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Essential elements necessary for meaningful publication and interpretation of reports of drug induced liver injury

Minimal Elements for Diagnosis and Publication of Cases of
Drug-Induced Liver Injury
Vijay K. Agarwal, MD,1 John G. McHutchison, MD,1 and Jay H. Hoofnagle, MD2 for the Drug-Induced Liver Injury Network (DILIN) 1Duke Clinical Research Institute and Duke University Medical Center, Durham, North Carolina, and 2 Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Keywords: acute liver failure, adverse drug reaction reporting systems, case reports,

Address for correspondence: Dr. John McHutchison, Duke Clinical Research Institute, Duke
University Medical Center, PO Box 17969, Durham, NC 27715. Phone: 919-668-7177. Fax: Coauthor e-mail addresses:
Minimal Elements for Reporting Drug-Induced Liver Injury Abbreviations: ALT, alanine aminotransferase; ANA, antinuclear antibody; AP, alkaline
phosphatase; CT, computerized tomography; DILI, drug-induced liver injury; ERCP, endoscopic retrograde cholangiopancreatography; HAV, hepatitis A virus; HBc, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; INR, international normalized ratio; MR, magnetic resonance; MRCP, magnetic resonance cholangiopancreatography; PT, Financial support: Funding for the DILIN network is provided by the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) under cooperative agreements: 1U01DK065201, 1U01DK065193, 1U01DK065184, 1U01DK065211, 1U01DK065238 and Potential Conflicts of Interest. Drs. Hoofnagle and Agarwal report no potential conflicts of
interest; Dr. McHutchison has received research support and acted as a scientific adviser for GlaxoSmithKline and Merck & Co., Inc. Acknowledgements: The authors thank Dr. James Rochon for conducting the statistical
Minimal Elements for Reporting Drug-Induced Liver Injury Abstract
Drug-induced liver disease is the single leading cause of acute liver failure in the United States. Accurate reporting of drug-induced liver injury is essential for early detection of hepatotoxicity and for developing a body of reliable, interpretable literature. We assessed the extent to which published case reports of drug-induced liver disease include sufficient clinical data for interpreting the cause of toxicity. We developed a list of 42 predetermined, specific minimal elements considered necessary in diagnosing and evaluating causality of drug-induced liver injury. A total of 97 published case reports or case series on hepatoxicity of 6 drugs (from 3 classes) were examined: amoxicillin/clavulanic acid (n=35), troglitazone (n=32), rosiglitazone (n=10), pioglitazone (n=8), zafirlukast (n=8), and montelukast (n=4). Some elements, such as patient age, sex, primary disease, and drug name, were reported in most if not all published case reports. However, many elements were under-reported. Some publications did not mention initial bilirubin levels (12%), many did not provide initial alkaline phosphatase levels (58%), and others gave vague descriptions of how other diagnoses were excluded ("tests for hepatitis A, B, and C were negative"). Data regarding serial liver test abnormalities were frequently absent. In the aggregate of cases, exclusion of other competing viral etiology was recorded less than half the time. Conclusion: Reports of drug-induced liver disease are often lacking in data needed for determining the cause of adverse effects. Efforts to promote and include a listing of essential elements in journal articles could significantly enhance the quality and clinical utility of published case reports of drug toxicity. Minimal Elements for Reporting Drug-Induced Liver Injury Drug-induced hepatotoxicity represents a significant proportion of acute liver disease cases (1) and is the single leading cause of acute liver failure in the United States (2). Drug- induced liver injury can be caused by an array of prescription medications, as well as herbal and dietary supplements (3). Accurate reporting of drug-induced liver disease is important for the early detection and awareness of drug-induced hepatotoxicity as well as for developing a prospective body of reliable, interpretable literature for agents that cause idiosyncratic hepatic injury. Published case reports that describe adverse events can provide significant clinical insight, especially for rare events that might not be detected in