Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update

In the paper

“the incidence of liver injury induced by cytotoxic T-lymphocyte antigen 4 inhibitors is higher than that induced by programmed cell death 1 inhibitors, particularly at high doses.”

What the sources say

• ?Not checked — no full text of the sourcecites [152] Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity from immune checkpoint inhibitors: a systematic review and management recommendation. Hepatology. 2020;72:315–329 source
• Disputed

  In “二、ICPIs相关肝毒性的发生率” (p. 2), the paper says that although CTLA-4 antibodies may cause more adverse reactions overall, current data show no clear difference in hepatotoxicity compared with PD-1/PD-L1 antibodies. In “四、ICPIs相关肝毒性的风险因素” (p. 2), the high-dose ipilimumab figures concern immune-related adverse reactions overall, not liver injury specifically. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  cites [153] Lei XH, Tang YY, Li J, Mao YM. Hepatotoxicity associated with tumor immune checkpoint inhibitors. (Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi) Chin J Hepatol. 2020;28:175–178 sourceExperimental — accuracy not yet measured

In the paper

“Meanwhile, the importance of antibiotics, and non-steroidal anti-inflammatory drugs such as APAP should not be overlooked since these are still the commonest causing agents of DILI in most western countries [21].”

What the sources say

• Partly supported

  The Results section reports that antimicrobials, mostly antibiotics, were the most common causative class in this U.S. cohort (45%). It reports only 3% of cases attributed to analgesics, largely nonsteroidal anti-inflammatory drugs, so it does not support calling them the commonest agents. The Methods specify enrollment for suspected non-acetaminophen DILI, and this U.S. study does not establish what is commonest across most Western countries. (LLM, conf=0.91)

  cites [21] Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340–1352 sourceExperimental — accuracy not yet measured

In the paper

“Liver biochemistry in approximately 7-13% of patients may not return to normal or baseline levels 6 months or 1 year after an acute DILI episode, which indicates that acute liver injury may develop into a chronic injury or delayed recovery [8].”

What the sources say

• Partly supported

  The Clinical presentations section reports that 13.00% of all DILI cases had persistent evidence of liver injury at least six months after onset. It also says that some patients classified as chronic at six months later normalized their liver chemistries, suggesting delayed recovery. The cited passages do not establish the 7% figure or a one-year rate, and the 13% denominator is all DILI cases rather than patients with acute DILI. (LLM, conf=0.86)

  cites [8] Shen T, Liu Y, Shang J, et al. Incidence and etiology of drug-induced liver injury in Mainland China. Gastroenterology. 2019;156:2230–2241 sourceExperimental — accuracy not yet measured

In the paper

“Prolonged cholestasis with progressive reduction of the interlobular bile ducts can lead to vanishing bile duct syndrome with a poor prognosis [74].”

What the sources say

• Supported

  The Conclusions (page not available) describe bile duct loss during cholestatic hepatitis as an ominous early indicator of possible vanishing bile duct syndrome. The Discussion (page not available) says bile duct loss has a poor prognosis, especially when moderate or severe, and reports cases of progressive cholestatic injury resulting in death or transplantation. (LLM, conf=0.88)

  cites [74] Bonkovsky HL, Kleiner DE, Gu J, et al. Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology. 2017;65:1267–1277 source

In the paper

“In China, a large cohort study suggests that HDS accounts for 57% of druginduced ALF [70].”

What the sources say

• Partly supported

  The Results (Drugs implicated in non-APAP drug-induced ALF) report that HDS accounted for 57.01% of cases in this Chinese cohort. The claim omits the study’s non-APAP restriction, so the figure is not established for all drug-induced ALF. (LLM, conf=0.88)

  cites [70] Han L, Huang A, Chen J, et al. Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study. Hepatol Int. 2023. https://doi.org/10.1007/s12072-023-10541-w sourceExperimental — accuracy not yet measured

In the paper

“Studies have shown that approximately 10% of cases that fulfill Hy's law will progress to ALF [5,64], and is associated increased mortality or need for liver transplantation [65][66][67][68].”

What the sources say

• Partly supported

  The Discussion (page not provided) says Hy’s rule predicts at least 10% liver transplantation and/or death in drug-induced hepatocellular jaundice, and the study observed 11.7% for those outcomes. The paper also says these patients are more prone to acute liver failure, but it does not report that approximately 10% of cases fulfilling Hy’s rule progress to acute liver failure; the claim substitutes a different outcome for the reported percentage. (LLM, conf=0.88)

  cites [5] Andrade RJ, Lucena MI, Fernández MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129:512–521 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not supplied) says hepatocellular jaundice consistent with Hy’s rule had approximately 10% mortality. The Comparison Between Nonsurvivors and Survivors section reports a 0.13 positive predictive value for death or transplantation among patients meeting the stated laboratory criteria. Neither passage establishes that approximately 10% progressed to acute liver failure (ALF); the cited outcome is different. (LLM, conf=0.87)

  cites [64] Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology. 2005;42:481–489 sourceExperimental — accuracy not yet measured

In the paper

“The novel DI-ALF-5 model was developed to predict transplant-free survival in non-APAP DI-ALF [70].”

What the sources say

• Supported

  The Results (Novel prediction nomogram development) state that the authors constructed the DIALF-5 model and evaluated its accuracy in predicting 21-day transplant-free survival. The Discussion states that it was developed for patients with non-APAP drug-induced acute liver failure. The claim’s “DI-ALF-5” refers to the paper’s “DIALF-5.” (LLM, conf=0.95)

  cites [70] Han L, Huang A, Chen J, et al. Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study. Hepatol Int. 2023. https://doi.org/10.1007/s12072-023-10541-w source

In the paper

“In a randomized placebo-controlled trial of adult non-APAP ALF (including DILI as the etiology), intravenous NAC improved transplant-free survival in early stage ALF with grade I-II coma [185].”

What the sources say

• Supported

  Methods > Study Population specifies adult eligibility and exclusion of acetaminophen overdose; Results > Study Population identifies 45 participants with drug-induced liver injury. Abstract > Methods describes random assignment to intravenous NAC or placebo, and Results > Study outcomes reports higher transplant-free survival with NAC among patients with grade I–II coma (52% versus 30%). Page numbers are unavailable in our copy. (LLM, conf=0.94)

  cites [185] Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137:3 source

In the paper

“In clinical trials, the incidence of all-grade liver injury due to different smallmolecule targeted drugs such as tyrosine kinase inhibitors is reportedly 5-55% [144-149].”

