March/April 2020

Clinical Matters: Diagnosing Liver Disease
By Scott Howell, DO, MPH&TM, CPE
Today’s Geriatric Medicine
Vol. 13 No. 2 P. 28

Noninvasive technology helps clinicians halt this critical health problem among elderly patients.

The aging process and its associated risk factors for most chronic diseases are influencing the expected lifespan of millions of Americans. Today’s geriatricians face new challenges in treating the nation’s older adults, especially as the population of those aged 65 years or older is expected to increase to more than 70 million people, or about 19% of the total population, in 2030.

Aging can also increase the risks for various liver diseases, including nonalcoholic fatty liver disease (NAFLD)—the accumulation of excess fat in the liver of people who drink little or no alcohol— and its more severe forms of nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Generally, the prevalence rate of NAFLD among adults is estimated to be 15% to 30%, with the prevalence rate increasing with age.

Given the significant impact of advanced liver disease on health and quality of life for older adults as well as the cost of care, clinicians treating older patients must be prepared to make timely identification and provide ongoing management of these serious conditions. For example, common comorbid factors of NAFLD, such as diabetes and obesity, can create progression of more substantial liver disease, such as NASH, cirrhosis, and hepatocellular carcinoma, as well as the development of cardiovascular disease.

The traditional approach to identifying liver disease begins with a blood test, which reveals liver enzymes that are released after a liver cell dies and may suggest inflammation. As appropriate and needed, this is followed by extracting a liver tissue sample—a percutaneous liver biopsy. This allows doctors to see signs of scar tissue and ballooning under a microscope to determine how far the disease has progressed.

This standard method, however, has been brought into question, not only because it is invasive and often painful but also for its inaccuracy. Scientists estimate that more than 30% of biopsy diagnoses may be wrong. Additionally, it adds another layer of cost to the diagnosis.

Fortunately, simple examination, early detection, and ongoing assessment methods are now available using noninvasive, cost-effective technologies. This can assist physicians in their diagnosis and management of liver disease and help prevent more serious conditions.

Understanding NAFLD
Insulin resistance—a primary cause of NAFLD—is a major component of metabolic syndrome, which is often observed in older adults. Aging, which is accompanied by abdominal obesity and excessive visceral fat, causes insulin resistance and an increased secretion of proinflammatory cytokines and, subsequently, often results in metabolic syndrome and type 2 diabetes. In a 2016 study by Wild and colleagues, age-adjusted readmittance rates for three-day hospital readmissions for patients with type 2 diabetes compared with those without (95% confidence intervals) varied between 1.27 (1.04 to 1.55) for autoimmune liver disease and 5.36 (4.41 to 6.51) for NAFLD. Among older adults, NAFLD is also linked to frailty, multimorbidity, and dementia.

Trends Raise Alarms for Growing Geriatric Population
According to the Dallas Heart Study, of those adults with NAFLD, 79% have normal aminotransferase levels. NASH increases the risk of cirrhosis and is now the most rapidly growing cause of hepatocellular carcinoma among US patients listed for liver transplantation.

People with NAFLD were found to have higher rates of cancer, with the greatest increase observed for gastrointestinal cancers, according to findings presented at the 2018 American Association for the Study of Liver Diseases (AASLD) Liver Meeting. These findings suggest that NAFLD related to obesity may be a key driver of the increased risk of cancer. Traditionally, viral hepatitis was assumed to be the primary factor responsible for rising incidence of liver cancer in the United States. Data from a recent study suggest that in patients 68 and older, metabolic disease was the highest and fastest-growing contributor to increasing cancer rates. Further research is needed to understand the impact of metabolic disease on liver cancer rates across the 1945–1965 birth cohort.

Risk of Cardiovascular Disease and Type 2 Diabetes
Studies also suggest that people with NAFLD have a greater chance of developing cardiovascular disease, the most common cause of death in those individuals. This means that follow-up of patients with NAFLD may be indicated to prevent major vascular events. Most striking is that simple steatosis will increase risk of cardiovascular disease mortality by two times over a shorter period than those with type 2 diabetes alone. Patients with prediabetes or type 2 diabetes and NAFLD are of particular concern. In fact, one study found that patients with elevated fat were at a twofold increased risk of developing type 2 diabetes.

