Urgent considerations

See Differentials for more details

Ascending cholangitis

Patients with ascending cholangitis may be identified by the highly specific Charcot triad (fever, jaundice, and right upper quadrant pain). However, Charcot triad has a sensitivity of 36%, so cannot be used to rule out ascending cholangitis.[51] Patients may report pale stools and dark urine as a result of cholestasis.

Ascending cholangitis can quickly become an acute, life-threatening infection that requires rapid evaluation and treatment. The causative organism is usually a gram-negative bacillus. Patients require early antibiotic therapy and intravenous fluid resuscitation. An ultrasound should be performed promptly to confirm the presence of an obstructed biliary tree.

Antibiotics alone do not provide sufficient treatment in the majority of patients. Definitive treatment is urgent decompression of the biliary tree, usually by endoscopic retrograde cholangiopancreatography.

Patients with ascending cholangitis can develop sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Clinical signs include tachycardia, tachypnea, acutely altered mental status, fever or hypothermia (temperature <97ºF [<36ºC]), poor capillary refill and mottling of the skin, hypotension, and decreased urine output.

In addition to fluid resuscitation and intravenous antibiotics, these patients require blood tests, including blood culture, venous lactate, glucose, complete blood count, blood urea nitrogen, serum liver function tests, C-reactive protein (CRP), and urine output monitoring. They may also require supplemental oxygen to maintain saturations 94% to 98% (or 88% to 92% for those at risk of hypercapnic respiratory failure), and admission to an intensive care unit.[52]

Massive hemolysis

Massive hemolysis as a cause of jaundice should be considered in the presence of falling hemoglobin and absence of overt blood loss. Immune hemolytic anemias generally have characteristic clinical findings, including rapid onset and progression, dark urine, and jaundice, with or without splenomegaly.

Laboratory findings are important in confirming a hemolytic process (e.g., increased lactate dehydrogenase and indirect bilirubin, and decreased haptoglobin) and in establishing an immunologic etiology (e.g., antiglobulin test results).

Early hematologic input is essential for consideration of high-dose intravenous corticosteroids or intravenous immunoglobulins.

Acute liver failure

Acute liver failure (ALF) is defined by jaundice, coagulopathy (INR >1.5), and hepatic encephalopathy in patients with no evidence of prior liver disease.[53]

Acetaminophen hepatotoxicity is the leading cause in the US and Western Europe, while acute viral hepatitis is the most common cause in much of the developing world. Other causes include idiosyncratic drug-induced liver injury, autoimmune hepatitis, Budd-Chiari syndrome, acute Wilson disease, and ischemia.

ALF may be characterized by a rapid deterioration in neurologic status and there is a high risk of complications including sepsis, cerebral edema, hemodynamic instability, and renal failure. Intensive care unit (ICU) monitoring is critical in providing optimal care of the patient, and to prevent and treat known complications of ALF.[54]

In addition to supportive therapy, the underlying cause should be treated. Determination of whether acetaminophen is responsible for ALF in an individual case is the most important factor to be addressed upon presentation.[55] Acetylcysteine should be administered in all cases of ALF due to acetaminophen overdose.

All patients with ALF should be considered for possible liver transplantation, and measures to transport patients to a liver transplant center should be explored as soon as the patient is stabilized.[56][57]

Acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is a distinct syndrome of acute hepatic decompensation in a patient with chronic liver disease. It develops following an acute hepatic insult, and is associated with other organ failures and high short-term mortality.[58][59]

ACLF excludes patients with known distinct entities such as acute liver failure and those with end-stage liver disease.[60]

Alcoholic hepatitis and chronic viral hepatitis are the most common underlying chronic liver diseases.[58]

Infection is a leading trigger of ACLF in Western countries and is reported in up to 40% of patients with ACLF at initial presentation.[59][61][62] Sepsis, active alcohol misuse, and relapse of chronic viral hepatitis are commonly reported precipitating factors, but up to 50% of ACLF cases have no identifiable trigger.[18]​[58]​​

Patients present with jaundice, coagulopathy, ascites, and/or hepatic encephalopathy. The kidneys, liver, coagulation, brain, circulation, and lungs are the most frequently affected organ systems.[63] Systemic inflammation with elevated white cell count and plasma levels of CRP is a hallmark of ACLF.[58]

ACLF is diagnosed using the CLIF Consortium Organ Failure score (CLIF-C OFs), which assesses bilirubin, creatinine, encephalopathy grade, international normalized ratio, mean arterial pressure, and PaO₂/FiO₂.[64]

Treatment of ACLF is based on organ support and management of associated complications.[54] Patients with ACLF should be considered for admission to an ICU and preferably be managed in a liver transplant center. Organ function should be monitored frequently and early treatment provided according to each specific organ in order to avoid a multiple organ failure.[59]

Decompensated liver cirrhosis

Patients with compensated liver cirrhosis due to any etiology can remain asymptomatic for many years.[65]​ They may not present until they have their first episode of decompensated liver disease with clinically overt signs of portal hypertension.