What the sources say

• Partly supported

  The Safety and Adverse-Event Profile reports that elevated liver aminotransferase levels were significantly more common with gefitinib than with carboplatin–paclitaxel. It does not provide the claimed 5–55% all-grade liver-injury range across different small-molecule targeted drugs; this trial examines gefitinib, not that broader drug class. (LLM, conf=0.84)

  cites [144] Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–957 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [145] Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–128 source
• ?Not checked — no full text of the sourcecites [146] Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–2388 source
• ?Not checked — no full text of the sourcecites [147] Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–246 source
• ?Not checked — no full text of the sourcecites [148] Wu Y-L, Zhou C, Hu C-P, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:213–222 source
• ?Not checked — no full text of the sourcecites [149] Shi YK, Wang L, Han BH, et al. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017;28:2443–2450 source

In the paper

“Liver transplantation can significantly increase survival by up to 66.2% [66,211,212].”

What the sources say

• ?Could not verify

  The Results section (page unavailable) reports how often patients with drug-induced liver failure received transplants, but not whether transplantation improved survival. A search for the 66.2% figure and for post-transplant survival comparisons found neither a survival benefit estimate nor that figure in our copy. (LLM, conf=0.74)

  cites [66] Hayashi PH, Rockey DC, Fontana RJ, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017;66:1275–1285 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (Outcomes) report 92.9% survival among transplant recipients and 66.2% overall survival in the drug-induced acute liver failure cohort. The 66.2% figure is overall survival, not the amount by which transplantation increased survival; the passage does not establish a statistically significant increase or address acute-on-chronic liver failure. (LLM, conf=0.89)

  cites [211] Reuben A, Koch DG, Lee WM. Drug-induced acute liver failure: results of a US multicenter, prospective study. Hepatology. 2010;52:2065–2076 sourceExperimental — accuracy not yet measured
• Partly supported

  The Liver transplantation section (page not provided) says transplantation contributed to lower overall mortality in acute liver failure and that transplant recipients had lower two-year mortality than specified non-transplanted survivors. It does not report a survival increase of 66.2%. The paper distinguishes acute liver failure from acute-on-chronic liver failure, so it does not support extending this claim to that population. (LLM, conf=0.88)

  cites [212] Stravitz RT, Lee WM. Acute liver failure. Lancet. 2019;394:869–881 sourceExperimental — accuracy not yet measured

In the paper

“L-ornithine-L-aspartate may be beneficial for the treatment of hyperammonemia in critical cases or liver failure [213][214][215][216][217].”

What the sources say

• Partly supported

  The review’s Exploratory outcomes section reports reduced blood ammonia concentrations with L-ornithine L-aspartate, and its discussion says the treatment might benefit people with hepatic encephalopathy. Its own review, however, concerns people with cirrhosis; it does not establish a benefit for critical cases or liver failure generally. (LLM, conf=0.84)

  cites [213] Goh ET, Stokes CS, Sidhu SS, Vilstrup H, Gluud LL, Morgan MY. l-Ornithine l-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2018;5:CD012410 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [214] Schmid M, Peck-Radosavljevic M, König F, Mittermaier C, Gangl A, Ferenci P. A double-blind, randomized, placebo-controlled trial of intravenous l-ornithine-l-aspartate on postural control in patients with cirrhosis. Liver Int. 2010;30:574–582 source
• ?Not checked — no full text of the sourcecites [215] Jain A, Sharma BC, Mahajan B, et al. l-Ornithine l-aspartate in acute treatment of severe hepatic encephalopathy: a double-blind randomized controlled trial. Hepatology. 2022;75:1194–1203 source
• Partly supported

  The Secondary Outcome Analyses report a significant reduction in blood ammonia with L-ornithine-L-aspartate versus placebo. However, Patients and Methods limits the trial to adults with cirrhosis and overt hepatic encephalopathy; terminally ill patients and those with acute-on-chronic liver failure were excluded. The result therefore does not establish benefit for critical cases or liver failure generally. (LLM, conf=0.88)

  cites [216] Sidhu SS, Sharma BC, Goyal O, Kishore H, Kaur N. l-Ornithine l-aspartate in bouts of overt hepatic encephalopathy. Hepatology. 2018;67:700–710 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [217] Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK. Efficacy of l-ornithine l-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology. 2009;136:2159–2168 source

In the paper

“A history of exposure to suspected HMs or HDS is the cornerstone of diagnosis [123].”

What the sources say

• Supported

  The Methods (Inclusion Criteria and Patient Ascertainment Procedures; page not provided) say investigators obtained patients’ chronological history of drug and HDS use. The Methods (Causality Assessment and Outcomes; page not provided) then describe assessing whether that use could have caused the liver injury. Together, these support the claim that exposure history is central to diagnosis, though the paper also requires evaluation for other causes. (LLM, conf=0.84)

  cites [123] Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the US drug-induced liver injury network. Hepatology. 2014;60:1399–1408 source

In the paper

“while 40-60 mg/d prednisone taper over 1-3 months may improve normalization of liver enzyme for iDILI [82,191].”

What the sources say

• Partly supported

  Table 9 in “Medical management of idiosyncratic patients with DILI” lists 40–60 mg of prednisone for selected patients and says corticosteroids can frequently be tapered over 1–3 months. The same section says a short course may benefit such patients, but it does not specifically say it improves normalization of liver enzymes; it also notes that the optimal dose and duration are unknown. (LLM, conf=0.85)

  cites [82] Fontana RJ, Liou I, Reuben A, et al. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury. Hepatology. 2023;77:1036–1065 sourceExperimental — accuracy not yet measured
• Partly supported

  Section 3.4 reports a higher liver-enzyme normalisation rate among corticosteroid-treated DILI patients. Section 3.1 reports a median initial dose of 40 mg/day and a median treatment duration of 59 days, but the Discussion says dosing and tapering varied and that the study could not evaluate outcomes specifically in patients with an autoimmune phenotype. It therefore does not establish the claimed benefit for a 40–60 mg/day prednisone taper over 1–3 months in immune-mediated DILI. (LLM, conf=0.90)

  cites [191] Niu H, Ma J, Medina-Caliz I, et al. Potential benefit and lack of serious risk from corticosteroids in drug-induced liver injury: an international, multicentre, propensity score-matched analysis. Aliment Pharmacol Ther. 2023;57:886–896 sourceExperimental — accuracy not yet measured