clinical trials. These reports can also increase awareness of issues possibly associated with a drug early in its development and use, which can thereby prompt further investigation. However, many publications or reports of drug- induced liver disease lack important or essential details for interpreting whether such episodes can be causally assigned to a specific drug or combination of drugs. In 1984, professionals interested in adverse drug events and editors of major medical journals met under the auspices of the Council for International Organizations of Medical Sciences and proposed guidelines for editors to adopt when reviewing adverse event reports submitted for publication (4). However, a descriptive analysis published in 2003 suggested that many major medical journals still have only minimal requirements for publishing adverse event reports, and some have none at all (5). To explore the extent to which published case reports include clinically relevant data, we created a list of predetermined, specific minimal elements that should be detailed in case reports of drug-induced liver injury. Then we examined individual case reports involving 6 specific drugs from 3 different classes to determine the frequency for Minimal Elements for Reporting Drug-Induced Liver Injury Experimental Procedures
Minimal Elements
As a part of the ongoing development and design of the Drug Induced Liver Injury Network (DILIN) (6), a list was developed of 18 elements that were considered necessary for diagnosis and adequate assessment of causality (Table 1). Many of these elements are required to complete the RUCAM causality assessment form (6-8). The elements included details of patient's age and sex, time of starting and stopping the implicated medication, the time of onset of symptoms and jaundice and results of laboratory tests at the onset of injury through the time to recovery. Other important elements related to exclusion of other causes of acute liver injury including viral hepatitis, other medications, autoimmune liver disease, biliary obstruction, Review of Case Reports
From the list of 18 elements, a check list of 42 components of the "minimal" elements was developed to be used to assess published case reports or case series of drug-induced liver disease. A total of 97 publications were reviewed, related to one of 6 specific drugs: amoxicillin/clavulanic acid (n = 35, 1992-2007) (9-17), troglitazone (n= 32, 1998-2008) (18- 35), rosiglitazone (n = 10, 2000-2008) (36-45), pioglitazone (n = 8, 2001-2007) (46-53), zafirlukast (n = 8, 2000-2002) (54-59), or montelukast (n = 4, 2003-2007) (60-63). Two of these drugs (amoxicillin/clavulanic acid and troglitazone) were chosen as examples of well- known causes of clinically apparent drug-induced liver disease. The other four were chosen as examples of agents that rarely cause liver injury but for which case reports have been important in documenting their potential for hepatotoxicity. Articles published before 1992 were not included because they predated availability of hepatitis C tests and advanced imaging techniques. Minimal Elements for Reporting Drug-Induced Liver Injury Each publication was assessed by two of the authors (VKA and JGM) independently for whether the 42 components were accurately recorded and included for each case in each publication (if there were multiple cases described). Elements were only recorded if they were described in the actual case report. Vague terminology such as "viral screen negative" was not considered Type of publication:
Each publication was also categorized by whether it was a single case report (n=23), a brief communication (n =7), a small case series (n= 46) or a letter to the editor (n=21). Finally each publication was categorized by type of journal in which it was published: major internal medicine journal (n =20), gastroenterology and liver subspeciality journal (n=49) and other (n = 28). The rates of including the minimal elements were assessed by these categories of type of Statistics:
