What causes acute liver failure?

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What causes acute liver failure?

Liver injury from drugs and toxins is currently the most common cause of acute liver failure=(ALF) in the US.

AcetaminophenAcetaminophen (one form of which is called Tylenol®) poisoning is by far the leading single cause of ALF in the US and is responsible for nearly 50% of all cases. Acetaminophen is an intrinsic, dose-dependent liver toxin, which means that if any given individual takes enough acetaminophen, they will develop severe liver injury, possible culminating in ALF (see Drug-Induced Hepatitis knol). Of note, ALF secondary to acetaminophen poisoning may result from the intentional ingestion of a large amount of acetaminophen (as part of a suicide attempt), or from unintentional overdosing due to a so-called “therapeutic misadventure.†In the latter situation, an individual taking acetaminophen for therapeutic purposes (e.g., pain or fever) unintentionally consumes excessive amounts without realizing this may cause liver damage. Typically, patients who try to commit suicide via acetaminophen overdose and develop ALF have almost always taken greater than 10 grams (20 x 500 mg tablets) and often more than 20 grams in a single ingestion. In contrast, the unintentional overdose group usually takes smaller doses but does so several times over an entire day or over several days before presenting with ALF, so that the total dose of acetaminophen ingested is usually still quite large. Since acetaminophen is in scores of over-the-counter

cold and flu products, it is not difficult to imagine how someone with severe flu symptoms might unwittingly overdose on acetaminophen. There are also almost certainly genetic and environmental factors that affect a given person’s threshold of toxicity. For example, alcohol abuse and prolonged fasting may be associated with enhanced susceptibility to acetaminophen toxicity.Many patients with unintentional ALF also have chronic pain and take pills containing within a single tablet both acetaminophen and an opiate such as codeine. Vicodin®, a combination of hydrocodone with acetaminophen, is the most common example of this type of medication, and it is currently one of the most frequently prescribed drugs in the US. Some patients with chronic pain who are prescribed Vicodin® and similar acetaminophen-opiate combinations, become tolerant to the opiate and need to take increasing amounts to control their pain. Addiction to these medications is also a common problem. Patients who are addicted to the opiate component, commonly crave more and more, and thereby

unwittingly consume increasing amounts of acetaminophen, ultimately leading to ALF.Although acetaminophen poisoning can cause profound liver injury, early institution of treatment with an antidote called N-acetyl cysteine (NAC) [Mucomyst®] can be life-saving. Therapy with NAC, which can be given either by mouth or by I.V. (intravenously), should be started promptly in the emergency room whenever acetaminophen overdose is suspected.MedicationsScores of drugs other than acetaminophen can also produce severe liver injury (see Drug Induced hepatitis Knol). Unlike acetaminophen, however, the vast majority of these drugs produce severe liver injury very rarely and not in a dose-dependent fashion.MushroomsCertain mushrooms,

notably Amanita phalloides (photo), also called the “death capâ€, contain very potent liver toxins. Indeed, consumption of even a single mushroom may result in severe liver damage. Unfortunately, amateur mushroom pickers all too commonly mistake Amanita phalloides for an edible variety. Eating Amanita phalloides results in a classic syndrome of severe nausea, vomiting, profuse diarrhea, and crampy abdominal pain that typically begins about 8-16 hours after eating the mushrooms. Within a day or two, severe liver damage can ensue, which can be life threatening even with medical therapy. Eating wild mushrooms is thus best avoided by all but the most experienced mushroom pickers.Viral hepatitisIn the past, viral hepatitis B (HBV) (see Hepatitis B knol) was one of the leading causes of ALF in the US, but its incidence has been declining. It is now a rare cause of ALF in the US,

accounting for about 5% of ALF cases. Hepatitis B infection may occur via sexual and parenteral transmission (e.g., from intravenous drug use). Vertical transmission of the virus from mother to child at the time of birth may also occur; this is very common in China and other parts of Asia. Patients with vertically acquired hepatitis B may suffer reactivation of previously dormant and clinically silent hepatitis B, especially when exposed to immunosupression (for example, from chemotherapy), and a severe reactivation may culminate in an illness resembling ALF. Remember to vaccinate close contacts of HBV cases. In such situations, treatment with nucleoside analogues (e.g., entecavir) is often tried to suppress the viral replication and reverse the ALF, but this is not always effective. Family members should be vaccinated against hepatitis B.Compared with hepatitis B, hepatitis A causes ALF less commonly in the US. Infection with hepatitis A virus

