A 27-year-old woman of Jewish descent presents with jaundice for the last week. She reports recently “battling a stubborn cold.” She has no other complaints and her past medical history is only significant for chronic rhinosinusitis. Laboratory studies reveal the following.
After a thorough chart review, it was discovered she had a liver biopsy performed 3 years prior to her visit, which revealed black granular pigment in the majority of hepatocytes.
Which of the following is the most likely diagnosis?
Dubin–Johnson syndrome. The patient in this question is presenting with conjugated hyperbilirubinemia with dark granular pigment present within hepatocytes. This is consistent with a diagnosis of the rare condition called Dubin–Johnson syndrome. This benign condition is most common in Jewish patients and presents clinically with jaundice and nonspecific complaints (fatigue, abdominal pain, malaise). The jaundice is very mild and usually only becomes apparent during an illness or oral contraceptive use. The problem in this condition is mildly defective bile secretion that results in conjugated hyperbilirubinemia. The liver is grossly black due to epinephrine metabolites located within the lysosomes (giving a dark granular appearance of the hepatocytes). Prognosis is excellent so treatment is not warranted (other than minimizing triggers). (A) Gilbert syndrome is characterized by unconjugated hyperbilirubinemia. (C) Rotor syndrome is also a disorder of hepatic bile secretion; however, hyperbilirubinemia of both unconjugated and conjugated bilirubin is seen and there are no pigmented granules in the hepatocytes. (D) Crigler–Najjar syndrome type 2 is characterized by unconjugated hyperbilirubinemia.
A 37-year-old man with a history of ulcerative colitis controlled with 5-aminosalicylic acid presents with malaise, pruritus, and fatigue for the past 4 months. He reports no fever, chills, or weight loss and takes no other medications. He has a temperature of 37°C, blood pressure of 118/80 mmHg, heart rate of 82 beats per minute, and a respiratory rate of 20 breaths per minute. Physical examination reveals tenderness to palpation in the right upper quadrant. There is no hepatomegaly and Murphy sign is negative. Laboratory results reveal an alkaline phosphatase level of 910 U/L, erythrocyte sedimentation rate (ESR) of 160 mm/h, and a positive p-ANCA antibody.
Which of the following is the most likely diagnosis in this patient?
Primary sclerosing cholangitis. This patient is presenting with signs, symptoms, and laboratory findings consistent with a diagnosis of primary sclerosing cholangitis (PSC), a chronic inflammatory disorder associated with fibrosis and stricturing of medium-sized and large intra- and extrahepatic bile ducts. Ultimately the bile duct destruction will cause endstage liver disease. Of note, the vast majority of patients who present with PSC have a diagnosis of ulcerative colitis. Patients typically present with pruritus and fatigue and laboratory tests reveal severely elevated alkaline phosphatase and bilirubin. Other associated findings include the presence of p-ANCA antibodies and elevated inflammatory markers. ERCP will demonstrate “beading” and liver biopsy typically shows periductal “onion-skin” fibrosis in addition to intrahepatic ductal destruction with lymphocytic infiltration. (A) Microscopic polyangiitis is a poorly understood autoimmune small-vessel vasculitis that is associated with p-ANCA antibodies. (B) Primary biliary cirrhosis is more common in women and is associated with anti-mitochondrial antibodies. (C) Drug toxicity often presents with acute hepatitis with severely elevated AST and ALT levels; however, this patient is only taking 5-ASA for his ulcerative colitis.
A 37-year-old man presents with weakness, fatigue, polydipsia, polyuria, and increased “skin color” for the last 4 months. Physical examination reveals hepatomegaly. Laboratory results reveal the following.
Which of the following malignancies is this patient at risk for?
