1439:
51:
672:
314:
761:; six of them metabolize 90% of drugs. There is a tremendous diversity of individual P-450 gene products, and this heterogeneity allows the liver to perform oxidation on a vast array of chemicals (including most drugs) in phase 1. Three important characteristics of the P-450 system have roles in drug-induced toxicity:
445:
1472:, however, the initial insult can be fatal. Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness.
1251:
Hepatotoxicity may manifest as triglyceride accumulation, which leads to either small-droplet (microvesicular) or large-droplet (macrovesicular) fatty liver. There is a separate type of steatosis by which phospholipid accumulation leads to a pattern similar to the diseases with inherited phospholipid
1446:
This remains a challenge in clinical practice due to a lack of reliable markers. Many other conditions lead to similar clinical as well as pathological pictures. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established,
207:
More than 900 drugs have been implicated in causing liver injury (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the
1455:
involves a scoring system that categorizes the suspicion into "definite or highly probable" (score > 8), "probable" (score 6–8), "possible" (score 3–5), "unlikely" (score 1–2) and "excluded" (score ≤ 0). In clinical practice, physicians put more emphasis on the presence or absence of similarity
1136:
is associated with infiltration of inflammatory cells. There can be three types of drug-induced hepatitis. (A) viral hepatitis is the most common, where histological features are similar to acute viral hepatitis. (B) in focal or non-specific hepatitis, scattered foci of cell necrosis may accompany
885:
Many substances can influence the P-450 enzyme mechanism. Drugs interact with the enzyme family in several ways. Drugs that modify cytochrome P-450 enzyme are referred to as either inhibitors or inducers. Enzyme inhibitors block the metabolic activity of one or several P-450 enzymes. This effect
273:
hepatotoxicity in susceptible individuals, which is not related to dose and has a variable latency period. This type of injury does not have a clear dose-response nor temporal relationship, and most often does not have predictive models. Idiosyncratic hepatotoxicity has led to the withdrawal of
344:
also plays a role in inducing toxicity. The risk of liver injury is influenced by several factors including the dose ingested, concurrent alcohol or other drug intake, interval between ingestion and antidote, etc. The dose toxic to the liver is quite variable from person to person and is often
1447:
but might be difficult, especially when idiosyncratic reaction is suspected. Simultaneous use of multiple drugs may add to the complexity. As in acetaminophen toxicity, well established, dose-dependent, pharmacological hepatotoxicity is easier to spot. Several clinical scales such as
1480:
An elevation in serum bilirubin level of more than 2 times ULN with associated transaminase rise is an ominous sign. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped
900:
Some drugs may share the same P-450 specificity and thus competitively block their biotransformation. This may lead to accumulation of drugs metabolized by the enzyme. This type of drug interaction may also reduce the rate of generation of toxic metabolites.
775:) in P-450 metabolism should be considered when patients exhibit unusual sensitivity or resistance to drug effects at normal doses. Such polymorphism is also responsible for variable drug response among patients of differing ethnic backgrounds.
393:
are so named due to their effect on the carbohydrate mechanism. They promote glycogen storage in the liver. An enlarged liver is a rare side-effect of long-term steroid use in children. The classical effect of prolonged use both in adult and
377:
Although individual analgesics rarely induce liver damage due to their widespread use, NSAIDs have emerged as a major group of drugs exhibiting hepatotoxicity. Both dose-dependent and idiosyncratic reactions have been documented. Aspirin and
3612:
683:) to make them suitable for elimination. This involves chemical transformations to (a) reduce fat solubility and (b) to change biological activity. Although almost all tissues in the body have some ability to metabolize chemicals,
737:
and many other rare chemical reactions. These processes tend to increase water solubility of the drug and can generate metabolites that are more chemically active and/or potentially toxic. Most of phase 2 reactions take place in
721:. Phase 1 reaction is generally speaking to prepare a drug for phase 2. However, many compounds can be metabolized by phase 2 directly or be excreted without any phase 2 reactions occurring. Phase 1 reaction involves
1332:
Drug-induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. More than 50 drugs have been implicated.
620:, an intracellular organelle that produces energy. Its dysfunction releases excessive amount of oxidants that, in turn, injure hepatic cells. Activation of some enzymes in the cytochrome P-450 system such as
1710:
Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SH, et al. (December 2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States".
1071:
level more than twice ULN, or (c) total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular (predominantly initial
410:
Isoniazide (INH) is one of the most commonly used drugs for tuberculosis; it is associated with mild elevation of liver enzymes in up to 20% of patients and severe hepatotoxicity in 1-2% of patients.
324:
also known as acetaminophen, and by the brand names of
Tylenol and Panadol, is usually well-tolerated in prescribed dose, but overdose is the most common cause of drug-induced liver disease and
1448:
1190:
Liver injury leads to impairment of bile flow and cases are predominated by itching and jaundice. Histology may show inflammation (cholestatic hepatitis) or it can be bland (without any
255:(higher concentrations cause more liver damage) and well characterized mechanisms of toxicity, such as directly damaging liver tissue or blocking a metabolic process. As in the case of
172:
The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g.
1404:
Neoplasms have been described with prolonged exposure to some medications or toxins. Hepatocellular carcinoma, angiosarcoma, and liver adenomas are the ones usually reported.
382:
are associated with intrinsic hepatotoxicity; idiosyncratic reaction has been associated with ibuprofen, sulindac, phenylbutazone, piroxicam, diclofenac and indomethacin.
886:
usually occurs immediately. On the other hand, inducers increase P-450 activity by increasing enzyme production, or, in the case of CYP2E1, preventing degradation in the
675:
Drug metabolism in liver: transferases are: glutathione, sulfate, acetate, glucoronic acid. P-450 is cytochrome P-450. Different pathways are shown for Drugs A, B and C.
345:
thought to be lower in chronic alcoholics. Measurement of blood level is important in assessing prognosis, higher levels predicting a worse prognosis. Administration of
609:, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and the spleen via
757:, is the most important family of metabolizing enzymes in the liver. Cytochrome P-450 is not a single enzyme, but rather consists of a closely related family of 50
2706:"Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways"
707:
substances (e.g., drugs, alcohol). The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.
299:
has been associated with hepatic toxicity, including some fatalities; however, such effects appear to be limited to doses taken over a period longer than 7 days.
2501:
613:
that bring drugs and xenobiotics in near-undiluted form. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process.
1485:). This is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or
2531:
Schoental R (April 1959). "Liver lesions in young rats suckled by mothers treated with the pyrrolizidine (Senecio) alkaloids, lasiocarpine and retrorsine".
1468:
In most cases, liver function will return to normal if the offending drug is stopped early. Additionally, the patient may require supportive treatment. In
336:-benzoquinone imine (NAPQI)) produced by cytochrome P-450 enzymes in the liver. In normal circumstances, this metabolite is detoxified by conjugating with
2345:
Sarich TC, Adams SP, Petricca G, Wright JM (1999). "Inhibition of isoniazid-induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor".
340:
in phase 2 reaction. In an overdose, a large amount of NAPQI is generated, which overwhelms the detoxification process and leads to liver cell damage.
1934:
Banankhah PS, Garnick KA, Greenblatt DJ (October 2016). "Ketoconazole-Associated Liver Injury in Drug-Drug
Interaction Studies in Healthy Volunteers".
