Liver disease can be categorized as acute, chronic, or fulminant. Accurately differentiating the acuity and severity of the disease process guides appropriate evaluation, treatment, and disposition.
Acute hepatitis typically presents with nausea, vomiting, and right upper quadrant abdominal pain. The patient with acute hepatitis can also have fever, jaundice, bilirubinuria, and an enlarged, tender liver. The most common causes are viral infection and toxic ingestion. Alcohol and acetaminophen are the most common toxic causes.
Patients with chronic hepatitis display evidence of long-standing hepatocellular damage. Cirrhotic patients with portal hypertension complain of abdominal pain and/or distention, abnormal bleeding (bruising, bleeding gums, epistaxis, blood in the stool), and lower body edema. They may also exhibit signs of infection, encephalopathy, ascites, and electrolyte derangement. Skin examination may reveal spider nevi, caput medusae, and other manifestations of abnormal shunting of blood to surface vessels.
Liver failure is the potential final common pathway for both acute and chronic liver disease. If there is a delay in seeking medical attention or a rapid acute course, fulminant liver failure can be the presenting disorder. For cirrhotic patients, the transition to liver failure is marked by the advent of coagulopathy, encephalopathy, abnormal fluid shifts, and hepatorenal syndrome.
Hepatitis A virus, hepatitis B virus, and hepatitis C virus are the most prevalent forms of viral hepatitis encountered in the ED. Hepatitis A virus is transmitted by fecal-oral contamination. Although it is popularly associated with improper food handling or oyster consumption, the most common transmission occurs from asymptomatic children to adults. Implementation of the hepatitis A vaccine in children has dramatically decreased overall rates of infection. Hepatitis A virus infection has an incubation period of 15 to 50 days, followed by a prodrome of nausea, vomiting, and malaise. About a week into the illness, patients may note dark urine (bilirubinuria). A few days later, they develop clay-colored stools and jaundice. Hepatitis A virus does not have a chronic component, and death from hepatic failure is rare.9
Hepatitis B virus is transmitted sexually, by blood transfusion, by contaminated needles, and by perinatal transmission. Incubation period is 1 to 3 months, and patients can be infectious for 5 to 15 weeks after onset of symptoms if they clear the infection. Individuals who develop chronic disease will remain infectious indefinitely. Chronic infection occurs in only 6% to 10% of patients who contract hepatitis B virus as adults, whereas 90% of infants and 30% of children under the age of 5 progress to chronic status, which underlines the importance of vaccination of infants and women of childbearing age.10 In the acute phase of hepatitis B virus, presentation to the ED is similar to that for hepatitis A virus, including complaints of malaise, nausea, vomiting, fever, abdominal pain, and jaundice.
Hepatitis C virus transmission occurs primarily through exposure to contaminated blood or blood products. In contrast to hepatitis A virus and hepatitis B virus, hepatitis C virus is most often asymptomatic in the acute phase of infection, and >75% of patients advance to the chronic stage. The rate of progression to liver failure varies and depends on the natural course of the virus and cofactors such as alcoholism and human immunodeficiency virus. Along with hepatitis B virus, hepatitis C virus is one of the most common causes of hepatocellular carcinoma. Of the patients who develop chronic hepatitis C virus, 1% to 5% will die of either cirrhosis or liver cancer.11
Hepatitis D virus is uncommon and is typically seen in people with preexisting chronic hepatitis B virus infection. Hepatitis D superinfection can result in a rapidly progressive or fulminant form of liver disease that carries a high short-term mortality rate. This variety of infection is most commonly associated with injection drug use.11
Acute illness with liver function test abnormalities also occurs with infection by other hepatotropic viruses such as cytomegalovirus, herpes simplex virus, Coxsackie virus, and Epstein-Barr virus. These agents are unlikely to cause clinically significant hepatitis in an otherwise healthy host.