Hepatocellular carcinoma. This patient is presenting with signs and symptoms consistent with a diagnosis of hereditary hemochromatosis, an autosomal recessive disorder that leads to increased iron deposition in various organs. “Bronze diabetes” is a term coined for this condition since patients often develop new-onset diabetes and skin hyperpigmentation. Iron deposition in the liver causes hepatomegaly (as seen in this patient), an elevated AST and ALT, and eventually cirrhosis. Diagnosis is suggested by elevated transferrin saturation (>45%) and serum ferritin levels (>200 ng/mL). If untreated, patients are at a significantly increased risk for developing hepatocellular carcinoma. (A) Cholangiocarcinoma originates in the bile ducts and is not associated with hereditary hemochromatosis. (B) Renal cell carcinoma has no relationship with hereditary hemochromatosis. (C) Pancreatic cancer may result from chronic pancreatitis, not hereditary hemochromatosis.
A 34-year-old man presents to the physician with right upper quadrant pain that began shortly after eating dinner at a Chinese restaurant. He describes the pain as “stabbing” and radiating to his right scapular region. He has vomited two times. He has an unremarkable past medical history but reportedly drinks 8 to 10 beers per day. Family history is significant for breast cancer on his mother’s side and rheumatoid arthritis on his father’s side. He has a temperature of 38.6°C, blood pressure of 118/80 mmHg, heart rate of 82 beats per minute, and a respiratory rate of 20 breaths per minute. Physical examination shows severe right upper quadrant pain on deep palpation, most pronounced on palpation after deep inspiration. Laboratory results reveal the following.
Which of the following is contributing to this patient’s disorder?
Gallstone obstruction in the cystic duct. The patient in this question is presenting with acute cholecystitis. He is presenting with fever, right upper quadrant pain after a fatty meal that radiates to the right scapula, and positive Murphy sign (pain on palpation in the right upper quadrant with cessation of inspiration). Additional nonspecific findings include vomiting, leukocytosis, and mild elevation in transaminases. Acute cholecystitis usually arises from gallstone formation that obstructs the cystic duct. The symptoms occur after eating a fatty meal because the fat stimulates gallbladder contraction and, in the presence of cystic duct obstruction, this leads to colicky pain. Infection results from stasis that contributes to bacterial growth in the gallbladder. (D) Importantly, alkaline phosphatase is not elevated in this patient with acute cholecystitis. If it were elevated (in addition to total bilirubin and direct bilirubin), this might indicate common bile duct obstruction in the setting of jaundice (choledocholithiasis). (A) Alcoholic liver disease does not present with this constellation of symptoms. (C) Similar to common bile duct obstruction, obstruction from a carcinoma of the head of the pancreas would cause severely elevated alkaline phosphatase levels and would normally present with weight loss and painless jaundice.
A 52-year-old woman presents with confusion that has worsened over the past week. Her partner reports that she has also noticed yellowing of the skin. Further history reveals that the patient has been taking a significant amount of over-the-counter pain medications due to diffuse joint pain. The patient drinks three glasses of wine per night and reports no illicit drug use. Physical examination is significant for tenderness to palpation in the right upper quadrant and hepatomegaly. Laboratory results reveal the following.
Which of the following is the underlying diagnosis?
Drug-induced acute liver failure. This patient is presenting with signs and symptoms consistent with a diagnosis of acute liver failure. Acute liver failure is distinguished by severely elevated transaminases, defective hepatic synthesis (coagulation abnormalities, elevated bilirubin), and hepatic encephalopathy. The most common causes of acute liver failure include medications, viral hepatitis, ischemic hepatopathy, acute fatty liver of pregnancy, and HELLP syndrome. Given this patient’s history of over-the-counter pain medications (likely acetaminophen), the diagnosis is likely drug-induced acute liver failure. Acetaminophen levels should be determined and the patient should begin treatment with N-acetylcysteine. (B) Acute alcoholic hepatitis alone usually only causes a mild to moderate elevation of AST and ALT levels. In addition, the AST:ALT ratio is usually greater than 2:1. (C) Nonalcoholic fatty liver disease is usually asymptomatic and presents with only mild elevations of AST and ALT levels. It is usually chronic in nature and mental status changes are rare, though in rare cases it can progress to end stage liver disease (ESLD). (D) Similar to nonalcoholic liver disease, chronic viral hepatitis is associated with mild elevations of AST and ALT levels and will not present with abnormal coagulation studies or hepatic encephalopathy. It also would not present with a 1- to 2-week course.
Click to expand