tended to have a longer stay in the ICU (median = 4.5 days) and hospital (17.0 days) compared to normonatremic recipients (median ICU stay = 3.0 days, hospital stay = 14.0 days; P = 0.02 and 0.08, respectively). There were 10 subjects that developed CPM, with an overall incidence of 0.5%. Although infrequent, the incidence of CPM did correlate with serum sodium levels (P < 0.01). Conclusion: Pre-OLT serum sodium does not have a statistically significant impact on survival following OLT. The incidence of CPM correlates with hyponatremia, although its overall incidence is low. Incorporation of serum sodium in organ allocation may not adversely affect the overall post-OLT outcome.
Hepatology 01/2009; 49(5):1610-5. · 11.66 Impact Factor
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ABSTRACT: Under the current liver-transplantation policy, donor organs are offered to patients with the highest risk of death.
Using data derived from all adult candidates for primary liver transplantation who were registered with the Organ Procurement and Transplantation Network in 2005 and 2006, we developed and validated a multivariable survival model to predict mortality at 90 days after registration. The predictor variable was the Model for End-Stage Liver Disease (MELD) score with and without the addition of the serum sodium concentration. The MELD score (on a scale of 6 to 40, with higher values indicating more severe disease) is calculated on the basis of the serum bilirubin and creatinine concentrations and the international normalized ratio for the prothrombin time.
In 2005, there were 6769 registrants, including 1781 who underwent liver transplantation and 422 who died within 90 days after registration on the waiting list. Both the MELD score and the serum sodium concentration were significantly associated with mortality (hazard ratio for death, 1.21 per MELD point and 1.05 per 1-unit decrease in the serum sodium concentration for values between 125 and 140 mmol per liter; P<0.001 for both variables). Furthermore, a significant interaction was found between the MELD score and the serum sodium concentration, indicating that the effect of the serum sodium concentration was greater in patients with a low MELD score. When applied to the data from 2006, when 477 patients died within 3 months after registration on the waiting list, the combination of the MELD score and the serum sodium concentration was considerably higher than the MELD score alone in 32 patients who died (7%). Thus, assignment of priority according to the MELD score combined with the serum sodium concentration might have resulted in transplantation and prevented death.
This population-wide study shows that the MELD score and the serum sodium concentration are important predictors of survival among candidates for liver transplantation.
New England Journal of Medicine 09/2008; 359(10):1018-26. · 53.30 Impact Factor
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ABSTRACT: For more than 60 years it has been known that profiles from the Minnesota Multiphasic Personality Inventory (MMPI), obtained from medical patients, are elevated when scores are plotted using general population norms. These elevations have been most apparent on the neurotic triad (NTd), the first 3 clinical scales on the MMPI profile. More than 45 years have passed since a nonreferred, normative sample of MMPIs was established from 50,000 consecutive medical outpatients. We present comparable but contemporary normative data for the revised MMPI (MMPI-2) based on a nonreferred sample of 1,243 family medicine outpatients (590 women; 653 men). As true for the original MMPI, contemporary medical outpatients have profiles that are significantly different, clinically and statistically, from the general population norms for the MMPI-2. This is particularly evident in elevations on the NTd. New normative tables of uniform medical T (UMT) scores were developed following the procedures used to create the uniform T scores for the MMPI-2. Measures of internal consistency are reported; test-retest reliability was established over a mean of 3.7 weeks, and results characterizing the stability of the validity and clinical scales are presented.
Journal of Clinical Psychology in Medical Settings 07/2008; 15(2):98-119. · 1.49 Impact Factor
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ABSTRACT: Serum aminotransferase [such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] is commonly used as an indicator of liver disease. The aim of the study was to determine the degree to which aminotransferase results are associated with increased mortality at the population level. All adult residents of Olmsted County, Minnesota, who had a health care encounter at Mayo Clinic, Rochester, in 1995 were identified and their AST or ALT results extracted from a laboratory database. These subjects were followed forward from January 1995 to April 2006 and their survival determined. To exclude patients with abnormal results because of a terminal illness, deaths within the first 2 years were excluded. The main outcome measure was survival. Standardized mortality ratios (SMRs) were calculated, based on Minnesota White death rates. During 1995, AST was measured at least once in 18,401 community residents, of whom 2,350 (13%) had results greater than the upper limit of normal (ULN). Of 6,823 subjects who had their ALT measured, 911 (13%) had results higher than ULN. Abnormal AST was associated with a significantly increased SMR (1.32 for 1-2x ULN and 1.78 for >2x ULN). SMR was also higher for abnormal ALT (SMR = 1.21 for 1-2x ULN and 1.51 for >2x ULN). In contrast, normal AST or ALT was associated with a risk of death lower than expected (SMR 0.95 for AST, 0.61 for ALT). CONCLUSION: Serum levels of AST and ALT obtained in a routine medical care setting are associated with future mortality in community residents.
