Table 1

Age
Sex
Race
PMH other than arrhythmias, drugsPresentation
Etoh use
AuthorsLabsPathology Duration and dosagesOutcome after diagnosis of AIC

163
M
W
CAD s/p CABG, DM, HLD, No etoh, (amiodarone, warfarin, aspirin, rosiglitazone, and lovastatin)
No other hepatotoxic drugs
Abdominal distensionPuli et al. [2]23.94
114
?
23
82
Micronodular cirrhosis, bridging fibrosis, lymphocytic infiltrate, macrophages, plasma cells, microvesicular steatosis, and lysosomal bodies on electron microscopy600 mg/day for 10 days, then 200 mg/day for 22.5 months cumulative dose of approx. 141 gSurvived

281
F
Digitoxin, alpha methyldopa
No DM, and no etoh
Cirrhosis diagnosed during studyGuigui et al. [3]15, 28
186,
?, 53
GGT 151,
PT 76%
Portal fibrosis, steatosis, PMN, myelin figures, dense deposits, and cirrhosis120 months, cumulative dosage of 520 g Could not establish an outcome

372
M
W
DM, HTN, and CKD
No etoh, (amiodarone,
simvastatin, and glipizide)
Ascites and fatigueAtiq et al. [5]32.49, 106, 147, ?, 75,
PT 20
Steatohepatitis, Mallory hyaline, neutrophilic infiltrate, and cirrhosis200 PO mg/day * 3 years
Cumulative dose of approx. 219 g
Died during the same admission due to complication of liver disease

467
F
AA
CAD, CHF, and s/p AICD
No etoh
ConfusionAtiq et al. [5]?
377
551
?
277
PT 12.7
Mallory hyaline, neutrophil infiltrate, pericellular/bridging fibrosis, and degenerating hepatocytes
(cirrhosis found on autopsy)
Low dose * 2 yearsDied 2 weeks after the workup due to cardiopulmonary failure

563
M
COPD, DM, and hypothyroidism
(digoxin, furosemide, and thyroxin)
Abnormal LFTs on screening Rigas et al. [6]?
59
207
?
28
Portal, central, and sinusoidal fibrosis and loss of lobular architecture and regenerative nodules, central vein sclerosis, Mallory bodies, lysosomal inclusion, and cirrhosis400 mg/day Amiodarone * 18 months
Cumulative dose 216
No information about the outcome

673
M
Heart failure, no significant etoh, complete right and left anterior hemiblock
(translated through Google)
Jaundice, hepatomegaly Capron-Chivrac et al. [7]269
55
708
68
?
224
GGT 781
Portal, periportal fibrosis, mixed inflammatory infiltrate, ductal proliferation, lysosomal inclusions, no Mallory bodies, and cirrhosis Amiodarone 100 mg/day * 5 days/wk * 2 months
Cumulative dose of 4 g
“We strongly suspect in this case cirrhosis may have been due to some other cause”
Died 2 months after stopping amiodarone, died of pulmonary edema

770
F
Weight loos and blurred visionChaabane et al. [8]Micronodular cirrhosis, steatohepatitis 200 mg/day * 15 years
Cumulative dose of approx. 1095 g
Could not establish an outcome

862
M
CAD, HTN, CHF, emphysema, pulmonary HTN, HLD, renal insufficiency, migraine, ulcerative colitis, cholelithiasis, and no etohProgressive weakness, abdominal discomfort, and jaundiceAnonymous [9]51.3
734
119
29
781
PT 12.4
Micronodular cirrhosis with ballooning degeneration of hepatocytes and Mallory bodies, some steatosis150–1000 mg/day, averaging 400 mg/day * 8.5 years Cumulative dose of approx. 1241 gDied 2 weeks after stopping medicine, probably hepatic encephalopathy

973
M
Obesity, moderate alcohol intake Fatigue, weakness Anonymous [9]34.2
?
115
?
67
Mallory bodies, minimal fatty change, and cirrhosisAmiodarone 300 mg/day * approx. 6 months
Cumulative dose of approx. 55 g
Survived for more than 3 years