Individual and aggregate drug data were summarized using simple descriptive statistics including medians and percents. Two-group comparisons were performed using the Wilcoxon- Mann-Whitney test; the Kruskal-Wallis test was applied for multi-group comparisons. All statistical analyses were performed using SAS version 9.1. Minimal Elements for Reporting Drug-Induced Liver Injury While some elements, such as patient age, sex, primary disease, and drug name, were reported in most if not all published reports, many elements were under-reported. The rates of reporting each of the 42 elements by implicated drug are shown in Table 2 and the ten most- and ten least-reported elements are shown in Table 3. No case report included all 42 elements. The percent missing elements in individual publications ranged from 9% to 81% with a median of 48%. Twelve percent of publications did not mention initial bilirubin levels; many did not provide initial alkaline phosphatase levels (58%), and others gave vague descriptions of how other diagnoses were excluded ("tests for hepatitis A, B, and C were negative"). Data regarding serial liver test abnormalities were often absent. In the aggregate of cases, exclusion of other competing viral etiology was recorded less than half the time (Figure 1). Overall, the trend of reporting was different for different classes of drugs (Figures 2-4). Serial labs were reported more frequently for events associated with the thiazolidinediones (ALT, 44%; alkaline phosphatase, 32%; bilirubin, 52%) than with leukotriene receptor antagonists (ALT, 25%; alkaline phosphatase, 17%; bilirubin, 25%), or with amoxicillin/clavulanic acid (ALT, 9%; alkaline phosphatase, 17%; bilirubin, 17%). Testing for viral hepatitis and liver imaging was done more often in toxicity cases reported with thiazolidinediones than leukotriene receptor antagonists. For cases involving amoxicillin/clavulanic acid, the frequency of performing individual hepatitis tests varied greatly, with IgM anti-HAV reported in 71% of cases and HBsAg reported in 26% of cases. Concomitant diseases were infrequently reported with amoxicillin/clavulanic acid (11%) and leukotriene receptor antagonists (33%) but more Minimal Elements for Reporting Drug-Induced Liver Injury The median percent of missing elements varied from 44% for the thiazolidinediones to 48% for amoxicillin/clavulanic acid and 49% for the leukotriene receptor antagonists (p = 0.34). No significant difference was observed by journal types, with median percent missing elements of 50% for major internal medicine journals, 48% for gastroenterology and liver subspeciality journals and 45% in other types (p = 0.23). However, there were significant differences by publication type (p < 0.001), with significantly fewer missing elements in single case reports (median = 33%) than in letters to the editor (median = 50%, p < 0.001) and small case series (median = 48%, p < 0.001); the comparison against brief communications reports (median = 43%) just failing to reach statistical significance (p = 0.07). No other pairwise comparisons by type of publication were statistically significant. Minimal Elements for Reporting Drug-Induced Liver Injury Discussion
In this analysis of 97 published case reports that attributed liver injury to a specific drug, all were lacking in at least some information important in determining the cause of the injury. Several publications did not contain information regarding important laboratory data, such as bilirubin or alkaline phosphatase levels. Even more common was a lack of specific information on testing for excluding viral hepatitis. The list of elements assessed in this study was considered the minimal required for an accurate assessment of causality in drug-induced liver disease. Thus, knowledge of the latency between the starting of the medication and onset of injury is essential in assessing the likelihood that the liver injury is due to the specific drug (8). Furthermore, the onset of injury needs to be defined as either date of onset of first symptoms, appearance of jaundice (or dark urine), or first abnormal laboratory tests found (which may occur days or weeks after actual onset). Identification of the pattern of liver injury (whether hepatocellular, cholestatic, or mixed) requires knowledge of serum ALT and alkaline phosphatase levels (and the upper limits of their normal range) at the onset of injury. Assessment of the severity of the injury requires knowledge of the peak serum bilirubin and prothrombin time or INR (6). Finally, assessment of causality in drug-induced liver injury requires information about "dechallenge" and the time to resolution after the medication is stopped, usually based upon serial laboratory tests for ALT, alkaline phosphatase, or bilirubin (4-8). Yet, these results were provided in less than half of published Drug-induced liver injury is a diagnosis of exclusion, and important conditions to exclude are hepatitis A, B, and C, alcoholic liver disease, biliary obstruction, and liver injury due to ischemia or other medications. Thus, minimal elements in presenting cases of drug-induced liver Minimal Elements for Reporting Drug-Induced Liver Injury injury should carefully define tests or elements in the clinical history for excluding these diagnoses. Indeed, in some situations other laboratory tests beyond what was considered minimal would be helpful, such as results of assays for anti-HEV to exclude hepatitis E, tests for lactate dehydrogenase and creatine kinase to exclude ischemic hepatitis, or ERCP (endoscopic retrograde cholangiopancreatography) or MRCP (magnetic resonance cholangio- pancreatography) to fully exclude biliary obstruction. Of course, an important other cause of liver injury is another medication or herbal being taken, which may have not been considered or mentioned. In this regard, testing for acetaminophen levels or adducts may be important to document the absence of a contribution by unintentional overdose of acetaminophen, particularly in patients with severe hepatocellular injury of sudden onset. The percentage of missing elements did not appear to vary by drug class or journal type but was less for single case studies as compared to letters to the editor and small case series. These differences are not unexpected, as single case reports are more focused and likely to report more relevant elements than case series or letters to the editor which may have strict limitations In some instances the lack of reporting of critical elements in publications may have been because the results were normal or negative and therefore just not mentioned. Yet negative results can be important. Features that are sometimes absent but are important in diagnosis include absence of fever, rash, or eosinophilia. More commonly, a lack of elements may be due to the fact that they were not done or not available. This lack should also be mentioned in reporting instances of drug-induced liver injury, as the information can be important in assessing the likelihood that the injury was due to the medication. Thus, the lack of pre-treatment levels of laboratory tests, the fact that some diagnostic tests were not done (such as HCV RNA, imaging Minimal Elements for Reporting Drug-Induced Liver Injury of the biliary tree or liver biopsy), or the absence of follow-up laboratory tests are important in These results support the need for a more standardized approach to the reporting of drug- induced liver injury. Perhaps most helpful would be a checklist of minimal elements that are considered essential for diagnosis and causality assessment of any cases of drug-induced liver injury. Also useful would be a secondary list of elements that are helpful in many situations, but are not always essential. Although similar standards were suggested by medical professionals and journal editors in 1985 (4), the suggestions were not adopted for widespread use (5). Yet, in the more than 20 years since then, the proliferation of the World Wide Web has made sharing of such guidelines potentially much easier. Publishing guidelines that have been adopted for widespread use include those developed by the CONSORT Group (http://www.consort- statement.org/) for reporting results of randomized clinical trials. The CONSORT Statement comprises a 22-item checklist, which is used for detailing design and conduct of a trial, and a flow diagram, which is used to display the progress of participants through a trial. The CONSORT Statement is easily accessible online, and adherence to it is currently required by many peer-reviewed journals. The minimal elements for case reports of hepatotoxicity could be posted on a publicly funded Web site, such as the National Library of Medicine (http://www.nlm.nih.gov/), with the goal that they would ultimately be adopted by journal editors Similar lists of minimal elements might be developed for other types of adverse drug reactions, such as cardiovascular events or renal toxicity. Many of the items on our list, such as dates of starting and stopping therapy and whether a re-challenge was performed, would be relevant for other suspected drug-associated reactions. Minimal Elements for Reporting Drug-Induced Liver Injury In conclusion, reports of drug-induced liver injury are generally lacking in data needed for determining the cause of adverse effects. Efforts to promote and include a listing of essential elements in journal articles could significantly enhance the quality and clinical utility of published case reports of drug toxicity. Minimal Elements for Reporting Drug-Induced Liver Injury REFERENCES