Hepatology 03/2008; 47(3):880-7. · 11.66 Impact Factor
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ABSTRACT: Serum aminotransferase [such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] is commonly used as an indicator of liver disease. The aim of the study was to determine the degree to which aminotransferase results are associated with increased mortality at the population level. All adult residents of Olmsted County, Minnesota, who had a health care encounter at Mayo Clinic, Rochester, in 1995 were identified and their AST or ALT results extracted from a laboratory database. These subjects were followed forward from January 1995 to April 2006 and their survival determined. To exclude patients with abnormal results because of a terminal illness, deaths within the first 2 years were excluded. The main outcome measure was survival. Standardized mortality ratios (SMRs) were calculated, based on Minnesota White death rates. During 1995, AST was measured at least once in 18,401 community residents, of whom 2,350 (13%) had results greater than the upper limit of normal (ULN). Of 6,823 subjects who had their ALT measured, 911 (13%) had results higher than ULN. Abnormal AST was associated with a significantly increased SMR (1.32 for 1–2× ULN and 1.78 for >2× ULN). SMR was also higher for abnormal ALT (SMR = 1.21 for 1–2× ULN and 1.51 for >2× ULN). In contrast, normal AST or ALT was associated with a risk of death lower than expected (SMR 0.95 for AST, 0.61 for ALT). Conclusion: Serum levels of AST and ALT obtained in a routine medical care setting are associated with future mortality in community residents. (HEPATOLOGY 2008;47:880–887.)
Hepatology 02/2008; 47(3):880 - 887. · 11.66 Impact Factor
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ABSTRACT: The usual method of estimating survival probabilities, namely the Kaplan-Meier method, is suboptimal in the analysis of deaths on the transplant waiting list. Death, transplantation, and withdrawal from list must all be considered. In this analysis, we applied the competing risk analysis method, which allows evaluating these end points individually and simultaneously, to compare the risk of waiting list death across era, blood types, liver disease diagnosis, and severity (Model for End-stage Liver Disease; MELD). Of 861 patients registered on the waiting list at Mayo Clinic Rochester between 1990 and 1999, 657 (76%) patients underwent transplantation, 82 (10%) died while waiting, 41 (5%) withdrew from the list, and 81 (9%) patients were still waiting as of February 2002. The risk of death at 3 years was 10% by the competing risk analysis. During the study period, the median time to transplantation increased from 45 to 517 days. In univariate analyses, there was no significant difference in the risk of death by era of listing (P = .25) or blood type (P = .31), whereas the risk of death was significantly higher in patients with alcohol-induced liver disease and those with higher MELD score (P < .01). A multivariable analysis showed that after adjusting for MELD, blood type, and diagnosis, patients listed in the latter era had higher mortality. In conclusion, the competing risk analysis method is useful in estimating the risk of death among patients awaiting liver transplantation.
Hepatology 02/2006; 43(2):345-51. · 11.66 Impact Factor
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ABSTRACT: The incidence of hepatocellular carcinoma (HCC) has been increasing in the United States. Although resource-intensive treatment modalities have been increasingly applied, these patients still have poor survival. We examined 2 nationally representative databases, the Multiple Cause of Death file and the Nationwide Inpatient Sample database, to examine trends in mortality and hospital service utilization related to HCC. Methods: In both databases, a priori criteria were used to identify cases of HCC. All other available diagnostic fields were examined to characterize coexistent liver disease. Age-, sex-, and race-specific mortality from HCC was calculated, and temporal changes in mortality rates were evaluated using the multivariable Poisson model. Hospital service utilization was estimated based on length of stay, total hospitalization charges, and principal procedures.
The age-, sex-, and race-specific mortality from HCC increased from 1.54 to 2.58 per 100,000 per year between 1980 and 1998. Male sex, African and Asian race, and increasing age were also associated with higher mortality. The estimated total charge for HCC hospitalizations nationwide increased from 241 million US dollars in 1988 to 509 million US dollars in 2000 after inflation adjustment. Commonly employed procedures in 2000 included angiography/embolization, resection, local ablative therapy, and liver transplantation.
In the recent past, mortality and hospital service utilization related to HCC increased substantially. Closer epidemiologic surveillance to understand causation of HCC at the population level and to help implement primary and secondary prevention is urgently warranted.