1064
M
Gout, CAD, and renal failure secondary to lead intoxication, MI, pulmonary edema, and sylvian microembolism
(digoxin, warfarin, diclofenac, amiodarone, and allopurinol)
Fatigue, weight loss,
1-2 alcoholic beverages on social occasions
Richer and Robert [10]12
149
176
?
112
INR 2.4
GGT 277
Ballooned hepatocytes, Mallory bodies, fibrosis, phospholipidosis, inflammatory infiltrate, and cirrhosis2.8 g * 4 days, then amiodarone 400 mg–600/day * 13 months,
cumulative dose of approx. 206 g
Died 69 days after cessation of therapy, due to hepatorenal syndrome

1174
M
Ischemic heart disease, CVA, poliomyelitis, carotid endarterectomy, and peripheral neuropathy
Etoh Consumption = negligible
Muscle weakness, hepatomegalyGilinsky et al. [11]133.4
110
275
16
231
PT 17
Fibrosis, Mallory hyaline, lysosomal inclusions,
amiodarone, and desmethylamiodarone conc. 0.6, 0.5 mg/L, respectively
Amiodarone
300–600 mg/day * 28 months
Cumulative dose of approx. 378 g
Died despite discontinuation of therapy, probably liver failure

1276
F
No significant past history other than recurrent SVTsAbdominal pain, anorexia, and wastingTordjman et al. [12]n
225
317
29
?
Mallory bodies, fibrosis, severely damaged hepatocytes, bile duct proliferation, and cirrhosis200 mg daily * 5 years
Cumulative dose od approx. 365 g
Died 2 weeks after evaluation due to hepatic encephalopathy

1377
F
Anorexia, abdominal pain, and malaise Rene et al. [13]20.52, 16
324, 39
10,
GGT 66
PT 70%
Micronodular cirrhosis, central and periportal fibrosis, and probable phospholipidosis
400 mg/day * 9 years
Cumulative dose of approx. 1314 g
Outcome could not be determined

1479
M
CAD s/p CABG, HLD hypothyroidism, and s/p pacemaker
(amiodarone, ASA, furosemide, atorvastatin, and ranitidine)
<2 units etoh/month
No herbal medicines
Upper GI bleed, lethargy * 2 months Singhal et al. [14]14
67
216
27
GGT 443
PMN infiltrate, reduplicating bile ducts in hepatic nodules, degenerating hepatocytes, Mallory bodies, extensive fibrosis, and cirrhosis200 PO mg/ day * 33 months
Cumulative dose of approx. 198 g
Died 3 months after diagnosis
despite of stopping amiodarone due to heart and renal failure and hepatic encephalopathy

1575
F
s/p MI, left ventricular aneurysm, and normal coronariesAbnormal LFTs
Bach et al. [15]?
140
850
?
?
Micronodular cirrhosis, portal fibrosis, Mallory bodies, ballooning hepatocytes, phospholipidosis, inflammatory cells, and lysosomal inclusions800 mg/day * 7 months, then 600 mg/day * 24 months, then 200 mg/day for 3 months
Cumulative dose of approx. 624 g
Survived for more than 3 years

1663
F
Mitral valve stenosis s/p replacement 5 years ago, moderate TR, no obesity, and no diabetes
(amiodarone, coumadin derivative)
Asthenia, anorexia, and weight loss of 8 kg for 5 months Martinez et al. [16]18.8
198
301
35
86,
GGT 475
PT 20%
Postmortem liver biopsy showed incipient cirrhosis, portal fibrosis, inflammatory ductal infiltration and mixed leukocytic infiltration, steatosis, Mallory bodies, and acidophilic change400 mg daily * 5 days/week, duration not specified, may be >12 years
Cumulative dose of approx. >1152 g
Died due to massive upper GI bleed during same admission