Galan MV, Potts JA, Silverman AL, Gordon SC. The burden of acute nonfulminant drug- induced hepatitis in a United States tertiary referral center. J Clin Gastroenterol 2005; Lee WM. Acute liver failure in the United States. Semin Liver Dis 2003; 23:217-226. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135:1924-1934. Venulet J. Informativity of adverse reactions data in medical publications. Drug Inf J Kelly WN. The quality of published adverse drug event reports. Ann Pharmacother 2003; Fontana RJ, Watkins PB, Bonkovsky HL, Chalasani N, Davern T, Serrano J, Rochon J for the DILIN Study Group. Drug-induced liver injury network (DILIN) prospective study: rationale, design and conduct. Drug Saf 2009; 32: 55-68. Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol 1990; 11:272-276. Amoxicillin-clavulanic acid-induced hepatitis. Am J Otolaryngol 2007; Minimal Elements for Reporting Drug-Induced Liver Injury Fontana RJ, Shakil AO, Greenson JK, Boyd I, Lee WM. Acute liver failure due to amoxicillin and amoxicillin/clavulanate. Dig Dis Sci 2005; 50:1785-1790. Andrade RJ, Lucena MI, Fernández MC, Vega JL, Camargo R. Hepatotoxicity in patients with cirrhosis, an often unrecognized problem: lessons from a fatal case related to amoxicillin/clavulanic acid. Dig Dis Sci 2001; 46:1416-1419. Rapidly progressive cholestasis: An unusual reaction to amoxicillin/clavulanic acid therapy in a child. J Pediatr 2000; 136:121-123. amoxicillin/clavulanic acid-related hepatotoxicity. Am J Gastroenterol 1998; 93:1363- amoxycillin/clavulanic acid (Augmentin). J Hepatol 1995; 23:278-282. Hautekeete ML, Brenard R, Horsmans Y, Henrion J, Verbist L, Derue G, et al. Liver injury related to amoxycillin-clavulanic acid: interlobular bile-duct lesions and extrahepatic manifestations. J Hepatol 1995; 22:71-77. amoxycillin-clavulanic acid combination. Clin Investig 1994; 72:616-618. Hepatitis associated with amoxycillin-clavulanic acid combination report of 15 cases. Gut Julie NL, Julie IM, Kende AI, Wilson GL. Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from troglitazone. Diabetologia 2008; 51:2108-2016. Minimal Elements for Reporting Drug-Induced Liver Injury Caldwell SH, Hespenheide EE, von Borstel RW. Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin. Dig Dis Sci 2001; Menon KVN, Angulo P, Lindor KD.Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus. Am J Gastroenterology Chaudhary MU, Simmons DL. Case of the month. Hepatic and renal failure in a patient taking troglitazone and metformin. J Ark Med Soc 2001; 98:16-19. Prendergast KA, Berg CL, Wisniewski R. Troglitazone-associated hepatotoxicity treated successfully with steroids. Ann Intern Med 2000; 133:751. Schiano T, Dolehide K, Hart J, Baker AL. Severe but reversible hepatitis induced by troglitazone. Dig Dis Sci 2000; 45:1039-1042. Li H, Heller DS, Leevy CB, Zierer KG, Klein KM. Troglitazone-induced fulminant hepatitis: report of a case with autopsy findings. J Diabetes Complications 2000; 14:175- Jagannath S, Rai R. Rapid-onset subfulminant liver failure associated with troglitazone. Kohlroser J, Mathai J, Reichheld J, Banner BF, Bonkovsky HL. Hepatotoxicity due to troglitazone: report of two cases and review of adverse events reported to the United States Food and Drug Administration. Am J Gastroenterol 2000; 95:272-276. Murphy EJ, Davern TJ, Shakil AO, Shick L, Masharani U, Chow H, et al. Troglitazone- induced fulminant hepatic failure. Acute Liver Failure Study Group. Dig Dis Sci 2000; Minimal Elements for Reporting Drug-Induced Liver Injury Fukano M, Amano S, Sato J, Yamamoto K, Adachi H, Okabe H, et al. Subacute hepatic failure associated with a new antidiabetic agent, troglitazone: a case report with autopsy examination. Hum Pathol 2000; 31:250-253. Malik AH, Prasad P, Saboorian MH, Thiele DL, Malet PF. Hepatic injury due to troglitazone. Dig Dis Sci 2000; 45:210-214. Bell DS, Ovalle F. Late-onset troglitazone-induced hepatic dysfunction. Diabetes Care Herrine SK, Choudhary C. Severe