Gastroenterology 08/2005; 129(2):486-93. · 11.68 Impact Factor
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ABSTRACT: We examined whether consideration of repeated model for end-stage liver disease (MELD) measurements for patients listed for liver transplantation improves predictive value beyond current MELD alone. Clinical data were extracted for all adult primary liver transplantation candidates from our institution who were listed with the United Network for Organ Sharing (UNOS) between 1990 and 1999. Serum creatinine, bilirubin, and international normalized ratio (INR) were obtained from an institutional laboratory database. Cox models were constructed using current MELD, change in MELD (Delta), and number of MELD scores to predict survival on the waiting list. Eight hundred and sixty-one patients met inclusion criteria, 639 underwent transplantation, and 80 died while waiting. A one-unit increment in current MELD imparted significant hazard ratios ranging from 1.12 to 1.19 in all models. Delta MELD was predictive of mortality univariately, but less predictive when current MELD was included, and not predictive when considered with both current and number of MELD scores. Overall, current MELD is the single most important determinant of mortality risk on the waiting list. Delta MELD is predictive of death only within 4 d of the event; however, part of this correlates with the dying process itself, thus limiting Delta MELD's utility in survival prediction models.
American Journal of Transplantation 12/2004; 4(11):1798-804. · 6.39 Impact Factor
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ABSTRACT: In previous studies about the natural history of chronic hepatitis C (CHC), age at the time of infection correlated with the rate at which hepatic fibrosis progresses. The presence of a competing risk, namely higher mortality from natural causes, may contribute to this observation. A simulation experiment was conducted to measure the magnitude of the effect of competing risks on the observed rate of fibrosis progression of CHC.
A computer-based probabilistic model was created in which fibrosis of CHC progressed from stage 0 to 4 (cirrhosis) in 20-year-old and 50-year-old male and female cohorts. The rate of fibrosis progression was randomly assigned to each simulated individual from a distribution common to all age- and sex-specific cohorts. The cohorts also experienced mortality from natural causes according to the 2000 census data.
The observed median time to reach cirrhosis for the 50-year-old cohorts was 20.4 +/- 0.2 years compared with 29.7 +/- 0.2 for the 20-year-old cohorts ( P < 0.01). The median time to reach cirrhosis in men was 24.2 +/- 0.6 years compared with 25.9 +/- 0.6 in women ( P = 0.01). Overall, the observed rate of progression was slowest among young women. Similarly, accelerating mortality from natural causes, simulating the impact of comorbid conditions that shorten survival, reduced the observed time to reach cirrhosis.
Even if the underlying rate of fibrosis progression in CHC was held constant, the time to reach cirrhosis will be observed to be substantially shorter in subjects with a higher competing mortality.
Gastroenterology 09/2004; 127(3):749-55. · 11.68 Impact Factor
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ABSTRACT: Despite a reduction in newly acquired hepatitis B virus (HBV) infections since the mid-1980s, HBV remains an important cause of liver disease in the U.S. We report the prevalence of chronic HBV infection in a U.S. community and describe demographic and clinical characteristics. The Rochester Epidemiology Project records healthcare encounters of residents of Olmsted County, Minnesota. For all cases with a potential diagnosis of hepatitis B in this database, complete medical records were reviewed to identify subjects who met the inclusion criteria, i.e., a clinician diagnosis of chronic HBV infection and a laboratory record of positive hepatitis B surface antigen (HBsAg). There were 191 residents with chronic HBV infection in the community, consisting of 53% Asian, 29% African, 13% Caucasian, and 5% other or unknown race. The overall age- and sex-adjusted prevalence of HBV in this community was 0.15% in 2000. The race-specific prevalence was highest among Asians (2.1%), followed by African Americans (1.9%). The prevalence among Caucasians was 0.02%. Overall, 86% were born outside the U.S., 98% of whom were non-Caucasian. A total of 131 residents were tested for HBV replicative status, of whom 27% had viral replication. Of those tested for aminotransferases (n = 184), 28% had an abnormal value at least once. In a multivariable regression analysis, replicative status was the most influential (odds ratio [OR] = 5.98, P <.01) factor associated with abnormal aminotransferase values, followed by male gender (OR = 3.69) and age greater than 40 years (OR = 2.32 per decade). In conclusion, in this Midwestern community, chronic HBV infection was predominantly seen in immigrants from endemic parts of the world.
Hepatology 03/2004; 39(3):811-6. · 11.66 Impact Factor