1758
M
CAD, MI
(amiodarone, aspirin, furosemide, diltiazem, isosorbide dinitrate, digoxin, famotidine)
No etoh, no herbs used
Abdominal distension and fatigueÇoban et al.
[17]
?
64
?
11
?
PT 16.9
GGT 133
Polymorph nuclear infiltrate, ductal proliferation, fibrosis, bridging necrosis, vacuolar degeneration, lysosomal inclusions (73+), and cirrhosis200 mg daily * 1 year, stopped due to side effects, restarted 200 mg daily * 6 years
Cumulative dose of approx. 511 g
Died 3 months after diagnosis due to hepatorenal syndrome and hepatic encephalopathy

1885
M
Ischemic heart disease
No obesity, no etoh, and no DM
Cardiac congestionOikawa
et al. [18]
20.52
81
452
?
35
GGT 210
PT 59%
Polymorph nuclear infiltrate, ductal proliferation, fibrosis, micro/macrovesicular steatosis, lysosomal inclusions, and cirrhosis
(cumulative dose given by author = 528)
400 mg daily * 17 days, then 200 mg daily for 84 months
Cumulative dose of approx. 518 g
Died 5 months after diagnosis due to renal failure and pneumonia

1949
M
Rheumatic heart disease, endocarditis, HTN, and DM
(amiodarone, acebutolol, and glibenclamide)
Pain in RUQ and feverLamproye et al. [19]n
n
n
n
*5ULN PT n
Micronodular cirrhosis, portal fibrosis, leukocytic infiltrates, Mallory bodies, micro and macrovesicular steatosis 400 mg/day * 5 days a week * 12 years
Cumulative dose of approx. 1152
No outcome given

2056
F
s/p pacemaker, goiter
No DM, no obesity, and no etoh abuse
(digoxin, acenocoumarin, and amiodarone )
Babany
et al. [20]
15
38
73
?
63
PT 100%
Micronodular cirrhosis, marked steatosis, inflammatory infiltrate, Mallory bodies, lysosomal inclusions (268 g cumulative dose given by author)
Amiodarone and N-desmethylamiodarone plasma conc. 0.42, 0.70 g/L
400 mg/day * 5 days per week 2 years, then 200 mg * 5 days per week * 11 months.
Cumulative dose of approx. 236 g
Survived for more than 10 months

2183
F
Angina pectoris
No DM, no obesity, and no etoh abuse
(amiodarone )
Hepatomegaly Babany
et al. [20]
15
63
139
?
139
PT 100%, GGT 460
Fibrosis, steatosis, Mallory bodies, inflammatory infiltrate, cirrhosis, and lysosomal inclusions on electron microscopy
(220 g cumulative dose given by author)
Amiodarone 200 mg/day * 3.5 years
Cumulative dose of approx. 256 g
Survived for more than 1.5 years

2268
F
Commissurotomy for mitral stenosis
No DM, No obesity, No etoh abuse
(hydroxyzine, amiodarone, tiodomarol, and clonazepam)
Abnormal LFTsBabany
et al. [20]
11
43
88
?
60
PT 100%
Moderate fibrosis, steatosis, polymorph nuclear infiltrate, Mallory bodies, cirrhosis, and lysosomal inclusions
(211 g cumulative dose given by author)
Amiodarone 200 mg daily * 5 days/week for 3 years, then 100 mg/day for 2 years, and then 200 mg/day * 6 months
Cumulative dose  approx. = 254 g
Survived at least more than 9 months

2368
M
No sig. PMH
(isosorbide, warfarin)
No etoh
No significant history besides arrhythmiaRinder
et al. [21]
?
180
422
?
?
Active cirrhosis, ongoing hepatocytes destruction, and Mallory bodies
(165 g given by author)
Loading dose for 1 month, then 400 mg/day * 13.5 months. Cumulative dose of approx. 162 gDied one month after discontinuation of drug due to hepatic encephalopathy and hepatorenal syndrome

