All questions
Question 1
A 62-year-old woman was treated for an uncomplicated urinary tract infection with a 7-day course of nitrofurantoin. Two weeks after completing the course, she develops profound fatigue, nausea, and dark urine. On examination, she is jaundiced. Laboratory studies show an AST of 850 U/L, ALT of 990 U/L, and a total bilirubin of 7.5 mg/dL. An extensive workup, including viral hepatitis serologies and autoimmune markers, is negative. An abdominal ultrasound is unremarkable.
What is the most likely diagnosis?
- Drug-induced liver injury (correct answer)
- Acute cholangitis
- Ischemic hepatitis
- Acute hepatitis E infection
Explanation: The patient's presentation with an acute, severe hepatocellular injury pattern shortly after exposure to a new medication known to cause hepatotoxicity is highly characteristic of drug-induced liver injury (DILI). Nitrofurantoin is a well-known cause of both acute and chronic DILI. The exclusion of other common causes of acute hepatitis (viral, autoimmune) further supports this diagnosis. Acute cholangitis would present with fever and a cholestatic picture. Ischemic hepatitis occurs in settings of hemodynamic instability.
Question 2
A 45-year-old woman presents with a 6-month history of progressive fatigue and generalized pruritus. On physical examination, she has several xanthelasmas around her eyes. Laboratory studies show a total bilirubin of 1.5 mg/dL, AST of 55 U/L, ALT of 60 U/L, and an alkaline phosphatase of 450 U/L. A subsequent test reveals a positive anti-mitochondrial antibody (AMA) titer of 1:160.
What is the most likely diagnosis?
- Primary biliary cholangitis (correct answer)
- Autoimmune hepatitis
- Primary sclerosing cholangitis
- Acute viral hepatitis
Explanation: This patient's presentation of a middle-aged woman with fatigue, pruritus, xanthelasmas, a cholestatic pattern of liver injury (markedly elevated alkaline phosphatase with near-normal transaminases), and a positive anti-mitochondrial antibody (AMA) is classic for primary biliary cholangitis (PBC). AMA is highly specific for PBC, found in about 95% of patients.
Question 3
A 28-year-old man presents to his primary care physician with a one-week history of nausea, vomiting, low-grade fever, and right upper quadrant abdominal pain. He recently returned from a 3-week backpacking trip in Southeast Asia where he reports eating from local food stalls. On examination, he has scleral icterus and tender hepatomegaly. Laboratory studies show an AST of 1200 U/L, ALT of 1500 U/L, and total bilirubin of 6.0 mg/dL.
Which of the following serologic markers is most specific for the diagnosis of his acute infection?
- Hepatitis A virus IgM antibody (correct answer)
- Hepatitis A virus IgG antibody
- Hepatitis B surface antigen
- Hepatitis C virus antibody
Explanation: The patient's symptoms, recent travel to an endemic area, and acute hepatocellular injury pattern are highly suggestive of acute hepatitis A. The diagnosis of acute hepatitis A is confirmed by the presence of IgM anti-HAV antibodies. IgG anti-HAV indicates prior infection or immunization and confers immunity. HBsAg and anti-HCV are markers for hepatitis B and C, respectively.
Question 4
A 58-year-old man with compensated cirrhosis secondary to chronic hepatitis C infection comes for a routine follow-up visit. He is asymptomatic and his liver function tests are stable. His Child-Pugh score is 6 (Class A).
Which of the following is the most appropriate screening strategy for hepatocellular carcinoma in this patient?
- Abdominal ultrasound every 6 months (correct answer)
- Serum alpha-fetoprotein level every 3 months
- CT scan of the abdomen with contrast annually
- No screening is necessary as he is compensated
Explanation: All patients with cirrhosis, regardless of etiology or compensation status, are at increased risk for developing hepatocellular carcinoma (HCC) and should undergo routine surveillance. The standard recommendation by major society guidelines is screening with an abdominal ultrasound every 6 months. Serum alpha-fetoprotein (AFP) may be used as an adjunct to ultrasound but is not recommended as a standalone screening test due to poor sensitivity and specificity. More frequent screening or annual CT scans are not the standard of care.
Question 5
A 55-year-old woman with a history of nonalcoholic steatohepatitis (NASH) presents with generalized fatigue. On physical examination, she is noted to have spider angiomata on her chest and palmar erythema. Laboratory results are significant for a platelet count of 95,000/mm³, an INR of 1.4, and a serum albumin of 3.1 g/dL. She denies any history of jaundice, ascites, or confusion.