1194:
inflammation). On rare occasions, it can produce features similar to primary biliary cirrhosis due to progressive destruction of small bile ducts (
771:
Each of the P-450 proteins is unique and accounts (to some extent) for the variation in drug metabolism between individuals. Genetic variations (
605:
Drugs continue to be taken off the market due to late discovery of hepatotoxicity. Due to its unique metabolism and close relationship with the
2372:
Schläppi B (1985). "The lack of hepatotoxicity in the rat with the new and reversible MAO-A inhibitor moclobemide in contrast to iproniazid".
3088:
3027:
3002:
1997:
1769:
1694:
1582:
2469:
242:
are classified as type A (intrinsic or pharmacological) or type B (idiosyncratic). Type A drug reaction accounts for 80% of all toxicities.
1451:/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage.
462:, which occur in some plants, can be toxic. Green tea extract is a growing cause of liver failure due to its inclusion in more products.
1079:(initial alkaline phosphatase rise) types. However they are not mutually exclusive and mixed types of injuries are often encountered.
1456:
between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in
1415:
1206:
2197:
O'Grady JG, Alexander GJ, Hayllar KM, Williams R (August 1989). "Early indicators of prognosis in fulminant hepatic failure".
184:), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g.,
3104:
2950:
Patel T, Roberts LR, Jones BA, Gores GJ (1998). "Dysregulation of apoptosis as a mechanism of liver disease: an overview".
349:, a precursor of glutathione, can limit the severity of the liver damage by capturing the toxic NAPQI. Those that develop
3048:
Lynch T, Price A (2007). "The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects".
169:
caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
3650:
3546:
Shah RR (November 1999). "Drug-induced hepatotoxicity: pharmacokinetic perspectives and strategies for risk reduction".
2511:
1885:
Dixit VA, Bharatam PV (July 2011). "Toxic metabolite formation from
Troglitazone (TGZ): new insights from a DFT study".
1195:
684:
200:, through pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called
3216:
Bénichou C (September 1990). "Criteria of drug-induced liver disorders. Report of an international consensus meeting".
2590:
266:
2655:"Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation"
3670:
1297:
366:
2915:
Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ (2002). "Mechanisms of hepatotoxicity".
3627:
1650:
Greenhough S, Hay DC (2012). "Stem Cell-Based
Toxicity Screening: Recent Advances in Hepatocyte Generation".
3450:"Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry"
91:
289:
has caused a number of cases of idiosyncratic liver injury, ranging everywhere from asymptomatic to fatal.
3079:
Concise Guide to Drug
Interaction Principles for Medical Practice: Cytochrome P450s, Ugts, P-Glycoproteins
1490:
1469:
1035:
1017:
772:
606:
503:
499:
459:
1253:
1378:
726:
648:
308:
239:
3258:"Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists"
2798:
McRae CA, Agarwal K, Mutimer D, Bassendine MF (May 2002). "Hepatitis associated with
Chinese herbs".
2704:
Zhou P, Gross S, Liu JH, Yu BY, Feng LL, Nolta J, Sharma V, Piwnica-Worms D, Qiu SX (December 2010).
1390:
1142:
1121:
1103:
1083:
1068:
1056:
947:
931:
817:
543:
491:
260:
221:
1501:
The following therapeutic drugs were withdrawn from the market primarily because of hepatotoxicity:
274:
several drugs from market even after rigorous clinical testing as part of the FDA approval process;
3675:
3665:
1989:
1307:
1107:
1072:
1064:
1052:
610:
479:
350:
325:
252:
228:
2434:
Kothari UC (February 1960). "Toxic and other side effects of nardil phenelzine sulphate W-1544A".
50:
3528:
3479:
3430:
3381:
3332:
3160:
2975:
2897:
2780:
2635:
2606:"ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury"
2312:
2263:
2130:
2087:
1959:
1867:
1736:
1667:
734:
519:
515:
2833:
Furukawa M, Kasajima S, Nakamura Y, Shouzushima M, Nagatani N, Takinishi A, et al. (2010).
2755:
Pak E, Esrason KT, Wu VH (June 2004). "Hepatotoxicity of herbal remedies: an emerging dilemma".
2476:
1547:
1268:
1761:
1755:
1438:
3555:
3520:
3471:
3422:
3373:
3324:
3289:
3233:
3198:
3152:
3084:
3057:
3023:
2998:
2967:
2932:
2856:
2815:
2772:
2737:
2686:
2627:
2572:
2548:
2451:
2416:
2381:
2354:
2304:
2255:
2214:
2179:
2122:
2079:
2044:
1993:
1951:
1902:
1859:
1824:
1775:
1765:
1728:
1690:
1632:
1578:
1452:
483:
177:
78:
3256:
Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI (2007).
1724:
1489:) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high
3510:
3461:
3412:
3363:
3316:
3279:
3269:
3225:
3190:
3142:
2959:
2924:
2887:
2846:
2807:
2764:
2727:
2717:
2676:
2666:
2617:
2540:
2443:
2408:
2294:
2245:
2206:
2169:
2161:
2114:
2071:
2034:
2026:
1981:
1943:
1894:
1851:
1814:
1806:
1720:
1659:
1622:
1614:
1542:
1486:
1419:
1384:
1210:
1001:
754:
213:
83:
1063:) are often used to indicate liver damage. Liver injury is defined as a rise in either (a)
436:
has been associated with abnormal liver tests. Toxic effects can develop from antibiotics.
259:
overdose, this type of injury occurs shortly after some threshold for toxicity is reached.
2502:"Foodborne Pathogenic Microorganisms and Natural Toxins Handbook: Pyrrolizidine Alkaloids"
2105:
Riordan SM, Williams R (2002). "Alcohol exposure and paracetamol-induced hepatotoxicity".
1574:
1568:
710:
507:
317:
Paracetomol (3D structure) overdose is the most common cause of drug-induced liver disease
227:
Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all
3573:
1982:
679:
The human body subjects most, but not all, compounds to various chemical processes (i.e.
328:
worldwide. Damage to the liver is not due to the drug itself but to a toxic metabolite (
2062:
James LP, Mayeux PR, Hinson JA (December 2003). "Acetaminophen-induced hepatotoxicity".
671:
3284:
3257:
3147:
3130:
3077:
2732:
2705:
2681:
2654:
2399:
Cook GC, Sherlock S (January 1965). "Jaundice And Its
Relation To Therapeutic Agents".
2174:
2149:
2039:
2014:
1819:
1794:
1627:
1602:
1411:
1313:
1238:
1234:
1005:
547:
455:
426:
390:
379:
358:
346:
313:
185:
3417:
3400:
2412:
1920:
3659:
3229:
2851:
2834:
2811:
2784:
2299:
2282:
2250:
2233:
2210:
2165:
1963:
1855:
1510:
1283:
1228:
1031:
1022:
980:
832:
808:
803:
279:
166:
100:
3434:
3164:
2979:
2901:
2604:
Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ (July 2014).
2316:
2267:
1871:
1740:
1671:
212:-derived hepatocyte-like cells, that are capable of detecting toxicity early in the
3532:
3483:
3385:
3336:
2639:
2506:
2091:
1526:
1502:
1457:
1287:
1276:
1224:
1099:
1048:
1013:
877:
845:
644:
617:
523:
362:
341:
296:
275:
208:
need for toxicity prediction models (e.g. DTI), and drug screening assays, such as
2234:"Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects"
2134:
282:(Trovan) are two prime examples of idiosyncratic hepatotoxins pulled from market.