In the paper

“The overall prognosis of DI-ALF/ACLF is poor, with 24% or 27.1% transplant-free survival.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [66] Hayashi PH, Rockey DC, Fontana RJ, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017;66:1275–1285 source
• Partly supported

  The Results (Outcomes; page not available) report 27.1% transplant-free survival for drug-induced acute liver failure, supporting the claim that its prognosis is poor. The paper does not report 24% transplant-free survival, and its Patients and Methods define the study population as having no apparent chronic liver disease, so its finding does not establish the prognosis of acute-on-chronic liver failure. (LLM, conf=0.90)

  cites [211] Reuben A, Koch DG, Lee WM. Drug-induced acute liver failure: results of a US multicenter, prospective study. Hepatology. 2010;52:2065–2076 sourceExperimental — accuracy not yet measured
• Partly supported

  The Drug-induced liver injury section describes a worse prognosis and says fewer than 25% recover after encephalopathy develops, but that is not an overall transplant-free survival rate. The Outcomes section gives 41% transplant-free survival for drug-induced liver injury, not 24% or 27.1%. The paper also distinguishes acute liver failure from acute-on-chronic liver failure rather than reporting an outcome for the latter. (LLM, conf=0.87)

  cites [212] Stravitz RT, Lee WM. Acute liver failure. Lancet. 2019;394:869–881 sourceExperimental — accuracy not yet measured

In the paper

“However, no significant benefits were observed with NAC in pediatric non-APAP-induced ALF [186].”

What the sources say

• Supported

  The Results (Study outcomes) found no significant difference in one-year survival between NAC and placebo, including in the reported subgroups. The Discussion likewise states that NAC did not improve one-year survival in children with non-APAP acute liver failure; it also reports significantly lower transplant-free survival with NAC. (LLM, conf=0.92)

  cites [186] Squires RH, Dhawan A, Alonso E, et al. Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial. Hepatology. 2013;57:1542–1549 source

In the paper

“The most common drugs that cause liver injury in China include TCM, HDS, anti-TB drugs, antineoplastic agents, and immunomodulators [8].”

What the sources say

• Not checked yetcites [8] Shen T, Liu Y, Shang J, et al. Incidence and etiology of drug-induced liver injury in Mainland China. Gastroenterology. 2019;156:2230–2241 source

In the paper

“The drugs that cause liver injury vary across countries and regions owing to the epidemiology of the primary disease, variations in prescribing habits, and population heterogeneity [15].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [15] Low EXS, Zheng Q, Chan E, Lim SG. Drug induced liver injury: east versus west—a systematic review and meta-analysis. Clin Mol Hepatol. 2020;26:142–154 source

In the paper

“In Asian countries, such as South Korea [7], Malaysia [16], Thailand [17], Singapore [18], Taiwan [19], India [20], and China [8], anti-TB drugs, herbal and alternative medications such as traditional Chinese medicine (TCM), and antibiotics are the leading causes of DILI.”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Suk KT, Kim DJ, Kim CH, et al. A prospective nationwide study of drug-induced liver injury in Korea. Am J Gastroenterol. 2012;107:1380–1387 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [16] Marzuki OA, Fauzi ARM, Ayoub S, Kamarul IM. Prevalence and risk factors of anti-tuberculosis drug-induced hepatitis in Malaysia. Singap Med J. 2008;49:688–693
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [17] Chirapongsathorn S, Sukeepaisarnjaroen W, Treeprasertsuk S, et al. Characteristics of drug-induced liver injury in chronic liver disease: results from the Thai Association for the Study of the Liver (THASL) DILI Registry. J Clin Transl Hepatol. 2023;11:88–96 source

In the paper

“Unlike AIH, most cases of DI-ALH rarely relapse in the long-term follow-up after the discontinuation of corticosteroid or immunosuppressive therapy [83,84], which is the key information that indicates the probability of DI-ALH, particularly for patients with a history of classical drug exposure.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [83] Björnsson E, Talwalkar J, Treeprasertsuk S, et al. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology. 2010;51:2040–2048 source
• ?Not checked — no full text of the sourcecites [84] Björnsson ES, Bergmann O, Jonasson JG, Grondal G, Gudbjornsson B, Olafsson S. Drug-induced autoimmune hepatitis: response to corticosteroids and lack of relapse after cessation of steroids. Clin Gastroenterol Hepatol. 2017;15:1635–1636 source

In the paper

“Genetic polymorphism of the CYP 450 enzyme may be associated with an increased risk of liver injury induced by certain drugs [46,47].”

What the sources say

• ?Not checked — no full text of the sourcecites [46] Stephens C, Lucena MI, Andrade RJ. Genetic risk factors in the development of idiosyncratic drug-induced liver injury. Expert Opin Drug Metab Toxicol. 2021;17:153–169 source
• Not checked yetcites [47] Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138:103–141 source

In the paper

“Similarly, some small-sample-size studies suggest that NAFLD may increase the risk of all-cause DILI [101][102][103].”

What the sources say

• ?Not checked — no full text of the sourcecites [101] Lammert C, Imler T, Teal E, Chalasani N. Patients with chronic liver disease suggestive of nonalcoholic fatty liver disease may be at higher risk for drug-induced liver injury. Clin Gastroenterol Hepatol. 2019;17:2814–2815 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [102] Liu Y-H, Guo Y, Xu H, Feng H, Chen D-Y. Impact of non-alcoholic simple fatty liver disease on antituberculosis drug-induced liver injury. Infect Drug Resist. 2021;14:3667–3671 source
• ?Not checked — no full text of the sourcecites [103] Tarantino G, Conca P, Basile V, et al. A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease. Hepatol Res. 2007;37:410–415 source

In the paper

“Liver biopsy can provide valuable histopathological information that may help clarify the diagnosis of DILI when it is difficult to exclude competing etiologies [52].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [52] Ahmad J, Barnhart HX, Bonacini M, et al. Value of liver biopsy in the diagnosis of drug-induced liver injury. J Hepatol. 2022;76:1070–1078 source

In the paper

“However, in populations with chronic liver disease including NAFLD, the risk of statin-induced DILI did not increase [104][105][106].”

