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Hepatology Board Review. Scott Gabbard, MD 06/09/2009. Question 1.

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Hepatology Board Review

Scott Gabbard, MD

06/09/2009


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Question 1

  • A 53-year-old man with hepatitis C and cirrhosis comes for a follow-up office visit. He feels fatigued but has no other new signs or symptoms. The patient has a history of alcohol abuse but has been abstinent for 8 months following a treatment program. He now attends weekly Alcoholics Anonymous meetings. Complications of the hepatitis C and cirrhosis have included ascites and encephalopathy, both of which are controlled by medications.

  • Physical examination discloses mild jaundice, spider angiomata, splenomegaly, and mild peripheral edema.

  • Labs: Hgb 13; Plt 80; AST and ALT in the 70s; total bili 3; INR 1.4; Alpha fetoprotein normal

  • Abdominal ultrasonography discloses a coarse echotexture of the liver, mild ascites, and a 2.2-cm hyperechoic hepatic mass that was not seen on previous imaging studies. A CT scan of the liver shows vascular enhancement of the mass.


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Question 1

  • What is the diagnosis?

    • Metastatic cancer

    • HCC

    • Focal nodular hyperplasia

    • Cavernous hemangioma

    • Regenerative nodule


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HCC

  • Answer: HCC

  • Patients with hepatitis C and cirrhosis are at increased risk for developing hepatocellular carcinoma, and the finding of a new hepatic mass with vascular enhancement in such patients almost certainly indicates hepatocellular carcinoma.

  • Although metastases are the most commonly diagnosed malignant hepatic masses in patients without cirrhosis, they are uncommon in patients with cirrhosis, especially those who do not have a history of another malignancy.

  • Focal nodular hyperplasia and cavernous hemangiomas are unusual in patients with cirrhosis and would not explain the finding of a new lesion.

  • Regenerative nodules may occur in patients with cirrhosis, but these nodules usually do not show vascular enhancement.


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Question 2

  • A 42-year-old woman has a 1-year history of progressive fatigue without dyspnea, chest pain, or other systemic symptoms. She sleeps well at night and does not have features of sleep apnea. The patient has hypothyroidism, managed with levothyroxine, and dysmenorrhea, treated with an estrogen/progesterone combination.

  • On physical examination, the thyroid is slightly enlarged but nontender. Xanthomas are present on the extensor surfaces. Abdominal examination discloses mild hepatomegaly.

  • Labs: CBC normal; AST 25; ALT 35; Alk phos 300; total bilirubin 1.1


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Question 2

  • In addition to a fasting serum lipid profile, which of the following studies would most likely help establish the diagnosis?

    • Antimitochondrial antibody

    • Serum 25-hydroxyvitamin D

    • Endoscopic retrograde cholangiopancreatography

    • Abdominal ultrasonography


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Primary biliary cirrhosis

  • Answer: Antimitochondrial antibody

  • This patient most likely has primary biliary cirrhosis.

  • Key words: fatigue, woman 40-60, other autoimmune disease, skin findings, metabolic bone disease

  • Diagnosis: Antimitochondrial antibody titer of 1:40 or more occur in >90% of patients with primary biliary cirrhosis. Then proceed with biopsy, which characteristically shows nonsuppurative cholangitis plus findings ranging from bile duct lesions to cirrhosis.

  • Treatment with ursodeoxycholic acid improves the biochemical profile, reduces pruritus, decreases progression to cirrhosis, and delays the need for liver transplantation.


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Question 3

  • A 66-year-old woman comes for her annual physical examination. She reports only mild fatigue. The patient has prediabetes that is managed by diet alone. She takes no medications and drinks one glass of wine each day.

  • On physical examination, blood pressure is 132/86 mm Hg. BMI is 32. The remainder of the examination is normal.

  • Labs: Hgb 13; Plts 80; AST 130; ALT 120; Total Bili 0.8; Albumin 2.9; Hepatitis serologies negative

  • Ultrasound demonstrates evidence of mild fatty infiltration of the liver


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Question 3

  • In addition to weight loss, which of the following is the most appropriate next step for managing this patient's liver chemistry abnormalities?