248:
or toxins that have a pharmacological (type A) hepatotoxicity are those that have
70:
3632:
3320:
3108:
1482:
1340:
1220:
1191:
1184:
1117:
1076:
1009:
984:
836:
743:
696:
692:
636:
527:
337:
321:
256:
217:
201:
173:
59:
2876:"Hepatoprotective activity of Clearliv a polyherbal formulation in Wistar rats"
2768:
3621:
2928:
2118:
1810:
1522:
1518:
1514:
1427:
1356:
1293:
1272:
1177:
1173:
1138:
988:
887:
868:
841:
827:
823:
799:
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656:
640:
625:
475:
433:
429:
395:
354:
293:
17:
2892:
2875:
2671:
3578:
2544:
1779:
1506:
1360:
1348:
1344:
1326:
1319:
1303:
1245:
1214:
1161:
1157:
1153:
1133:
1060:
1039:
1027:
863:
854:
850:
812:
722:
704:
652:
633:
629:
419:
399:
209:
189:
181:
96:
3559:
3524:
3475:
3426:
3377:
3328:
3293:
3274:
3202:
3061:
2963:
2936:
2860:
2819:
2776:
2741:
2690:
2631:
2576:
2552:
2455:
2420:
2358:
2259:
2183:
2126:
2083:
2075:
2048:
2030:
1955:
1906:
1732:
1636:
3237:
3156:
2995:
2971:
2571:. National Institute of Diabetes and Digestive and Kidney Diseases. 2012.
2447:
2385:
2308:
2218:
1828:
353:
can still recover spontaneously, but may require transplantation if poor
2722:
2622:
2605:
1863:
1530:
1398:
1095:
872:
859:
700:
660:
3604:
3194:
2566:
2835:"Toxic hepatitis induced by show-wu-pian, a Chinese herbal preparation"
1663:
1618:
1423:
1352:
1264:
1167:
1086:
patterns of liver injury from drug-induced damage are discussed below.
758:
739:
539:
511:
487:
263:
is commonly used to induce acute type A liver injury in animal models.
197:
3515:
3498:
3466:
3449:
3368:
3351:
3083:. Washington, DC: American Psychiatric Association. pp. 167–396.
1898:
1793:
Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK (April 1998).
3616:
3499:"Outcome and prognostic markers in severe drug-induced liver disease"
1947:
750:
621:
66:
3131:"Update: clinically significant cytochrome P-450 drug interactions"
3307:
Arundel C, Lewis JH (2007). "Drug-induced liver disease in 2006".
1437:
996:
992:
687:
in the liver is the principal "metabolic clearing house" for both
670:
471:
448:
443:
312:
245:
158:
63:
3181:
Mumoli N, Cei M, Cosimi A (2006). "Drug-related hepatotoxicity".
2653:
Kim YJ, Choi MS, Park YB, Kim SR, Lee MK, Jung UJ (August 2013).
1098:
where the injury is largely confined to a particular zone of the
1067:
level more than three times of upper limit of normal (ULN), (b)
495:
423:
286:
193:
2874:
Kumar EP, Kumar A, Parasuraman S, Rajan VR, Emerson SF (2013).
444:
746:
enzymes. Phase 1 are typically more suitable for elimination.
2993:
Blumenthal D, Brunton L, Parker K, Lazo JS, Buxton I (2006).
2283:"Hepatomegaly following short-term high-dose steroid therapy"
890:. There is usually a delay before enzyme activity increases.
62:. Other causes were excluded with extensive investigations.
3646:
458:
containing mushrooms, kava, and aflatoxin producing molds.
2330:
Alpers DH, Sabesin SM (1982). Schiff L, Schiff ER (eds.).
269:(type B) injury occurs without warning, when agents cause
1603:"A simple model to solve a complex drug toxicity problem"
3448:
Andrade RJ, Lucena MI, Kaplowitz N, et al. (2006).
1094:
This is the most common type of drug-induced liver cell
1141:
infiltration. (C) chronic hepatitis is very similar to
1371:
These result from injury to the vascular endothelium.
742:
and involve conjugation with endogenous compounds via
220:
injury to the liver, which manifests only as abnormal
1573:. New York: Lang Medical Books/McGraw-Hill. pp.
1570:
Current diagnosis & treatment in gastroenterology
1442:
Algorithm for suspected drug-induced hepatic toxicity
3594:
1975:
1973:
1106:
and severe disturbance of liver function leading to
3598:
1842:Zimmerman HJ (1978). "Drug-induced liver disease".
90:
77:
40:
35:
3076:
1047:Chemicals produce a wide variety of clinical and
2015:"Acetaminophen hepatotoxicity: NO to the rescue"
3251:
3249:
3247:
3176:
3174:
3043:
3041:
3039:
2334:. Philadelphia: JB Lippincott. pp. 813–45.
2232:Manov I, Motanis H, Frumin I, Iancu TC (2006).
1145:clinically, serologically, and histologically.
753:located in the endoplasmic reticulum, known as
2591:"Liver Damage from Supplements is on the Rise"
1596:
1594:
196:, though the causal mechanism is unknown, and
3075:Oesterheld JR, Cozza KL, Armstrong S (2003).
3022:. Cheltenham, UK: Nelson Thornes Publishers.
1988:. Edinburgh: Churchill Livingstone. pp.
1760:. Oxford : Oxford University Press. pp.
1687:GI/Liver Secrets: with STUDENT CONSULT Access
1567:Friedman SE, Grendell JH, McQuaid KR (2003).
8:
176:) and sometimes even when introduced within
3401:"Anticoagulants and transaminase elevation"
3595:
1102:. It may manifest as a very high level of
1051:hepatic injury. Biochemical markers (e.g.
784:
639:. This promotes further liver damage. Non-
49:
32:
3514:
3465:
3416:
3367:
3283:
3273:
3146:
2891:
2850:
2731:
2721:
2680:
2670:
2621:
2298:
2249:
2173:
2038:
1818:
1626:
624:also lead to oxidative stress. Injury to
27:Liver damage caused by a drug or chemical
2880:Archives of Medicine and Health Sciences
1725:10.7326/0003-4819-137-12-200212170-00007
3018:Skett, Paul; Gibson, G. Gordon (2001).
1559:
165:(DILI) is a cause of acute and chronic
911:Patterns of drug-induced liver disease
107:
663:) also have a role in the mechanism.
7:
2281:Iancu TC, Shiloh H, Dembo L (1986).
2150:"Paracetamol, alcohol and the liver"
713:is usually divided into two phases:
432:, are associated with liver damage.
373:Nonsteroidal anti-inflammatory drugs
131:Toxic liver disease with cholestasis
3189:(20): 2191–3, author reply 2191–3.
