The Intractable Hepato-Biliary Diseases Study Group in Japan, Health Labor Science Research Grants from Research on Measures for Intractable Diseases


Acute Liver Failure

Last Update: February 22, 2022

1. What kind of disease is it?

The liver plays important roles in biological activities, such as synthesizing the substances required by the body and detoxifying and excreting drugs and harmful substances. Fulminant hepatitis is a disease that occurs due to the sudden breakdown of large amounts of the liver cells that carry out liver functions, which leads to decreased liver functions. When liver function decreases, it loses the ability to produce the coagulation factors required to coagulate blood and consciousness disorders (hepatic encephalopathy) due to the accumulation of harmful substances. Within eight weeks after the appearance of symptoms that are identical to those of acute hepatitis in an otherwise healthy person, e.g., overall listlessness, nausea, poor appetite, hepatic encephalopathy appears. Then, once the level of coagulation factors in the blood falls below a certain point, the patient is diagnosed with fulminant hepatitis.
Even if liver cells are destroyed, the liver is fully capable of producing more liver cells. As a result, in most cases of acute hepatitis, the liver is naturally able to recover from a temporary loss of healthy liver cells, and thus, the patient can recover without any particular treatment. However, in the case of fulminant hepatitis, liver cells are destroyed on an extremely large scale and at a speed that exceeds the liver's ability to replace them with healthy cells. As a result, without treatment, the disease is fatal in many cases. Throughout the world, the general term "acute liver failure" is commonly used.

2. How many people are affected by this disease?

In Japan, the number of fulminant hepatitis patients is estimated to be approximately 400 per year. This is approximately 1% of all patients with acute hepatitis.

3. What sort of people are susceptible to this disease?

Fulminant hepatitis occurs at all ages, from newborns to the elderly and in both males and females. Recently, there has been a trend toward an increase in fulminant hepatitis onset in carriers of the hepatitis B virus and patients who have undergone pharmacotherapy for diseases other than liver disease. Hepatitis B carriers should be aware that they may develop fulminant hepatitis even if their liver functions are normal. They should consult with a medical professional immediately if their urine is brownish or if they suspect jaundice in the form of yellowing of the skin or the whites of the eyes.
The hepatitis B virus is transmitted through sexual contact, and thus fulminant hepatitis can occur in people other than carriers and those with a history of infection. If one's partner is a carrier of the hepatitis B virus, it is possible to be vaccinated against it.

Topic: Fulminant hepatitis caused by reactivated hepatitis B virus

Hepatitis B virus carriers can develop fulminant hepatitis if administered immunosuppressive drugs such as corticosteroids for other diseases or anti-cancer drugs. Even those who have previously been infected with the hepatitis B virus and have been cured (those with a history of infection) can develop fulminant hepatitis after the administration of immunosuppressive drugs and anti-cancer drugs, although with less frequency than carriers.
This is known as reactivated hepatitis B virus. As it has a high mortality rate, there is a need to exert extreme caution to prevent the reactivation of the hepatitis B virus.
Prior to being treated for other diseases using these drugs, a patient should consult with their attending physician, be examined by a liver specialist when necessary, and take the necessary measures to prevent reactivation.

4. Are the causes of this disease known?

The causes of fulminant hepatitis include infection with hepatitis virus, drug allergy, and autoimmune hepatitis. In Japan, hepatitis B infection is the most common, as approximately 40% of all patients with hepatitis have hepatitis B. The disease occurs when a hepatitis B virus carrier experiences symptom or when a person has sexual relations with a hepatitis B virus carrier. Although it may occur due to hepatitis A virus infection, the prevalence varies depending upon whether hepatitis A virus is prevalent in any given year. Its frequency among those with hepatitis C infection is low, but there are cases in which the patient develops fulminant hepatitis.
After hepatitis B virus infection, the next most common cause of fulminant hepatitis is "unknown," which accounts for approximately 30% of all cases. Cases traced to drug allergy or autoimmune hepatitis account for no more than 10% of the total number of cases. However, some percentage of the patients classified as "cause unknown" may either have been infected with hepatitis virus and do not know it or maybe included among those with drug allergy or autoimmune hepatitis. Thus, we must gain a better understanding of the actual status of patients in the future. In cases in which hepatitis A or B virus is the cause, it remains unknown why only some of these patients suffer from increasing disease severity that develops into fulminant hepatitis, although the cause of their acute hepatitis was the same.

