Liver Labs
A 63-year-old patient presents with new jaundice. The clinician is deciding whether to investigate hemolysis or biliary obstruction first.
What is fractionation of bilirubin into direct and indirect fractions?
The initial laboratory distinction is between predominant unconjugated and conjugated hyperbilirubinemia. Indirect predominance directs evaluation toward hemolysis or impaired uptake/conjugation; direct predominance requires assessment for hepatocellular injury or cholestasis.
This hepatic enzyme converts bilirubin into a water-soluble form that can be actively transported into bile
What is conjugation with glucuronic acid by UDP-glucuronosyltransferase?
A 70-year-old man has painless jaundice, weight loss, and a markedly elevated alkaline phosphatase level. The clinician suspects obstruction of the extrahepatic biliary tree.
Best initial imaging?
What is right-upper-quadrant ultrasonography?
When cholestasis or extrahepatic obstruction is suspected, right-upper-quadrant ultrasound is an appropriate initial imaging study to assess for biliary dilation.
A patient has a positive HBsAg, positive anti-HBe, low HBV DNA, and normal aminotransferase levels. What phase of Hep B infection are they?
What is chronic hepatitis B infection?
This pattern indicates persistent HBV infection with low viral replication and minimal biochemical activity. It contrasts with the high-replicative phase, which features HBeAg positivity, high HBV DNA, and elevated aminotransferases.
A 68-year-old woman with diffuse bone pain has an elevated alkaline phosphatase level. AST, ALT, bilirubin, and GGT are normal.
Likely cause?
What is a nonhepatic, likely bone, source of alkaline phosphatase?
Alkaline phosphatase is produced by several tissues, including liver and bone. An elevated alkaline phosphatase with normal GGT or 5′-nucleotidase suggests a nonhepatic source.
Increased ALP suggest increased osteoblast activity & bone formation
A man presents with 2 days of progressive jaundice, intense generalized pruritus, dark urine, and clay-colored stools. He reports several episodes of postprandial right-upper-quadrant pain over the past year, with nausea after fatty meals. He has no fever or confusion. Laboratory studies show:
Why is his urine dark but stool pale?
Pt has conjugated hyperbilirubinemia secondary to choledocolithiasis
Conjugated bilirubin is water-soluble and can be excreted in urine, causing dark urine. Reduced delivery of bile pigments to the intestine decreases stercobilin formation and produces pale stools.
A healthy 19-year-old college student develops mild scleral icterus during fasting before examinations. Total bilirubin is elevated, predominantly unconjugated, while AST, ALT, alkaline phosphatase, and GGT are normal.
Diagnosis?
What is Gilbert syndrome?
Isolated unconjugated hyperbilirubinemia can result from impaired bilirubin uptake or conjugation. Gilbert syndrome is a common cause when other liver chemistry tests are normal.
A 27-year-old man presents with jaundice and fatigue 6 weeks after sharing injection equipment. Anti-HCV testing is negative, but HCV RNA is detectable in serum.
Which stage of hepatitis is this pt in? (acute or chronic)
What is acute hepatitis C infection?
HCV RNA can become detectable approximately 2 weeks after exposure, whereas anti-HCV antibodies may not appear until several weeks later. A negative antibody test therefore does not exclude early acute infection.
A 54-year-old man with long-standing heavy alcohol use presents with jaundice and abdominal tenderness. His AST is 280 U/L, and his ALT is 110 U/L.
Diagnosis?
What is alcohol-associated hepatitis?
An AST-to-ALT ratio greater than 2 strongly supports alcohol-associated liver disease. AST is usually below 400 U/L in this condition.
A 46 y/o woman who is 30 weeks gestation develops episodic right-upper-quadrant pain, dark urine, pale stools, and jaundice. Laboratory studies show a marked alkaline phosphatase elevation, elevated GGT, and predominantly conjugated hyperbilirubinemia.
What is the likely cause of her cholestasis?
What is progesterone?
Pregnancy increases the risk of intrahepatic cholestasis of pregnancy (ICP) because rising estrogen and progesterone levels impair hepatic bile-acid handling, particularly in genetically susceptible patients. The result is reduced bile flow within the liver and accumulation of bile acids in maternal serum.
A 35-year-old patient presents with fatigue and jaundice. Laboratory studies show elevated unconjugated bilirubin, increased lactate dehydrogenase, low haptoglobin, and reticulocytosis. AST, ALT, alkaline phosphatase, and GGT are normal.
Diagnosis?
What is hemolysis causing isolated unconjugated hyperbilirubinemia?
Overproduction of bilirubin from hemolysis causes an increase in indirect bilirubin without a primary hepatocellular or cholestatic pattern.haptoglobin decreases because it binds free hemoglobin
A pregnant woman in her third trimester develops acute hepatitis after consuming contaminated water while traveling. She develops rapidly worsening jaundice, coagulopathy, and confusion. Diagnosis?