1381:: Chemotherapeutic agents, bush tea
3148:10.1002/j.1875-9114.1998.tb03830.x
1757:Textbook of adverse drug reactions
129:Toxic liver disease with hepatitis
25:
3418:10.1161/CIRCULATIONAHA.105.603100
418:There are also cases where other
2852:10.2169/internalmedicine.49.3509
2812:10.1097/00042737-200205000-00015
2300:10.1097/00005176-198601000-00008
2251:10.1111/j.1745-7254.2006.00278.x
2166:10.1046/j.1365-2125.2000.00167.x
1856:10.2165/00003495-197816010-00002
1416:combined oral contraceptive pill
414:Other hydrazine derivative drugs
117:Drug-induced liver injury (DILI)
3020:Introduction to drug metabolism
2287:J. Pediatr. Gastroenterol. Nutr
1980:Keeffe EB, Friedman LM (2004).
925:
922:
919:
916:
793:
790:
787:
560:
216:process. Chemicals often cause
3548:Adverse Drug React Toxicol Rev
3497:Björnsson E, Olsson R (2005).
3399:Arora N, Goldhaber SZ (2006).
632:cells lead to accumulation of
422:derivative drugs, such as the
192:(two prominent examples being
127:Drug-induced hepatic granuloma
1:
2475:. Davis. 2017. Archived from
2413:10.1016/s0140-6736(65)90969-4
2013:Wallace JL (September 2004).
780:2. Change in enzyme activity:
125:Drug-induced hepatic fibrosis
123:Drug-induced hepatic necrosis
3651:National Library of Medicine
3321:10.1097/MOG.0b013e3280b17dfb
3230:10.1016/0168-8278(90)90124-a
2997:. McGraw-Hill Professional.
2512:Food and Drug Administration
2211:10.1016/0016-5085(89)90081-4
685:smooth endoplasmic reticulum
563:drug-induced hepatotoxicity
58:Drug-induced hepatitis with
3574:Drug-Induced Hepatotoxicity
2800:Eur J Gastroenterol Hepatol
1689:. Saint Louis: C.V. Mosby.
591:Duration and dosage of drug
514:. Chinese herbal remedies:
137:Toxin-induced liver disease
3692:
3350:Reuben A (February 2004).
2769:10.1177/152692480401400203
2148:Prescott LF (April 2000).
1984:Handbook of liver diseases
1458:amoxycillin-clauvonic acid
1298:total parenteral nutrition
1252:metabolism defects (e.g.,
895:3. Competitive inhibition:
306:
174:acetaminophen, paracetamol
157:) implies chemical-driven
139:Drug-induced liver disease
3309:Curr. Opin. Gastroenterol
3050:American Family Physician
2119:10.1080/13556210220120424
1811:10.1136/bmj.316.7140.1295
163:Drug-induced liver injury
141:Drug-induced liver damage
57:
48:
2893:10.4103/2321-4848.123023
2672:10.3748/wjg.v19.i29.4689
1795:"Adverse drug reactions"
1207:Oral contraceptive pills
667:Drug metabolism in liver
597:Drug-to-drug interaction
582:Underlying liver disease
2929:10.1093/toxsci/65.2.166
2616:(7): 950–66, quiz 967.
2545:10.1002/path.1700770220
2347:J. Pharmacol. Exp. Ther
1601:Dixit VA (March 2019).
1391:Hepatic vein thrombosis
1279:(especially if expired)
1196:vanishing duct syndrome
1172:(c) Chronic hepatitis:
1134:hepatocellular necrosis
616:Many chemicals damage
500:pyrrolizidine alkaloids
460:Pyrrolizidine alkaloids
367:King's College Criteria
143:Hepatogenous poisoning
119:Toxin-induced hepatitis
3275:10.3748/wjg.v13.i3.329
3262:World J. Gastroenterol
2964:10.1055/s-2007-1007147
2076:10.1124/dmd.31.12.1499
2031:10.1038/sj.bjp.0705781
1921:"Ketoconazole Tablets"
1470:acetaminophen toxicity
1443:
1292:(c) Phospholipidosis:
1018:Hormonal contraception
676:
607:gastrointestinal tract
451:
318:
240:Adverse drug reactions
121:Drug-induced hepatitis
3649:at the United States
3129:Michalets EL (1998).
2659:World J Gastroenterol
2448:10.1176/ajp.116.8.746
2374:Arzneimittelforschung
2332:Diseases of the liver
1441:
1393:: Oral contraceptives
1379:Venoocclusive disease
1166:(b) Focal hepatitis:
1152:(a) Viral hepatitis:
766:1. Genetic diversity:
695:, steroid hormones,
674:
647:, collagen-producing
447:
316:
309:Paracetamol poisoning
2723:10.1096/fj.10-163311
2623:10.1038/ajg.2014.131
1308:nucleoside analogues
1282:(b) Macrovesicular:
1263:(a) Microvesicular:
1143:autoimmune hepatitis
1122:carbon tetrachloride
1057:alkaline phosphatase
561:Factors influencing
544:carbon tetrachloride
466:Alternative remedies
261:Carbon tetrachloride
253:dose-response curves
229:acute liver failures
3195:10.1056/NEJMc060733
2482:on October 27, 2017
2238:Acta Pharmacol. Sin
2154:Br J Clin Pharmacol
1685:McNally PF (2006).
1387:: Anabolic steroids
1108:acute liver failure
1073:Alanine transferase
1053:alanine transferase
913:
351:acute liver failure
326:acute liver failure
135:Toxic liver disease
2610:Am J Gastroenterol
2533:J Pathol Bacteriol
1664:10.1007/BF03256896
1619:10.1039/c8tx00261d
1444:
1219:(b) Inflammatory:
1084:histo-pathological
909:
905:Patterns of injury
677:
579:Nutritional status
573:Ethnicity and race
470:Examples include:
452:
319:
222:liver enzyme tests
178:therapeutic ranges
3671:Diseases of liver
3642:
3641:
3516:10.1002/hep.20800
3467:10.1002/hep.21424
3369:10.1002/hep.20081
3090:978-1-58562-111-8
3029:978-0-7487-6011-4
3004:978-0-07-146804-6
2064:Drug Metab Dispos
1999:978-0-443-06633-7
1899:10.1021/tx200110h
1771:978-0-19-261479-7
1754:Davies D (1985).
1696:978-1-56053-618-5
1584:978-0-8385-1551-8
1453:CIOMS/RUCAM scale
1254:Tay–Sachs disease
1132:In this pattern,
1045:
1044:
883:
882:
791:Potent inhibitors
691:chemicals (e.g.,
603:
602:
538:Examples include
454:Examples include
148:
147:
106:
105:
30:Medical condition
16:(Redirected from
3683:
3596:
3581:
3570:
3564:
3563:
3543:
3537:
3536:
3518:
3494:
3488:
3487:
3469:
3445:
3439:
3438:
3420:
3411:(15): e698–702.
3396:
3390:
3389:
3371:
3347:
3341:
3340:
3304:
3298:
3297:
3287:
3277:
3253:
3242:
3241:
3213:
3207:
3206:
3178:
3169:
3168:
3150:
3126:
3120:
3119:
3117:
3116:
3107:. Archived from
3101:
3095:
3094:
3082:
3072:
3066:
3065:
3045:
3034:
3033:
3015:
3009:
3008:
2990:
2984:
2983:
2952:Semin. Liver Dis
2947:
2941:
2940:
2912:
2906:
2905:
2895:
2871:
2865:
2864:
2854:
2830:
2824:
2823:
2795:
2789:
2788:
2752:
2746:
2745:
2735:
2725:
2701:
2695:
2694:
2684:
2674:
2665:(29): 4689–701.
