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Liver Disease Is Leading Cause of Death for People with Chronic Hepatitis B


Advanced liver disease caused by hepatitis B virus (HBV) -- including hepatocellular carcinoma (HCC) and decompensated cirrhosis -- accounted for more than 40% of deaths of people with chronic hepatitis B in a large health maintenance organization, researchers reported in the December 12, 2012, advance online edition of Hepatology.

Over years or decades chronic HBV infection can lead to severe liver damage including advanced fibrosis, cirrhosis (scarring), and HCC, a form of primary liver cancer. Ultimately, untreated hepatitis B can result in decompensated disease, liver failure, liver transplantation, or death.

Jean-Luc Szpakowski and Lue-Yen Tucker from Kaiser Permanente looked at the natural history of HBV infection in a U.S. population comprised largely of people of Asian descent.

The researchers identified the causes of death for 6689 health plan members infected with HBV who were followed between March 1996 and December 2005. The analysis included 3445 men and 3244 women. A majority (68%) were of Asian/Pacific Islander (API) descent, 12% were white, and 20% were of other or unknown race/ethnicity. Most had not been treated with antiviral therapy for hepatitis B.

Causes of death were classified as HBV-related (subdivided into decompensated cirrhosis and HCC), all types of cancer, cardiovascular disease, and other or unknown causes. Decompensated cirrhosis was defined as having ascites (abdominal fluid accumulation), portal hypertension, or hepatic encephalopathy.


  • A total of 439 patents died during the study period, 307 of whom were men.
  • The overall mortality rate was 7.5 per 1000 person-years.
  • 205 total deaths -- including 165 among men -- were related to HBV infection.
  • Men had higher overall 10-year death rates than women:

o   Total deaths: 8.9% vs 4.1%;

o   HBV-related deaths: 4.8% vs 1.2%.

  • Approximately 40% of all deaths in patients over age 40 were HBV-related.
  • The death rate from HCC was 2 times higher than that of deaths from decompensated cirrhosis.
  • Deaths due to HCC accounted 70% of all cancer deaths among men and 37% among women.
  • In a multivariate analysis, older age, male sex, and pre-existing comorbidities (such as kidney disease, diabetes, and cardiovascular disease) were significant predictors of all-cause mortality.
  • However, only older age predicted death due to HBV-related causes:

o   Men age 40-64 years: odds ratio (OR) 7.8 or nearly 8-fold higher risk;

o   Men age 65 or older: OR 34.4;

o   Women age 40-64 years: OR 11.4;

o   Women age 65 or older: OR 50.0.

"HBV was the cause of death in over 40% of those who died during the study, and the mortality increased markedly with increasing age over 40 in males and over 50 in females," the study authors concluded. "HBV-related mortality was 4 times more common in males than in females and was as common in non-Asians as in those of API origin."

"This has implications for the priority that should be given to age-appropriate HCC screening in this population," they recommended. "Even more important are the appropriate screening for HBV in high-risk populations, appropriate use of anti-HBV medications, and ultimate eradication of this disease through universal HBV vaccination."



J-L Szpakowski and L-Y Tucker. Causes of death in patients with hepatitis B: A natural history cohort study in the United States. Hepatology. December 12, 2012 (Epub ahead of print).