What the sources say

• ?Not checked — no full text of the sourcecites [104] Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology. 2004;126:1287–1292 source
• ?Not checked — no full text of the sourcecites [105] Cohen DE, Anania FA, Chalasani N. An assessment of statin safety by hepatologists. Am J Cardiol. 2006;97:77C-81C source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [106] Lewis JH, Mortensen ME, Zweig S, Fusco MJ, Medoff JR, Belder R. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology. 2007;46:1453–1463 source

In the paper

“Current evidence suggests that decompensated cirrhosis may affect drug metabolism in the liver and hepatocyte regeneration after acute liver injury, which may increase the risk of critical illness or prolong the time to recovery [100,[109][110][111].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [100,[109][110][111]

In the paper

“HLA polymorphisms associated with certain drugs have also been reported [1].”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Li X, Tang J, Mao Y. Incidence and risk factors of drug-induced liver injury. Liver Int. 2022;42:1999–2014 source

In the paper

“Prospective research conducted in the DILIN used a structured expert opinion process (SEOP) for causality assessment [62].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [62] Rockey DC, Seeff LB, Rochon J, et al. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the Roussel–Uclaf causality assessment method. Hepatology. 2010;51:2117–2126 source

In the paper

“However, due to various confounding factors in most retrospective cohorts, the risk of HBV or HCV infection remains in doubt.”

In the paper

“Although the exact mechanism of PA-HSOS remains known, the destruction of hepatic sinusoidal endothelial cells in the liver acinus by toxic metabolites of PA and long persistence of PA metabolites especially pyrrole protein adducts in vivo may play an important role in the toxicity [86][87][88].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [86] Wang Z, Han H, Wang C, et al. Hepatotoxicity of pyrrolizidine alkaloid compound intermedine: comparison with other pyrrolizidine alkaloids and its toxicological mechanism. Toxins (Basel). 2021;13:849 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [87] Yang X-Q, Ye J, Li X, Li Q, Song Y-H. Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis, treatment, and outcomes. World J Gastroenterol. 2019;25:3753–3763 source
• ?Not checked — no full text of the sourcecites [88] Chen Y, Xiong F, Wang W, et al. The long persistence of pyrrolizidine alkaloid-derived pyrrole-protein adducts in vivo: Kinetic study following multiple exposures of a pyrrolizidine alkaloid containing extract of Gynura japonica. Toxicol Lett. 2020;323:41–47 source

In the paper

“Another validated model incorporating the Model for End-Stage Liver Disease score, the serum albumin level, and the Charlson comorbidity index as parameters may be useful in predicting the 6-month risk of death in patients with DILI [71].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [71] Ghabril M, Gu J, Yoder L, et al. Development and validation of a model consisting of comorbidity burden to calculate risk of death within 6 months for patients with suspected drug-induced liver injury. Gastroenterology. 2019;157(5):1245–1252 source

In the paper

“There is insufficient evidence suggesting that currently reported drug-and host-related risk factors can increase all-cause susceptibility to iDILI [1,27].”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Li X, Tang J, Mao Y. Incidence and risk factors of drug-induced liver injury. Liver Int. 2022;42:1999–2014 source
• ?Not checked — no full text of the sourcecites [27] Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116:878–898 source

In the paper

“Recent studies suggest that liver biopsy can significantly affect the score of Roussel-Uclaf causality assessment method (RUCAM) [52].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [52] Ahmad J, Barnhart HX, Bonacini M, et al. Value of liver biopsy in the diagnosis of drug-induced liver injury. J Hepatol. 2022;76:1070–1078 source

In the paper

“Current evidence does not support the opinion that diabetes or obesity increase susceptibility to all-cause DILI [5], although they may increase the risk of liver injury induced by certain drugs such as tamoxifen and methotrexate [44,45].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [44] Bruno S, Maisonneuve P, Castellana P, et al. Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial. BMJ. 2005;330:932 source
• ?Not checked — no full text of the sourcecites [45] Rosenberg P, Urwitz H, Johannesson A, et al. Psoriasis patients with diabetes type 2 are at high risk of developing liver fibrosis during methotrexate treatment. J Hepatol. 2007;46:1111–1118 source

In the paper

“Approximately 7-24% of acute DILI cases can transition to chronic injury, which presents with signs of chronic DILI [3,5,21,24,25].”

What the sources say

• ?Not checked — no full text of the sourcecites [3] Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144(7):1419–1425 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [5] Andrade RJ, Lucena MI, Fernández MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129:512–521 source
• Not checked yetcites [21] Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340–1352 source

In the paper

“However, this method requires external validation from regions other than US and Spain since it was developed based on case data from Drug-Induced Liver Injury Network (DILIN) and the Spanish DILI Registry [61].”

What the sources say

• ?Not checked — no full text of the sourcecites [61] Hayashi PH, Lucena MI, Fontana RJ. RECAM: a new and improved, computerized causality assessment tool for DILI diagnosis. Am J Gastroenterol. 2022;117:1387–1389 source

In the paper

“Tetracycline is currently the only known drug to increase the risk of DILI development during pregnancy [43].”

What the sources say

• ?Not checked — no full text of the sourcecites [43] Kunelis CT, Peters JL, Edmondson HA. Fatty liver of pregnancy and its relationship to tetracycline therapy. Am J Med. 1965;38:359–377 source

In the paper

“Similarly, rifampin, a strong CYP inducer, has been demonstrated to increase the incidence of hepatotoxicity when administered together with isoniazid as an anti-TB treatment [36,37].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [36] Zhuang X, Li L, Liu T, et al. Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: a review. Front Pharmacol. 2022;13:1037814 source
• Not checked yetcites [37] Rifadin IV (rifampin for injection USP). [package insert]. 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050420s073,050627s012lbl.pdf. Accessed 31 Oct 2023

In the paper

“However, older age is associated with an increased risk of liver injury induced by isoniazid, amoxicillin-clavulanate, and nitrofurantoin [38][39][40].”

What the sources say

• ?Not checked — no full text of the sourcecites [38] Lucena MI, Sanabria J, García-Cortes M, Stephens C, Andrade RJ. Drug-induced liver injury in older people. Lancet Gastroenterol Hepatol. 2020;5:862–874 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [39] Gaude GS, Chaudhury A, Hattiholi J. Drug-induced hepatitis and the risk factors for liver injury in pulmonary tuberculosis patients. J Fam Med Prim Care. 2015;4:238–243 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [40] Weersink RA, Alvarez-Alvarez I, Medina-Cáliz I, et al. Clinical characteristics and outcome of drug-induced liver injury in the older patients: from the young-old to the oldest-old. Clin Pharmacol Ther. 2021;109:1147–1158 source

In the paper

“The actual incidence of HDS-DILI remains unclear because of the lack of high-quality epidemiologic data.”