Possible presentations include jaundice, ascites, variceal hemorrhage, hepatic encephalopathy, or liver synthetic dysfunction including coagulopathy. The first hepatic decompensation event significantly increases the risk that further complications of liver cirrhosis and decompensation episodes will occur.[50]

Patients with advanced stages of liver disease are much more susceptible to infection, the most frequent trigger of hepatic decompensation.[63]

All patients require blood tests (complete blood count, CRP, blood chemistries, serum liver functions tests, coagulation studies, glucose, calcium, phosphate, magnesium) and a comprehensive screen for infection, including blood and urine cultures, chest x-ray, and ascitic tap.[66][67]​ Concomitant treatment for alcohol detoxification, variceal bleeding, infection, acute kidney injury, hyponatremia, or hepatic encephalopathy may be necessary. Patients with decompensated cirrhosis should be referred urgently to a hepatologist.

Acute alcoholic hepatitis

Alcoholic hepatitis is a syndrome of progressive inflammatory liver injury associated with heavy alcohol intake. When alcoholic hepatitis is of sufficient severity to cause jaundice, hepatic encephalopathy, or coagulopathy, mortality can be substantial.

Patients present with subacute onset of fever, hepatomegaly, leukocytosis, marked impairment of liver function (e.g., jaundice, coagulopathy), and manifestations of portal hypertension (e.g., ascites, hepatic encephalopathy, variceal hemorrhage).

Complications include bacterial peritonitis, upper gastrointestinal bleeding, and fluid and electrolyte abnormalities.​​ The Glasgow Alcoholic Hepatitis Score or the Model for End-Stage Liver Disease (MELD) score allow the identification of patients with severe alcoholic hepatitis.[68] [ Glasgow Alcoholic Hepatitis Score Opens in new window ] [ MELD Score for End-Stage Liver Disease (NOT appropriate for patients under the age of 12) Opens in new window ]

Urgent upper gastrointestinal endoscopy is indicated to evaluate and treat varices if the patient presents with melena or hematemesis.

Infection may be both the precipitant for decompensation and a leading factor of poor outcome in alcoholic hepatitis. Send urine and blood cultures and request chest radiography.

In the absence of infection, corticosteroids may be beneficial in patients with severe alcoholic hepatitis (MELD >20) with no other contraindications.[18][69][70]​ If corticosteroids are used initially, response should be assessed using the Lille criteria, and the corticosteroid discontinued if there is no objective response.[18]​[71][72]​​ The American College of Gastroenterology does not recommend use of pentoxifylline for patients with severe alcoholic hepatitis.[18][73]​​

Malnutrition and sarcopenia are common in patients hospitalized with alcoholic hepatitis. Ensure adequate protein and caloric intake; B complex vitamins and zinc should be replaced. Use of either oral nutritional supplements or enteric nutrition support should be considered.[18]

Heart failure

Jaundice is a rare first manifestation of heart failure. The mechanism is most commonly hepatic congestion, although acute ischemic hepatitis may occur following a myocardial infarction. Jaundice caused by heart failure is usually mild and accompanied by dyspnea.[74]

On examination, patients may have hepatomegaly and hepatojugular reflux. Other signs of heart failure include cardiomegaly, elevated jugular venous pressure, third heart sound gallop rhythm, rales, signs of pleural effusion, and peripheral edema. Marked elevation of alanine aminotransferase occurs in ischemic hepatitis.[74]

Investigations include serum troponin, electrocardiogram, chest x-ray, and echocardiogram. Management is the timely treatment of the underlying cardiac condition. Reducing hepatic congestion by controlling the patient’s heart failure generally leads to an improvement in their jaundice.

Leptospirosis

People who work outdoors, with animals, or who swim in contaminated lakes and rivers, are at risk. Hepatosplenomegaly, abdominal tenderness, jaundice, and bilateral conjunctival suffusion may be elicited in both the acute/initial and immune phases of the disease. Weil disease, the most severe form of leptospirosis, is characterized by jaundice, hemorrhage, and renal failure.

Effective management of leptospirosis involves a combination of antibiotic therapy and aggressive supportive therapy for patients with organ damage. Patients must be monitored for signs of volume depletion and hemorrhage. Physicians should ensure adequate hydration, and correct coagulopathy and electrolyte disturbances.

Severe leptospirosis is treated with intravenous antibiotic therapy. Benzylpenicillin is recommended as the first-line treatment, with ceftriaxone as an alternative agent.[75]

Use of this content is subject to our disclaimer