What is fulminant hepatitis E infection?
Hepatitis E is usually self-limited, but pregnant patients have an increased risk of acute liver failure and hepatic decompensation.
A 58-year-old man with a history of chronic hepatitis C presents with ascites, splenomegaly, and easy bruising. Laboratory studies are ordered to assess his hepatic synthetic function.
Which laboratory tests should be ordered?
What is Serum albumin, prothrombin time/INR, and platelet count?
Albumin and PT/INR assess hepatic production of proteins and clotting factors, while thrombocytopenia may reflect cirrhosis-related reduced thrombopoietin production and portal-hypertension-associated hypersplenism.
A patient with cholestasis develops steatorrhea and deficiencies of vitamins A, D, E, and K. The missing substance normally facilitates intestinal lipid digestion and absorption. What is the missing substance?
What are bile acids?
Bile acids are required for effective lipid digestion and absorption. Cholestasis reduces bile-acid delivery to the duodenum, causing fat malabsorption and deficiency of fat-soluble vitamins.
A 21-year-old patient presents with acute liver failure. Bilirubin is markedly elevated, but alkaline phosphatase is unexpectedly low. Further evaluation shows a low ceruloplasmin level and increased urinary copper excretion.
Diagnosis?
What is Wilson disease?
Wilson disease may cause acute liver failure with disproportionately high bilirubin relative to alkaline phosphatase. Diagnostic testing includes serum ceruloplasmin and urinary copper measurements.
A newborn is delivered to a mother whose prenatal testing is positive for hepatitis B surface antigen. The infant is clinically well and weighs 3,200 g.
What should be administered to the newborn within the first 12 hours of life?
What are the first dose of the hepatitis B vaccine and one dose of hepatitis B immune globulin?
Infants born to an HBsAg-positive mother require both active immunization with hepatitis B vaccine and passive immunization with HBIG within 12 hours of birth. The infant should then complete the hepatitis B vaccine series and undergo postvaccination serologic testing. Without prophylaxis, perinatal infection carries a high risk of chronic hepatitis B, which can later lead to cirrhosis or hepatocellular carcinoma.
A 36-year-old man with a history of inflammatory bowel disease has recurrent jaundice and laboratory evidence of cholestasis. Imaging reveals multifocal strictures and dilations throughout the biliary tree.
Which antibody result would confirm the diangosis?
What is p-ANCA?
Primary Sclerosing Cholangitis Associations:
- (+) p-ANCA, men, ulcerative colitis, cirrhosis = late complication
A 49-year-old woman has several years of fatigue and generalized pruritus. Laboratory studies show a cholestatic pattern, and imaging does not demonstrate extrahepatic biliary obstruction. Labs = (+) AMA.
Diagnosis?
Primary biliary cholangitis is an intrahepatic cholestatic disease involving progressive destruction of small intrahepatic bile ducts.
Associations: (+) AMA, common in women (avg. age = 40) with autoimmune conditions
A 48-year-old man presents with progressive jaundice, intense pruritus, dark urine, and clay-colored stools. Laboratory studies show predominantly conjugated hyperbilirubinemia, markedly elevated ALP and GGT, and only mild aminotransferase elevation. RUQ US shows dilated intrahepatic and extrahepatic bile ducts but does not clearly identify the obstructing lesion. The patient has lost 9 kg over 3 months and has a palpable, nontender gallbladder.
What is malignant extrahepatic biliary obstruction, most likely from pancreatic head adenocarcinoma?
This is a posthepatic cholestatic pattern: direct bilirubin, ALP, and GGT are disproportionately elevated, while AST and ALT are only mildly increased. Conjugated bilirubin is water-soluble, so it appears in urine and causes dark urine. Obstruction prevents bilirubin from reaching the intestine, decreasing urobilinogen and stercobilin formation, which produces pale stools. Progressive painless jaundice, weight loss, and a palpable nontender gallbladder favor pancreatic head malignancy over episodic stone disease.
A 29-year-old woman presents with jaundice, fatigue, and amenorrhea. Laboratory studies show markedly elevated aminotransferases, increased IgG, and positive antinuclear and anti–smooth muscle antibodies. Viral hepatitis testing is negative. Liver biopsy demonstrates interface hepatitis with a plasma-cell-rich inflammatory infiltrate.
Diagnosis?
What is autoimmune hepatitis?
autoimmune hepatitis is associated with hypergammaglobulinemia, ANA or ASMA positivity, and interface hepatitis with prominent plasma cells. Diagnosis requires integrating serology, exclusion of viral hepatitis, and histology. Corticosteroids, often combined with azathioprine, are the mainstay of treatment.