January/February 2018

Hepatic Disease: The ABCs of NAFLD and NASH
By Debra Sanders, PhD, RN, GCNS-BC, FNGNA
Today's Geriatric Medicine
Vol. 11 No. 1 P. 10

The combination of age-related changes in the liver and significant increases in chronic conditions such as obesity, hypertension, hypercholesterolemia, and diabetes heightens elders' risk of diseases of the liver.

Although the liver does not undergo common degenerative diseases like those in other body systems such as the circulatory and skeletal systems, it does experience some age-related changes that may increase older adults' vulnerability to acute liver injury and, therefore, deserves some consideration and attention.

Aging is associated with gradual changes in hepatic structure and function that may contribute to increased risk of liver disease and ensuing increased mortality. The volume and blood flow of the liver decreases over time. In people aged 65 and older, a 35% decrease in the liver's blood volume may occur, primarily in the form of a mass of functional hepatocytes. Accumulation of dense undegradable protein aggregates (lipofuscin) that form due to protein damage and oxidative stress can increase over time. This characteristic "brown atrophy" change in an aging liver can give the organ a darkened color from lipofuscin pigment in the hepatocytes.1

Hepatocyte concentration of P450 enzymes decreases with aging, leading to difficulties with drug metabolism, particularly phase I reactions (hepatic first-pass uptake). This finding in combination with declining hepatocyte mass and hepatic blood flow, raises concern for altered clearance of many medications as well as drug-induced liver injury.2

Despite these gradual age-related changes, the liver is fairly tolerant to both acute and chronic insults with reasonably good ability to recover and regenerate. However, the aging process may cause the regenerative process to take a bit longer following an insult, as the mechanisms involved in this regeneration are complex.

Age-related changes in the liver coupled with a dramatic increase in chronic conditions such as obesity, hypertension, hypercholesterolemia, and diabetes put older adults at increasing risk for disease of the liver. Fatty liver disease is rapidly becoming a threat in the aging population.

Fatty Liver Disease: NAFLD and NASH
Over the past two decades or so, nonalcoholic fatty liver disease (NAFLD) or fatty liver, has become the most common liver disease seen in the Unites States, affecting as many as 25% of adults, with increased prevalence as age increases.2,3 NAFLD is more common in middle-aged and older males than in females and is often characterized by hepatic fat accumulation (steatosis) in the absence of regular alcohol consumption. Although often asymptomatic, the presence of this fat can lead to inflammation, chronic fibrosis, and ultimately liver damage. Once inflammation occurs, the condition is referred to as nonalcoholic steatohepatitis (NASH). Inflamed and damaged liver cells can undergo fibrosis and in advanced stages, lead to liver cirrhosis and potentially even hepatic cancer.

NAFLD and NASH are thought to be consequences of metabolic syndrome, a cluster of manifestations that occur due to increased abdominal fat, reduced ability to use the hormone insulin, increased blood pressure, and elevated levels of triglycerides. Furthermore, metabolic syndrome can escalate the risk for heart disease, stroke, and diabetes.3,4 Older adults may have more risk factors for NAFLD such as hypertension, diabetes, hyperlipidemia, and obesity, and may also be at risk for hepatic and nonhepatic complications of the disease.

Assessing NFALD and NASH
Patients can be asymptomatic with nonspecific findings such as fatigue, weakness, or increased sensation of fullness or pressure over the right upper quadrant of the abdomen at the time of assessment and evaluation. Elevation in liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), may indicate the presence of inflammation. When further evaluation does not yield a causative reason for elevated enzymes such as viral hepatitis, medications, or excess alcohol intake, NASH may be suspected.

An ultrasound, a noninvasive test, may initially be performed when liver disease is suspected. A CT scan or MRI, both of which are more specific than ultrasonography, can be ordered for a more detailed picture of the liver and surrounding organs, although they may be unable to discriminate between nonalcoholic and alcoholic disease. MRI elastography involves MRI with patterning formed by sound waves that can help differentiate areas of fibrosis and scarring. Liver biopsy, although regarded as the gold standard for diagnosis, may be reserved for patients with positive symptoms of disease and abnormal liver function tests or when other tests are inconclusive. Although liver biopsy is associated with some risk, it is often the most accurate method of determining fibrosis and scarring.

Additional blood tests that may help to determine severity of disease may include complete blood count, liver enzymes and function tests, fasting blood glucose, hemoglobin A1c, lipid profile, and screening for celiac disease. The NAFLD Fibrosis Score is a noninvasive tool that can be used to estimate scarring in patients with suspected NAFLD or NASH.5 The NAFLD Fibrosis Score uses age and BMI along with laboratory data (ALT, AST platelets, and albumin) in estimating scarring in NAFLD and may serve as an adjunct in evaluating patients and potentially identifying those who should proceed to liver biopsy or more rigorous monitoring.

