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G28 Gastroenterology
Liver Toronto Notes 2019
Liver
Investigations of Hepatobiliary Disease
A . Tests of Liver Function
Table 14. Liver Function Tests
Test
Prothrombin Time (PT or INR)
Serum Albumin
Serum Direct Bilirubin*
What Do Levels Correlate With?
Hepatic protein synthesis
All coagulation factors except VIII
Hepatic protein synthesis (and other causes listed in next column)
Hepatic excretion from hepatocyte to biliary system
Increased by
Hepatocellular dysfunction Vitamin K deficiency (due to malnutrition, malabsorption, etc.)
Hepatocellular dysfunction Malnutrition
Renal or GI losses Significant inflammation Malignancy
Liver dysfunction
How to Interpret
PT/INR will promptly correct if vitamin K is administered, so increased PT/INR in absence of vitamin K deficiency is a reliable marker of hepatocellular dysfunction
Rule out potential causes other than hepatocellular dysfunction
Conjugation is preserved even in end stage liver failure, thus increased direct bilirubin indicates liver dysfunction
All clotting factors except factor VIII and von Willebrand factor are exclusively synthesized in the liver. Factor VIII is also produced in the endothelium. In cirrhosis, risk of bleeding does not correlate closely with elevations in INR/PTT since so many of the proteins in the coagulation cascade are affected
ALT > AST = most causes of hepatitis
AST > ALT = alcoholic liver disease or other causes of hepatitis (i.e. non-alcoholic liver disease) that have progressed to advanced cirrhosis
Serum Transaminases >1000 due to
• Viral hepatitis
• Drugs/toxins
• Autoimmune hepatitis
• Hepatic ischemia
• Less often, common bile duct stone
Alcoholic hepatitis: history of recent alcohol, RUQ abdominal pain, AST/ALT>2, AST usually <300, low grade fever, mildly elevated WBC
Major Sources of ALP
• Hepatobiliary tree • Bone
• Placenta
*Serum Bilirubin
• canaliculus breakdown product of hemoglobin; metabolized in the reticuloendothelial system of liver, transported through biliary system, excreted via gut • direct bilirubin = conjugated; indirect = unconjugated bilirubin
B . Tests of Liver Injury
• disproportionatelyincreasedASTorALT=hepatocellulardamage
■ ALT more specific to liver; AST from multiple sources (especially muscle) ■ elevation of both highly suggestive of liver injury
■ most common cause of elevated ALT is fatty liver
• disproportionatelyincreasedALP(andGGT)=cholestasis(stasisofbileflow)
■ if ALP is elevated alone, rule out bone disease by fractionating ALP and/or checking GGT ■ if ALP elevation out of proportion to ALT/AST elevation, consider:
1. obstruction of common bile duct (e.g. extraluminal = pancreatic cancer, lymphoma; intraluminal = stones, cholangiocarcinoma, sclerosing cholangitis, helminths)
2. destruction of microscopic ducts (e.g. PBC)
3. bile acid transporter defects (e.g. drugs, intrahepatic cholestasis of pregnancy) 4. infiltration of the liver (e.g. liver metastases, lymphoma, granulomas, amyloid)
Acute Viral Hepatitis (General)
Definition
• viralhepatitislasting<6mo
Clinical Features
• mostaresubclinical
• flu-likeprodromemayprecedejaundiceby1-2wk
■ nausea/vomiting, anorexia, headaches, fatigue, myalgia, low-grade fever, arthralgia, and urticaria (especially HBV)
• onlysomeprogresstoicteric(clinicaljaundice)phase,lastingdaystoweeks ■ pale stools and dark urine 1-5 d prior to icteric phase
■ hepatomegalyandRUQpain
■ splenomegaly and cervical lymphadenopathy (10-20% of cases)
Investigations
• ASTandALT(>10-20xnormalinhepatocellularnecrosis)
• ALPminimallyelevated
• viralserology,particularlytheIgMantibodydirectedtothevirus
Treatment
• supportive(hydration,diet)
• usuallyresolvesspontaneously,butifsevereHBVinfection,treatmentwithentecavirshouldbe
considered; in anicteric hepatitis C, anti-viral treatment should be considered (see hepatitis C)
• indicationsforhospitalization:encephalopathy,coagulopathy,severevomiting,hypoglycemia
Prognosis
• poorprognosticindicators:comorbidities,persistentlyhighbilirubin(>340mmol;20mg/dL), increased INR, decreased albumin, hypoglycemia