2650:
2644:
2643:
2625:
2601:
2595:
2594:
2587:
2581:
2580:
2563:
2557:
2556:
2528:
2522:
2521:
2519:
2518:
2510:. United States
2498:
2492:
2491:
2489:
2487:
2481:
2474:
2466:
2460:
2459:
2431:
2425:
2424:
2396:
2390:
2389:
2369:
2363:
2362:
2342:
2336:
2335:
2327:
2321:
2320:
2302:
2278:
2272:
2271:
2253:
2229:
2223:
2222:
2199:Gastroenterology
2194:
2188:
2187:
2177:
2145:
2139:
2138:
2102:
2096:
2095:
2070:(12): 1499–506.
2059:
2053:
2052:
2042:
2010:
2004:
2003:
1987:
1977:
1968:
1967:
1948:10.1002/jcph.711
1942:(10): 1196–202.
1936:J Clin Pharmacol
1931:
1925:
1924:
1917:
1911:
1910:
1887:Chem Res Toxicol
1882:
1876:
1875:
1839:
1833:
1832:
1822:
1805:(7140): 1295–8.
1790:
1784:
1783:
1751:
1745:
1744:
1707:
1701:
1700:
1682:
1676:
1675:
1647:
1641:
1640:
1630:
1598:
1589:
1588:
1564:
1543:Hepatoprotection
1487:Gilbert syndrome
1420:anabolic steroid
1385:Peliosis hepatis
1367:Vascular lesions
1211:anabolic steroid
1002:Anabolic steroid
914:
908:
785:
755:cytochrome P-450
637:inside the liver
594:Enzyme induction
558:
557:
534:Industrial toxin
440:Natural products
365:is present (see
292:Oral use of the
214:drug development
155:hepatic toxicity
108:
84:Gastroenterology
53:
33:
21:
3691:
3690:
3686:
3685:
3684:
3682:
3681:
3680:
3656:
3655:
3643:
3638:
3637:
3607:
3593:
3587:
3585:
3584:
3571:
3567:
3545:
3544:
3540:
3496:
3495:
3491:
3447:
3446:
3442:
3398:
3397:
3393:
3349:
3348:
3344:
3306:
3305:
3301:
3255:
3254:
3245:
3215:
3214:
3210:
3183:N. Engl. J. Med
3180:
3179:
3172:
3135:Pharmacotherapy
3128:
3127:
3123:
3114:
3112:
3103:
3102:
3098:
3091:
3074:
3073:
3069:
3047:
3046:
3037:
3030:
3017:
3016:
3012:
3005:
2992:
2991:
2987:
2949:
2948:
2944:
2914:
2913:
2909:
2873:
2872:
2868:
2845:(15): 1537–40.
2832:
2831:
2827:
2797:
2796:
2792:
2757:Prog Transplant
2754:
2753:
2749:
2716:(12): 4722–32.
2703:
2702:
2698:
2652:
2651:
2647:
2603:
2602:
2598:
2589:
2588:
2584:
2565:
2564:
2560:
2530:
2529:
2525:
2516:
2514:
2500:
2499:
2495:
2485:
2483:
2479:
2472:
2468:
2467:
2463:
2436:Am J Psychiatry
2433:
2432:
2428:
2407:(7378): 175–9.
2398:
2397:
2393:
2371:
2370:
2366:
2344:
2343:
2339:
2329:
2328:
2324:
2280:
2279:
2275:
2231:
2230:
2226:
2196:
2195:
2191:
2147:
2146:
2142:
2104:
2103:
2099:
2061:
2060:
2056:
2012:
2011:
2007:
2000:
1979:
1978:
1971:
1933:
1932:
1928:
1919:
1918:
1914:
1884:
1883:
1879:
1841:
1840:
1836:
1792:
1791:
1787:
1772:
1753:
1752:
1748:
1709:
1708:
1704:
1697:
1684:
1683:
1679:
1649:
1648:
1644:
1600:
1599:
1592:
1585:
1566:
1565:
1561:
1556:
1548:Reye's syndrome
1539:
1499:
1497:Drugs withdrawn
1478:
1466:
1436:
1402:
1369:
1330:
1269:Reye's syndrome
1249:
1188:
1130:
1114:Causes include:
1092:
1075:elevation) and
1038:
1034:
1030:
1026:
1016:
1012:
1008:
1004:
995:
991:
987:
983:
963:ALT: ALP ratio
958:≥ Twofold rise
942:≥ Twofold rise
917:Type of injury:
907:
876:
867:
849:
840:
831:
816:
807:
788:Potent inducers
711:Drug metabolism
669:
562:
556:
536:
468:
442:
416:
408:
391:Glucocorticoids
388:
386:Glucocorticoids
375:
311:
305:
271:non-predictable
237:
190:herbal remedies
142:
140:
138:
136:
134:
133:Toxic hepatitis
132:
130:
128:
126:
124:
122:
120:
118:
31:
28:
23:
22:
15:
12:
11:
5:
3689:
3687:
3679:
3678:
3673:
3668:
3658:
3657:
3654:
3653:
3640:
3639:
3636:
3635:
3624:
3608:
3603:
3602:
3600:
3599:Classification
3592:
3591:External links
3589:
3583:
3582:
3565:
3554:(4): 181–233.
3538:
3489:
3440:
3391:
3342:
3299:
3243:
3208:
3170:
3121:
3096:
3089:
3067:
3035:
3028:
3010:
3003:
2985:
2942:
2907:
2866:
2825:
2790:
2747:
2696:
2645:
2596:
2593:. 19 May 2017.
2582:
2558:
2523:
2493:
2461:
2426:
2391:
2364:
2353:(2): 695–702.
2337:
2322:
2273:
2224:
2189:
2160:(4): 291–301.
2140:
2113:(2): 191–206.
2097:
2054:
2019:Br J Pharmacol
2005:
1998:
1969:
1926:
1912:
1893:(7): 1113–22.
1877:
1834:
1785:
1770:
1746:
1719:(12): 947–54.
1713:Ann Intern Med
1702:
1695:
1677:
1642:
1613:(2): 157–171.