Risks of Liver Complications
NAFLD tends to be diagnosed in older patients and, due to its silent course, liver failure is often the first presentation at diagnosis of NAFLD-related cirrhosis (38% to 45%). Once cirrhosis decompensates, patients with NAFLD have a rapidly progressive hepatic deterioration leading to similar overall and liver-related mortality as cirrhosis of other etiologies.

Liver Transplantation
The number of older adults with complicated liver cirrhosis has grown during the past two decades. Given this, more older people need liver transplantation. Transplant recipients older than 60 years showed lower survival rates (one-year survival rate of 64%; five-year survival rate of 59%) compared with those between 45 and 60 years of age. The differences are mainly due to kidney dysfunction accompanying cardiopulmonary diseases. However, recent studies reported that clinical outcomes after liver transplantation in the elderly are almost similar to those of young people if their individual surgery risks are considered to select the right candidate for liver transplantation.

Chronic Kidney Disease
The presence and severity of NAFLD has been related to the incidence and stage of chronic kidney disease. While the presence of chronic kidney disease increases overall mortality in people with NALFD as compared with the general population, this relationship is independent of the traditional risk factors associated with chronic kidney disease.

Treatment and Prevention Options
The American Diabetes Association has recommended the evaluation of comorbidities that may affect management, such as NAFLD. For older patients, the identification of advanced fibrosis and cirrhosis is essential for risk factor reductions, medical management, and improvement in daily activities and quality of life.

Fortunately, NAFLD can be reversible if caught in the early stages. Current treatments for NAFLD are to control body weight by changing lifestyle and improving insulin resistance. If body weight is decreased through a medium level of dietary restrictions and increased body activity by 5% to 10%, it can reduce the fat accumulated inside the liver by approximately 40%. Also, exercise and diet therapy for older adults can reduce the fat accumulation in the liver and improve hyperlipidemia, hypertension, and insulin resistance.

An optimized treatment strategy for NAFLD requires a multidisciplinary approach. A nonpharmacological approach to treatment, such as diet, proper calorie intake, and physical exercise, should be tailored individually and encompass the physical limitations of most older patients.

There are no drugs to treat liver disease, but treatments are expected to be approved as early as 2021. The risks and benefits of any drug treatment must be balanced to mitigate adverse events and pharmacological interactions. More accurate understanding of the molecular mechanisms of geriatric NAFLD can help in identifying the most appropriate diagnostic and therapeutic approach for individual older patients.

Noninvasive Methods to Examine Liver Health
A growing number of health care providers treating older adults have started adopting noninvasive screening methods that can detect NAFLD in the absence of indications or warning signs. FibroScan, for example, is a 10-minute examination that offers quick insight into liver health, measuring liver fat content and liver stiffness associated with fibrosis and cirrhosis.

Test scores provide immediate information to help guide treatments and/or referral to a specialist. A yearly NAFLD examination may become standard practice similar to A1c blood sugar testing. What’s more, FibroScan is covered by Medicare, Medicaid, and other insurance plans.

The point of these tools is that they can quickly and easily measure the amount of liver stiffness and fat to better target more expensive or more invasive diagnostic procedures, saving time and resources for clinicians by identifying patients who don’t need additional assessment.

Patients are low risk if they have very low FibroScan readings of under five or six, but those with FibroScan readings above 10 who have risk factors for advanced hepatic fibrosis, are older than 50, have diabetes, or have three or more risk factors and metabolic syndrome should see a liver specialist.

American Diabetes Association (ADA) guidelines recommend screening patients with type 2 diabetes for NAFLD. These patients have a higher all-cause mortality than those without NAFLD.

ADA Standards of Medical Care recommend that patients with type 2 diabetes or prediabetes and elevated liver enzymes (alanine aminotransferase) or fatty liver on ultrasound should be evaluated for the presence of NASH and liver fibrosis.