These findings are most suggestive of which of the following conditions?
- Decompensated cirrhosis
- Acute liver failure
- Compensated cirrhosis (correct answer)
- Portal vein thrombosis
Explanation: This patient exhibits both physical stigmata (spider angiomata, palmar erythema) and laboratory evidence (thrombocytopenia, elevated INR, hypoalbuminemia) of cirrhosis, which reflects impaired hepatic synthetic function and portal hypertension. Cirrhosis is defined as compensated when these features are present without overt clinical decompensating events such as variceal hemorrhage, ascites, or hepatic encephalopathy. Since the patient denies these complications, her condition is best described as compensated cirrhosis.
Question 6
A 70-year-old man with a history of cirrhosis due to hepatitis C is brought to the emergency department by his daughter for a 2-day history of worsening confusion and sleep-wake cycle reversal. On examination, he is disoriented to time and place and has a prominent asterixis. His daughter mentions he has been constipated for the past 3 days.
In addition to identifying and treating the precipitating factor, which of the following is the most appropriate initial pharmacologic treatment for his condition?
- Lactulose (correct answer)
- Propranolol
- Furosemide
- Rifaximin
Explanation: This patient is presenting with overt hepatic encephalopathy (HE), likely precipitated by constipation. The first-line treatment for HE is lactulose, a non-absorbable disaccharide. It works by acidifying the gut to trap ammonia as non-absorbable ammonium and by promoting its cathartic removal. Rifaximin is an effective second-line agent, typically added to lactulose in patients with recurrent HE. Propranolol is used for variceal prophylaxis, and furosemide is used for ascites management.
Question 7
A 48-year-old man with a history of type 2 diabetes and hyperlipidemia is found to have abnormal liver function tests on a routine wellness check. His AST is 120 U/L and ALT is 150 U/L. Alkaline phosphatase and total bilirubin are within normal limits. His BMI is 34 kg/m². He drinks one glass of wine per week. Hepatitis serologies are negative.
What is the most likely cause of this patient's abnormal liver enzymes?
- Nonalcoholic fatty liver disease (correct answer)
- Alcoholic liver disease
- Autoimmune hepatitis
- Wilson disease
Explanation: This patient has multiple components of the metabolic syndrome (obesity, diabetes, hyperlipidemia), which are major risk factors for nonalcoholic fatty liver disease (NAFLD). The typical laboratory pattern for NAFLD is a mild to moderate elevation of aminotransferases with an AST:ALT ratio of less than 1, which is seen in this case. His minimal alcohol intake makes alcoholic liver disease unlikely, which also typically presents with an AST:ALT ratio >2. Autoimmune hepatitis usually has much higher aminotransferase levels, and Wilson disease is a rare genetic disorder typically presenting in younger individuals.
Question 8
A 58-year-old man with decompensated cirrhosis and ascites is hospitalized for worsening renal function. His baseline serum creatinine was 1.1 mg/dL, and it has risen to 2.8 mg/dL over the past 48 hours. He is oliguric. Urinalysis shows no casts, protein, or red blood cells. A fluid challenge with intravenous albumin fails to improve his creatinine. A renal ultrasound shows no evidence of hydronephrosis.
In addition to continuing albumin infusion, which medication regimen is the most appropriate treatment for this patient's condition?
- Midodrine and octreotide (correct answer)
- Furosemide and spironolactone
- Norepinephrine infusion
- Intravenous ceftriaxone
Explanation: This patient meets the diagnostic criteria for hepatorenal syndrome type 1 (HRS-AKI), a functional renal failure due to severe splanchnic and systemic vasodilation in advanced cirrhosis. The standard of care for treatment is the combination of albumin with splanchnic vasoconstrictors. The most commonly used regimen is midodrine (an oral alpha-1 agonist) and octreotide (a somatostatin analog). Norepinephrine can be used in an ICU setting. Diuretics are contraindicated as they would worsen intravascular volume depletion. Antibiotics would be indicated if an infection like SBP was the trigger, but are not the primary treatment for HRS itself.
Question 9
A 22-year-old male medical student presents for evaluation after his friends noticed a yellowish tinge to his eyes. This occurred during his final exam period, a time of significant stress and poor sleep. He feels well otherwise, with no abdominal pain, nausea, or fatigue. Laboratory testing reveals a total bilirubin of 2.5 mg/dL and a direct bilirubin of 0.3 mg/dL. AST, ALT, alkaline phosphatase, and a complete blood count are all within normal limits.