In the paper

“Failure to recover from liver injury within 6 months after acute DILI suggests an increased risk of delayed recovery or chronic injury.”

In the paper

“Some patients may present with unexplained chronic liver injury, chronic hepatitis, or even cirrhosis at their first medical visit [78].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [78] Medina-Caliz I, Robles-Diaz M, Garcia-Muñoz B, et al. Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury. J Hepatol. 2016;65:532–542 source

In the paper

“In China, HMs such as Polygonum multiflorum, Tripterygium wilfordii, Dioscorea bulbifera, Cullen corylifolium, Senecio scandens, Epimedium, Gynura japonica, and their decoctions or patent medicines have been reported to potentially cause liver injury.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Online Resource 2

In the paper

“Therefore, there is insufficient evidence to suggest that an underlying liver disease increases the risk of all-cause DILI.”

In the paper

“Studies have shown that approximately 10% of cases that fulfill Hy's law will progress to ALF [5,64], and is associated increased mortality or need for liver transplantation [65][66][67][68].”

What the sources say

• ?Not checked — no full text of the sourcecites [65] Wang Y, Zou C, Wee A, et al. Comparison of the prognostic models for mortality in idiosyncratic drug-induced liver injury. Hepatol Int. 2023;17:488–498 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [66] Hayashi PH, Rockey DC, Fontana RJ, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017;66:1275–1285 source
• ?Not checked — no full text of the sourcecites [67] Ye J-H, Ho Y-F, On AWF, et al. Trends in reporting drug-associated liver injuries in Taiwan: a focus on amiodarone. Int J Clin Pharm. 2018;40:911–920 source

In the paper

“Current evidence does not support the opinion that diabetes or obesity increase susceptibility to all-cause DILI [5], although they may increase the risk of liver injury induced by certain drugs such as tamoxifen and methotrexate [44,45].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [5] Andrade RJ, Lucena MI, Fernández MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129:512–521 source

In the paper

“Concomitant drugs can modulate the metabolism of other drugs through induction, inhibition, or substrate competition, and particularly the CYP 450 reaction, thus affecting the individual risk of iDILI [35].”

What the sources say

• ?Not checked — no full text of the sourcecites [35] Yu K, Geng X, Chen M, et al. High daily dose and being a substrate of cytochrome P450 enzymes are two important predictors of drug-induced liver injury. Drug Metab Dispos. 2014;42:744–750 source

In the paper

“Older age, dyslipidemia, and acute episode severity are risk factors for chronic injury and delayed recovery [75].”

What the sources say

• ?Not checked — no full text of the sourcecites [75] Amacher DE, Chalasani N. Drug-induced hepatic steatosis. Semin Liver Dis. 2014;34:205–214 source

In the paper

“The in vivo formation of RM plays an important role in iDILI pathophysiology, and integration of RM into the new “rule-of-two” model can precisely predict the risk and severity of iDILI [31].”

What the sources say

• ?Not checked — no full text of the sourcecites [31] Chen M, Borlak J, Tong W. High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury. Hepatology. 2013;58:388–396 source

In the paper

“DILI patients with pre-existing liver disease have reported to demonstrate an increased risk of 6-month mortality at 4.5% in validation cohort and 8.5% in discovery cohort in a DILIN study [71].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [71] Ghabril M, Gu J, Yoder L, et al. Development and validation of a model consisting of comorbidity burden to calculate risk of death within 6 months for patients with suspected drug-induced liver injury. Gastroenterology. 2019;157(5):1245–1252 source

In the paper

“For example, in patients with Child-Pugh class B and decompensated cirrhosis (class C), the hepatotoxicity of protease inhibitors for hepatitis C and obeticholic acid for primary biliary cholangitis is significantly increased [107,108].”

What the sources say

• ?Not checked — no full text of the sourcecites [107] Hoofnagle JH. Hepatic decompensation during direct-acting antiviral therapy of chronic hepatitis C. J Hepatol. 2016;64:763–765 source
• Not checked yetcites [108] LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Obeticholic Acid. https://www.ncbi.nlm.nih.gov/books/NBK548806/. Accessed 10 Dec 2019.

In the paper

“However, female are more susceptible to minocycline-and nitrofurantoin-induced autoimmune hepatitis (AIH) than are male [41].”

What the sources say

• Not checked yetcites [41] Andrade RJ, Aithal GP, de Boer YS, et al. Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): an expert opinion meeting report. J Hepatol. 2023;79:853–866 source

In the paper

“HDS-DILI in Asia is mainly associated with HMs, termed HILI [59].”

What the sources say

• ?Not checked — no full text of the sourcecites [59] Devarbhavi H, Aithal G, Treeprasertsuk S, et al. Drug-induced liver injury: Asia Pacific Association of Study of liver consensus guidelines. Hepatol Int. 2021;15:258–282 source

In the paper

“Recently developed Drum Tower Severity Scoring (DTSS) system integrating the levels of ALT, TBil, fibrinogen, and peak portal vein velocity was reported to predict the outcome of anticoagulation therapy in PA-HSOS [92].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [92] Wang X, Zhang W, Zhang M, et al. Development of a Drum Tower Severity Scoring (DTSS) system for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Hepatol Int. 2022;16:669–679 source

In the paper

“It is important to note that the currently reported genetic polymorphisms (HLA or non-HLA) associated with an increased risk of drug-specific DILI may also be associated with certain physiologic or other diseases; thus, further validation is required before its clinical use.”

In the paper

“Study have shown that heavy alcohol consumption is not a risk factor for worse outcomes in iDILI [42].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [42] Dakhoul L, Ghabril M, Gu J, Navarro V, Chalasani N, Serrano J. Heavy consumption of alcohol is not associated with worse outcomes in patients with idiosyncratic drug-induced liver injury compared to non-drinkers. Clin Gastroenterol Hepatol. 2018;16:722–729 source

In the paper

“The original criteria of risk factors in RUCAM is removed in RECAM for lack of diagnostic value, so is competing medications to encourage assessment of each culprit drug.”

What the sources say

• Not checked yetcites [60] Hayashi PH, Lucena MI, Fontana RJ, et al. A revised electronic version of RUCAM for the diagnosis of DILI. Hepatology. 2022;76:18–31 source

In the paper

“Although there are some ambiguities regarding how to score certain sections as well as suboptimal reliability, RUCAM can provide systematic and framed guidance for the assessment of patients with suspected DILI and is the most widely used tool [26,27,51,59].”