2464
F
WPW syndrome, no significant PMH
(amiodarone, diuretic, and beta blocker)
No etoh used
Weakness, bedridden, and ascites Shepherd et al. [22]44
172
150
?
?
Micronodular cirrhosis with extensive necrosis of regenerating nodules, fibrosis, and swollen hepatocytes600 mg/day * 4 years
Cumulative dose of approx. 876 g
Died due to bronchopneumonia, diagnosis of cirrhosis made at postmortem

2576
M
Ischemic heart disease, pulmonary edema
(amiodarone, isosorbide dinitrate, furosemide, and potassium)
No etoh
Jeyamalar et al. [23]?
66
148
35
69
PT normal
Moderate inflammatory cells, nodules enclosed in fibrous bands, fatty, bile ductules proliferation change, and early cirrhosis
Total cumulative dose 215 g
600 mg/day * 1 week, 400 mg/day * 1 month, and 200 mg * 5 days/week * 4 years
Estimated dose = 208.2 g
Survived for more than 4 years

2667
M
Hypertrophic obstructive cardiomyopathy, s/p ICD, no obesity, no etoh, and no DMB/L hand tremor Ishida et al. [24]32.49
88
463
?
167
PT 17.4
Micronodular cirrhosis, swollen hepatocytes, proliferating bile ductules, inflammatory infiltrate, micro/macrovesicular steatosis, Mallory bodies, and lysosomal inclusion bodies
Calculated dose comes out to 158
200 mg/day * 26 months
Cumulative dose of 206 g
Died 8 days after admission due to prerenal failure

2757
M

MILethargy, abdominal distensionHarrison and Elias [25]Micronodular cirrhosis, proliferating bile ducts, neutrophil infiltrate, Ballooning degeneration of hepatocytes, Mallory hyaline, lysosomal inclusion bodies, and epithelioid granulomas200 mg twice/day * 4 years 6 months
Cumulative dose of approx. 657 g
Needed liver transplant

2877
F
HTN, DM, hypothyroidism, and GERD (Lisinopril, glimepiride, esomeprazole, levothyroxine, amiodarone, furosemide, spironolactone, propranolol, and isosorbide dinitrate)
No obesity, no alcohol
New onset ascites and variceal hemorrhage
Abdominal distension, lower extremity swelling, and SOB
Raja et al. [26]10.26
54
216
39
32
INR 1.2
GGT 230
Lymphocytic infiltration, macro/microvesicular steatosis, Mallory hyaline, ballooning degeneration, pericellular fibrosis, cirrhosis, and bridging fibrous septaAmiodarone 200 mg/day * 3 years
Cumulative dose of approx. 219 g
(No herbal medicines)
Survived more than 6 months confirmed with author

2977
M
CAD, s/p MI, s/p CABG, hep. B infection, and CHF
No etoh for last 14 years
(serum amiodarone and N-desmethylamiodarone levels = 3 & 2.6 mg/L)
Fatigue, weight loss, and abdominal swelling Flaharty et al. [27]46.17
223
459
30
124
PT 39
GGT 738
Marked fibrosis, inflammatory infiltrate Mallory bodies, cirrhosis, proliferating ductules, and lysosomal inclusions
Cumulative dose of 202 g (given by author)
1200 mg * 13 days, 400–600 mg/day * 12 months
Cumulative dose of approx. 200 g
Died on day 21 of hospitalization due to bradycardia episode

3062
F
W
No etohWeakness and jaundice Snir et al. [28]92.3, 520
329, 22
131
GGT 1493
Micronodular cirrhosis, moderate to severe fibrosis of portal tract, pericellular fibrosis, Mallory bodies, and cirrhosis on postmortem
Amiodarone 800 mg/day dose * 1 year
Estimated cumulative dose = 292 g
Died due to liver failure 3 weeks after stopping drug