    • Rosiglitasone and repeat LFTs in 6 months

    • Alcohol counseling

    • Liver biopsy

    • Evaluation for liver transplant


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NAFLD

  • Answer: Liver biopsy

  • Although a liver biopsy is not required for all patients with NAFLD, biopsy should be considered for those who are older than 45 years of age, are obese, have diabetes mellitus, or have a serum aspartate aminotransferase to serum alanine aminotransferase ratio (AST:ALT) >1, as these may be predictors of fibrosis.

  • Rosiglitazone or pioglitazone may be indicated for patients with nonalcoholic steatohepatitis and features of the metabolic syndrome in order to prevent progression of the liver disease.


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Question 4

  • A 44-year-old man was recently found to have abnormal serologic test results for viral hepatitis when he attempted to donate blood. The patient is asymptomatic. He used injection drugs and drank alcohol excessively for 2 years 25 years ago but has not used either drugs or alcohol since. Medical history is otherwise unremarkable, and he takes no medications.

  • Physical examination discloses a BMI of 23, no stigmata of chronic liver disease, and a normal-sized liver.

  • Labs: AST 50; ALT 70; total bili 0.9; HbsAg negative; anti-HBs positive; IgG anti-HBc positive; IgM anti-HBc negative; anti-HCV positive


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Question 4

  • Which study should be done next?

    • Hepatitis B e antigen (HBeAg)

    • Hepatitis B virus DNA (HBV DNA)

    • Hepatitis C virus RNA (HCV RNA)

    • IgM antibody to hepatitis A virus (IgM anti-HAV)


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Hepatitis C Virus

  • Answer: HCV viral RNA

  • This patient has elevated serum aminotransferase values and positive antibodies to hepatitis C virus (anti-HCV). In a patient with a history of injection drug use, these findings are highly suggestive of hepatitis C, and an HCV RNA study should be done to confirm the presence of viremia.

  • Positive tests for antibody to hepatitis B surface antigen (anti-HBs) and IgG antibody to hepatitis B core antigen (IgG anti-HBc) are consistent with immunity from prior infection, and determination of hepatitis B e antigen (HBeAg) and HBV DNA is therefore not necessary.

  • Testing for IgM antibody to hepatitis A virus (IgM anti-HAV) is not indicated because acute hepatitis A tends to cause systemic symptoms, jaundice, and more marked elevations in serum aminotransferase values.


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Question 5

  • A 30-year-old woman is evaluated because of an abnormal serum total bilirubin level detected when she had a life insurance examination. Medical history is unremarkable. Her only medication is an oral contraceptive agent. Physical examination is normal.

  • Labs: Hgb 13; MCV 90; Total bilirubin 2.4; Direct bilirubin 0.2; AST 23; ALT 25; Alk phos 90


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Question 5

  • Which of the following is the most appropriate management at this time?

    • Discontinue the oral contraceptive agent

    • Repeat the liver chemistry tests in 3 months

    • Evaluate for the presence of hemolysis

    • Schedule abdominal ultrasonography

    • No additional diagnostic studies are indicated


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Gilbert’s syndrome

  • Answer: Do nothing (very appealing to all the third years here)

  • This patient has indirect (unconjugated) hyperbilirubinemia, which in an asymptomatic patient with a normal hemoglobin level and otherwise normal liver tests is suggestive of Gilbert's syndrome.

  • Gilbert's syndrome is the most common inherited disorder of bilirubin metabolism. In adults, it is a benign disorder, and no additional diagnostic studies or therapy is required at this time.

  • Cholestasis due to an oral contraceptive agent will cause conjugated (direct) hyperbilirubinemia and an elevated serum alkaline phosphatase level

  • Patients with hemolysis significant enough to cause unconjugated hyperbilirubinemia generally have a low hemoglobin level and abnormal values for mean corpuscular volume


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Question 6

  • A 37-year-old woman has a 1-week history of fatigue, jaundice, and slight fever. The patient has hypothyroidism for which she has taken levothyroxine for the past 10 years. She traveled to Mexico 5 months ago and received one dose of hepatitis A vaccine before her trip. Physical examination discloses mild jaundice and hepatomegaly.

