J Viral Hepat. 2014 Dec;21(12):938-43.

Association between chronic hepatitis C virus infection and low muscle mass in US adults.

Gowda C, Compher C, Amorosa VK, Lo Re V 3rd.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.



Given that low muscle mass can lead to worse health outcomes in patients with chronic infections, we assessed whether chronic hepatitis C virus (HCV) infection was associated with low muscle mass among US adults. We performed a cross-sectional study of the National Health Examination and Nutrition Study (1999-2010). Chronic HCV-infected patients had detectable HCV RNA. Low muscle mass was defined as <10th percentile for mid-upper arm circumference (MUAC). Multivariable logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of low muscle mass associated with chronic HCV. Among 18 513 adults, chronic HCV-infected patients (n = 303) had a higher prevalence of low muscle mass than uninfected persons (13.8% vs 6.7%; aOR, 2.22; 95% CI, 1.39-3.56), and this association remained when analyses were repeated among persons without significant liver fibrosis (aOR, 2.12; 95% CI, 1.30-3.47). This study demonstrates that chronic HCV infection is associated with low muscle mass, as assessed by MUAC measurements, even in the absence of advanced liver disease.

KEYWORDS: NHANES; chronic hepatitis C; low muscle mass; malnutrition

PMID: 24989435



Using data from the National Health and Nutrition Examination Survey (1999-2010), we demonstrated that chronic hepatitis C virus (HCV) infection was associated with a two-fold increased likelihood of low muscle mass in U.S. adults. Importantly, this association persisted even among those without advanced liver disease, suggesting that mechanisms other than hepatic decompensation are important for the development of malnutrition. Additionally, 90% of chronic HCV-infected individuals identified with low muscle mass had a normal body weight by body mass index (BMI). Thus, low muscle mass appears to be an important and early indicator of malnutrition in chronic HCV infection.

Skeletal muscle wasting is observed in many chronic infections, including tuberculosis and HIV. Importantly, among people affected by chronic infections, low muscle mass has been shown to be an independent predictor of worse health outcomes, including functional impairment, accelerated progression to AIDS, and increased mortality. Chronic viral hepatitis may similarly induce adverse changes in a patient’s nutritional status and contribute to muscle loss via a number of potential mechanisms, even prior to the development of cirrhosis (Figure 1).

 CG Fig1Figure 1. Conceptual model for association between low muscle mass and viral hepatitis.


First, persistent hepatitis C viremia may induce both chronic hepatic and systemic inflammation, which could stimulate increased metabolic demands on the body through heightened cellular activity. Second, hepatitis-induced liver injury could impair cellular processes, such as glycogenesis, gluconeogenesis, and protein synthesis, leading to subsequent muscle breakdown and alterations in the body’s available nutritional store. In addition, chronic viral hepatitis can lead to insulin resistance and the development of metabolic syndrome with associated steatohepatitis, and this direct liver injury could contribute to muscle loss. Viral hepatitis is associated with chronic kidney disease, which might independently predispose to muscle mass loss through inadequate dietary intake, inflammation and the activation of proteolytic pathways. Finally, HCV infection is associated with alcohol and substance abuse, which may contribute independently to malnutrition. In our study, we found that alcohol use was an important risk factor for low muscle mass among chronic HCV-infected persons in the U.S.

This is one of the first studies to demonstrate that nutritional health may be affected by viral hepatitis infection, even prior to the development of advanced liver disease. Although nutrition is generally recognized as an important component of health, it is often neglected and rarely addressed during clinical visits because there are competing priorities during the limited time available for clinical assessments. In addition, most clinicians rely on BMI as the primary marker of nutritional status, but this parameter does not adequately assess the nutritional status, particularly of protein malnutrition, of patients with viral hepatitis. As shown in our study, the majority of chronic HCV-infected individuals with low muscle mass had a normal body weight by BMI.

Early determination of patients with low muscle mass will enable clinicians to identify those who would maximally benefit from nutritional interventions and thus could be referred to a nutritionist or dietician. Determination of factors associated with low muscle mass will help further identify at-risk patients who might benefit from nutritional interventions even prior to the development of low muscle mass. Patients could access knowledgeable nutrition specialists in order to learn about programs that would provide increased access to food, education on healthy diets, and integration of physical activity and/or resistance training. Furthermore, clinicians may prioritize patients with low muscle mass to receive HCV treatment. Importantly, in HCV-infected patients, even with successful HCV eradication, residual liver injury can persist and still may lead to low muscle mass and subsequent poor health outcomes. Thus, nutritional interventions would remain a critical aspect in the management of these patients as well. Nutritional programs have favorable risk-benefit profiles and are cost-effective, making them feasible, especially in resource-limited areas where viral hepatitis is prevalent.

The use of anthropometric measurements, such as mid-arm muscle circumference, to assess muscle mass status in this study is innovative. Anthropometric measurements accurately capture the early loss of peripheral tissue stores of protein and muscle and may be feasibly implemented in clinical settings, enabling the detection of low muscle mass at earlier stages than can be identified on a routine physical examination. In addition, these measurements can be successfully implemented in and reproduced across different clinical settings without requiring specialized equipment, intensive training, or invasive techniques and may be particularly feasible in resource-constrained settings. Furthermore, the use of anthropometry to evaluate nutrition status in chronic liver disease is less likely to be subject to misclassification compared to other traditional nutrition measures, such as BMI or serum markers (e.g. albumin, prealbumin).

Ultimately, this work will have important public health benefits by identifying strategies to improve outcomes among chronic HCV-infected patients, particularly in resource-constrained settings with limited access to antiviral therapy or transplantation.




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