A toxic insult to the liver can cause acute hepatitis and/or fulminant liver failure. The most common of these is acetaminophen overdose. Acetaminophen accounts for >40% of liver failure cases in the United States and one third of deaths secondary to toxic ingestion. Patients develop nausea, vomiting, and abdominal pain. They may also give a history of an acute overdose of acetaminophen or chronic use of one or more acetaminophen-containing pain medicines. Up to 28% of patients with acetaminophen overdose will develop liver failure. The likelihood of liver failure depends on time from ingestion to presentation, the dose ingested, and the baseline health status of the patient.12 Tylenol overdose is reviewed more completely in chapter 190, "Acetaminophen."
In addition to acetaminophen, there are a variety of prescription medications (antibiotics and statins prominent among them), herbal remedies, and dietary supplements that have been associated with acute hepatitis and liver failure. The list of prescription medications that have been implicated in liver disease is so long that it is prudent to refer to a pharmaceutical database to identify a potential culprit when toxic insult is suspected. Some of the most common herbal remedies that have been implicated in hepatic injury are listed in Table 80–2.
Common Herbal Remedies Known to Cause Hepatic Toxicity
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Common Herbal Remedies Known to Cause Hepatic Toxicity
|Herbal Remedy ||Application ||Nature of Injury |
|Black cohosh (Actea racemosa/cimiifuga racemosa) ||Menopausal symptoms ||Hepatic necrosis and bridging fibrosis |
|Chaparral (Larrea ridentate) ||Antioxidant, health tonic ||Cholestasis, chronic hepatitis, cholangitis, cirrhosis |
|Comfrey (Symphytum) ||Broken bones, wound healing, reduce joint inflammation ||Hepatic veno-occlusive disease |
|Echinacea (E. angustifolia, E. pallida, E. purpurea) ||Respiratory infections, fever, immune booster ||Acute cholestatic autoimmune hepatitis |
|Kava (Piper methysticum) ||Anxiolytic, sleeping aid ||Acute and chronic hepatitis, cholestasis, fulminant hepatic failure |
|Kombucha "mushroom" tea ||Weight loss, increasing T-cell count, well-being, antiaging ||Acute liver failure, hepatitis, acute renal failure with hyperthermia and lactic acidosis |
|Ma huang (Ephedra sinica) ||Weight loss ||Acute hepatitis |
|Mistletoe (Viscum album) ||Hypertension, insomnia, epilepsy, asthma, infertility, urinary disorders ||Acute hepatitis |
|Noni juice (Morinda citrifolia) ||Health tonic ||Subacute hepatic failure, acute hepatitis |
|Prostata (Serenoa repens); saw palmetto ||Benign prostatic hyperplasia ||Cholestatic hepatitis |
|Senna (Cassia angustifolia) ||Laxative ||Acute hepatitis, acute cholestatic hepatitis, acute liver failure |
|Skullcap (Scutellaria baicalensis) ||Sedative, anti-inflammatory ||Hepatic veno-occlusive disease, cholestasis, hepatitis |
|St John's wort (Hypericum perforatum) ||Anti-depressant ||Cytochrome P-450 induction, serotonin syndrome |
|Valerian (Valeriana officinalis) ||Sedative, anxiolytic ||Hepatitis |
Alcoholic liver disease can range from asymptomatic, reversible fatty liver to acute alcoholic hepatitis, cirrhosis, or a combination of acute and cirrhotic features. The diagnosis of alcoholic liver disease carries a 35% 5-year survival rate. If a patient has asymptomatic liver disease (i.e., fatty liver seen on imaging), but the patient's drinking continues and acute alcoholic hepatitis develops, the mortality can be much higher.13 A history of consistent heavy alcohol use (mean intake at presentation of 100 grams or more) is thought to be required for development of significant alcoholic liver disease.14 However, information is often difficult to elicit from the patient or family, and the patient may have stopped drinking before ED presentation. Other nonhepatic features of alcohol abuse, such as malnutrition, stocking-glove neuropathy, and cardiomyopathy, can be clues to alcohol-induced liver disease.
Mushroom poisoning is an uncommon but important cause of acute hepatitis with a high risk of liver failure. Amanita phalloides ("death cap") is the most lethal of the more than 50 types of mushrooms that are toxic to humans. For detailed discussion, see chapter 219, "Mushroom Poisoning."
