Practice Essentials
Cirrhosis is defined histologically as a diffuse hepatic process characterized by fibrosis and conversion of the normal liver architecture into structurally abnormal nodules. The progression of liver injury to cirrhosis may occur over several weeks to years.
Signs and symptoms
Some patients with cirrhosis are completely asymptomatic and have a reasonably normal life expectancy. Other individuals have a multitude of the most severe symptoms of end-stage liver disease and a limited chance for survival. Common signs and symptoms may stem from decreased hepatic synthetic function (eg, coagulopathy), portal hypertension (eg, variceal bleeding), or decreased detoxification capabilities of the liver (eg, hepatic encephalopathy).
Portal hypertension
Portal hypertension can have prehepatic, intrahepatic, or posthepatic causes. Budd-Chiari syndrome, a posthepatic cause, is characterized by the following symptoms:
Hepatomegaly
Abdominal pain
Ascites
Ascites is suggested by the following findings on physical examination:
Abdominal distention
Bulging flanks
Shifting dullness
Elicitation of a “puddle sign” in patients in the knee-elbow position
Hepatic encephalopathy
The symptoms of hepatic encephalopathy may range from mild to severe and may be observed in as many as 70% of patients with cirrhosis. Symptoms are graded on the following scale:
Grade 0 – Subclinical; normal mental status but minimal changes in memory, concentration, intellectual function, coordination
Grade 1 – Mild confusion, euphoria or depression, decreased attention, slowing of ability to perform mental tasks, irritability, disorder of sleep pattern (ie, inverted sleep cycle)
Grade 2 – Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, intermittent disorientation (usually with regard to time)
Grade 3 – Somnolent, but arousable state; inability to perform mental tasks; disorientation with regard to time and place; marked confusion; amnesia; occasional fits of rage; speech is present but incomprehensible
Grade 4 – Coma, with or without response to painful stimuli
Findings on physical examination in hepatic encephalopathy include asterixis and fetor hepaticus.
Additional signs and symptoms
Many patients with cirrhosis experience fatigue, anorexia, weight loss, and muscle wasting. Cutaneous manifestations of cirrhosis include jaundice, spider angiomata, skin telangiectasias (“paper money skin”), palmar erythema, white nails, disappearance of lunulae, and finger clubbing, especially in the setting of hepatopulmonary syndrome.
Diagnosis
Hepatorenal syndrome
Hepatorenal syndrome is diagnosed when a creatinine clearance rate of less than 40 mL/min is present or when a serum creatinine level of greater than 1.5 mg/dL, a urine volume of less than 500 mL/day, and a urine sodium level of less than 10 mEq/L are present.
Urine osmolality is greater than plasma osmolality.
Portal hypertension
During angiography, a catheter is placed selectively via either the transjugular or transfemoral route into the hepatic vein to measure portal pressure.
Hepatic encephalopathy
An elevated arterial or free venous serum ammonia level is the classic laboratory abnormality reported in patients with hepatic encephalopathy.
Electroencephalography may be helpful in the initial workup of a patient with cirrhosis and altered mental status, when ruling out seizure activity may be necessary.
Computed tomography (CT) scanning and MRI studies of the brain may be important in ruling out intracranial lesions when the diagnosis of hepatic encephalopathy is in question.
Ascites
Paracentesis is essential in determining whether ascites is caused by portal hypertension or by another process.
Management
Specific medical therapies may be applied to many liver diseases in an effort to diminish symptoms and to prevent or forestall the development of cirrhosis. Examples of such treatments include the following:
Prednisone and azathioprine – For autoimmune hepatitis
Interferon and other antiviral agents – For hepatitis B and C
Phlebotomy – For hemochromatosis
Ursodeoxycholic acid and obeticholic acid – For primary biliary cholangitis
Trientine and zinc – For Wilson disease
Once cirrhosis develops, treatment is aimed at the management of complications as they arise. Examples include the following:
Hepatorenal syndrome – Kidney function usually recovers when patients with cirrhosis and hepatorenal syndrome undergo liver transplantation; patients with early hepatorenal syndrome may be salvaged by aggressive expansion of intravascular volume with albumin and fresh frozen plasma and by the avoidance of diuretics
Hepatic encephalopathy – Pharmacologic treatment includes the administration of lactulose and antibiotics
Ascites – Treatment can include sodium restriction and the use of diuretics, large-volume paracentesis, and shunts (peritoneovenous, portosystemic, transjugular intrahepatic portosystemic)
Liver transplantation
Patients should be referred for consideration for liver transplantation after the first signs of hepatic decompensation.