  • Labs: CBC normal; TSH normal; AST 310; ALT 450; Alk phos 180; total bili 2.3


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Question 6

  • Which will confirm the diagnosis?

    • Antimitochondrial antibody

    • Antinuclear antibody and anti–smooth muscle antibody

    • IgM antibody to hepatitis A virus (IgM anti-HAV)

    • Serum acetaminophen

    • Endoscopic retrograde cholangiopancreatography


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Autoimmune hepatitis

  • Answer: ANA and AMSA (and antibody to liver/kidney microsome type 1)

  • This patient most likely has autoimmune hepatitis because of her concomitant autoimmune thyroid disease and abnormal liver test results. Antinuclear antibody and anti–smooth muscle antibody titers should therefore be obtained; titers >1:80 for both assays support the diagnosis.

  • Key words: woman 20-40; concomitant autoimmune disease (thyroiditis, UC, synovitis)

  • Prednisone alone or prednisone plus azathioprine is effective in inducing remissions in patients with autoimmune hepatitis.


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Question 7

  • A 23-year-old woman has an 8-month history of dyspnea and dry cough. Medical history is unremarkable, and her only medication is an oral contraceptive agent.

  • On physical examination, vital signs are normal. Crackles are heard in both lung fields. Cardiac examination is normal. Abdominal examination discloses mild hepatomegaly.

  • Labs: CBC normal; AST 45; ALT 55; Alk phos 430

  • A chest radiograph shows mild diffuse pulmonary infiltrates. Heart size is normal. A tuberculin skin test is negative. Abdominal ultrasonography shows mild hepatomegaly without bile duct dilatation.


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Question 7

  • What is the most likely diagnosis?

    • Amyloid

    • Sarcoid

    • Tuberculosis

    • Primary biliary cirrhosis

    • OCP induced cholestasis


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Liver sarcoidosis

  • Answer: Sarcoidosis

  • A high serum alkaline phosphatase level is commonly associated with an infiltrative liver disorder, and the presence of pulmonary infiltrates and hepatomegaly are suggestive of sarcoidosis.

  • Amyloid is usually accompanied by evidence of other organ involvement, such as the nephrotic syndrome or neuropathy. In addition, amyloidosis is rare in patients this young.

  • Liver biopsy showing noncaseating granulomas will confirm the diagnosis of sarcoidosis.

  • The majority of patients are asymptomatic, and thus do not require specific treatment


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Question 8

  • A 26-year-old woman who is 36 weeks pregnant is evaluated because of right-sided abdominal pain. The patient has had mild preeclampsia for 4 weeks. She vomited twice this morning but is able to drink liquids. She also developed a nosebleed this morning.

  • On physical examination, blood continues to ooze from her nostrils. Temperature is normal, pulse rate is 105/min, and blood pressure is 135/85 mm Hg. Abdominal examination discloses right upper quadrant tenderness and uterine enlargement consistent with gestational age. There is 2+ bilateral lower extremity edema.

  • Labs: Hgb 8; WBC 9.5; Plt 45; AST 160; ALT 170; total bili 4.8; INR 1.0


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Question 8

  • Which of the following is most appropriate at this time?

    • Prompt delivery of the infant

    • Endoscopic retrograde cholangiopancreatography

    • Administration of a corticosteroid

    • Administration of acyclovir

    • Administration of magnesium sulfate


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HELLP

  • Answer: Prompt delivery of the infant

  • This patient has HELLP syndrome (hemolysis, elevated liver enzymes, low platelets).

  • HELLP develops in 5% to 10% of pregnancies associated with preeclampsia or eclampsia.

  • Diagnosis:

    • microangiopathic hemolytic anemia with an abnormal peripheral blood smear, low serum haptoglobin, and elevated serum indirect bilirubin and lactate dehydrogenase levels

    • serum aspartate aminotransferase value greater than twice the upper limit of normal

    • thrombocytopenia with a platelet count <100

  • The treatment of choice is prompt delivery of the infant. Following delivery, the mother's condition often resolves within 48 hours


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    Question 10

    • A 42-year-old man is evaluated after an elevated serum alkaline phosphatase value was noted during a life insurance examination. The patient does not have pruritus, abdominal pain, or jaundice. He has had loose bowel movements for many years and occasionally has rectal bleeding, which he attributes to hemorrhoids. Physical examination is unremarkable.