1590:
1583:
1558:
1557:
1555:
1552:
1551:
1550:
1545:
1538:
1535:
1498:
1495:
1477:
1474:
1465:
1462:
1435:
1432:
1431:
1430:
1412:Vinyl chloride
1409:
1401:
1396:
1395:
1394:
1388:
1382:
1376:
1368:
1365:
1364:
1363:
1338:
1329:
1324:
1323:
1322:
1318:(f) Hormonal:
1316:
1314:Corticosteroid
1310:
1300:
1290:
1280:
1261:
1248:
1243:
1242:
1241:
1239:flucloxacillin
1235:Chlorpromazine
1231:
1217:
1203:
1187:
1182:
1181:
1180:
1170:
1164:
1150:
1129:
1126:
1125:
1124:
1115:
1091:
1090:Zonal Necrosis
1088:
1043:
1042:
1020:
1006:Chlorpromazine
999:
978:
974:
973:
970:
967:
964:
960:
959:
956:
955:≥ Twofold rise
953:
950:
944:
943:
940:
937:
936:≥ Twofold rise
934:
928:
927:
924:
921:
920:Hepatocellular
918:
906:
903:
898:
897:
881:
880:
857:
821:
818:St John's wort
796:
795:
792:
789:
783:
782:
769:
768:
668:
665:
649:stellate cells
643:cells such as
601:
600:
599:
598:
595:
592:
589:
586:
585:Renal function
583:
580:
577:
574:
571:
565:
564:
555:
552:
548:vinyl chloride
535:
532:
504:Horse chestnut
467:
464:
456:alpha-Amanitin
441:
438:
427:antidepressant
415:
412:
407:
404:
398:population is
387:
384:
380:phenylbutazone
374:
371:
359:encephalopathy
357:signs such as
347:Acetylcysteine
307:Main article:
304:
301:
278:(Rezulin) and
236:
233:
186:alpha-amanitin
151:Hepatotoxicity
146:
145:
113:
112:
104:
103:
94:
88:
87:
81:
75:
74:
55:
54:
46:
45:
44:see below list
42:
38:
37:
36:Hepatotoxicity
29:
26:
24:
18:Liver toxicity
14:
13:
10:
9:
6:
4:
3:
2:
3688:
3677:
3674:
3672:
3669:
3667:
3664:
3663:
3661:
3652:
3648:
3645:
3644:
3634:
3630:
3629:
3625:
3623:
3619:
3618:
3614:
3610:
3609:
3606:
3601:
3597:
3590:
3588:
3580:
3576:
3575:
3569:
3566:
3561:
3557:
3553:
3549:
3542:
3539:
3534:
3530:
3526:
3522:
3517:
3512:
3508:
3504:
3500:
3493:
3490:
3485:
3481:
3477:
3473:
3468:
3463:
3460:(6): 1581–8.
3459:
3455:
3451:
3444:
3441:
3436:
3432:
3428:
3424:
3419:
3414:
3410:
3406:
3402:
3395:
3392:
3387:
3383:
3379:
3375:
3370:
3365:
3361:
3357:
3353:
3346:
3343:
3338:
3334:
3330:
3326:
3322:
3318:
3315:(3): 244–54.
3314:
3310:
3303:
3300:
3295:
3291:
3286:
3281:
3276:
3271:
3268:(3): 329–40.
3267:
3263:
3259:
3252:
3250:
3248:
3244:
3239:
3235:
3231:
3227:
3223:
3219:
3212:
3209:
3204:
3200:
3196:
3192:
3188:
3184:
3177:
3175:
3171:
3166:
3162:
3158:
3154:
3149:
3144:
3141:(1): 84–112.
3140:
3136:
3132:
3125:
3122:
3111:on 2007-10-10
3110:
3106:
3100:
3097:
3092:
3086:
3081:
3080:
3071:
3068:
3063:
3059:
3055:
3051:
3044:
3042:
3040:
3036:
3031:
3025:
3021:
3014:
3011:
3006:
3000:
2996:
2989:
2986:
2981:
2977:
2973:
2969:
2965:
2961:
2958:(2): 105–14.
2957:
2953:
2946:
2943:
2938:
2934:
2930:
2926:
2923:(2): 166–76.
2922:
2918:
2911:
2908:
2903:
2899:
2894:
2889:
2885:
2881:
2877:
2870:
2867:
2862:
2858:
2853:
2848:
2844:
2840:
2836:
2829:
2826:
2821:
2817:
2813:
2809:
2806:(5): 559–62.
2805:
2801:
2794:
2791:
2786:
2782:
2778:
2774:
2770:
2766:
2762:
2758:
2751:
2748:
2743:
2739:
2734:
2729:
2724:
2719:
2715:
2711:
2707:
2700:
2697:
2692:
2688:
2683:
2678:
2673:
2668:
2664:
2660:
2656:
2649:
2646:
2641:
2637:
2633:
2629:
2624:
2619:
2615:
2611:
2607:
2600:
2597:
2592:
2586:
2583:
2578:
2574:
2570:
2569:
2562:
2559:
2554:
2550:
2546:
2542:
2539:(2): 485–95.
2538:
2534:
2527:
2524:
2513:
2509:
2508:
2503:
2497:
2494:
2478:
2471:
2470:"Amoxicillin"
2465:
2462:
2457:
2453:
2449:
2445:
2441:
2437:
2430:
2427:
2422:
2418:
2414:
2410:
2406:
2402:
2395:
2392:
2387:
2383:
2379:
2375:
2368:
2365:
2360:
2356:
2352:
2348:
2341:
2338:
2333:
2326:
2323:
2318:
2314:
2310:
2306:
2301:
2296:
2292:
2288:
2284:
2277:
2274:
2269:
2265:
2261:
2257:
2252:
2247:
2244:(3): 259–72.
2243:
2239:
2235:
2228:
2225:
2220:
2216:
2212:
2208:
2205:(2): 439–45.
2204:
2200:
2193:
2190:
2185:
2181:
2176:
2171:
2167:
2163:
2159:
2155:
2151:
2144:
2141:
2136:
2132:
2128:
2124:
2120:
2116:
2112:
2108:
2101:
2098:
2093:
2089:
2085:
2081:
2077:
2073:
2069:
2065:
2058:
2055:
2050:
2046:
2041:
2036:
2032:
2028:
2024:
2020:
2016:
2009:
2006:
2001:
1995:
1991:
1986:
1985:
1976:
1974:
1970:
1965:
1961:
1957:
1953:
1949:
1945:
1941:
1937:
1930:
1927:
1922:
1916:
1913:
1908:
1904:
1900:
1896:
1892:
1888:
1881:
1878:
1873:
1869:
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1861:
1857:
1853:
1849:
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1826:
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1576:
1572:
1571:
1563:
1560:
1553:
1549:
1546:
1544:
1541:
1540:
1536:
1534:
1532:
1528:
1524:
1520:
1516:
1512:
1511:trovafloxacin
1508:
1504:
1496:
1494:
1492:
1488:
1484:
1475:
1473:
1471:
1463:
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1459:
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1440:
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1429:
1425:
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1325:
1321:
1317:
1315:
1311:
1309:
1305:
1301:
1299:
1295:
1291:
1289:
1285:
1284:Acetaminophen
1281:
1278:
1274:
1270:
1266:
1262:
1259:
1258:
1257:
1255:
1247:
1244:
1240:
1236:
1232:
1230:
1229:carbamazepine
1226:
1222:
1218:
1216:
1212:
1208:
1204:
1201:
1200:
1199:
1197:
1193:
1186:
1183:
1179:
1175:
1171:
1169:
1165:
1163:
1159:
1155:
1151:
1148:
1147:
1146:
1144:
1140:
1135:
1127:
1123:
1119:
1116:
1113:
1112:
1111:
1109:
1105:
1101:
1097:
1089:
1087:
1085:
1080:
1078:
1074:
1070:
1066:
1062:
1058:
1054:
1050:
1041:
1037:
1033:
1032:Carbamazepine
1029:
1024:
1023:Amitriptyline
1021:
1019:
1015:
1011:
1007:
1003:
1000:
998:
994:
990:
986:
982:
981:Acetaminophen
979:
976:
975:
971:
968:
965:
962:
961:
957:
954:
951:
949:
946:
945:
941:
938:
935:
933:
930:
929:
915:
912:
904:
902:
896:
893:
892:
891:
889:
879:
874:
870:
865:
861:
858:
856:
852:
847:
843:
838:
834:
833:Ciprofloxacin
829:
825:
822:
819:
814:
810:
809:Phenobarbital
805:
804:Carbamazepine
801:
798:
797:
786:
781:
778:
777:
776:
774:
767:
764:
763:
762:
760:
756:
752:
747:
745:
741:
736:
732:
728:
724:
720:
716:
712:
708:
706:
702:
698:
694:
690:
686:
682:
673:
666:
664:
662:
658:
654:
650:
646:
645:Kupffer cells
642:
638:
635:
631:
627:
623:
619:
614:
612:
608:
596:
593:
590:
587:
584:
581:
578:
575:
572:
569:
568:
567:
566:
559:
553:
551:
549:
545:
541:
533:
531:
529:
525:
521:
517:
513:
509:
505:
501:
497:
493:
489:
485:
481:
477:
473:
465:
463:
461:
457:
450:
446:
439:
437:
435:
431:
428:
425:
421:
413:
411:
405:
403:
401:
397:
392:
385:
383:
381:
372:
370:
368:
364:
360:
356:
352:
348:
343:
339:
335:
331:
327:
323:
315:
310:
302:
300:
298:
295:
290:
288:
283:
281:
280:trovafloxacin
277:
272:
268:
267:Idiosyncratic
264:
262:
258:
254:
251:
247:
243:
241:
234:
232:
230:
225:
223:
219:
215:
211:
205:
203:
199:
195:
191:
187:
183:
179:
175:
170:
168:
167:liver disease
164:
160:
156:
152:
144:
115:
114:
110:
109:
102:
101:liver failure
98:
95:
93:
92:Complications
89:
85:
82:
80:
76:
72:
71:H&E stain
68:
65:
61:
56:
52:
47:
43:
39:
34:
19:
3626:
3611:
3586:
3572:
3568:
3551:
3547:
3541:
3509:(2): 481–9.
