Scott: One Man's Experience Surviving Acute Liver Failure
Monday the 29th of February, 2016, is a leap day Scott will not soon forget. It’s the day when he went from feeling he had a bad case of the flu—to the shock of learning that both his liver and kidneys were failing. In an instant, his thoughts racing as he confronted his mortality at only 34 years of age, he recalls thinking, “What if I actually do need a new liver?... Is this really going to happen?” Luckily for Scott, his condition had been the subject of decades of intense research efforts supported by the NIDDK, including clinical trials testing new treatments for acute liver failure.
From Aches and Pains to Organ Failure in 24 Hours
“Every single joint ached…. I just figured I had the flu,” says Scott. But tests of his liver and kidney functions came back with alarming results.
In late February of 2016, Scott was feeling ill with fever, muscle aches, and nausea. Staying home sick in Ruckersville, Virginia all week from his job as a production art manager at a T-shirt design company in nearby Charlottesville, he started to feel better, then took a turn for the worse on Sunday night. “Every single joint ached. It hurt to move,” he remembers. With a high fever that caused him to sweat through his bathrobe and sheets, and nausea limiting his water intake, he became profoundly weak. “I was walking in my kitchen, trying to make some tea, and had to put myself on the floor rather gently,” he recalls. After losing consciousness, he later woke up and remembers thinking “I’ve got to get back to bed.” When the local sheriff came by at the request of his company to check up on him, he was able to answer the door and agreed to have an ambulance called. “I just wasn’t feeling right.... I just figured I had the flu,” says Scott.
“‘You look fine, but your numbers say you are not fine…. You are going to be sent to the hospital,’” Scott recalls his doctors saying.
At the local outpatient emergency room on Sunday, February 28th, the staff treated his dehydration with intravenous saline. Scott called his workplace to let them know where he was and that he would likely be out for a few more days. As he understood it, the treatment plan was “…we’re going to get some fluids in you, we’re going to get you kind of stable there, and then we’re going to see if you can keep fluids down … if you can do that, we’ll send you home.” But over the next day and into early Monday, it became clear that something more serious was going on. Tests of his liver and kidney functions came back with alarming results: possible kidney and liver failure. He recalls the doctors telling him, “You look fine, but your numbers say you are not fine…. You are going to be sent to the hospital.” The staff quickly called around to area hospitals to see which intensive care units had beds available. He was ultimately transferred an hour's drive away to Virginia Commonwealth University (VCU) in Richmond. In the early hours of Monday, February 29th, Scott was driven by ambulance to VCU, feeling awful and vomiting blood. "It was a pretty long drive," he recalls.
The doctors were perplexed as to the cause of his sudden organ failure, particularly in someone so young without any previous history of liver or kidney problems. They questioned him repeatedly about his lifestyle and whether he had taken any medications recently, particularly the pain reliever acetaminophen. But Scott reported that he had deliberately avoided taking any acetaminophen during his illness because he was made aware of its potentially harmful effects on the liver by friends who were doctors. Instead, he had taken only aspirin for pain relief during the past week. They also asked him routine questions to test his mental clarity, considering that his organ failure had elevated ammonia levels in his body to a point that can cause cognitive impairment and even coma. “They kept asking, ‘What day is it? Who’s the President?,’” Scott recalls. Despite his discomfort and precarious situation, he retained his sense of humor. When asked once again by his doctors if he took drugs, he waved his hand attached to the intravenous (IV) drip, saying, “You mean this stuff?”
The medical team continued to search for clues to the cause of his organ failure. The sudden onset and marked abnormalities in his liver test results would usually point to an acetaminophen overdose, but Scott had not taken the drug. To help find out the cause, they took a liver biopsy, which showed small droplets of fat in the liver cells. Such changes are typical of a now-rare condition called “Reye syndrome,” a disease caused by a “perfect storm” of severe viral infection and aspirin. Aspirin in the recommended dosage is usually harmless, but can cause problems if taken during infections with chicken pox or influenza, particularly at higher doses. Though the doctors were not entirely sure that aspirin was the cause, they proceeded with treating his organ failure. Scott was put on dialysis and a special diet for his kidney failure. For his liver, he was treated with a drug called N-acetylcysteine, which is a safe and effective treatment when given early for acute liver failure. Also, on the afternoon of Tuesday, March 1st, they offered him the opportunity to participate in a clinical trial testing another, new treatment for acute liver failure. Though he was reluctant at first to take an experimental drug, after thoroughly reviewing the paperwork and discussing it with the study doctors, he agreed to participate. As a backup, his doctors also set up meetings the following day, a Wednesday, with the liver transplant committee, to prepare for the worst-case scenario: the need for a life-saving organ transplant, assuming a donor liver would be available. That Wednesday night, with the situation clearly dire, he finally called his family, whom he had been reluctant to contact for fear of upsetting them unnecessarily.
Acute Liver Failure and Reye Syndrome
Acute liver failure or “ALF” is relatively rare in the United States, but can be caused by over-the-counter and prescription drugs, dietary supplements, and herbal remedies. Its most common cause in this country is the over-the-counter pain reliever acetaminophen. However, in Scott’s case, he had avoided taking acetaminophen during his illness, taking aspirin instead. Aspirin, the most commonly used pain-reliever or fever-reducer in the world, is a rare, but sometimes life-threatening, contributor to ALF. ALF from aspirin is called “Reye syndrome;” it was first reported by Dr. Douglas Reye in Australia in 1963 in children who had recently had a severe viral infection such as influenza B or chicken pox. Subsequently, more and more reports of Reye syndrome in children came in from around the world, peaking in the 1970s and 1980s. In the United States, staff of state health departments, the Centers for Disease Control and Prevention, and others, including NIH staff, reviewed case reports and conducted careful epidemiological surveys that linked Reye syndrome to the use of aspirin during the early phase of viral illness, mainly in children. This led to wide-scale public warnings in the 1980s advising that aspirin not be used in children, after which reported cases in the United States fell precipitously, from more than 500 per year before 1986 to less than 2 cases per year since then. Although rare, the syndrome is still seen from time to time, almost always in children, but sometimes in young adults.