CHRONIC HEPATITIS AND CIRRHOSIS
Most patients live for years with hepatitis B virus, hepatitis C virus, NASH, or alcoholic hepatitis without symptoms. During the asymptomatic period, normal liver parenchyma is being gradually replaced by scar tissue, and hepatic disease can manifest as mild transaminase elevation or, in cases of NASH and alcoholic hepatitis, as an incidental finding of fatty liver on abdominal imaging studies. When a critical amount of liver parenchyma is replaced by fibrotic tissue, symptoms of cirrhosis develop, such as abdominal pain, ascites, SBP, general weakness resulting from electrolyte derangement, or altered mental status due to hepatic encephalopathy.
One of the hallmarks of cirrhosis, ascites causes a protuberant abdomen, and a fluid wave is produced on physical exam. Intra-abdominal fluid can displace the diaphragm upward and produce sympathetic pleural effusion with the possibility of respiratory compromise. Smaller amounts of ascites can be difficult to identify on examination; bedside ultrasound can be particularly helpful in patients in whom the presence of ascites is uncertain (Figure 80–1).
Sonographic image of ascitic fluid showing bowel loops and an edematous gallbladder wall, a common finding in patients with ascites. [Courtesy of and used with permission of Michael S. Antonis, DO, sonographer.]
Spontaneous Bacterial Peritonitis
SBP is a subtle yet crucial complication of ascites. The survival rate for patients with a first episode of SBP is 68.1% at 1 month and 30.8% at 6 months. This is probably a result of acute infection occurring in the fragile setting of advanced liver disease.15 Although common in cirrhotic patients—roughly 30% of ascitic patients will develop SBP in a given year—SBP is difficult to diagnose because signs of abdominal pain and fever are not always present, and physical examination does not always demonstrate abdominal tenderness. Consequently, patients who are diagnosed with ascites for the first time, or who have ascites and develop fever, abdominal pain, GI bleeding, or encephalopathy, should undergo paracentesis to check for SBP.
Hepatorenal syndrome is a complication of cirrhosis that often accompanies SBP. It is defined as acute renal failure in a patient with histologically normal kidneys in the presence of preexisting chronic or acute hepatic failure. The cause is not well understood. There are two types of hepatorenal syndrome. Type 1 is more serious and is identified by progressive oliguria and doubling of serum creatinine over a 2-week period. Type 2 is represented by a gradual impairment in renal function that may or may not advance beyond moderate dysfunction. The discovery of abrupt renal failure in a cirrhotic patient that cannot be attributed to any other cause should be viewed as a marker of extreme morbidity. Median survival for type 1 hepatorenal syndrome without medical treatment is 2 weeks.16
Hepatic encephalopathy is a poorly understood phenomenon attributed to the accumulation of nitrogenous waste products normally metabolized by the liver. Hepatic encephalopathy causes a spectrum of illness ranging from chronic fatigue or mild confusion to acute lethargy.
The development of hepatic encephalopathy suggests either that the liver is no longer able to metabolize the usual supply of nitrogenous waste or that the supply of such waste has increased. Sources of increased supply include protein loads from a large meal or from occult GI bleeding. In addition to progressive liver disease, constipation, hypo- or hyperglycemia, alcohol withdrawal, hypoperfusion states such as sepsis, and iatrogenic interventions can also compromise the liver's metabolic capacity. Hepatic encephalopathy is a common complication after transjugular intrahepatic portosystemic shunt, a procedure in which portal blood is shunted to the inferior vena cava, bypassing the liver. Although this procedure may succeed in reducing portal hypertension and variceal bleeding, it also slows metabolism of nitrogenous wastes by reducing hepatic blood flow. Adding or removing antibiotics from a patient's medicine regimen can also precipitate encephalopathy by changing the intestinal flora and altering the gut's ability to metabolize proteins.17
To appreciate the presence or worsening of encephalopathy, determine if there are changes in personality, worsening dementia, a decrease in levels of consciousness, or declining neuromuscular function. Table 80–3 lists clinical stages of encephalopathy. Asterixis, which characterizes stage II, is elicited by having the patient hold the arms straight up and extending the wrists. The hands begin to flap repetitively. Another manifestation of asterixis is back-and-forth tongue movement when the tongue is extended. A patient with known encephalopathy in stage I or II who is otherwise well and has no other acute comorbidities may be managed as an outpatient after consultation with the primary care physician or gastroenterologist.