What is the most likely diagnosis?
- Gilbert syndrome (correct answer)
- Crigler-Najjar syndrome type II
- Dubin-Johnson syndrome
- Acute viral hepatitis
Explanation: This patient presents with asymptomatic, mild, unconjugated (indirect) hyperbilirubinemia, exacerbated by stress. This is the classic presentation of Gilbert syndrome, a benign inherited disorder of bilirubin conjugation due to reduced activity of the UGT1A1 enzyme. The key features are isolated unconjugated hyperbilirubinemia with otherwise normal liver function tests and no evidence of hemolysis. Crigler-Najjar is a more severe conjugation defect. Dubin-Johnson and Rotor syndromes cause conjugated hyperbilirubinemia. Acute viral hepatitis would cause significantly elevated aminotransferases.
Question 10
A 32-year-old woman presents with a 3-month history of fatigue, malaise, and intermittent pain in her wrists and knees. She does not drink alcohol or use illicit drugs. Laboratory studies show an AST of 450 U/L, ALT of 510 U/L, total protein of 8.5 g/dL, and albumin of 3.8 g/dL. Serologies for hepatitis A, B, and C are negative.
Which of the following additional laboratory findings would be most consistent with the suspected diagnosis?
- Positive anti-smooth muscle antibodies (correct answer)
- Positive anti-mitochondrial antibodies
- Low serum ceruloplasmin
- Elevated serum ferritin and transferrin saturation
Explanation: The patient's presentation of a young woman with a significant hepatocellular injury pattern, arthralgias, and hypergammaglobulinemia (indicated by the elevated total protein with normal albumin, known as the globulin gap) is highly suggestive of autoimmune hepatitis (AIH). The diagnosis of type 1 AIH is supported by the presence of autoantibodies, most commonly anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (ASMA). Anti-mitochondrial antibodies are for PBC. Low ceruloplasmin suggests Wilson disease. Elevated iron studies suggest hemochromatosis.
Question 11
A 45-year-old man with type 2 diabetes, obesity, and persistently elevated aminotransferases (ALT consistently higher than AST) is being evaluated for nonalcoholic fatty liver disease. An ultrasound confirms the presence of hepatic steatosis. The physician wants to assess for the presence of advanced fibrosis or cirrhosis to guide management and prognosis.
Which of the following is the most appropriate initial non-invasive test to stage the degree of liver fibrosis?
- Transient elastography (FibroScan) (correct answer)
- Serum alpha-fetoprotein
- Magnetic resonance cholangiopancreatography (MRCP)
- Liver biopsy
Explanation: Liver biopsy is the gold standard for staging fibrosis but is invasive and carries risks. Non-invasive tests are now the preferred initial approach. Transient elastography (FibroScan) is a validated, widely used ultrasound-based technology that measures liver stiffness. Increased liver stiffness correlates directly with the degree of hepatic fibrosis and is an excellent tool to non-invasively identify patients with advanced fibrosis or cirrhosis. Serum AFP is a tumor marker, not a fibrosis marker. MRCP is used to evaluate the biliary tree. While biopsy is the gold standard, it is not the appropriate initial non-invasive test.
Question 12
A 65-year-old man with cirrhosis due to hepatitis C has massive ascites that is poorly responsive to a regimen of 400 mg spironolactone and 160 mg furosemide daily. He adheres to a strict low-sodium diet but continues to require large-volume paracentesis every 2 weeks for symptomatic relief. His MELD score is 18. He has no history of overt hepatic encephalopathy.
Which of the following interventions is most likely to provide long-term control of his ascites?
- Transjugular intrahepatic portosystemic shunt (TIPS) (correct answer)
- Initiation of midodrine therapy
- Placement of a peritoneovenous shunt
- Continued serial large-volume paracentesis with albumin
Explanation: This patient has refractory ascites, defined as ascites that is unresponsive to maximal diuretic therapy and sodium restriction. While serial large-volume paracentesis (LVP) can manage symptoms, it does not provide long-term control. The most effective treatment for refractory ascites is the placement of a transjugular intrahepatic portosystemic shunt (TIPS). TIPS creates a low-resistance channel between the portal vein and a hepatic vein, effectively decompressing the portal system and controlling the ascites in the majority of patients. Midodrine offers modest benefit, and peritoneovenous shunts are rarely used due to high complication rates. Liver transplantation is the ultimate cure, but TIPS is the specific intervention to control the ascites.