Reye syndrome is marked by dysfunction in the mitochondria - structures within cells that generate their energy - causing a build-up of fat in the liver and lactic acid in the blood. This likely occurred in Scott when he took aspirin during his infection with a flu-like virus. Along with the acute liver failure of Reye syndrome, ammonia levels rise in the blood and enter the brain, where they can cause swelling, as well as confusion, altered consciousness, and even coma. The syndrome also causes depletion of another energy source within the liver: glycogen, a stored form of glucose, as the body tries to compensate for the failing mitochondria. If appropriate medical care is not received, the syndrome can swiftly turn fatal. Fortunately, the effects of Reye syndrome can reverse spontaneously once aspirin is stopped. Its negative consequences can be managed by supporting the patient during the dangerous period of severe liver and kidney failure, so that the injury is not permanent and the organs recover with time.
STOPping Acute Liver Failure in Its Tracks
In Scott’s case, his doctors attributed his acute liver failure to an adult form of Reye syndrome, caused by his use of aspirin in combination with his flu-like viral infection. After consenting to participate in the clinical trial, called “STOP-ALF,” he was treated over the next few days with an experimental drug called ornithine phenylacetate, delivered intravenously, in addition to the other standard medical treatments he received. Based on promising results from prior research, the doctors hoped that the drug would detoxify the ammonia buildup caused by his failing liver and thereby protect his brain while the liver and kidneys slowly recovered. The doctors continued to monitor his liver and kidney functions, which soon started to improve, obviating any further discussion of a transplant. His mother stayed nearby and acted as an advocate for Scott, taking notes during visits from the doctors and handling calls to his health insurance company. During his second week in the hospital, his liver function numbers were back to normal, while the kidneys took some additional time to recover. By the time he left the hospital on March 15th, his liver had fully recovered, but he was scheduled to come back for more dialysis. Fortunately, at that later appointment, he was informed that his kidneys had improved to the point where dialysis was no longer required. He has continued to return to VCU to check in with his doctors there.
The STOP-ALF trial is part of a larger research effort supported by the NIDDK called the Acute Liver Failure Study Group, a group of clinical centers throughout the country committed to advancing understanding of acute liver failure and improving its care. The Study Group has documented the increasing frequency of acute liver failure due to drugs in the United States. In 2009, the Study Group published results of a large clinical trial showing that N-acetylcysteine was successful as an early treatment for non-acetaminophen-related acute liver failure, a finding that led to the main course of treatment chosen for Scott. More recent work by the Study Group highlights the steady improvement over the past several years in outcomes and survival for people experiencing acute liver failure, particularly in those who do not receive a liver transplant, which may be due in part to wider use of the N-acetylcysteine treatment.
Another NIDDK-led research effort, the Drug-Induced Liver Injury Network, collects and analyzes data from people with severe liver injury caused not only by over-the-counter and prescription drugs, but also by alternative medicines, such as herbal products and dietary supplements. This research has helped doctors to better understand and diagnose liver injury caused by drugs and other agents. The NIDDK also partners with the NIH’s Library of Medicine on the “LiverTox” website (http://livertox.nih.gov/), which features sample cases of people with drug-induced liver injury based on the Network’s data, as well as a database summarizing liver injuries caused by drugs, including aspirin, acetaminophen, and various herbal and dietary supplements.
Life After Surviving Acute Liver Failure
All signs indicate that Scott has made a full recovery from his liver and kidney injury. In mid-April 2016, he was able to return to work and conquer the “tsunami” of email received during his absence. He has also been able to get back to enjoying his hobbies, including building model cars and seeking real project cars to work on. However, his stamina remains limited, as he notices in his regular activities, such as when he uses his push lawnmower on his half-acre property. Although he is cleared to take a reduced dose of acetaminophen as needed for everyday pain, he avoids all over-the-counter pain relievers - especially aspirin - as well as alcohol, to protect his recovering liver. “If I get a headache, I will grin and bear it,” he states resolutely.
A silver lining of Scott’s experience with acute liver failure and the extended hospital stay is his renewed commitment to better health. “I was a smoker, and so I said … maybe I should use this as an opportunity to quit,” he says. Now, in the time he previously used for smoke breaks, he instead takes a walk around his office building. He also eats more healthfully after his experience on the special renal diet. He continues to have his health monitored by his primary care physician and the doctors at VCU.
“If it helps other people,” Scott says of his participation in the STOP-ALF clinical trial, “I’m more than happy to participate.”
Overall, his experience with participating in the STOP-ALF clinical trial was a positive one that Scott would recommend to others who might find themselves in similar circumstances. “If it helps other people, I’m more than happy to participate and do follow-up,” he says, though he urges anyone considering enrolling in a clinical trial to be fully informed, including asking the medical staff any questions they might have. “It was a scary experience,” he says, summing up his ordeal with acute liver failure. “But I definitely had faith in the doctors,” he says appreciatively. And, he adds, “every time I’ve gone back to do the follow-up, I’ll check in on the ward and see some of the nurses there just to thank them.”
“It was a scary experience,” Scott says, summing up his ordeal with acute liver failure. “But I definitely had faith in the doctors,” he adds appreciatively.
This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.