hepatotoxicity associated with troglitazone. Ann Intern Vella A, de Groen PC, Dinneen SF. Fatal hepatotoxicity associated with troglitazone. Shibuya A, Watanabe M, Fujita Y, Saigenji K, Kuwao S, Takahashi H, et al. An autopsy case of troglitazone-induced fulminant hepatitis. Diabetes Care 1998; 21:2140-2143. Neuschwander-Tetri BA, Isley WL, Oki JC, Ramrakhiani S, Quiason SG, Phillips NJ, et al. Troglitazone-induced hepatic failure leading to liver transplantation. A case report. Gitlin N, Julie NL, Spurr CL, Lim KN, Juarbe HM. Two cases of severe clinical and histologic hepatotoxicity associated with troglitazone. Ann Intern Med 1998; 129:36-38. El-Naggar MHM, Helmy A, Moawad M, Al-Omary M, Al-Kadhi Y, Habib B. Late-onset rosiglitazone-associated acute liver failure in a patient with Hodgkin's lymphoma. Ann Su DH, Lai MY, Wu HP. Liver failure in a patient receiving rosiglitazone therapy. Diabet Minimal Elements for Reporting Drug-Induced Liver Injury Menees SB, Anderson MA, Chensue SW, Moseley RH. Hepatic injury in a patient taking rosiglitazone. J Clin Gastroenterol 2005; 39:638-640. Dhawan M, Agrawal R, Ravi J, Gulati S, Silverman J, Nathan G, et al. Rosiglitane- induced granulomatous hepatitis. J Clin Gastroenterol 2002; 34:582-584. Bonkovsky HL, Azar R, Bird S, Szabo G, Banner B. Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone. Gouda HE, Khan A, Schwartz J, Cohen RI. Liver failure in a patient treated with long- term rosiglitazone therapy. Am J Med 2001; 111:584-585. Ravinuthala RS, Nori U. Rosiglitazone toxicity. Ann Intern Med 2000; 133:658. Hachey DM, O'Neil MP, Force RW. Isolated elevation of alkaline phosphatase level associated with rosiglitazone. Ann Intern Med 2000; 133:752 Forman LM, Simmons DA, Diamond RH. Hepatic failure in a patient taking rosiglitazone. Ann Intern Med 2000; 132:118-121. Al-Salman J, Arjomand H, Kemp DG, Mittal M. Hepatocellular injury in a patient receiving rosiglitazone. A case report. Ann Intern Med 2000; 132:121-124. Martínez Odriozola P, Ibarmia Lahuerta J, Gutiérrez Macías A, de la Villa FM. [A new case: pioglitazone hepatotoxicity] Med Clin (Barc) 2007; 129:158-159. Arotçarena R, Bigué JP, Etcharry F, Pariente A. [Pioglitazone-induced acute severe hepatitis] Gastroenterol Clin Biol 2004; 28(6-7 Pt 1): 610-611. French. Marcy TR, Britton ML, Blevins SM. Second-generation thiazolidinediones and hepatotoxicity. Ann Pharmacother 2004; 38:1419-1423. Minimal Elements for Reporting Drug-Induced Liver Injury Pinto AG, Cummings OW, Chalasani N. Severe but reversible cholestatic liver injury after pioglitazone therapy. Ann Inter Med 2002; 137:857. Nagasaka S, Abe T, Kawakami A, Kusaka I, Nakamura T, Ishikawa S, et al. Pioglitazone-induced hepatic injury in a patient previously receiving troglitazone with success. Diabetes Medicine 2002; 19:344-348. May LD, Lefkowitch JH, Kram MT, Rubin DE. Mixed hepatocellular-cholestatic liver injury after pioglitazone therapy. Ann Intern Med 2002; 136:449-452. Chase MP, Yarze JC. Pioglitazone-associated fulminant hepatic failure. Am J Maeda K. Hepatocellular injury in a patient receiving pioglitazone. Ann Intern Med Soy M, Ozer H, Canataroglue A, Gumurdulu D, Erken E. Vasculities induced by zafirlukast therapy. Clin Rheumatol 2002; 21:328-329. Torres M, Reddy KR. Severe liver injury. Ann Intern Med 2001; 135:550. Moles JR, Primo J, Fernandez JM, Hinojosa JE. Acute hepatocellular injury associated with zafirlukast [Letter]. J Hepatol 2001; 35:541-542. Danese S, De Vitis I, Gasbarrini A. Severe liver injury associated with zafirlukast [Letter]. Actis GC, Morgando A, Lagget M, David E, Rizzetto M. Zafirlukast-related hepatitis: report of a further case [Letter]. J Hepatol 2001; 35:539-541. Reinus JF, Persky S, Burkiewicz JS, Quan D, Bass NM, Davern TJ. Severe liver injury after treatment with the leukotriene receptor antagonist zafirlukast. Ann Intern Med 2000; Minimal Elements for Reporting Drug-Induced Liver Injury supplements during chronic treatment with m Goldstein MF, Anoia J, Black M. Montelukast-induced hepatitis. Ann Int Med 2004; Sass DA, Chopra KB, Wu T. A case of montelukast-induced hepatotoxicity. Am J Russmann S, Iselin HU, Meier D, Zimmermann A, Simon HU, Caduff P, et al. Acute hepatitis associated with montelukast. J Hepatol 2003; 38:694-695. Minimal Elements for Reporting Drug-Induced Liver Injury Table 1. Minimal Elements for Reporting Drug-Induced Liver Injury.