3506:
3502:
3492:
3457:
3453:
3443:
3408:
3404:
3394:
3362:(2): 574–8.
3359:
3355:
3345:
3312:
3308:
3302:
3265:
3261:
3224:(2): 272–6.
3221:
3217:
3211:
3186:
3182:
3138:
3134:
3124:
3113:. Retrieved
3109:the original
3105:"P450 Table"
3099:
3078:
3070:
3056:(3): 391–6.
3053:
3049:
3019:
3013:
2994:
2988:
2955:
2951:
2945:
2920:
2917:Toxicol. Sci
2916:
2910:
2886:(2): 120–5.
2883:
2879:
2869:
2842:
2838:
2828:
2803:
2799:
2793:
2760:
2756:
2750:
2713:
2709:
2699:
2662:
2658:
2648:
2613:
2609:
2599:
2585:
2567:
2561:
2536:
2532:
2526:
2515:. Retrieved
2507:Bad Bug Book
2505:
2496:
2484:. Retrieved
2477:the original
2464:
2442:(8): 746–7.
2439:
2435:
2429:
2404:
2400:
2394:
2380:(5): 800–3.
2377:
2373:
2367:
2350:
2346:
2340:
2331:
2325:
2290:
2286:
2276:
2241:
2237:
2227:
2202:
2198:
2192:
2157:
2153:
2143:
2110:
2106:
2100:
2067:
2063:
2057:
2022:
2018:
2008:
1983:
1939:
1935:
1929:
1915:
1890:
1886:
1880:
1850:(1): 25–45.
1847:
1843:
1837:
1802:
1798:
1788:
1756:
1749:
1716:
1712:
1705:
1686:
1680:
1658:(2): 85–89.
1655:
1651:
1645:
1610:
1606:
1569:
1562:
1527:ximelagatran
1503:Troglitazone
1500:
1479:
1467:
1445:
1403:
1370:
1331:
1288:methotrexate
1277:tetracycline
1250:
1233:(c) Ductal:
1225:co-amoxiclav
1189:
1131:
1100:liver lobule
1093:
1081:
1049:pathological
1046:
1014:Erythromycin
910:
899:
894:
884:
878:Theophylline
846:Erythromycin
779:
773:polymorphism
770:
765:
748:
718:
714:
709:
678:
618:mitochondria
615:
611:portal veins
604:
537:
524:Shou Wu Pian
469:
453:
417:
409:
389:
376:
363:coagulopathy
342:Nitric oxide
333:
329:
320:
297:ketoconazole
291:
284:
276:Troglitazone
270:
265:
249:
244:
238:
226:
206:
202:hepatotoxins
171:
162:
154:
150:
149:
116:
86:, Toxicology
3405:Circulation
2763:(2): 91–6.
2293:(1): 41–6.
2107:Addict Biol
1607:Toxicol Res
1341:Allopurinol
1221:Allopurinol
1205:(a) Bland:
1192:parenchymal
1185:Cholestasis
1139:lymphocytic
1118:Paracetamol
1077:cholestatic
1036:Sulfonamide
1010:Clopidogrel
985:Allopurinol
923:Cholestatic
837:Fluconazole
794:Substrates
749:A group of
744:transferase
697:fatty acids
693:cholesterol
641:parenchymal
528:Bai Xian Pi
516:Jin Bu Huan
472:Ackee fruit
449:Ackee fruit
338:glutathione
322:Paracetamol
303:Paracetamol
257:paracetamol
250:predictable
218:subclinical
60:granulomata
41:Other names
3676:Hepatology
3666:Toxicology
3660:Categories
3503:Hepatology
3454:Hepatology
3356:Hepatology
3352:"Hy's law"
3115:2007-09-29
2839:Intern Med
2517:2009-07-11
2025:(1): 1–2.
1554:References
1523:nefazodone
1519:nimesulide
1515:ebrotidine
1428:thorotrast
1357:penicillin
1294:Amiodarone
1273:ketoprofen
1178:diclofenac
1174:Methyldopa
989:Amiodarone
888:proteasome
869:Omeprazole
842:Fluoxetine
828:Cimetidine
824:Amiodarone
800:Rifampicin
731:hydrolysis
689:endogenous
681:metabolism
657:neutrophil
653:leukocytes
626:hepatocyte
476:Bajiaolian
434:Phenelzine
430:iproniazid
396:paediatric
355:prognostic
294:antifungal
3579:eMedicine
3218:J Hepatol
2785:208042609
2486:March 24,
1964:206060985
1652:Pharm Med
1507:bromfenac
1476:Prognosis
1464:Treatment
1434:Diagnosis
1361:quinidine
1349:isoniazid
1345:phenytoin
1327:Granuloma
1320:Tamoxifen
1304:Antiviral
1246:Steatosis
1215:androgens
1162:phenytoin
1158:isoniazid
1154:Halothane
1128:Hepatitis
1082:Specific
1061:bilirubin
1040:Phenytoin
1028:Enalapril
977:Examples
864:Clozapine
855:Diltiazem
851:Isoniazid
813:Phenytoin
735:hydration
727:reduction
723:oxidation
705:exogenous
634:bile acid
630:bile duct
588:Pregnancy
554:Mechanism
420:hydrazine
406:Isoniazid
400:steatosis
285:The herb
210:stem cell
182:halothane
111:Synonyms
97:Cirrhosis
79:Specialty
3647:LiverTox
3560:10687025
3525:16025496
3476:17133470
3435:32207352
3427:16618822
3378:14768020
3329:17414839
3294:17230599
3203:16710915
3165:18552904
3062:17708140
2980:28395693
2937:11812920
2902:98429527
2861:20686286
2820:11984156
2777:15264453
2742:20696856
2691:23922466
2632:24935270
2577:31643176
2568:GreenTea
2553:13642195
2456:14411298
2421:14238042
2359:10215642
2317:35749798
2268:26874901
2260:16490160
2184:10759684
2127:12006215
2084:14625346
2049:15345657
1956:26829173
1907:21657230
1872:45207777
1780:12558288
1741:11390513
1733:12484709
1672:15893493
1637:30997019
1537:See also
1531:pemoline
1483:Hy's Law
1399:Neoplasm
1096:necrosis
966:High, ≥5
873:Losartan
860:Caffeine
759:isoforms
701:proteins
661:monocyte
508:Valerian
506:leaves,
498:leaves,
492:Garcinia
484:Copaltra
332:-acetyl-
161:damage.