The ADA also recommends noninvasive tests such as elastography or fibrosis biomarkers to assess risk of fibrosis, but referral to a liver specialist and liver biopsy may be required for definitive diagnosis.

While the AASLD does not recommend routine screening for NAFLD or NASH, it does recommend FibroScan as part of an overall approach to identifying patients with NAFLD or NASH. It suggests there should be a high index of suspicion for NAFLD and NASH in patients with type 2 diabetes. Clinical decision aids, such as NAFLD fibrosis score, fibrosis-4 index, or vibration controlled transient elastography (VCTE), can be used to identify those at low or high risk for advanced fibrosis (bridging fibrosis or cirrhosis).

Identifying Asymptomatic Patients
An interim look at an ongoing study of 10,000 patients with no history of liver disease was conducted in community-based endoscopy centers by the Florida Research Institute, a division of Florida Digestive Health Specialists. Only 43% of patients evaluated had what are considered normal livers based on a FibroScan assessment alone, while the remainder had some form of liver abnormality, ranging from elevated liver fat to liver fibrosis, including 13% suspected of having undiagnosed liver fibrosis or cirrhosis.

It’s important to note that the vast majority of patients had no symptoms. While further workup is recommended to confirm the extent of liver disease in these patients, this analysis of the first 367 patients suggests a significant rate of undiagnosed NAFLD in the population studied.

This prospective study evaluated patients with no history of liver disease, undergoing routine endoscopic procedures between June 2017 and January 2018 vs a matched control of patients not undergoing a liver health assessment. Patients were risk stratified based on FibroScan, which utilizes VCTE and controlled attenuation parameter (CAP) surrogate scores of liver fibrosis and liver fat, respectively. The study team examined electronic medical records within 90 days after the procedures to determine and compare prevalence of NAFLD.

Results showed 53% of patients studied had excess fat in their livers as identified by the CAP, of which 64% likely had grade 3 liver fat, as identified by a CAP score of ≥279 dBm. More concerning, only 43% of patients evaluated had what would be considered normal livers (stiffness <7kPa and CAP <248dBm). These results underscore the importance of identifying asymptomatic long term care patients who may be at risk for advancing disease and can be targeted for earlier intervention. Keep in mind that this research noted dramatic rise in liver disease compared with the previous decade and indicated a growing need for ongoing assessment.

Educating Patients
Patients need to understand that the liver, as the second-largest organ in the body, performs about 500 important jobs, including removing toxins, clearing medication from the body, and metabolizing food. It also adjusts cholesterol levels, stores and regulates glucose levels, builds proteins, makes bile (which aids the absorption of fats), stores sugar for when it’s needed, and regulates hormone levels.

Patients also need to know that NAFLD affects people who aren’t heavy drinkers. In fact, it’s caused primarily by metabolism and obesity—sedentary lifestyles and unhealthful diets—and may not produce clear symptoms. Obesity often causes severe damage to the body and can cause insulin resistance by generating too much blood sugar and increasing free fatty acids that circulate in the blood and liver cells, a condition common among those with type 2 diabetes. While most patients with excess liver fat will not have progressive liver disease, those who do will face an increase in the risk of NAFLD, liver fibrosis, cirrhosis or, ultimately, liver cancer.

Given the rise in adult obesity rates in the country, more Americans will begin to experience liver damage and associated health issues. In fact, significant and rising obesity rates are seen across America, with states having rates ranging from 25% to 38% of the adult population, with the highest being in West Virginia and the lowest in Colorado, according to the most recent Behavioral Risk Factor Surveillance System data.

While most patients are asymptomatic, NAFLD is sometimes associated with fatigue, weakness, loss of appetite, nausea, weight loss, and abdominal pain. Increased liver enzymes may be associated with the disease but are not always a sign of liver disease. For now, noninvasive examination and early detection of disease in high-risk patients are the best options for preventing serious conditions from developing.

— Scott Howell, DO, MPH&TM, CPE, is an advisor to Echosens, a high-technology company offering the FibroScan family of products.