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Metabolic Syndrome Hikes Mortality in Hepatitis C
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MedPage Today
April 24, 2009
WHEELING, W.Va., April 24 -- Patients with hepatitis C infection appear more likely to die from the condition if they also suffer from one or more components of metabolic syndrome, a researcher said.
Excess body weight and hypertension both significantly heightened the risk of liver-related mortality in hepatitis C patients, according to data from the third National Health and Nutrition Examination Survey (NHANES) series, reported Zobair Younossi, M.D., of Inova Health System in Falls Church, Va.
Those two factors as well as the third component of metabolic syndrome -- type 2 diabetes -- also made death from all causes more likely during the study period, said Dr. Younossi.
He spoke with MedPage Today by telephone from Copenhagen, Denmark, in advance of his formal presentation of the data at the annual meeting of the European Association for the Study of the Liver.
Action Points
* Explain to interested patients that progression of hepatitis C is influenced by a variety of factors and comorbid conditions,
* Explain that the study did not address the effects of treatment of hypertension, obesity, or diabetes or insulin resistance on survival of HCV-infected patients.
Earlier research had found numerous factors associated with more rapid progression of hepatitis C infection, Dr. Younossi said, including components of metabolic syndrome individually and, perhaps, together.
To explore the relationship, Dr. Younossi and his colleagues analyzed data from NHANES III, conducted from 1988 to 1994. The data also include mortality follow-up information through 2000, a median of 8.5 years.
Out of more than 31,000 NHANES participants, the researchers identified 264 with hepatitis C and 13,004 without liver disease who could serve as controls.
Only survey participants with complete records for numerous clinical parameters were eligible for inclusion in the study.
The researchers found that hepatitis C cases were more likely than controls to have insulin resistance, as defined by a HOMA score of at least 3 -- 37.4% of cases versus 22.5% of controls (P=0.02) -- and were dramatically more likely to smoke (64.0% versus 26.6%, P<0.001).
A diagnosis of type 2 diabetes was moderately more common among cases as well.
On the other hand, the hepatitis C cases showed somewhat lower rates of hypertension, obesity, and metabolic syndrome.
But the 51 deaths among the hepatitis C cases were disproportionately concentrated in those with the latter conditions.
With multivariate analysis, the researchers calculated the following adjusted hazard ratios for all-cause mortality in hepatitis C cases, compared with controls:
* Type 2 diabetes: HR 2.14 (95% CI 2.11 to 2.16)
* Higher body mass index: HR 1.05 (95% 1.05 to 1.06)
* Hypertension: HR 1.41 (95% CI 1.39 to 1.42)
For liver-related death only, two of these three factors were also strong predictors in the hepatitis C cases:
* Higher BMI: HR 1.28 (95% CI 1.27 to 1.28)
* Hypertension: HR 3.75 (95% CI 3.65 to 3.85)
Dr. Younossi said that patients with any of the components of metabolic syndrome should be treated for them, and those with hepatitis C are no exception.
But he cautioned that only a prospective trial could confirm that successful treatment of metabolic syndrome or its components would improve survival in hepatitis C patients.
He also noted several limitations of the study: lack of liver biopsy or genotype data for hepatitis C cases, a relatively short follow-up, and the potential underestimation of hepatitis C prevalence in NHANES data.
Session Title: GENERAL SESSION 4 & CLOSING
Presentation Date: Apr 26, 2009
TYPE 2 DIABETES (DM), OBESITY AND HYPERTENSION (HTN) ARE ASSOCIATED WITH MORTALITY IN HEPATITIS C (HCV) PATIENTS
N. Rafiq1,2, M. Stepanova1,2, B. Lam1, Z. Younossi1,2
1Center for Liver Diseases, Inova Fairfax Hospital, Inova Health System, 2Center for Integrated Research, Inova Health System, Falls Church, VA, USA
Background: Recent data suggests that components of metabolic syndrome (MS) are associated with adverse outcomes in HCV patients.
Aim: To determine the impact of components of MS on mortality of HCV patients.
Methods: We utilized the Third National Health and Nutrition Examination Survey (NHANES III) and Linked Mortality Files. HCV was defined as positive HCV RNA by PCR assay. Subjects without other causes of chronic liver disease such as presumed NAFLD, elevated serum aminotransferases (ALT> 40 U/L, AST> 37 U/L in men, and ALT> 31 U/L, AST>31 U/L in women), excessive alcohol use (>10 grams/day in women and > 20 grams/day in men), elevated transferrin saturation (>50%) and positive hepatitis Bs antigen were designated controls without liver disease. HCV patients were compared to HCV-negative individuals and controls without liver disease using Rao-Scott chi-square statistics. Adjusted hazard ratios (AHR, 95% CI) for overall mortality and cause-specific mortality were calculated for HCV patients using persons without HCV. Cox proportional hazard model was used for calculation of AHR for independent risk factors, and for the presence of HCV as a potential risk factor for overall mortality and cause-specific mortalities. MS was defined according to ATP-III and insulin resistance (IR) was defined as HOMA>3.0.
Results: Cohort included 15,866 individuals with complete data. Among those, 264 patients were HCV-positive, and 13,004 were considered controls. HCV patients had more IR (37.4±3.2% vs. 22.8±0.9%, p< 0.0001) and higher rate of DM (9.2±2.3% vs. 5.5±0.3%, p=0.0885) than controls. In comparison to the HCV-negative patients, HCV patients had higher overall mortality (AHR=2.80, 2.79-2.81), higher liver-related mortality (AHR=17.96, 17.80-18.12), higher DM-related mortality (AHR=18.55, 18.36-18.74) and higher mortality from solid organ malignancy (AHR=1.601, 1.587-1.616). In HCV-infected patients, top 3 predictors of liver related mortality were having higher BMI, presence of IR and elevated serum cholesterol. In HCV patients, increased overall mortality was associated with components of MS [DM (AHR=2.139, 2.11-2.16), higher BMI (AHR=1.054, 1.53-1.055) and HTN (AHR=1.408, 1.394-1.422)]. In HCV patients, increased liver-related mortality was associated with higher BMI (AHR=1.275, 1.274-1.277) and HTN (AHR=3.751, 3.653-3.851).
Conclusions: Components of MS are associated with overall and liver-related mortality in HCV infected patients.
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