A 65-year-old woman presents with acute liver failure characterized by jaundice, coagulopathy (INR 2.8), and markedly elevated transaminases (ALT 2500 U/L, AST 3000 U/L). Her family reports she has been taking over-the-counter acetaminophen for chronic back pain, often exceeding the recommended daily dose because she believed “more is better.” She also has difficulty understanding complex medical instructions and avoids doctor visits due to lack of reliable transportation. Which underlying social determinant of health was the MOST critical factor leading to her acetaminophen-induced liver injury?

A 65-year-old man, admitted to the critical care unit for severe sepsis secondary to pneumonia, is currently intubated on assist-control ventilation and receiving a low-dose norepinephrine infusion for blood pressure support. Over the past 48 hours, while recovering from the initial septic insult, he has developed new onset fatigue, dark urine, and mild pruritus. His central venous catheter remains in place. His current medications include vancomycin, piperacillin/tazobactam (started 7 days ago for pneumonia), pantoprazole, and scheduled acetaminophen 650 mg every 8 hours (started 5 days ago for fever).
Recent labs:
* Day 1 (admission): AST 35 U/L, ALT 40 U/L, ALP 80 U/L, Total Bilirubin 0.8 mg/dL
* Day 7 (current): AST 450 U/L, ALT 600 U/L, ALP 180 U/L, Total Bilirubin 4.2 mg/dL, INR 1.5, Eosinophils 6% (previously 1%)
Viral hepatitis serologies (HAV, HBV, HCV) are negative. Abdominal ultrasound shows no biliary obstruction.

Given this patient’s clinical presentation and laboratory findings, which of the following is the MOST likely diagnosis for his acute liver injury?

A 62-year-old man (weight 75 kg) is in the ICU on mechanical ventilation for severe community-acquired pneumonia. He has required a continuous norepinephrine infusion at 0.2 mcg/kg/min for septic shock for the past 48 hours, with MAPs maintained between 60–65 mm Hg and a peak lactate of 4.2 mmol/L. On ICU admission, his liver function tests (LFTs) were normal. Over the past 48 hours, LFTs have evolved to ALT 850 U/L (ULN 40), AST 780 U/L (ULN 40), ALP 120 U/L (ULN 120), total bilirubin 2.5 mg/dL (ULN 1.2). On ICU day 3 (48 hours ago), he was started on an IV amiodarone bolus followed by a continuous infusion for new-onset atrial fibrillation. An abdominal ultrasound shows no biliary obstruction. Hepatitis A, B, and C serologies are negative. ANA and anti–smooth muscle antibodies are negative. He has no history of chronic liver disease or significant alcohol use. His R-value [(ALT/ULN ALT) ÷ (ALP/ULN ALP)] is 21.25. Which of the following is the MOST likely primary etiology of his acute liver injury?

A 62-year-old man is admitted to the critical care unit for septic shock secondary to pneumonia. He is on assist-control ventilation and a continuous norepinephrine infusion via a central line. He has been receiving intravenous amoxicillin/clavulanate for 7 days. Over the past 24 hours his total bilirubin has risen to 8.8 mg/dL, and he is visibly jaundiced. Laboratory results: ALT 1,450 U/L (ULN 40), AST 1,100 U/L (ULN 40), ALP 180 U/L (ULN 120), INR 2.2. Viral hepatitis serologies (HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, HCV RNA) and autoimmune markers (ANA, anti–smooth muscle antibody) are negative. Abdominal ultrasound shows no biliary obstruction. On neurologic exam he is drowsy but arousable, intermittently disoriented to time, and has asterixis. Which of the following is the MOST appropriate immediate management strategy?

A 34-year-old female (weight 70 kg) is admitted to the ICU, intubated and on assist-control ventilation, with a continuous norepinephrine infusion via a central line for hemodynamic support. She was found unresponsive at home approximately 10 hours after ingesting an unknown quantity of acetaminophen tablets (empty bottle at the scene). Her serum acetaminophen concentration 10 hours post-ingestion is 75 mcg/mL. Initial labs reveal: alanine aminotransferase (ALT) 4500 U/L (ULN 40), aspartate aminotransferase (AST) 6200 U/L (ULN 40), total bilirubin 3.8 mg/dL (ULN 1.2 mg/dL), INR 2.8 (normal < 1.1), and ammonia 85 mcg/dL (ULN 35 mcg/dL). The R-value is > 5, indicating a hepatocellular pattern of injury. She is lethargic with asterixis. Viral hepatitis serologies are negative, and abdominal ultrasound shows no biliary obstruction. Considering the patient’s presentation and the most likely etiology of her acute liver failure, which of the following pharmacologic interventions should be prioritized as first-line to mitigate ongoing liver injury?

