In a nation understandably consumed with worries about the coronavirus pandemic, it’s easy to forget that a host of other stubborn health problems in the United States persist and will continue to challenge the system even if a vaccine for COVID-19 becomes widely available.
For example, diabetes, obesity and high cholesterol are among the chronic-disease contributors to another problem that is far less familiar but equally widespread and damaging. It’s nonalcoholic fatty liver disease (NAFLD), an often silent enemy that affects as many as one in three adults and one in 10 children in the country, according to the American Liver Foundation.
As its name suggests, nonalcoholic fatty liver disease is caused by a buildup of fat cells in the liver, a vital organ responsible for a host of functions, including purifying blood from the digestive tract. Left untreated, fatty livers can swell, stiffen and scar, triggering a cascade of ailments in other parts of the body. In the most extreme cases, NAFLD can lead to liver failure, liver cancer or transplant. Importantly, the problems aren’t attributable to alcohol consumption.
Nonalcoholic fatty liver disease
The good news is that in many cases an early diagnosis of nonalcoholic fatty liver disease can help people arrest or even reverse liver damage. Therein lies a big challenge, though, said Dr. Thomas Jensen, assistant professor of Medicine-Endocrinology/Metabolism/Diabetes at the University of Colorado School of Medicine on the Anschutz Medical Campus. There are few symptoms of NAFLD, even after it has progressed to nonalcoholic steatohepatitis (NASH), which inflames the liver and damages its cells.
“The disease can sneak up on people,” Jensen said. “They might go along with the disease for years and not even know about it until it gets to a much worse state.”
In addition, Jensen said, people struggling with diabetes, obesity, high cholesterol and/or high triglycerides often aren’t aware that these metabolic problems play a big role in nonalcoholic fatty liver disease or the additional havoc the disease can wreak.
Help in the Nonalcoholic Fatty Liver Disease Clinic
“It’s a complex disorder affecting multiple systems in the body,” Jensen said, which is why he and liver specialist Dr. Amanda Wieland, assistant professor of Medicine-Gastroenterology at CU, created the Nonalcoholic Fatty Liver Disease Clinic at UCHealth University of Colorado Hospital on the Anschutz Medical Campus. The multidisciplinary clinic also gets important help from nurse practitioners, nutritionists, diabetes educators and other providers.
Jensen and Wieland generally see patients together in the clinic’s twice-monthly sessions, with Jensen focusing on helping patients in the early stages of their disease make changes to prevent further progression and Wieland working with those with more advanced disease, such as cirrhosis (severe scarring that causes irreversible damage), which may require liver transplants.
“We make each other better at what we do,” Jensen said.
Both Jensen and Wieland stress the importance of not only identifying patients at risk for NAFLD, but emphasizing the importance of controlling it.
“A big job for us is explaining the disease in understandable ways,” Wieland said. One such powerful message: Nonalcoholic fatty liver disease is becoming the leading indicator for liver transplant, but that result is not inevitable.
“We tell them that changes they make now are going to make you healthy for yourself and your family, so you don’t have to have a transplant,” Wieland said.
Diagnosis and control of nonalcoholic fatty liver disease
The first step toward change, of course, is getting patients in the clinic. The clinic’s referral sources include primary care providers, and UCHealth’s Endocrinology and Diabetes, Hepatology and Sleep Medicine clinics. Patients receive screenings to confirm and assess the severity of the disease. The gold standard is a liver biopsy, but the NAFLD Clinic extensively uses a bedside device called FibroScan, which uses a sound-emitting probe to assess the liver’s stiffness and degree of nonalcoholic fatty liver disease. Blood tests that measure increases in liver enzymes are also helpful, but not always reliable, Jensen said.
Although there is as yet no FDA-approved medication to treat nonalcoholic fatty liver disease, patients are far from helpless to combat it. Jensen works with many to make lifestyle changes, including monitoring their caloric intake; moving their diets away from fat and sugar and toward high-fiber foods; and exercising regularly. He gets help in this area from Amy Vance, a diabetes educator with UCHealth who also works specifically on nutritional issues with NAFLD patients. Shannon Christen, also a diabetes educator and a registered dietitian, focuses on helping patients manage their cholesterol and triglyceride levels.
Wieland noted that some patients may benefit from bariatric weight loss surgery, which has been shown in some cases to reverse liver scarring. Obstructive sleep apnea, treatable with weight loss and continuous positive airway pressure (CPAP) support, may be another culprit in the progression of nonalcoholic fatty liver disease – including in children, as suggested by a CU School of Medicine study conducted at Children’s Hospital Colorado. Sleep medicine specialists play an important role in these cases.
Heading off severe damage from NAFLD
Jensen said that no one can predict with certainty whether nonalcoholic fatty liver disease will progress in any individual, but he explains to his patients the measurable benefits of working toward improving their liver health, like controlling their blood sugar, decreasing insulin resistance, lowering their cholesterol and triglyceride levels, and so on. And he emphasizes that they can accomplish the changes themselves.
“When patients feel empowered that they can have a positive effect on their health in the long-term, that’s really a motivating factor,” Jensen said
A phase 3 randomized clinical trial of the first medication specifically to treat nonalcoholic steatohepatitis also offers hope. The national trial – UCH was a site, with Wieland as principal investigator – dubbed REGENERATE tests the effectiveness of obeticholic acid (trade name Ocaliva) in reversing liver scarring, without worsening NASH, versus a placebo. The medication is already approved to treat other liver diseases. Wieland said an initial assessment of the REGENERATE trial data is expected sometime in June.