What the sources say

• ?Not checked — no full text of the sourcecites [26] EASL Clinical Practice Guidelines. Drug-induced liver injury. J Hepatol. 2019;70:1222–1261 source
• ?Not checked — no full text of the sourcecites [27] Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116:878–898 source
• ?Not checked — no full text of the sourcecites [51] Drug-induced liver injury (DILI): current status and future directions for drug development and the post-market setting. A consensus by a CIOMS Working Group. Geneva, Switzerland: Council for International Organizations of Medical Sciences (CIOMS). 2020. https://cioms.ch/wp-content/uploads/2020/06/CIOMS_DILI_Web_16Jun2020.pdf. Accessed 1 Apr 2023 source
• ?Not checked — no full text of the sourcecites [59] Devarbhavi H, Aithal G, Treeprasertsuk S, et al. Drug-induced liver injury: Asia Pacific Association of Study of liver consensus guidelines. Hepatol Int. 2021;15:258–282 source

In the paper

“Although there are some ambiguities regarding how to score certain sections as well as suboptimal reliability, RUCAM can provide systematic and framed guidance for the assessment of patients with suspected DILI and is the most widely used tool [26,27,51,59].”

What the sources say

• ?Not checked — no full text of the sourcecites [26] EASL Clinical Practice Guidelines. Drug-induced liver injury. J Hepatol. 2019;70:1222–1261 source
• ?Not checked — no full text of the sourcecites [27] Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116:878–898 source
• ?Not checked — no full text of the sourcecites [51] Drug-induced liver injury (DILI): current status and future directions for drug development and the post-market setting. A consensus by a CIOMS Working Group. Geneva, Switzerland: Council for International Organizations of Medical Sciences (CIOMS). 2020. https://cioms.ch/wp-content/uploads/2020/06/CIOMS_DILI_Web_16Jun2020.pdf. Accessed 1 Apr 2023 source
• ?Not checked — no full text of the sourcecites [59] Devarbhavi H, Aithal G, Treeprasertsuk S, et al. Drug-induced liver injury: Asia Pacific Association of Study of liver consensus guidelines. Hepatol Int. 2021;15:258–282 source

In the paper

“Patients with cholestasis have a higher risk of chronicity or delayed recovery.”

In the paper

“In China, vascular liver diseases such as HSOS and hepatic vein occlusive disease (caused by the consumption of plants containing pyrrolizidine alkaloids [PA] such as Gynura segetum) are common [85].”

What the sources say

• Not checked yetcites [85] Hepatobiliary Cooperative Group of Chinese Society of Gastroenterology. Expert consensus on diagnosis and treatment of pyrrolidine alkaloids-related sinusoidal obstruction syndrome (2017, Nanjing). Zhong Hua Xiao Hua Za Zhi. 2017;513–22.

In the paper

“Although some methods have been reported to assess causality in adverse drug reactions, including DILI, the value of non-liver-specific methods are limited [55,56].”

What the sources say

• ?Not checked — no full text of the sourcecites [55] García-Cortés M, Lucena MI, Pachkoria K, Borraz Y, Hidalgo R, Andrade RJ. Evaluation of naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury. Aliment Pharmacol Ther. 2008;27:780–789 source
• ?Not checked — no full text of the sourcecites [56] Lucena MI, Camargo R, Andrade RJ, Perez-Sanchez CJ, De La Cuesta FS. Comparison of two clinical scales for causality assessment in hepatotoxicity. Hepatology. 2001;33:123–130 source

In the paper

“A drug with high lipophilicity (log of octanol-water partition coefficient, LogP > 3) and daily dose > 100 mg, referred to as the “ruleof-two,” may be associated with an increased risk of iDILI [31].”

What the sources say

• ?Not checked — no full text of the sourcecites [31] Chen M, Borlak J, Tong W. High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury. Hepatology. 2013;58:388–396 source

In the paper

“The ALF study group models based on etiology and coma severity can predict transplantfree survival in ALF [69].”

What the sources say

• Not checked yetcites [69] Koch DG, Tillman H, Durkalski V, Lee WM, Reuben A. Development of a model to predict transplant-free survival of patients with acute liver failure. Clin Gastroenterol Hepatol. 2016;14:1199–1206 source

In the paper

“Hepatotoxicity of cyclosporin A, bosentan, troglitazone, and imatinib are probably associated with inhibition of BSEP function [32][33][34].”

What the sources say

• ?Not checked — no full text of the sourcecites [32] Aleo MD, Luo Y, Swiss R, Bonin PD, Potter DM, Will Y. Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump. Hepatology. 2014;60:1015–1022 source
• ?Not checked — no full text of the sourcecites [33] Tazuma S. Cyclosporin A and cholestasis: Its mechanism(s) and clinical relevancy. Hepatol Res. 2006;34:135–136 source
• ?Not checked — no full text of the sourcecites [34] Morgan RE, Trauner M, van Staden CJ, et al. Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010;118:485–500 source

In the paper

“A recent genome-wide association study suggested that a missense variant (rs2476601) in protein tyrosine phosphatase non-receptor type 22 can increase the risk of liver injury induced by various drugs (e.g., amoxicillin-clavulanate, terbinafine, flucloxacillin, and haloperidol) [48].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [48] Cirulli ET, Nicoletti P, Abramson K, et al. A missense variant in PTPN22 is a risk factor for drug-induced liver injury. Gastroenterology. 2019;156(6):1707–1716 source

In the paper

“Pyrrole protein adducts detected in the patient's blood have a retrospective significance for diagnosis [91].”

What the sources say

• Not checked yetcites [91] Gao H, Ruan JQ, Chen J, et al. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome. Drug Des Dev Ther. 2015;9:4861–4868 source

In the paper

“The in vivo formation of RM plays an important role in iDILI pathophysiology, and integration of RM into the new “rule-of-two” model can precisely predict the risk and severity of iDILI [31].”

What the sources say

• ?Not checked — no full text of the sourcecites [31] Chen M, Borlak J, Tong W. High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury. Hepatology. 2013;58:388–396 source

In the paper

“High lipophilicity of a drug may increase the risk of iDILI [30].”

What the sources say

• ?Not checked — no full text of the sourcecites [30] Hughes JD, Blagg J, Price DA, et al. Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett. 2008;18:4872–4875 source

In the paper

“DILI with pre-existing liver disease is not rare because of the high global prevalence of non-alcoholic fatty liver disease (NAFLD) and the heavy burden of hepatitis B virus (HBV) infection and NAFLD in China [21].”