Question 13
A 55-year-old man with known cirrhosis is brought to the emergency department after vomiting a large amount of bright red blood. His blood pressure is 90/50 mm Hg, and his heart rate is 120/min. Two large-bore intravenous lines are established, and crystalloid infusion is initiated.
In addition to hemodynamic resuscitation and securing the airway, which of the following is the most important initial pharmacologic intervention?
- Intravenous octreotide (correct answer)
- Intravenous vitamin K
- Infusion of fresh frozen plasma
- Oral lactulose
Explanation: This patient is presenting with an acute variceal hemorrhage, a life-threatening complication of portal hypertension. The immediate management goals include resuscitation and control of bleeding. Vasoactive medications that reduce portal pressure should be started as soon as variceal bleeding is suspected. Octreotide, a somatostatin analog, causes splanchnic vasoconstriction, reducing portal blood flow and pressure. It should be administered immediately. While correction of coagulopathy with vitamin K or FFP may be necessary, octreotide is the primary pharmacologic agent to control the active bleeding. Lactulose is used for hepatic encephalopathy.
Question 14
A 62-year-old man with a long history of alcohol use disorder is diagnosed with cirrhosis. He presents with gradually increasing abdominal girth and bilateral lower extremity edema over the past month. Physical examination is notable for shifting dullness and a positive fluid wave. A diagnostic paracentesis confirms new-onset, uncomplicated ascites.
What is the most appropriate initial medical management for this patient's ascites?
- Furosemide and spironolactone (correct answer)
- Therapeutic paracentesis alone
- Transjugular intrahepatic portosystemic shunt (TIPS)
- Dietary sodium restriction alone
Explanation: The initial management of moderate ascites due to cirrhosis involves dietary sodium restriction (less than 2 grams/day) combined with diuretic therapy. The standard diuretic regimen is a combination of an aldosterone antagonist (spironolactone) and a loop diuretic (furosemide), typically in a 100 mg to 40 mg ratio, to maintain normokalemia. Sodium restriction alone is insufficient for most patients, and therapeutic paracentesis is reserved for tense or large-volume ascites. TIPS is a second-line therapy for refractory ascites.
Question 15
A 65-year-old man with a history of intravenous drug use in his youth undergoes screening labs as part of a new patient visit. The results show a positive antibody test for hepatitis C virus (anti-HCV). He is asymptomatic and his liver function tests are normal.
Which of the following is the most appropriate next step to confirm the diagnosis and guide management?
- Order a hepatitis C virus RNA test (correct answer)
- Reassure the patient that this indicates a past, resolved infection
- Schedule the patient for a liver biopsy
- Check for HBsAg and anti-HBs
Explanation: A positive anti-HCV antibody indicates exposure to the hepatitis C virus, but it does not differentiate between a current, active infection and a past, resolved infection (as up to 25% of individuals spontaneously clear the virus). Therefore, the essential next step is to test for the presence of viral genetic material using a quantitative HCV RNA polymerase chain reaction (PCR) test. A detectable HCV RNA level confirms chronic infection and is required before initiating direct-acting antiviral therapy. Liver biopsy is no longer routinely needed for diagnosis or treatment decisions.
Question 16
A 54-year-old man with newly diagnosed cirrhosis secondary to NASH undergoes a screening upper endoscopy. The procedure reveals medium-sized esophageal varices without any high-risk stigmata such as red wale marks. He has no prior history of gastrointestinal bleeding.
Which of the following is the most appropriate management to prevent a first variceal hemorrhage?
- Initiate therapy with nadolol (correct answer)
- Perform prophylactic endoscopic variceal ligation
- Place a transjugular intrahepatic portosystemic shunt (TIPS)
- Repeat endoscopy in one year
Explanation: This patient requires primary prophylaxis to prevent a first variceal bleed. For patients with medium or large varices, first-line options include either a nonselective beta-blocker (e.g., propranolol, nadolol) or endoscopic variceal ligation (EVL). Nonselective beta-blockers reduce portal pressure by decreasing cardiac output and causing splanchnic vasoconstriction. Both are effective, but beta-blockers are often preferred as the initial strategy due to lower cost and non-invasiveness. Repeating endoscopy in one year without treatment is inappropriate given the size of the varices. TIPS is not used for primary prophylaxis.
Question 17
A 67-year-old man with cirrhosis due to alcohol use is hospitalized for management of tense ascites. He has a low-grade fever of 37.9°C (100.2°F) and mild abdominal tenderness. A diagnostic paracentesis is performed, and the ascitic fluid analysis shows a white blood cell count of 500/mm³ with 70% neutrophils.
