Drug-induced liver disease (DILI) - Case discussion

1. 閱讀文獻：http://www.nature.com/ajg/journal/v109/n7/pdf/ajg2014131a.pdf

2. Case Discussion：依分派案例進行分組報告，各組報告時間為 15 min (可推派代表或輪流報告)，討

論 10 min。

3. 報告內容包括：

(1) Introduction：Patient profile & clinical course

(2) Evaluation:

i. 可能原因之排除：是否有其他導致或加重的原因?

ii. 時序相關性：Drug profile & Laboratory data

iii. 藥物可能性：Drug review (先由 database 中 review 各個藥物有無肝毒性相關報告)

iv. 評估懷疑藥物之肝毒性型態：包括 incidence、latency time、pattern、recovery time

Drug Incidence Type Onset Recovery Is it

文獻報告
rate time time reversible?
(+/-)

v. 評分-RUCAM assessment: https://livertox.nih.gov/livertoxrucamv5.pdf

vi. Your opinion

4. 討論中，您們遇到的問題或困難?
 Female
姓名 張 OO 姓別 Case 1

60 yr 147.5 cm/54 kg
年齡 身高/體重

Social Hx Drinking (-) Smoking (-) Betel nut (-) NKDA

Present
107/6/10 因 fever, tea color urine in recent 2 days 而至 ER 求診，suspected pneumonia (chest
illness

X-ray), hyperbilirubinemia r/o cholangitis 而入院進一步治療

Invasive pneumonia Aspergillosis

診斷
Acute hepatitis/drug-related
Past Hx - Recent discharge due to Invasive pulmonary Aspergillosis (107/5/25)
- R’t common iliac artery stenosis post stenting (100/10) r’t DVT under coumadin
- Symptomatic BG stones s/p cholecystectomy 10+ yr ago
Mx Voriconazole (200) 1# qd since 107/5/25~107/6/11
Propafenone (150) 2# bid (105/8/10~now)
Warfarin (5) 0.5# qn (105/8/19~now)
Lab 1.Anti-HBc (+), HBsAg (-), HCV Ab (-)
(107) 2.Abdominal echo: Normal liver parenchymal echo pattern without abnormal focal
space-occupying lesion is found.
5/10 5/25 5/26 6/10 6/12 6/16 6/19 6/21 6/27 7/4 7/5 7/10 7/20 8/14
日期

Scr 0.93 1.17 1.02 0.86 0.93 0.86 0.89 0.88 1.01 0.97
AST 34 121 182 493 251 151 133 86 32 29 28
ALT 15 16 10 419 187 162 230 188 144 112 82 67 24 27
BIL-T 0.6 1.8 0.6 0.5 0.9 0.6 0.6 0.5 0.6 0.4 0.9
BIL-D 1.1 0.3
ALK-P 361 234 299 324 289 228 250
WBC 4.4 4.2 6.2 4.3 3.7 3.8
Seg 51.7 45.5 87.4 59.3 50.0 43.3
 Female
姓名 施 OO 姓別 Case 2

39 yr 163 cm/47.6 kg
年齡 身高/體重

Social Hx Drinking (-) Smoking (-) Betel nut (-) NKDA Chinese herb (-) Travel history(-)
Present She had icteric sclera, nausea, watery diarrhea (>5 times/day), abdominal cramping pain since
illness 107/5/19, AGE was suspected. However, progressive jaundice (she started to noticed yellowish
skin since 5/21), general malaise, poor appetite, tea-color urine and epigastric dull pain were
noticed. She was admitted for further management at 107/5/25.
Jaundice
診斷
Acute hepatitis with liver decompensation
Past Hx Hepatitis B
Systemic lupus erythematous (diagnosed for 17 yr)
HBsAg (+), HBeAg(-), viral load <20 IU/mL (2018/1/15)
Mx
Prednisolone (5) 1# qd (107/6/12~now)(106/5/5~107/6/12 使用 8#6#4#3#2#1#/day)

Hydroxychloroquine (200) 1# bid (106/5/5~107/6/12)

Azathioprine (50) 2# qd (107/1/12~107/6/6)
Meloxicam (15) 1# hs (107/3/21~107/6/12)
Lab 1/25 4/15 5/24 5/26 5/29 6/1 6/5 6/9 6/15 6/20 7/4 7/18 8/19 10/3
日期
(107)
AST 40 1306 685 441 411 540 502 324 124 42 62 29 46
ALT 30 30 796 507 313 309 348 388 411 230 73 50 32 40
BIL-T 0.5 22.2 18.9 18.6 19.3 18.9 15.4 7.9 7.0 4.0 1.9 0.9 0.5
BIL-D 19.3 1.5
ALK-P 100
WBC 5.0 5.8 4.2 4.2 6.8 8.5 6.1 6.2 8.4 7.2 7.5 4.4
Seg 77.0 51 76 72.7 89.3 72.0 80.7 44
HVB Ab (-), anti-HBe (+), HBsAg (+), HBeAg (-), HAV Ab (-), HCV Ab (-)
PT (INR)= 1.67 & thrombocytopenia (plt= 77K)(107/5/24)
Abdominal echo: No biliary tree dilatation.
 Male
姓名 黃 OO 姓別 Case 3

27 yr 180 cm/97.7 kg
年齡 身高/體重

Social Hx Drinking (-) Smoking (-) Betel nut (-) NKDA Traveling hx (-) Contact hx (-)
Present Fever & skin rash for 5 days (107/3/21 ER: Rash with papule, sort throat, rhinitis, myalgia,
illness headache). He visited LMD & Tamiflu was prescribed for three days though influenza rapid test
showed negative. However, intermittent fever was noted, and he started to cough with whitish
sputum. The facial skin rash radiation to trunk (chest & back) and in the form of maculopapule
form. He was admitted at 107/3/24.
Dx: DRESS
診斷

Past Hx Systemic disease (-)

Mx Doxycyclin (100) 1# bid since 107/2/10~107/3/22 (for acne treatment)
107/3/17 Tamiflu (75) 1# bid x 5 days (fever, cough, itching facial rash since 3/16)
Dextromethorphan (15) 1# tid x 5 days
Ambroxol (30) 1# tid x 5 days
107/3/21 Diclofenac (25) 1# tid x 3 days (fever up to 39C)
107/3/24 Cefuroxime (750) 2 vial q8h (NCKUH ER: DX: suspected pneumonia, fever, rash)
Diphenhydramine (30) 1 amp q8h
Lab 3/22 3/24 3/27 3/30 4/11 6/6 8/1
日期
(107)
AST 146 119 50 48 29 33 26
ALT 574 421 181 100 47 32 20
BIL-T 0.7 0.9 1.0 0.5
WBC 13.3 14.5 17.9 15.3 14.6 13.6 9.1
Seg 41.4 42.1 35 52 80.4 77.7 62.2
Eos 2.1 7.2 21 18 1.8 3.7 5.4
1. PE: Conjuctivitis, injected throat, but no neck lymphadenopathy and clear breathing sound.
2. Skin biopsy: Vacuolar interface dermatitis with necrotic keratinocytes, consistent with
morbiliform drug eruption.
3. Blood culture (-)
4. Adenovirus Ag (-), Dengue Ag (-),CMV Ab(IgM) (-), HBs Ag (-), Anti-HBs Ab (-), HCV Ab (-)