5. Is this disease hereditary?

Fulminant hepatitis is not hereditary. However, if a mother is a carrier of the hepatitis B virus, it is often passed to her children during childbirth, making them carriers. If a person's parents, siblings, or children are diagnosed as hepatitis B carriers, it is recommended that they undergo a blood test to confirm whether they are also carriers.

6. What are the symptoms of this disease?

The initial symptoms often include cold-like symptoms such as fever and muscle aches, overall listlessness, and poor appetite. These are followed by brownish-colored urine and jaundice. In some cases, the initial symptoms are mild, and the patient only realizes they are sick upon the appearance of jaundice.
In cases of acute hepatitis, overall listlessness occurs after jaundice appears and the initial symptoms are mild, but in cases in which this develops into fulminant hepatitis, the symptoms persist or worsen until the patient develops hepatic encephalopathy.
Hepatic encephalopathy patients suffer from a variety of severity levels. They may remain unaware that their daytime and nighttime sleeping rhythm has reversed or that their clothing or posture is not proper, they may mistake locations, people, or the time, and they may become excited and violent. As the condition increases in severity, they may remain asleep and unresponsive to voices or pain stimuli, a state which is referred to as "hepatic coma."
In cases of fulminant hepatitis, organs throughout the body suffer from disorders with high frequency. These disorders include microbial infection, abnormalities of the kidneys, lungs, heart, digestive tract, and blood coagulation. Thus, a wide range of symptoms is continuously observed, including fever, difficulty breathing, swelling, bloody diarrhea, and bleeding from inside the mouth or from an injection site.

7. How is this disease treated?

In cases in which the hepatitis B virus is the cause, antivirals including nucleic acid analogs such as entecavir and interferon are most commonly utilized. In cases in which autoimmune hepatitis or drug allergy is the cause, large amounts of corticosteroids are delivered via IV. When these treatments are performed prior to the appearance of hepatic encephalopathy, they can usually suppress progression to fulminant hepatitis.
In cases in which a patient has already developed fulminant hepatitis, regardless of the cause, artificial liver adjuvant therapy is performed to compensate for the decrease in liver function. This supplies the body with the substances it needs and removes harmful substances. This treatment involves either removing the components of the blood other than the blood corpuscles (i.e., the blood plasma) and replacing it with plasma from a healthy person (plasmapheresis) and hemodialysis, which is normally used for patients with diseased kidneys (hemofiltration dialysis). Normally, both methods are used in combination. Treatment for systemic organ disorders may also be required. Once the patient survives the period of decreased liver function due to these treatments, the liver will regenerate, and the patient is no longer likely to die.
However, these treatments do not always lead to a recovery of liver functions in some cases of fulminant hepatitis. When this happens, liver transplantation is sometimes performed. Liver transplantation can be performed using a brain-dead person's liver, or it can be performed using part of the liver of a close living relative (segmental liver transplantation from a living donor). In Japan, the latter is widely utilized. Previously, segmental liver transplantation from a living donor was done mainly on children, but recently it has come to be more aggressively performed on adults. A revision of the law in 2010 led to an increase in the number of brain-dead donor liver transplantations, and as a result, many fulminant hepatitis patients now undergo brain-dead donor liver transplantation.

8. What is the course of this disease?

Fulminant hepatitis is divided by the period passed from the first identification of symptoms until the appearance of hepatic encephalopathy: within ten days (acute) and 11 or more days (sub-acute). The course of acute fulminant hepatitis is good.
The results of an effort to gather data between 2010 and 2014 from major hospitals throughout Japan about patients with fulminant hepatitis indicated that approximately 40% of patients who underwent medical therapies only (no liver transplantation) and survived had acute fulminant hepatitis while approximately 25% who survived had sub-acute fulminant hepatitis. Many of those whose disease was caused by the hepatitis A virus had acute fulminant hepatitis, and while the course was previously good, in recent years, the increase in older people in the population has led to a decline in the vital prognosis. Also, from year to year, the number of patients who undergo brain-dead donor liver transplantation is increasing, and among these patients, the survival rate is approximately 50% for those with acute disease and 40% for those with sub-acute disease.
Normally, all patients who survive because of liver transplantation are cured and suffer no sequelae. Moreover, even some patients whose disease advances to liver cirrhosis and require subsequent treatment are cured. After surviving as a result of liver transplantation, patients must take immunosuppressive drugs for the rest of their lives to prevent the rejection of the transplanted liver.

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