is usually transmitted by a fecal-oral route and may occur sporadically or in the setting of food or water borne outbreaks. An infamous outbreak of hepatitis A in the Pittsburgh area in 2003 resulted in more than 650 cases of hepatitis and 4 deaths from ALF. Mortality from hepatitis A increases with patient age, and that occurred in this instance. The outbreak ultimately was traced to tainted green onions used and salsa served at a local Mexican restaurant. During outbreaks of hepatitis A, it is important for close contacts of ill individuals to be treated with intravenous immunoglobulin and hepatitis A vaccine.Other viruses, including cytomegalovirus (CMV), herpes simplex virus (HSV), and adenovirus, can rarely result in ALF, especially in immunocompromised patients such as those undergoing bone marrow transplant. Hepatitis E virus (HEV) is very rare in the US, but is a relatively common cause of ALF in certain parts of the world, including

India. HEV is spread in a fashion similar to HAV. Pregnant woman infected with HEV appear to be particularly at risk for developing ALF. Hepatitis C (see HCV knol) is a very common cause of cirrhosis in the US but rarely if ever causes ALF.Metabolic diseasesSeveral metabolic diseases may affect the liver and represent rare causes of ALF. The most common metabolic disease causing ALF in adults is Disease, a rare hereditary disorder associated with abnormal accumulation of copper in the liver and other organs. disease typically effects children, adolescents, and young adults, but has been occasionally reported in older individuals as well. Characteristically, patients with ALF from disease will present with concomitant anemia from hemolysis (red cell destruction), a brownish-green pigmented ring at the junction of the white and colored parts of the eye (the so-called

Kaiser-Fleisher ring), and an unusual biochemical pattern of liver injury, which are often clues to the diagnosis. Although disease often responds to medical therapy with drugs that bind and remove copper from the body, when ALF develops the prognosis for recovery is grim, and liver transplant is usually required.Other metabolic diseases, including alpha-1 antitrypsin deficiency and tyrosinemia, can be associated with ALF in children but are extremely rare in adults.Other conditionsSeveral other conditions that affect the liver can also cause ALF. Autoimmune hepatitis is a relatively rare condition in which the immune system of the affected individual attacks the liver in a process that is broadly analogous to liver transplant rejection, only without the transplant. In essence, the body attacks itself. Why this occurs is not well understood, but the condition is much

more common in women than in men, similar to other autoimmune conditions like rheumatoid arthritis and lupus. Fortunately, autoimmune hepatitis usually responds to immunosuppressive therapy with steroids, but medical treatment may not be successful when the patient has advanced liver failure.ALF may rarely occur in pregnancy, usually during the last trimester and most often in patients with preeclampsia (pregnancy-associated hypertension and loss of protein in the urine). Several different forms of acute liver failure may occur in this setting. Fortunately, most patients with pregnancy-related ALF recover following expeditious delivery of the infant.An abrupt and profound interruption of blood flow to the liver can lead to ALF, although this is rare because the liver has an unusually rich blood supply from both veins and arteries. Such so-called “shock liver†typically occurs in the setting of cardiac arrest, but can also be observed

with severe heat stroke, massive tumor infiltration of the liver, or when the veins normally draining blood from the liver are blocked in a relatively rare condition called Budd Chiari Syndrome.Indeterminate ALFWhen all is said and done, after an extensive evaluation that includes blood testing, radiological studies, and often even liver biopsy, the cause of ALF in at least 15% of adult cases in the US remain enigmatic. This group, called indeterminate ALF, is probably comprised of multiple different causes, including esoteric viral infections, unrecognized toxic exposures, autoimmune and metabolic diseases. One recent study from the Acute Liver Failure Study Group (see below) demonstrated that nearly 20% patients with indeterminate ALF had previously unrecognized acetaminophen poisoning when their blood was tested with a novel assay for acetaminophen-protein adducts present in the

blood after acetaminophen overdose. This suggests that acetaminophen poisoning is an even bigger problem than previously realized. ;

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What is acute liver failure?How common is acute liver failure?What causes acute liver failure?AcetaminophenMedicationsMushroomsViral hepatitisMetabolic diseasesOther conditionsIndeterminate ALFWhat are the symptoms of acute liver failure?How is acute liver failure diagnosed?What is the prognosis of acute liver failure?How is acute liver failure treated?Cerebral edemaRenal failureLiver TransplantationHow can acute liver failure be prevented?What does the future hold for acute liver failure?References:......