Diabetes, obesity and hypertension increase mortality in hepatitis C patients

The specific impact of metabolic syndrome on mortality in hepatitis C patients has been revealed by new research to be presented on Sunday April 26 at EASL 2009, the Annual Meeting of the European Association for the Study of the Liver in Copenhagen, Denmark.

According to the results of the research, type 2 diabetes (DM), obesity and hypertension (HTN) are associated with overall and liver related mortality in hepatitis C (HCV) infected patients. In HCV-infected patients, the top three predictors of liver related mortality were having higher body mass index (BMI), presence of insulin resistance (IR) and elevated serum cholesterol. Overall mortality in HCV patients was most linked to metabolic syndrome, higher BMI and hypertension.

Metabolic syndrome is a combination of medical problems that increase risks of cardiovascular disease and diabetes. It affects one in five people, and prevalence increases with age. Recent data have suggested that metabolic syndrome is associated with adverse outcomes in HCV patients. This study set out to assess which aspects of metabolic syndrome are of most risk to such HCV patients and to quantify their specific impact on mortality.

Professor Zobair Younossi MD, MPH from the Center for Liver Diseases at Inova Fairfax Hospital and the Executive Director of Betty and Guy Beatty's Center for Integrated Research, Virginia, USA, who led the study, said: "Exploring the risk factors associated with adverse outcomes in HCV patients helps us to better understand the complex nature of this highly prevalent disease. This study shows a clear association between key components of metabolic syndrome and mortality in HCV patients and demonstrates the importance of lifestyle improvements and coaching in the management of HCV patients, to potentially minimise the onset and impact of metabolic syndrome and its associated mortality risks."

Researchers in this study utilised 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 with 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. The 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.

The 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 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).

Dr Younossi added "This is the largest population-based study to provide the strongest evidence confirming an association between components of MS, especially type 2 diabetes and obesity, with adverse mortality outcomes for HCV infected patients. These data should help us not only develop better targeted treatment strategies for HCV patients but also encourage public health policies to address the increasing epidemic of obesity and type 2 diabetes that may affect a large number of population, including those infected with HCV".

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