3184
F
W
HTN, CHF, obesity
(amiodarone, felodipine, furosemide, potassium supplement, aspirin, and cisapride)
No other drugs
No etoh
Dark brown urine for 7 daysChang et al. [29]142
130
610
30
50
Portal fibrosis, pericellular sinusoidal fibrosis, lysosomal inclusions, Mallory bodies, and cirrhosis
1.3/1.3 amiodarone/
desmethylamiodarone serum levels
400 mg/day * 5 years
Cumulative dose = 730 g
Died 4 months after diagnosis despite of stopping drug, no cause of death established

3272
M
Korean
HTN
(amiodarone, felodipine, HCTZ, and aspirin)
No etoh
EF 70%
Sudden onset abdominal distensionSung and Yoon [30]46.1
317
137
27
237
GGT 385
INR 1.32
Cirrhosis, polymorphnuclear infiltrate, Mallory bodies, ballooning degeneration, and lysosomal inclusionsAmiodarone 200 mg/day * 5 years
Estimated cumulativ dose = 365 g
Survived, amiodarone discontinued, and other antiarrhythmic started

3364
F
Unstable recurrent angina, ventricular aneurysm, and MI
No etoh, no DM
For surgical resection of ventricular aneurysm Poucell et al. [31]12
?
188
38
82
PT 11
Micronodular cirrhosis, Mallory bodies, ballooning, macrovesicular steatosis, fibrosis, inflammation, pleomorphic mitochondria, and lysosomal inclusion600 mg * 5 days/wk * 2 years
Cumulative dose of 288
Died shortly after liver biopsy, cause unknown may be MI, and no postmortem

3462
M
Etoh 85 g/day, s/p MI, CAD Hepatomegaly despite normal LFTs * 1 year, presented for liver biopsyPoucell et al. [31]8.5
?
98
37
80
PT 11
Micro nodular cirrhosis, Mallory bodies, ballooning, macro vesicular steatosis, fibrosis, inflammation, pleomorphic mitochondria, lysosomal inclusion600 mg * 5 days/wk * 2 years
Cumulative dose 288 g
Continued on amiodarone and survived

3570
M
Alcoholic cardiomyopathy, adrenal insufficiency
(amiodarone, hydrocortisone)
Etoh was DC when heart problem diagnosed
Jaundice, pruritus, and deterioration of conditionSalti et al. [32]481
95
1451
?
92
GGT 1231
Portal and septal fibrosis, polymorph infiltrate, Mallory bodies, lysosomal inclusions, macrovesicular steatosis, and cirrhosis Amiodarone 200 mg * 5 days/wk * 2 years
Estimated cumulative
dose of 96
Survived for more than 5 months at least

3677
F
A fibWeakness, nausea, vomiting, abdominal distension, lethargy, and confusionChandraprakasam and Whitcraft [33]?
192
122
?
162
Neutrophilic satellitosis, Mallory hyaline, foam cells representing phospholipidosis, macrovesicular steatosis, and cirrhosisAmiodarone 200 mg/day * 4 years
Cumulative dose = 292
No information about outcome

3768
M
Depression, heart failure
(digoxin, doxepin, and bumetanide)
Vomiting and muscle weakness of one month durationLim et al. [34]28
142
854
29
?
400 mg/day * 5 months, then 600 mg/day for 16 months
Cumulative dose of approx. 348 g
Died due to liver failure 5 months after diagnosis despite of stopping amiodarone

: number, DM: diabetes mellitus, HTN: hypertension, HLD: hyperlipidemia, CAD: coronary artery disease, CABG: coronary artery bypass grafting, SVT: supra ventricular tachycardia, CHF: congestive heart failure, etoh: alcohol, HCTZ: hydrochlorothiazide, ASA: aspirin, SOB: shortness of breath, n: normal, TR: tricuspid regurgitation, ULN: upper limit of normal, and W: white.
Labs are written in the following sequence, Bili, AST, ALK P, Albumin, and ALT in all tables. AST, ALT, ALK P, and GGT values are given in IU/L, bilirubin is given as Mmol: micromole/L (2–17) normal range, albumin is given as g/L.
*ULN stands for upper limits of the normal and the written lab is for ALT being 5 times the ULN.