    • Labs: Hgb 12; MCV 75; AST 45; ALT 55; Alk phos 620; total bilirubin 2.0; direct bilirubin 1.6


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    Question 10

    • Which of the following diagnostic studies is most appropriate at this time?

      • ERCP

      • RUQ US

      • CT abd/pelvis

      • HIDA scan

      • CEA level


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    Primary sclerosing cholangitis

    • Answer: ERCP

    • Most patients with primary sclerosing cholangitis also have ulcerative colitis. Because of his chronic loose bowel movements and rectal bleeding, this patient is also likely to have this inflammatory bowel disorder.

    • Key words: men aged 20-30, ulcerative colitis, recurrent bacterial cholangitis

    • The diagnosis is confirmed when either endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography shows a “string of beads” pattern of the biliary tree

    • Treatment: supportive until liver transplant


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    Question 11

    • A 22-year-old woman with hepatitis C becomes pregnant for the first time. She is at 10 weeks gestation, and the pregnancy has been uneventful. Hepatitis C was diagnosed 5 years ago and was believed to be acquired following blood transfusions when the patient was 3 years old and was being treated for hemolytic uremic syndrome. The patient is HCV genotype 1 and has an HCV RNA viral load of 3 million copies/mL. Liver biopsy 6 months ago showed grade 1 (mild) inflammation and stage 0 (no) fibrosis.

    • Physical examination is normal.

    • Labs: CBC normal; LFTs normal; albumin normal; INR normal; HIV negative; HBs negative; anti-HBs positive;


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    Question 11

    • Which of the following is most appropriate?

      • Administer pegylated interferon and ribavirin to the mother now

      • Administer pegylated interferon to the mother now

      • Administer pegylated interferon and ribavirin to the infant soon after birth

      • Check the serum HCV RNA in the infant 4 months after birth


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    Vertical HCV transmission

    • Answer: Check the serum HCV RNA in the infant 4 months after birth

    • The overall risk of maternal–fetal transmission of hepatitis C is about 5%.

    • Mother-to-fetus placental transfer of antibody to hepatitis C virus (anti-HCV) is common, and anti-HCV can be detected in the newborn for up to 15 months.


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    Question 12

    • A 67-year-old man has a 1-year history of idiopathic chronic pancreatitis. Because of diarrhea, pancreatic enzyme supplements were started at the time of diagnosis. The patient currently takes 10,000 units of an enteric-coated enzyme preparation in one total dose during each meal. However, his diarrhea has persisted, and he has lost 2.6 kg (6 lb). He does not have lower abdominal pain. Stools are light-colored, and the patient describes what appears to be “oil” in the toilet bowl after defecation.


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    Question 12

    • Which of the following is the most appropriate therapy at this time?

      • Add omeprazole to the current enzyme regimen

      • Increase his enzymes to 6 pills with each meal (60,000 units/meal)

      • Space enzymes out before, during, and after each meal (3 pills with each meal)

      • Change to another brand of pancreatic enzyme supplements


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    Pancreatic enzymes

    • Answer: Space enzymes out before, during, and after each meal (3 pills with each meal)

    • Approximately 30,000 units of lipase are required with each meal for pancreatic enzyme supplementation.

    • The supplements need to be spaced out before, during, and after meals to better mimic endogenous enzyme secretion.


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    Question 13

    • A 49-year-old man is evaluated because of progressive jaundice, mild right upper quadrant abdominal pain, and weight loss over the last 3 months. The patient has a 25-year history of primary sclerosing cholangitis but has not seen a physician for more than 10 years. He takes no medications and drinks two cans of beer each evening.

    • On physical examination, he is cachectic and jaundiced. Abdominal examination discloses a firm liver edge and moderate ascites.

    • Labs: Hgb 11; Plts 75; total bili 5.8; AST 75; ALT 82; Alk phos 1000

    • RUQ US shows a nodular liver with moderate dilatation of the intrahepatic bile ducts, splenomegaly, and ascites.