A 48-year-old female was admitted 10 days ago for a urinary tract infection and started on nitrofurantoin. Over the past 3 days, she has developed jaundice, dark urine, a diffuse maculopapular rash, and malaise. Her laboratory results are: ALT 1200 U/L (ULN 40), AST 980 U/L (ULN 40), ALP 150 U/L (ULN 120), total bilirubin 8.5 mg/dL (ULN 1.2), INR 1.8, and albumin 2.8 g/dL. She is alert and oriented without hepatic encephalopathy. The R-value is 24, eosinophils are elevated at 8%, and autoimmune serologies (ANA, anti–smooth muscle antibody) are positive. Nitrofurantoin was discontinued 24 hours ago, but her liver enzymes continue to worsen despite drug withdrawal. Given this presentation of severe immune-mediated hepatocellular drug-induced liver injury, which of the following adjunctive pharmacologic therapies is most appropriate at this time?

A 62-year-old man in the intensive care unit for severe sepsis is mechanically ventilated and receiving a norepinephrine infusion via a central line. Five days ago, he was started on piperacillin–tazobactam for a suspected intra-abdominal infection. Today he develops new-onset jaundice and dark urine. Laboratory tests reveal ALT 850 U/L (baseline 30), AST 780 U/L (baseline 25), ALP 180 U/L (baseline 90), total bilirubin 5.2 mg/dL (baseline 0.8), and INR 1.8 (baseline 1.1). An extensive workup for other causes of acute liver injury is unrevealing, and piperacillin–tazobactam has been discontinued due to suspected drug-induced liver injury. Given this patient’s acute liver failure, what is the most important next step in optimizing his medication management?

A 68-year-old male with severe sepsis is on assist-control ventilation and norepinephrine via a central line. He developed acute kidney injury requiring continuous renal replacement therapy (CRRT) yesterday. Over the past 48 hours, his liver enzymes have worsened: ALT 450 U/L (ULN 40), AST 380 U/L (ULN 35), ALP 180 U/L (ULN 120), total bilirubin 5.2 mg/dL (ULN 1.2), and an R-value of 7.5 indicating a hepatocellular pattern of injury. His serum albumin is 2.3 g/dL, INR is 1.8, he has mild ascites and no encephalopathy, corresponding to a Child-Pugh score of 8 (Class B hepatic impairment). He was started on piperacillin-tazobactam 5 days ago for presumed intra-abdominal infection, and all other causes of liver injury have been excluded. He is receiving hydromorphone 0.5 mg IV every 2 hours for pain. What is the most appropriate adjustment to his hydromorphone regimen?

A 65-year-old man presents to the ICU with severe sepsis and septic shock secondary to pneumonia. He was intubated and mechanically ventilated 8 days ago and required a peak norepinephrine infusion of 0.2 mcg/kg/min, which has been weaned to 0.05 mcg/kg/min to maintain a mean arterial pressure of 65–70 mmHg. His current vital signs are temperature 37.2 °C, blood pressure 118/72 mmHg, heart rate 92 bpm, respiratory rate 16 breaths/min, and oxygen saturation 98% on ventilator settings. He was started on piperacillin/tazobactam seven days ago. His home medications include atorvastatin 40 mg daily for the past 5 years. Today, he is noted to have new-onset jaundice and right upper quadrant tenderness without rebound or guarding; the liver edge is non‐tender and not enlarged. Laboratory studies show ALT 800 U/L (ULN 40), AST 750 U/L (ULN 40), alkaline phosphatase 150 U/L (ULN 120), and total bilirubin 5.0 mg/dL (ULN 1.2). The R value [(ALT/ULN)/(ALP/ULN)] is 16, indicating a hepatocellular pattern of injury. Which of the following is the most appropriate initial diagnostic evaluation to determine the etiology of this patient’s acute liver injury?

A 62-year-old man is admitted to the critical care unit, intubated and on assist-control ventilation, receiving a continuous norepinephrine infusion via a central venous catheter for septic shock. His medical history is notable for a 6-week course of nitrofurantoin for recurrent urinary tract infections, which concluded last week. Over the past 72 hours, his liver function tests have worsened: AST 850 U/L (baseline 30), ALT 920 U/L (baseline 35), ALP 150 U/L (baseline 90), total bilirubin 4.8 mg/dL (baseline 0.7), and INR 1.8 (baseline 1.1). He is icteric on exam, and a neurological exam reveals no focal deficits. Viral hepatitis panel and autoimmune markers are pending. Which of the following is the most critical indicator of this patient’s progression to acute liver failure?