An Age-Period-Cohort Analysis of the Impact of Hepatitis B Vaccines on Hepatocellular Carcinoma in the United States Public

Abstract

Background: In the United States, chronic hepatitis B infection accounts for approximately 20% of HCC cases.Despite broader hepatitis B vaccine recommendations, current data suggest that HCC mortality increased between 1980 and 2001. In this study, we used an age-period-cohort (APC) analysis of HCC hospitalizations between 1996 and 2011 to examine trends of hepatitis B infection and determine the impact of hepatitis B vaccines on rates of HCC in the United States.

Methods: We estimated hospitalization rates for HCC using the Nationwide Inpatient Sample database.To determine the rate of HCC in individuals with a chronic hepatitis B diagnosis, a combination of ICD-9-CM codes was used. Age, period and birth cohort effects on risk of hospitalization for HCC with a hepatitis B diagnosis were also estimated for each sex using a logistic regression model.

Results: The rate of HCC with chronic hepatitis B diagnosis declined between 1996-2011. Logistic modeling showed a large increase in the log likelihood of all reduced models compared to the full APC model demonstrating that age, period, and birth cohort effects should all be taken in to account. For males and females the likelihood ratio test statistic was smallest for the PC model vs. the APC model followed by the AC vs. APC model, suggesting that birth cohort effects play an important role in risk of HCC with a chronic hepatitis B diagnosis in both males and females. Logistic regression of birth cohort effects alone showed a dramatic decrease in risk of hospitalization for HCC in both males and females born after the introduction of the hepatitis B vaccine.

Conclusion: This study demonstrates that this increase in HCC rates seen over the past two decades may not be due to chronic hepatitis B infection. Modeling of birth cohort specific effects show that broadening hepatitis B vaccine recommendations may be associated with the reduction in risk hospitalization for HCC with a chronic hepatitis B diagnosis. Given this trend, HCV infection and changing immigration trends may be playing an increasing large role in increasing HCC trends over the past decade.

Table of Contents

CHAPTER 1

BACKGROUND...1

PART 1: Hepatitis B Pathogenesis and Diagnosis...1

PART 2: Outcomes of Hepatitis B Infection...1

PART 3: Epidemiology of HBV Infection and HCC...7

PART 4: HBV Prevention...8

References...12

CHAPTER 2

ABSTRACT...15

Background...15

Methods...15

Results...16

Conclusions...16

INTRODUCTION...18

METHODS...19

Data Sources...19

Definition of Outcomes...19

Statistical Analysis...20

RESULTS...23

Birth Cohort Effect...24

Age Effect...24

Period Effect...25

DISCUSSION...26

CONCLUSION...27

REFERENCES...28

FIGURES/TABLES...30

CHAPTER 3

PUBLIC HEALTH IMPLICATIONS...36

REFERENCES...38

About this Master's Thesis

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• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Mot-clé	Hepatits B Hepatocellular Carcinoma
Committee Chair / Thesis Advisor	Omer, Saad B, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs Hospital or other health care provider

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