Weight Loss: A Modifiable Lifestyle Parameter That Can Alter HCV Liver Disease Progression
Stuart C. Gordon, MD
Posting Date: September 30, 2009
Clinical Professor of Medicine
Wayne State University School of Medicine
Director, Hepatology Section
Henry Ford Hospital
Detroit , Michigan
Fat infiltration in the liver was initially recognized as a cardinal histologic finding of non-A, non-B hepatitis. However, in the early days of hepatitis C, an understanding of the possible interaction between steatosis and the severity of underlying liver disease was lacking. In fact, early hepatitis C antiviral studies did not even record patient weight or body mass index (BMI).[1] Not until the late 1990s did the first reports emerge that hepatic steatosis accelerates the progression of hepatitis C virus (HCV)–induced liver damage. Today, it is generally accepted that obesity worsens the histologic severity of HCV disease.[2-5] A logical question, therefore, is whether weight reduction ameliorates liver damage and whether weight changes also influence clinical outcomes.
Everhart and colleagues[6] addressed this question in the current study in which they investigated the effects of weight-related conditions, including steatosis, on disease outcomes among 985 HCV-infected patients enrolled in the HALT-C trial (Capsule Summary). Patients enrolled in the HALT-C trial, all of whom had advanced fibrosis (ie, bridging fibrosis or cirrhosis), had high BMIs at the outset—one half were obese—suggesting that these subjects were at risk for advanced disease. During follow-up, patients who gained weight had worse outcomes compared with those who did not gain weight. Disease outcomes included worsening fibrosis, hepatic decompensation, and death from liver disease. By contrast, patients who lost weight had a decrease in such outcomes and exhibited improvements in inflammation. According to the authors, “the association of weight change with outcomes is the most immediate clinically significant finding of this analysis.”[6] In fact, a comparison of patients who lost weight vs those who gained weight revealed changes in hepatic inflammation comparable to patients who received interferon vs those who did not. These data suggest that a decrease in weight could produce similar improvement in the grade of liver disease as interferon therapy.
This study indicates that weight is arguably the most meaningful modifiable lifestyle parameter that can affect disease progression. The clinical implications of the findings are enormous and self-evident: Clinicians are obliged to better counsel their patients with chronic HCV infection on the impact of weight. Perhaps instead of admonishing patients to never again sip an alcoholic beverage, the focus of the discussion should advocate weight reduction. These findings are particularly salient in the current era in which the HCV epidemic and the obesity epidemic are running a collision course.[7] Indeed, obesity likely acts as a 2-hit cofactor that worsens other liver diseases, not just hepatitis C.[8] No future research will allow the opportunity to duplicate the findings of this report; therefore, this study represents a landmark piece of work that can be extrapolated to all liver diseases and that should change clinical practice.
The current antiviral treatment landscape, although improving, remains bleak for HCV-infected patients with advanced disease. Current and future treatment regimens remain toxic, expensive, and suboptimal. As the nation debates who will pay for such treatment, the current paper underscores the “personal responsibility” option: Lifestyle modification affects outcomes in hepatitis C (and liver disease) just as it does for diabetes, heart disease, and lung disease.[9-12] Clinicians can now cite proof that weight loss improves HCV-associated liver disease whereas weight gain worsens it. These findings should shift the framework of doctor-patient discussions in the clinical setting and encourage a broad approach to patient management that goes beyond HCV therapy alone.
References
1. Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. N Engl J Med. 1989;321:1501-1506.
2. Charlton MR, Pockros PJ, Harrison SA. Impact of obesity on treatment of chronic hepatitis C. Hepatology. 2006;43:1177-1186.
3. Leandro G, Mangia A, Hui J, et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology. 2006;130:1636-1642.
4. Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology. 2001;33:1358-1364.
5. Kallwitz ER, Layden-Almer J, Dhamija M, et al. Ethnicity and body mass index are associated with hepatitis C presentation and progression. Clin Gastroenterol Hepatol. 2009;[Epub ahead of print].
6. Everhart JE, Lok AS, Kim HY, et al. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology. 2009;137:549-557.
7. Sanyal AJ. Fatty liver disease. Semin Liver Dis. 2008;28:337.
8. Powell EE, Ali A, Clouston AD, et al. Steatosis is a cofactor in liver injury in hemochromatosis. Gastroenterology. 2005;129:1937-1943.
9. Hickman IJ, Clouston AD, Macdonald GA , et al. Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C. Gut. 2002;51:89-94.
10. Hickman IJ, Jonsson JR, Prins JB, et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut. 2004;53:413-419.
11. St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2009;50:68-76.
12. Missiha SB, Ostrowski M, Heathcote EJ. Disease progression in chronic hepatitis C: modifiable and nonmodifiable factors. Gastroenterology. 2008;134:1699-1714.