What the sources say

• Not checked yetcites [21] Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340–1352 source

In the paper

“For instance, during anti-infection therapy with vancomycin and anti-epileptic treatment with lamotrigine, standardized therapeutic drug monitoring can reduce the toxicity caused by the irrational use of medication [220].”

What the sources say

• ?Not checked — no full text of the sourcecites [220] He N, Su S, Ye Z, et al. Evidence-based guideline for therapeutic drug monitoring of vancomycin: 2020 update by the division of therapeutic drug monitoring. Chin Pharmacol Soc Clin Infect Dis. 2020;71:S363–S371 source

In the paper

“Cases fulfilling Hy's law in clinical trials have both predictive and prognostic value for the risk of hepatotoxicity associated with new drugs.”

What the sources say

• Not checked yetcites [183] U.S. Department of Health and Human Services FDA, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for Industry. Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 2009. https://www.fda.gov/media/116737/download.

In the paper

“In China, AT-DILI accounted for 22-31.3% of the investigated cases of DILI [119].”

What the sources say

• ?Not checked — no full text of the sourcecites [119] Zhou Y, Yang L, Liao Z, He X, Zhou Y, Guo H. Epidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese literature including 21,789 patients. Eur J Gastroenterol Hepatol. 2013;25:825–829 source

In the paper

“Therefore, the RUCAM score may show reduced reliability in the causality assessment of suspected HDS-DILI or HILI [27].”

What the sources say

• ?Not checked — no full text of the sourcecites [27] Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116:878–898 source

In the paper

“The incidence of ICI-related hepatitis depends on the class of drugs, dose, and whether they are used as monotherapy or combination therapy [152,153].”

What the sources say

• ?Not checked — no full text of the sourcecites [152] Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity from immune checkpoint inhibitors: a systematic review and management recommendation. Hepatology. 2020;72:315–329 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [153] Lei XH, Tang YY, Li J, Mao YM. Hepatotoxicity associated with tumor immune checkpoint inhibitors. (Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi) Chin J Hepatol. 2020;28:175–178 source

In the paper

“the severity grading of liver injury caused by antineoplastic drugs is usually based on a single liver biochemical marker according to the Common Terminology Criteria for Adverse Events in clinical trials of antineoplastic drugs [173]”

What the sources say

• Not checked yetcites [173] US Department Of Health And Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. 2009. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed 1 Apr 2023

In the paper

“High mobility group box 1, a damage-associated molecular pattern molecule, has been reported to be associated with the pathogenesis of DILI [176].”

What the sources say

• ?Not checked — no full text of the sourcecites [176] Clarke JI, Dear JW, Antoine DJ. Recent advances in biomarkers and therapeutic interventions for hepatic drug safety—false dawn or new horizon? Expert Opin Drug Saf. 2016;15:625–634 source

In the paper

“Antineoplastic agents are important causes of DILI.”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Li X, Tang J, Mao Y. Incidence and risk factors of drug-induced liver injury. Liver Int. 2022;42:1999–2014 source

In the paper

“Most patients present with hepatocellular ICI-related hepatitis, which is characterized by a significant elevation in ALT or AST levels [155]”

What the sources say

• ?Not checked — no full text of the sourcecites [155] De Martin E, Michot J-M, Papouin B, et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol. 2018;68:1181–1190 source

In the paper

“Studies have suggested that an artificial liver (e.g., plasma replacement therapy or a double plasma molecular absorption system) may improve transplant-free survival [218].”

What the sources say

• ?Not checked — no full text of the sourcecites [218] Larsen FS, Schmidt LE, Bernsmeier C, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol. 2016;64:69–78 source

In the paper

“Therefore, liver transplantation is currently the most effective treatment for patients with DI-ALF and ACLF.”

In the paper

“Its potential value in confirming or excluding hepatocellular injury in cases of elevated ALT levels from a suspected extrahepatic origin (e.g., muscle) has been evaluated [26,175].”

What the sources say

• ?Not checked — no full text of the sourcecites [26] EASL Clinical Practice Guidelines. Drug-induced liver injury. J Hepatol. 2019;70:1222–1261 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [175] McGill MR, Staggs VS, Sharpe MR, Lee WM, Jaeschke H. Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome. Hepatology. 2014;60:1336–1345 source

In the paper

“However, ICI-related hepatotoxicity is an indirect form of DILI [22,152].”

What the sources say

• ?Not checked — no full text of the sourcecites [22] Hoofnagle JH, Björnsson ES. Drug-induced liver injury—types and phenotypes. N Engl J Med. 2019;381:264–273 source
• ?Not checked — no full text of the sourcecites [152] Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity from immune checkpoint inhibitors: a systematic review and management recommendation. Hepatology. 2020;72:315–329 source

In the paper

“Studies suggest that indicators of impaired liver function such as TBil, INR, and albumin are more severe in patients with AT-DILI than in those with DILI caused by other drugs [138]; however, additional studies are needed for validation.”

What the sources say

• ?Not checked — no full text of the sourcecites [138] Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105:2396–2404 source

In the paper

“patients may present with ICIrelated cholangitis characterized by a significant elevation in ALP or GGT levels [156].”

What the sources say

• ?Not checked — no full text of the sourcecites [156] Yildirim S, Deniz K, Doğan E, Başkol M, Gürsoy Ş, Özkan M. Ipilimumab-associated cholestatic hepatitis: a case report and literature review. Melanoma Res. 2017;27:380–382 source

In the paper

“ICI-related hepatotoxicity usually occurs in the first 4-12 weeks or after the administration of 1-3 doses [154].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [154] Suzman DL, Pelosof L, Rosenberg A, Avigan MI. Hepatotoxicity of immune checkpoint inhibitors: an evolving picture of risk associated with a vital class of immunotherapy agents. Liver Int. 2018;38:976–987 source

In the paper

“patients who do not develop liver injury with the previous regimen and develop liver injury after the administration of the latter regimen have an increased likelihood of the latter causing DILI.”

In the paper

“A small number of patients may present with a specific clinical phenotype, such as nodular regenerative hyperplasia [157].”

What the sources say

• ?Not checked — no full text of the sourcecites [157] LoPiccolo J, Brener MI, Oshima K, Lipson EJ, Hamilton JP. Nodular regenerative hyperplasia associated with immune checkpoint blockade. Hepatology. 2018;68:2431–2433 source

In the paper

“It has been shown to promote ALT and AST normalization in patients with acute DILI when administrated intravenously 200 mg/ day for at least 2 weeks [194].”