Treatment and Intervention
The goal of intervention is to prevent progression of disease and, in mild cases, to reverse the injury and reduce the risk of fibrosis. Since there currently is no specific therapy nor medication to treat NAFLD or NASH, the most critical recommendations are to address lifestyle and risk profile. Lifestyle modifications are the first-line approach to managing NAFLD and NASH and include diet, exercise, limiting alcohol use, and avoiding unnecessary medications. Weight loss into a healthy range can help to reverse mild disease to some extent and may improve liver function tests in patients with NAFLD and NASH. Weight loss in combination with diet modifications, such as lowering fat intake and limiting high-carbohydrate food items, may not only improve NAFLD and NASH but also reduce the incidence of diabetes, hypercholesterolemia, obesity, and hypertension. Even a modest 10% loss in body weight may be enough to reduce liver fat and associated inflammation.6

Vigorous exercise should be employed, with a primary care provider's approval, to supplement dietary changes for weight loss. Thirty minutes of exercise most days of the week may be beneficial. Moreover, exercise in tandem with weight loss may influence other medical conditions such as hypertension, diabetes, and hypercholesterolemia.

Experimental approaches to treating NAFLD and NASH include antioxidants and antidiabetic medications. Antioxidants such as vitamin E (800 IU per day) may help to reduce the oxidative stress within the liver cells and, therefore, oppose liver fat and inflammation. However, long-term effectiveness and identification of individuals who are the best candidates for treatment remain controversial. Likewise, because insulin resistance may play a role in the disease process, antidiabetic medications such as metformin (Glucophage), pioglitazone (Actos), and rosiglitazone (Avandia) may have a role in making the body more sensitive to insulin and thereby decreasing liver injury. Long-term effectiveness and safety profiles need to be established.7

Liver protective strategies may also play a significant role in minimizing stress on the liver. Limiting alcohol consumption is reasonable to prevent damage to liver cells and resultant scarring. Additionally, cautious use of prescription medications, over-the-counter medications, and herbal preparations needs to be instituted. Because many medications are involved in the first-pass hepatic uptake, which is decreased in older adults by virtue of the aging process, a patient's primary care provider must be involved and consulted for all medication use.

Lastly, rigorous control of cholesterol and triglycerides, blood pressure, and blood sugars should be adopted to minimize the impact of these comorbid conditions on liver inflammation.

Conclusion
NAFLD and NASH may play an important role in aging and age-related liver disease. NAFLD that progresses to NASH contributes to a significant burden of disease, cirrhosis, and potentially hepatic cancer, and substantially impacts quality of life and longevity. Proper identification and management of disease and reducing risk profile is imperative. Nonpharmacologic intervention, namely diet, exercise, and weight loss, will be paramount in attempting to minimize or even reverse disease. Primary care providers are instrumental in having a high index of suspicion for disease and serving as catalysts for lifestyle change to promote liver health.

— Debra Sanders, PhD, RN, GCNS-BC, FNGNA, is an assistant professor of nursing at Bloomsburg University of Pennsylvania and a board-certified gerontologic clinical nurse specialist.

References
1. Kim IH, Kisseleva T, Brenner DA. Aging and liver disease. Curr Opin Gastroenterol. 2015;31(3):184-191.

2. Tajiri K, Shimizu Y. Liver physiology and liver diseases in the elderly. World J Gastroenterol. 2013;19(46):8459-8467.

3. Bertolotti M, Lonardo A, Mussi C, et al. Nonalcoholic fatty liver disease and aging: epidemiology to management. World J Gastroenterol. 2014;20(39):14185-14204.

4. Nonalcoholic fatty liver disease. Mayo Clinic website. https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567

5. Treeprasertsuk S, Björnsson E, Enders F, Suwanwalaikorn S, Lindor KD. NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol. 2013;19(8):1219-1229.

6. Marks JW. Fatty liver (nonalcoholic fatty liver disease, nonalcoholic steatohepatitis). MedicineNet.com website. https://www.medicinenet.com/fatty_liver/article.htm. Updated September 27, 2017.

7. Nonalcoholic fatty liver disease & NASH. National Institute of Diabetes and Digestive and Kidney Diseases website. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash

KEY TAKE-HOME POINTS
Both nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) involve an abnormal amount of fat in the liver cells. NASH further involves inflammation within the liver, which may damage and scar the liver.

NAFLD and NASH can occur in people who drink little or no alcohol, especially those who are middle aged or overweight.

Older adults with fatty liver disease may feel well and be asymptomatic until the disease is more advanced. NASH can lead to cirrhosis in which the liver becomes scarred and permanently damaged. NASH may be suspected if blood tests of liver enzymes are elevated. Liver biopsy is the gold standard for diagnosis in patients at high risk of disease. No specific treatment exists, but the following are integral to appropriate management:

• consuming a diet rich in fruits, vegetables, whole grains, and protein;

• achieving thirty minutes of vigorous exercise most days of the week;

• reducing calories per day to achieve at least a 10% weight loss;

• limiting alcohol intake;

• lowering cholesterol and triglyceride levels;

• if diabetic, controlling blood sugar levels; and

• monitoring via primary care provider all prescription, over-the-counter, and herbal medications.