What is the most appropriate next step in management?
- Initiate empiric third-generation cephalosporin therapy (correct answer)
- Repeat paracentesis in 24 hours to confirm the findings
- Administer intravenous albumin
- Await ascitic fluid culture results before initiating treatment
Explanation: The diagnosis of spontaneous bacterial peritonitis (SBP) is made when the ascitic fluid absolute neutrophil count (ANC) is ≥250 cells/mm³. This patient's ANC is 350 cells/mm³ (500 cells/mm³ * 0.70). Treatment should not be delayed pending culture results, as SBP carries significant mortality. The standard of care is to initiate empiric antibiotic therapy immediately with a third-generation cephalosporin, such as cefotaxime or ceftriaxone. Albumin is often given adjunctively, particularly in patients with renal dysfunction or hyperbilirubinemia, but initiating antibiotics is the critical first step.
Question 18
A 60-year-old woman with cirrhosis and ascites is admitted to the hospital for an acute variceal hemorrhage. The bleeding is successfully controlled with endoscopic band ligation. A diagnostic paracentesis performed on admission reveals an ascitic fluid total protein concentration of 0.8 g/dL. She has no prior history of spontaneous bacterial peritonitis (SBP).
Upon discharge, which of the following is the most appropriate long-term management to prevent SBP?
- Prophylactic daily ciprofloxacin (correct answer)
- Weekly therapeutic paracentesis
- Placement of a TIPS
- No prophylaxis is indicated at this time
Explanation: Patients with cirrhosis are at high risk for developing SBP in the setting of an acute gastrointestinal hemorrhage. Prophylaxis against SBP is indicated for these patients, typically for a short course during and after the bleeding episode, and often continued long-term if other risk factors are present. Another major indication for long-term primary SBP prophylaxis is an ascitic fluid protein concentration <1.5 g/dL with advanced liver failure. This patient meets both criteria (hemorrhage and low ascitic protein), making long-term prophylaxis with a fluoroquinolone (e.g., ciprofloxacin, norfloxacin) or trimethoprim-sulfamethoxazole appropriate.
Question 19
A 68-year-old man with known cirrhosis from chronic alcohol use undergoes a routine 6-month screening abdominal ultrasound. The scan reveals a new 2.5 cm, solid, heterogeneous lesion in the right lobe of the liver. His serum alpha-fetoprotein level is 25 ng/mL (normal <20 ng/mL).
Which of the following is the most appropriate next step in the diagnostic workup of this lesion?
- Multiphasic contrast-enhanced CT scan or MRI of the abdomen (correct answer)
- Percutaneous biopsy of the liver lesion
- Repeat ultrasound in 3 months to assess for growth
- Palliative care consultation
Explanation: In a patient with cirrhosis, a new liver lesion >1 cm found on screening ultrasound is suspicious for hepatocellular carcinoma (HCC). The standard diagnostic algorithm is to proceed with dynamic, multiphasic, contrast-enhanced imaging, either a 4-phase CT scan or an MRI. HCC has a characteristic vascular pattern of arterial phase hyperenhancement followed by venous or delayed phase 'washout,' which is often sufficient for a non-invasive diagnosis. Biopsy is typically reserved for lesions with an atypical imaging appearance. Repeating the ultrasound would cause an unacceptable delay in diagnosis.
Question 20
A 35-year-old man who emigrated from China 10 years ago undergoes a routine health screening. His laboratory results are as follows: HBsAg: Positive, Anti-HBs: Negative, HBeAg: Negative, Anti-HBe: Positive, Total anti-HBc: Positive. His ALT is 85 U/L (normal <40 U/L) and his HBV DNA level is 5,000 IU/mL.
Which of the following best describes this patient's condition?
- Acute hepatitis B infection
- Chronic HBeAg-negative hepatitis B (correct answer)
- Resolved hepatitis B infection
- Immune due to vaccination
Explanation: The presence of HBsAg for more than 6 months indicates chronic hepatitis B infection. The patient is HBeAg-negative and anti-HBe positive, with detectable HBV DNA and elevated ALT. This profile is characteristic of chronic HBeAg-negative hepatitis B (also known as the immune-active or reactivation phase), which is a common phase of chronic HBV and often requires treatment. Acute infection would be marked by positive IgM anti-HBc. Resolved infection would be HBsAg-negative and anti-HBs positive. Immunity from vaccination is marked by isolated anti-HBs positivity.