• Definition: inflammation of hepatocytes

» Multiple causes, including viral infection, toxin, fatty liver infiltration of pregnancy, sepsis, congestive heart failure.

• Viral hepatitis

» Symptoms in order of incidence: dark urine, fatigue, anorexia, nausea, fever, emesis, headache, abdominal discomfort, light-colored stool, pruritus.

» Hepatitis A

– Fecal-oral transmission; blood transmission is rare.

– Chronic disease or carrier state does not exist.

» Hepatitis B

– Parenteral, oral-oral, sexual transmission.

– HBsAg indicates infectivity.

– HBcAg indicates high infectivity.

– HBsAg presence for >6 mo suggests a chronic carrier state (1-10% become chronic).

– Chronic active disease often progresses to cirrhosis.

» Hepatitis C

– Causes most posttransfusion hepatitis.

– Chronic liver disease develops in 80% of infected pts & 20% of these will develop cirrhosis.

– Sexual & casual household contact w/ saliva is inefficient means of transmission.

» Hepatitis D

– Requires the presence of hepatitis B for its expression.

– Hepatitis B vaccination prevents hepatitis D.

» Epstein-Barr virus (EBV): usually produces mild hepatitis associated w/ infectious mononucleosis

» Cytomegalovirus (CMV): CMV is present in most adults; liver disease is mild & nonchronic

• Drug-induced

» Toxins: alcohol, carbon tetrachloride, vinyl chloride

» Therapeutic drugs most frequently implicated: isoniazid, methyldopa, rifampin, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs (NSAIDs)

» Halothane produces two types of hepatotoxicity:

– Mild self-limited postop toxicity due to changes in hepatic blood flow that affect hepatic oxygenation

– Halothane hepatitis, a life-threatening immune-mediated response after repeat exposure to halothane via trifluoroacetyl metabolite (less likely in pediatric pts)

» Isoflurane/enflurane/desflurane/sevoflurane, like halothane, can produce mild self-limited postop toxicity due to changes in hepatic blood flow. However, they all maintain blood flow similarly & better than halothane

– These compounds, w/ exception of sevoflurane, may be capable of producing a more severe immune-mediated hepatitis but undergo less extensive metabolism than halothane

Issues/Evaluation

• Elective surgery should be postponed for pts w/ acute hepatocellular injury due to increased morbidity & mortality.

» One study found a 31% mortality rate for pts undergoing exploratory laparotomy w/ unsuspected parenchymal liver disease.

» Another study noted a 9.5% mortality rate for pts w/ acute viral hepatitis undergoing laparotomy.

• Severely jaundiced pts (>8 mg/dL) are more likely to develop postop renal failure & sepsis.

• Decreased perfusion of the liver, which occurs during all anesthetics, neuraxial & general, may be responsible for poor outcomes in pts w/ parenchymal liver disease.

• Liver perfusion is affected most greatly by procedures anatomically adjacent (eg, cholecystectomy).

• Rule out acute liver failure (as opposed to merely acute hepatitis).

» Findings in acute liver failure can include encephalopathy, cerebral edema, coagulopathy, renal failure, infection, hypoglycemia, etc.

» See also Coexisting Disease chapter "Acute Liver Failure."

• Blood glucose may be low w/ severe liver injury & should be corrected.

• Thrombocytopenia should be corrected if present.

• Evaluate LFTs & viral serology if appropriate.

» Prothrombin time: assesses current liver synthetic function

– May be prolonged by vitamin K deficiency; consider vitamin K administration if this is suspected

» Aspartate aminotransferase (AST), alanine aminotransferase (ALT):

– Found in large quantity in the liver.

– Levels >500 U/L occur w/ acute hepatocellular injury.

– Modest injury <300 U/L occurs in a variety of conditions (eg, acute or chronic hepatocellular injury, infiltrative disease, biliary obstruction).

– ALT is generally more sensitive than AST for viral hepatitis.

– AST is elevated twofold in excess of ALT in alcoholic liver disease.

– If transaminase levels are >3 times normal, nonelective procedures requiring general or regional anesthetic should be postponed & a gastroenterologist consulted.

– Lower elevations require repeat evaluation to assess for worsening levels, stable levels, or improvement in levels as well as viral hepatitis serologies.

– Surgery may proceed if moderately elevated transaminase levels are stable or trending down & viral serologies are negative; otherwise, seek gastroenterology consult.

» Albumin

– Synthesized by liver

– Half-life of 14-21 days, so is not beneficial for evaluation of acute disease

» Alkaline phosphatase (AP): present in bone, intestine, liver. AP is elevated in biliary obstruction, cholestasis, space-occupying lesions, infiltrative diseases.

» Gamma-glutamyl transpeptidase (GGT)

– Increases in GGT & AP tend to occur in similar diseases.

– GGT is elevated in pts ingesting certain agents (eg, alcohol, barbiturates, phenytoin).

» Lactate dehydrogenase (LDH): abundant in the liver but may arise from many sources, including red blood cells, as during hemolysis

» Total bilirubin (a byproduct of heme degradation) is either conjugated (direct-acting, water-soluble, renally excreted) or unconjugated (indirect-acting, protein-bound).

– Jaundice is apparent when levels exceed 3-4 mg/dL.

– Indirect bilirubin increases w/ hemolysis, Gilbert's or Crigler-Najjar syndrome, heart failure, or portosystemic shunting.

– Direct bilirubin increases w/ hepatocellular dysfunction or biliary tract obstruction.

Management

• Drug disposition may be difficult to predict.

» Isoflurane, desflurane, sevoflurane may be best for maintenance of hepatic blood flow; consider supplementation w/ nitrous oxide & IV agents (which may have delayed clearance).

» Pseudocholinesterase deficiency is rare such that succinylcholine & mivacurium action should not be prolonged.

» Atracurium & cis-atracurium are cleared independent of liver function.

» Vecuronium & rocuronium are unlikely to be prolonged unless large doses are used.

• To optimize liver perfusion & prevent secondary ischemic injury, minimize hypotension & hypoxia & maintain normocarbia.

• Administer fresh-frozen plasma for coagulopathy.

• Consider monitoring of blood glucose, acid-base status, coagulation profile, urine output.

• Be alert to worsening liver function after surgical stress.

• Severe postop jaundice may be related to hypotension, hypoxia, multiple transfusions.

• "Shock liver" is a condition caused by marked or prolonged hypotension.

» Typical findings include

– Tenfold increase in transaminase levels

– Coagulopathy

– Possibly liver failure

» A milder form can be seen in pts after cardiopulmonary bypass.

• Reversible, minor abnormalities in LFTs can be detected in up to 50% of all patients postop.

• Postop jaundice is present in 20% of all patients after major surgery.

• Causes of postop jaundice (can be distinguished by LFT evaluation).

» Increased bilirubin

– Hemolysis

– Hemolysis of transfused blood

– Resorption of hematoma

» Hepatic damage

– Intrahepatic cholestasis

– Circulatory failure

– Drug-induced

– Pre-existing disease

» Obstructive

– Common bile duct stone

– Bile duct injury

– Pancreatitis

» Other

– Gilbert's disease (7-10% of patients) exacerbated by fasting state, cholecystitis

Joseph Cotten, MD, PhD