A slow decline into serious illness
For a relatively small fraction of patients with nonalcoholic fatty liver disease, the disease damages the liver so severely that they need transplants. That can lead to a delicate job for the clinic, Wieland said: helping very sick, frequently malnourished people stay healthy enough to withstand the rigors of a liver transplant. One such person was Jim Darouze of Aurora. His case illustrates how insidious and destructive NAFLD can be without early intervention.
Darouze, 66, moved to Colorado from his native California in 1973, married Vickie and had two children, Peter and Lindsay. He worked in the truck equipment business for more than four decades, and was manager for OJ Watson, an equipment manufacturer and distributor in Denver, for 20-plus years before life-threatening liver disease forced him to retire in 2018.
As Jensen said, the damage of nonalcoholic fatty liver disease often arrives silently and goes unnoticed while health problems mount. Darouze’s case illustrates his point. He was a hard worker, both before and after he got sick. Workweeks of 50 hours or more were standard during his long stint with OJ Watson.
“He worked a lot of hours, wore a lot of hats,” Vickie said.
The long hours took a slow toll. He was less active, “as work took over,” Jim said. His weight steadily crept upward, eventually climbing to 275 pounds from the 185 he weighed when he got married.
About 20 years ago, he learned he had Type 2 diabetes, which he struggled to control while continuing to work his long work hours.
“There were a lot of options to go out and eat and different food choices,” Vickie acknowledged. The struggle to control his diabetes led to worsening vision and nerve pain in his feet. He was tired all the time. Eventually not feeling well became the norm.
“It sneaks up on you,” Vickie said.
Fatty liver and a downward spiral
Meanwhile, blood tests also showed elevated liver enzyme levels, a warning sign of nonalcoholic fatty liver disease. A liver specialist eventually diagnosed him with NASH and advised him to go on a low-fat diet. Jim continued to struggle without consistent help and a clear understanding of the serious problems NASH could lead to.
“We didn’t know what it meant down the road,” Vickie said.
In 2011, his health problems took a frightening turn. After complaining of not feeling well, he suddenly vomited blood and continued to do so as Vickie rushed him to a Denver hospital. The cause was enlarged veins in the esophagus called varices; these, in turn, occurred because Darouze’s damaged liver couldn’t handle normal blood flow. By now the liver damage had advanced to cirrhosis. He spent nearly a week in the ICU to recover from surgery that placed bands around the varices to stop the bleeding.
Darouze returned to work after this ordeal, but his health continued a downward spiral. In 2016, he said, his bosses began to notice that his normally sharp concentration and focus lapsed.
“I got cloudy and foggy. It was hard to think,” Darouze recalled. “As time went on, it became more and more difficult to do even the simplest tasks,”
He’d taken pride in being able to do math problems in his head, but that ability vanished. He eventually learned that he had encephalopathy: his liver damage led to a buildup of toxins that attacked his brain.
Another recurrent problem was ascites: severe swelling in his abdomen that had to be drained – up to 11 liters in one instance.
Help from the clinic
In June of 2018, Darouze finally got a referral to the nonalcoholic fatty liver disease Clinic at University of Colorado Hospital, where he and Vickie met with Wieland. After assessing his liver damage, she put him on the list for a transplant. That began another difficult journey, during which he battled to remain healthy enough to stay on the transplant list – all while he desperately needed a new liver to survive.
Darouze struggled through with non-epileptic seizures so severe that he badly injured a rotator cuff in his shoulder; a life-threatening bout of sepsis; and surgery for a cancerous lesion on his chin that eventually led to another surgery and an extended ICU stay.
Through it all, however, the NAFLD Clinic worked with him to manage his liver disease. Jensen and Vance, the diabetes educator, helped him get his diabetes under control with an improved diet and a continuous glucose monitoring system. Darouze meanwhile worked hard in physical therapy to recover from his rotator cuff injury and regain his strength.
In June 2019, Wieland brought in transplant surgeon Dr. James Pomposelli to meet with him. Darouze expected bad news, but Pomposelli had a different message. You keep bouncing back, Pomposelli said. You can do this, but you have a short window of time.
On to transplant – and recovery
On July 4, Jim and Vickie were preparing to go to a barbecue with daughter Lindsay in Erie, when they got the call that a liver was available for him. Jim checked into a room at UCH, watched fireworks through the window and spent a sleepless night before surgery the next day with Dr. Trevor Nydam. The procedure extended from the 5th into the 6th, and Darouze stayed five weeks in the hospital, but today he continues to recover with his new liver.
Life hasn’t been easy, Darouze readily admits. He’s struggled with a viral infection and more problems with his esophagus. But last December he felt he turned a corner and has steadily gained strength. Having reached the brink of death, he now looks forward to spending happy days ahead with his family, including his two granddaughters, Savannah and Charlotte, and a new grandson, Matthew.
Darouze is grateful for the compassionate care he received from the NAFLD Clinic and all his providers at UCH, as well as his church, family and friends.
“That’s an important element of recovery,” he said.
Wieland noted that Darouze can take much credit himself for his recovery. For example, the immunosuppressant medications he has to take post-transplant can trigger metabolic issues that can again put him at risk for fatty liver disease. Darouze isn’t about to go back to where he was.
“We want to make sure patients never forget that after transplant it’s important to manage your health,” she said. “Jim has done that and kept the risks under control.”