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    Question 13

    • Which of the following is the most likely diagnosis?

      • Choledocholithiasis

      • Metastatic colon cancer

      • Pancreatic adenocarcinoma

      • Cholangiocarcinoma

      • Hepatocellular carcinoma


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    Cholangiocarcinoma

    • Patients with primary sclerosing cholangitis have a 10% to 30% lifetime risk of developing cholangiocarcinoma.

    • Approximately 60% to 80% of cholangiocarcinomas arise near the porta hepatis (Klatskin's tumor), 20% are located in the distal bile duct, and <5% are intrahepatic

    • Approximately 90% of patients have obstructive jaundice, and patients with advanced disease may have hepatomegaly or a distended palpable gallbladder (Courvoisier's sign)

    • Treatment: hepatic resection if tumor is confined to intrahepatic ducts


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    Question 14

    • A 42-year-old woman has a 2-week history of jaundice, low-grade fever, and fatigue. Medical history is noncontributory. The patient lives in Honduras but was born in the United States and returned to this country when she became ill. She has consumed at least one bottle of rum daily for 15 years and has taken acetaminophen, 1 g daily, for the past 3 days. She has no history of injection drug use, blood transfusions, or known exposure to anyone with hepatitis.

    • On physical examination, temperature is 37.9 °C (102.9 °F), pulse rate is 100/min and regular, and blood pressure is 110/70 mm Hg. Jaundice, spider angiomata, and mild muscle wasting are noted. Abdominal examination shows mild splenomegaly, no hepatomegaly, and no ascites.

    • Labs: Hgb 12.8; WBC 4; Plts 90; AST 125; ALT 57; Total bili 6; Direct bili 4; INR 2.4; Albumin 3.4; IgG anti-HAV positive


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    Question 14

    • Which of the following is the most likely diagnosis?

      • Hepatitis A

      • Sepsis

      • Acetaminophen hepatotoxicity

      • Alcoholic hepatitis

      • Autoimmune hepatitis


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    Alcoholic hepatitis

    • Fever, alcoholism, findings consistent with chronic liver disease, and a serum aspartate aminotransferase to serum alanine aminotransferase ratio (AST:ALT) >2 are associated with alcoholic hepatitis.

    • The discriminant function (DF) uses the patient's prothrombin time (PT) and serum bilirubin level to estimate disease severity: (DF = 4.6 [PTpatient - PTcontrol] + serum bilirubin [mg/dL]). A DF score of >32 identifies patients with a 50% mortality rate within 30 days.

    • Treatment options for DF>32: pentoxifylline, prednisolone


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    Question 15

    • A 24-year-old woman comes to the emergency department because of acute right upper quadrant abdominal pain and syncope. Medical history is unremarkable. On physical examination, pulse rate is 124/min and regular, and blood pressure is 80/60 mm Hg. The abdomen is distended but nontender. An urgent CT scan demonstrates a 5-cm lesion in the liver and high-density fluid in the peritoneal cavity, consistent with blood.

    • The patient's condition stabilizes following administration of intravenous fluids and blood transfusions. Physical examination discloses abdominal distention. There are no stigmata of chronic liver disease.

    • Labs: Hgb 7, WBC 12; Plts 200; AST 34; alpha-fetoprotein 3.5; alk phos 150


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    Question 15

    • Which of the following is the most likely diagnosis?

      • Hepatocellular carcinoma

      • Hepatic cyst

      • Focal nodular hyperplasia

      • Hepatic adenoma

      • Cavernous hemangioma


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    Liver masses

    • Hepatic adenomas are the most likely benign liver tumor to cause bleeding.

      • Hepatic adenomas are estrogen sensitive and should be resected whenever possible because of their potential for becoming malignant and their risk for bleeding.

    • Cavernous hemangiomas are benign lesions that are found in 2% of the general population.

    • Pyogenic liver abscesses are most likely due to biliary tract infection

    • An amebic abscess to Entamoeba histolytica should be suspected in a patient from a developing country who presents with a liver mass and symptoms suggestive of an infection.

      • Treatment: flagyl


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    References

    • MKSAP

    • UpToDate.com


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