We present the case of a 65-year-old (weight, 80 Kg, height, 150 cm) Sri Lankan black woman, known to have LTBI treated with INH and dyslipidemia. She was diagnosed with LTBI based on a positive purified protein derivative test. The patient's main indication for LTBI treatment was recent arrival (within 5 years) from a high prevalence country. She presented to the emergency department with epigastric and right sided flank pain of one-week duration. The history goes back to one week prior to admission when the patient started to experience pain along with one episode of vomiting and dark (tea-colored) urine without any other urinary symptoms. She reported a severe pain of 8/10, relieved by sitting and lying forward and worsened by lying backwards. The patient denied any nausea, diarrhea, constipation, or fever prior to the presentation.
Her past medical history includes LTBI (6 months prior to the presentation with no laboratory and clinical monitoring for the isoniazid treatment) and dyslipidemia without any known liver disease. Her medications are Rimifon  (INH) 150 mg two tablets by mouth once daily and Panadol  (Acetaminophen) 500 mg two tablets by mouth as needed for headache. The patient was previously on Liponorm  (Atorvastatin) 10 mg one tablet by mouth once daily and Neurobion  (Vitamin B12, 200 mcg, Vitamin B6, 200 mg, and Vitamin B1, 100 mg) both of which were discontinued when INH was initiated (6 months prior to the presentation). The patient works as a housekeeper; she denied any known drug or food allergies, the use of recreational drugs, tobacco smoke, or alcohol.
Her vital signs were as follows: blood pressure of 120/78 mmHg, heart rate of 83 beats per minute, respiratory rate of 15 breaths per minute, and a body temperature of 36.2 C. Her review of systems was normal except for icteric sclera, pale conjunctiva, and epigastric tenderness. Pending laboratory results, she was given Perfalgan  (acetaminophen) 1 g IV STAT for pain and normal saline 0.9% 1 L every 24 hours. The patient's laboratory data upon admission are shown in Table 1.
The patient was admitted to the internal medicine service for further investigation. INH was discontinued and medication orders were the following: Profenid  (ketoprofen) 100 mg IV every 8 hours as needed for pain, Nexium  (Esomeprazole) 40 mg IV once daily, and Buscopan  (Scopolamine Butylbromide) 1 ampoule of 20 mg IV every 8 hours as needed for abdominal pain. Based on negative infectious serology, hepatitis A, hepatitis B, hepatitis C, cytomegalovirus (CMV), and Epstein-Barr virus were all ruled out. The patient had a positive CMV IgG Ab (160 AU/mL) suggesting a previous infection. Hepatic autoimmune disease was ruled out as well based on negative immunology markers. An abdominal ultrasound showed a normal liver size of 11 cm, perihepatic fluid effusion, and pericholecystic edema that are most probably related to hepatitis rather than cholecystitis. CT scan of the abdomen and pelvis showed a diffusely thickened gallbladder wall with neither the evidence of obstructive process nor portal vein thrombosis. After ruling out all the possible causes of acute hepatitis in our patient, the final diagnosis was made as INH-induced acute hepatitis.
Throughout the hospital stay, there was a slight reduction (around 15% from baseline) in liver function tests (LFTs); however INR and bilirubin remained elevated. The patient was clinically improving and her laboratory values were slightly better. Upon physician's order, the patient was discharged on Nexium 40 mg one tablet by mouth daily for one week. The patient did not resume the isoniazid treatment upon discharge after the initial hospital admission.
Six days later, the patient was readmitted to the hospital for abdominal distention and increased upper right quadrant pain that radiated to the flanks and increases with food intake and exertion. She also reported decreased appetite, fatigue, and dyspnea with exertion. Upon readmission, she presented with jaundice, icteric sclera, dark urine, and prominent ascites confirmed by wave fluid test. In the ER, she received Nexium 40 mg IV, Profenid 100 mg IV STAT, and NS 0.9% 500 mL every 24 hours which was increased to 1 L every 24 hours when her blood pressure dropped to 85/55 mmHg. Laboratory values were the following: total bilirubin 27.8 mg/dL, gamma-GTP 95 U/L, ALP 283 U/L, ALT (SGPT) 873 U/L, AST (SGOT) 1582 U/L, amylase 164 U/L, lipase 65 U/L, Cr 0.66 mg/dL, and INR 2.28. Bilirubin was also detected in urine. Accordingly, the patient was admitted to the internal medicine floor for fulminant hepatic failure due to INH.
In an attempt to normalize INR, multiple administrations of Konakion  (Phytomenadione) were given. Profenid was discontinued due to the increased risk of bleeding and Buscopan 20 mg IV every 8 hours as needed for abdominal pain was ordered. Furthermore, Primperan  (Metoclopramide) 10 mg IV STAT, one vial of Albumin (20%) IV STAT, and morphine sulfate 2 mg SC STAT twice for pain were given. The patient had several episodes of hypotension responsive to fluid resuscitation with NS. The ultrasound showed diffused and clear moderate ascites as well as marked edematous thickening of the gallbladder wall with clear content related to intra-abdominal fluid effusion. The patient developed hypoglycemia (32-37 mg/dL) and oxygen saturation dropped to 86%. Due to deterioration, reduced level of consciousness, and poor response to oxygen, she was intubated and transferred to the intensive care unit.
On physical exam she was unresponsive, her pupils were middilated, and nonreactive, her lungs had few scattered rhonchi, and she had abdominal distention and ascites. She had metabolic acidosis (pH 6.8) and multiple doses of sodium bicarbonate were administered. The patient was consistently hypoglycemic and hypotensive despite fluid resuscitation and vasopressor administration. Serum creatinine increased from 0.66 mg/dL to 2.34 mg/dL in two days confirming acute kidney injury. She was also suffering from severe coagulopathy and hepatic encephalopathy. Additionally, blood cultures revealed a sensitive Escherichia coli and sputum cultures showed alpha-Streptococcus and Neisseria species. The patient had cardiorespiratory failure necessitating cardiopulmonary resuscitation (CPR). Spontaneous circulation was achieved after 15 minutes of CPR. Unfortunately, this was followed by a second cardiac arrest and despite maximal hemodynamic support, the patient passed away.