3633:D056486
3533:2742529
3484:9067701
3386:5916660
3337:5842491
3285:4065885
3238:2254635
3157:9469685
2972:9606808
2733:2992378
2710:FASEB J
2682:3732841
2640:2417493
2386:4026902
2309:3944744
2219:2490426
2175:2014937
2092:1556558
2040:1575258
1829:9554902
1820:1113033
1628:6417485
1575:664–679
1424:arsenic
1408:Causes:
1375:Causes:
1353:quinine
1337:Causes:
1265:Aspirin
1260:Causes:
1202:Causes:
1168:Aspirin
1149:Causes:
969:Low, ≤2
751:enzymes
740:cytosol
719:phase 2
715:phase 1
540:arsenic
520:Ephedra
512:Comfrey
488:Cycasin
480:Camphor
198:comfrey
188:), and
3558:
3531:
3523:
3482:
3474:
3433:
3425:
3384:
3376:
3335:
3327:
3292:
3282:
3236:
3201:
3163:
3155:
3087:
3060:
3026:
3001:
2978:
2970:
2935:
2900:
2859:
2818:
2783:
2775:
2740:
2730:
2689:
2679:
2638:
2630:
2575:
2551:
2454:
2419:
2401:Lancet
2384:
2357:
2315:
2307:
2266:
2258:
2217:
2182:
2172:
2135:370682
2133:
2125:
2090:
2082:
2047:
2037:
1996:
1992:–123.
1962:
1954:
1905:
1870:
1864:352664
1862:
1827:
1817:
1778:
1768:
1739:
1731:
1693:
1670:
1635:
1625:
1581:
952:Normal
939:Normal
926:Mixed
703:) and
655:(i.e.
651:, and
622:CYP2E1
576:Gender
546:, and
235:Causes
180:(e.g.
153:(from
67:biopsy
3622:K71.0
3529:S2CID
3480:S2CID
3431:S2CID
3382:S2CID
3333:S2CID
3161:S2CID
2976:S2CID
2898:S2CID
2781:S2CID
2636:S2CID
2480:(PDF)
2473:(PDF)
2313:S2CID
2264:S2CID
2131:S2CID
2088:S2CID
1960:S2CID
1868:S2CID
1844:Drugs
1762:18–45
1737:S2CID
1668:S2CID
1449:CIOMS
997:NSAID
993:HAART
246:Drugs
159:liver
64:Liver
3628:MeSH
3556:PMID
3521:PMID
3472:PMID
3423:PMID
3374:PMID
3325:PMID
3290:PMID
3234:PMID
3199:PMID
3153:PMID
3085:ISBN
3058:PMID
3024:ISBN
2999:ISBN
2968:PMID
2933:PMID
2857:PMID
2816:PMID
2773:PMID
2738:PMID
2687:PMID
2628:PMID
2573:PMID
2549:PMID
2488:2017
2452:PMID
2417:PMID
2382:PMID
2355:PMID
2305:PMID
2256:PMID
2215:PMID
2180:PMID
2123:PMID
2080:PMID
2045:PMID
1994:ISBN
1952:PMID
1903:PMID
1860:PMID
1825:PMID
1776:OCLC
1766:ISBN
1729:PMID
1691:ISBN
1633:PMID
1579:ISBN
1529:and
1312:(e)
1302:(d)
1059:and
972:2–5
717:and
659:and
628:and
496:Kava
424:MAOI
287:kava
194:kava
3613:ICD
3577:at
3511:doi
3462:doi
3413:doi
3409:113
3364:doi
3317:doi
3280:PMC
3270:doi
3226:doi
3191:doi
3187:354
3143:doi
2960:doi
2925:doi
2888:doi
2847:doi
2808:doi
2765:doi
2728:PMC
2718:doi
2677:PMC
2667:doi
2618:doi
2614:109
2541:doi
2444:doi
2440:116
2409:doi
2351:289
2295:doi
2246:doi
2207:doi
2170:PMC
2162:doi
2115:doi
2072:doi
2035:PMC
2027:doi
2023:143
1990:104
1944:doi
1895:doi
1852:doi
1815:PMC
1807:doi
1803:316
1799:BMJ
1721:doi
1717:137
1660:doi
1623:PMC
1615:doi
1491:AST
1460:).
1271:),
1198:).
1104:ALT
1069:ALP
1065:ALT
948:ALP
932:ALT
570:Age
369:).
361:or
3662::
3631::
3620::
3617:10
3552:18
3550:.
3527:.
3519:.
3507:42
3505:.
3501:.
3478:.
3470:.
3458:44
3456:.
3452:.
3429:.
3421:.
3407:.
3403:.
3380:.
3372:.
3360:39
3358:.
3354:.
3331:.
3323:.
3313:23
3311:.
3288:.
3278:.
3266:13
3264:.
3260:.
3246:^
3232:.
3222:11
3220:.
3197:.
3185:.
3173:^
3159:.
3151:.
3139:18
3137:.
3133:.
3054:76
3052:.
3038:^
2974:.
2966:.
2956:18
2954:.
2931:.
2921:65
2919:.
2896:.
2882:.
2878:.
2855:.
2843:49
2841:.
2837:.
2814:.
2804:14
2802:.
2779:.
2771:.
2761:14
2759:.
2736:.
2726:.
2714:24
2712:.
2708:.
2685:.
2675:.
2663:19
2661:.
2657:.
2634:.
2626:.
2612:.
2608:.
2547:.
2537:77
2535:.
2504:.
2450:.
2438:.
2415:.
2403:.
2378:35
2376:.
2349:.
2311:.
2303:.
2289:.
2285:.
2262:.
2254:.
2242:27
2240:.
2236:.
2213:.
2203:97
2201:.
2178:.
2168:.
2158:49
2156:.
2152:.
2129:.
2121:.
2109:.
2086:.
2078:.
2068:31
2066:.
2043:.
2033:.
2021:.
2017:.
1972:^
1958:.
1950:.
1940:56
1938:.
1901:.
1891:24
1889:.
1866:.
1858:.
1848:16
1846:.
1823:.
1813:.
1801:.
1797:.
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1727:.
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1654:.
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1533:.
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1418:,
1414:,
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1355:,
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1237:,
1227:,
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1120:,
1110:.
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99:,
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3562:.
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