Stages of Clinical Hepatic Encephalopathy
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Stages of Clinical Hepatic Encephalopathy
|Stage ||Features |
|I ||General apathy |
|II ||Lethargy, drowsiness, variable orientation, asterixis |
|III ||Stupor with hyperreflexia, extensor plantar reflexes |
|IV ||Coma |
Hepatic encephalopathy is a diagnosis of exclusion. In the cirrhotic patient with altered mental status or lethargy, first exclude multiple other causes. This holds true even in the presence of an elevated serum ammonia level. Patients with end-stage liver disease are typically coagulopathic and may develop a spontaneous or traumatic subdural hematoma. Decreased hepatic gluconeogenesis and glycogen stores and poor nutritional status increase the risk of hypoglycemia and nutritional encephalopathies such as Wernicke-Korsakoff syndrome. Cirrhotic patients often are treated with diuretics and can develop hyper- or hyponatremia. Altered mental status can result form decreased hepatic clearance of drugs such as benzodiazepines and opiates, prolonging the effect and resulting in accidental overdose. Renal failure and sepsis are other considerations. Always exclude upper GI bleeding as a precipitant of hepatic encephalopathy, because the protein in the blood can translocate across the bowel of the cirrhotic patient.
Gastroesophageal varices and hemorrhage are complications of cirrhosis that are covered in chapter 75, "Upper Gastrointestinal Bleeding."
Liver failure is the final common pathway for several types of liver disease. Progression to liver failure is varied and depends largely on comorbid entities, such as human immunodeficiency virus/acquired immunodeficiency syndrome, diabetes, obesity, continued injection drug use, and alcohol intake. There are roughly 2000 cases per year in the United States. Patients who develop acute liver failure have an extremely poor prognosis, with survival rates of <30%.18 Among the most common of the entities that present as acute liver failure in the United States are acetaminophen overdose (46%), indeterminate causes (14%), other drugs (11%), hepatitis B virus (7%), and autoimmune hepatitis.3
The clinical hallmarks of acute liver failure are hepatic encephalopathy, hepatorenal syndrome, and coagulopathy. The electrolyte imbalances seen in chronic liver disease can become extreme. Cerebral edema and intracranial hypertension are the most ominous complications. The catabolic nature of liver failure leads to negative nitrogen balance and immunodeficiency. Other clinical findings in acute liver failure include hypotension, hypoglycemia, and relative adrenal insufficiency. ED evaluation should include assessment for sepsis. Recognize when a patient has progressed from cirrhosis to failure or presents with acute hepatic failure, because transfer to a transplant center may be the most appropriate disposition.
Gilbert's syndrome is a familial liver disorder that produces occasional elevations in liver function tests and bilirubin. This syndrome does not cause cirrhosis or affect the synthetic or metabolic functions of the liver. Wilson's disease, hemochromatosis, and α1-antitrypsin deficiency are familial disorders that can lead to severe chronic disease and liver failure. Autoimmune hepatitis is a progressive, chronic disease that is presumably triggered by viral hepatitis or by medications. Primary biliary cirrhosis is a presumably autoimmune disorder with a chronic or chronic-degenerative course.
PRE- AND POSTHEPATIC VENOUS THROMBOSIS
Vascular diseases of the liver are rare but important, because timely diagnosis and treatment can improve outcome. Portal vein thrombosis affects the prehepatic portal venous system and is associated with hypercoagulable states such as polycythemia vera; with deficiencies in proteins C and S, antithrombin 3, and factor V Leiden; and with abdominal trauma, sepsis, pancreatitis, cirrhosis, or hepatocellular carcinoma. The major symptom is abdominal pain; occasionally ascites can occur. Splenomegaly can occur without hepatomegaly on physical examination.19 Hepatic vein thrombosis (posthepatic), or Budd-Chiari syndrome, has both acute and chronic presentations, including abdominal pain, hepatomegaly, and ascites. Associated conditions include coagulopathies, polycythemia vera, paroxysmal nocturnal hemoglobinuria, and congenital webs of the vena cava.20