What the sources say

• ?Not checked — no full text of the sourcecites [194] Wang Y, Wang Z, Gao M, et al. Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug-induced liver injury: a phase II trial. Liver Int. 2019;39:2102–2111 source

In the paper

“However, the exact efficacy remains to be confirmed by a high-level of evidence [196].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [196] Niu H, Sanabria-Cabrera J, Alvarez-Alvarez I, et al. Prevention and management of idiosyncratic drug-induced liver injury: systematic review and meta-analysis of randomised clinical trials. Pharmacol Res. 2021;164: 105404 source

In the paper

“The RUCAM score, combined with expert opinion, may be the best current practical causality assessment method for establishing a diagnosis of HDS-DILI or HILI [27,59].”

What the sources say

• ?Not checked — no full text of the sourcecites [27] Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116:878–898 source
• ?Not checked — no full text of the sourcecites [59] Devarbhavi H, Aithal G, Treeprasertsuk S, et al. Drug-induced liver injury: Asia Pacific Association of Study of liver consensus guidelines. Hepatol Int. 2021;15:258–282 source

In the paper

“More than half of patients with ICI-related hepatotoxicity have extrahepatic immune-related adverse events (irAEs) [158]”

What the sources say

• ?Not checked — no full text of the sourcecites [158] Huffman BM, Kottschade LA, Kamath PS, Markovic SN. Hepatotoxicity after immune checkpoint inhibitor therapy in melanoma: natural progression and management. Am J Clin Oncol. 2018;41:760–765 source

In the paper

“Although rare, ALF may occur in 0.1-0.2% of patients [159][160][161][162].”

What the sources say

• Not checked yetcites [159] Yervoy (Ipilimumab) Prescribing Information. 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125377s073lbl.pdf. Accessed 1 Apr 2023
• Not checked yetcites [160] Imfinzi (Durvalumab) Prescribing Information. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761069s018lbl.pdf. Accessed 1 Apr 2023
• Not checked yetcites [161] Tecentriq (Atezolizumab) Prescribing Information. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761034s042lbl.pdf. Accessed 1 Apr 2023
• Not checked yetcites [162] Bavencio (Avelumab) Prescribing Information. 2019. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761049s006lbl.pdf. Accessed 1 Apr 2023

In the paper

“A more definite sign of severe hepatotoxicity is the presence of elevated liver enzyme levels accompanied by elevated TBil levels after drug administration [183].”

What the sources say

• Not checked yetcites [183] U.S. Department of Health and Human Services FDA, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for Industry. Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 2009. https://www.fda.gov/media/116737/download.

In the paper

“For instance, during anti-infection therapy with vancomycin and anti-epileptic treatment with lamotrigine, standardized therapeutic drug monitoring can reduce the toxicity caused by the irrational use of medication [220].”

What the sources say

• ?Not checked — no full text of the sourcecites [220] He N, Su S, Ye Z, et al. Evidence-based guideline for therapeutic drug monitoring of vancomycin: 2020 update by the division of therapeutic drug monitoring. Chin Pharmacol Soc Clin Infect Dis. 2020;71:S363–S371 source

In the paper

“The integrated evidence-chain method [136] emphasizes excluding concomitant chemical drugs and sourcing the suspected herb, which is theoretically helpful in defining HDS-DILI or HILI.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [136] China State Drug Administration. Technical guidelines for clinical evaluation of liver injury induced by traditional Chinese medicine. Lin Chuang Gan Dan Bing Za Zhi 2018;34:1403–9

In the paper

“Cytokeratin 18, macrophage colonystimulating factor receptor 1, and osteopontin have also been identified as DILI biomarkers that predict a poor prognosis [177].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [177] Church RJ, Kullak-Ublick GA, Aubrecht J, et al. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: an international collaborative effort. Hepatology. 2019;69:760–773 source

In the paper

“a low titer of anti-nuclear antibody may be detected in a small number of patients [155].”

What the sources say

• ?Not checked — no full text of the sourcecites [155] De Martin E, Michot J-M, Papouin B, et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol. 2018;68:1181–1190 source

In the paper

“several potential biomarkers associated with the risk of liver injury caused by specific drugs or HMs have been reported, such as HLA-B*35:01, immune factors, and metabolic markers that may be associated with the risk of Polygonum multiflorum-induced liver injury [178][179][180].”

What the sources say

• ?Not checked — no full text of the sourcecites [178] Li C, Rao T, Chen X, et al. HLA-B*35:01 allele is a potential biomarker for predicting polygonum multiflorum-induced liver injury in humans. Hepatology. 2019;70:346–357 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [179] Tu C, Niu M, Wei A-W, et al. Susceptibility-related cytokine panel for prediction of polygonum multiflorum-induced hepatotoxicity in humans. J Inflamm Res. 2021;14:645–655 source
• ?Not checked — no full text of the sourcecites [180] Zhang L, Niu M, Wei A-W, et al. Risk profiling using metabolomic characteristics for susceptible individuals of drug-induced liver injury caused by polygonum multiflorum. Arch Toxicol. 2020;94:245–256 source

In the paper

“and some present with cholestatic or mixed type.”

What the sources say

• ?Not checked — no full text of the sourcecites [155] De Martin E, Michot J-M, Papouin B, et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol. 2018;68:1181–1190 source

In the paper

“Finding one to two such cases in clinical trials is considered highly predictive that the drug has a higher risk of causing ALF when administered to a larger population.”

What the sources say

• Not checked yetcites [183] U.S. Department of Health and Human Services FDA, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for Industry. Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 2009. https://www.fda.gov/media/116737/download.

In the paper

“The conventional use of corticosteroids for DILI is not supported by a high-level of evidence.”

In the paper

“The presence of irAEs in other organs may also contribute to the diagnosis of ICI-related hepatotoxicity.”

In the paper

“The incidence of any grade of ICI-related hepatitis is usually < 10% with monotherapy”

What the sources say

• ?Not checked — no full text of the sourcecites [152] Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity from immune checkpoint inhibitors: a systematic review and management recommendation. Hepatology. 2020;72:315–329 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [153] Lei XH, Tang YY, Li J, Mao YM. Hepatotoxicity associated with tumor immune checkpoint inhibitors. (Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi) Chin J Hepatol. 2020;28:175–178 source