Minimal Elements
Primary disease (for which drug was prescribed) Concomitant diseases (with special mention of heart failure or episodes of hypotension, sepsis, Pertinent past medical history (including previous exposure to drug, previous reaction to drug or other drugs, history of liver disease, and risk factors for liver disease, such as alcohol use) Dates of start and discontinuation of therapy (or time from onset of event) List of pertinent symptoms (fatigue, weakness, nausea, anorexia, abdominal pain, dark urine, Pertinent physical findings at the time of presentation (with special mention of whether or not there is fever, rash, jaundice, hepatic tenderness, or signs of chronic liver disease) Medication history (other meds taken in the 3 months before onset of liver injury with dose, Date or time of first abnormal laboratory test Laboratory test results from before drug exposure (specifically liver tests) Initial laboratory results at presentation (bilirubin, ALT, AP, INR or PT, and eosinophil Minimal Elements for Reporting Drug-Induced Liver Injury Laboratory results needed to exclude other causes (IgM anti-HAV, IgM anti-HBc, HBsAg, Course of serum bilirubin, ALT, AP, and INR levels (preferably in a table with entries dated from time of starting and stopping the drug and until resolution) Imaging studies (abdominal ultrasound, CT, or MR) Liver biopsy results (if obtained and date of procedure in relation to episode of DILI) Whether re-challenge with the same medication was done and, if so, results of the challenge. ALT, alanine aminotransferase; ANA, antinuclear antibody; AP, alkaline phosphatase; DILI, drug-induced liver injury; HAV, hepatitis A virus; HBc, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; INR, international normalized ratio; PT, prothrombin time; CT, computerized tomography; MR, magnetic resonance. Minimal Elements for Reporting Drug-Induced Liver Injury Table 2. Elements Included in Case Reports of Drug-Induced Liver Disease.

Amoxicillin/
Clavulanic
Troglitazone
Rosiglitazone
Pioglitazone
Zafirlukast
Montelukast
Minimal Elements for Reporting Drug-Induced Liver Injury Values are percentages. aWhether re-challenge with the same medication was reported as being done or not. ALT, alanine aminotransferase; ANA, antinuclear antibody; AP, alkaline phosphatase; HAV, hepatitis A virus; HBc, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; INR, international normalized ratio; PT, prothrombin time. Minimal Elements for Reporting Drug-Induced Liver Injury
Table 3. Most- and Least-Commonly Reported Elements Included in Case Reports of
Drug-Induced Liver Disease Among 3 Classes of Drugs.

Percent Cases
aWhether re-challenge with the same medication was reported as being done or not. ALT, alanine aminotransferase; AP, alkaline phosphatase; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus.
Minimal Elements for Reporting Drug-Induced Liver Injury Figure Legends
Figure 1. Exclusion of a Competing Viral Etiology.
Among 97 published case reports of drug-
induced liver disease related to specific drugs, fewer than half specified whether competing viral etiologies were excluded. "Viral Screen Negative" represents percent of cases for which results of tests for competing etiology were vaguely reported (for example, "tests for hepatitis A, B, and C were negative"). ALT, alanine aminotransferase; ANA, antinuclear antibody; AP, alkaline phosphatase; HAV, hepatitis A virus; HBc, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus. Figure 2. Minimal Elements Reported in Published Case Reports of Hepatotoxicity With
Thiazolidinediones. Reports were regarding either troglitazone (n= 32), rosiglitazone (n= 10),
and pioglitazone (n= 8). "Re-challenge" refers to whether a re-challenge with the same medication was reported as being done or not. ALT, alanine aminotransferase; ANA, antinuclear antibody; AP, alkaline phosphatase; HAV, hepatitis A virus; HBc, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus. Figure 3. Minimal Elements Reported in Published Case Reports of Hepatotoxicity With
Leukotriene Receptor Antagonists. Reports were regarding either zafirlukast (n=8) or
montelukast (n= 4). "Re-challenge" refers to whether a re-challenge with the same medication Minimal Elements for Reporting Drug-Induced Liver Injury Figure 4. Minimal Elements Reported in Published Case Reports of Hepatotoxicity With
Amoxicillin/Clavulanic Acid (n = 35). "Re-challenge" refers to whether a re-challenge with the
same medication was reported as being done or not. Percent Cases Reporting
Viral Screen
Percent Cases
Serial AP
Anti-HCV
Serial ALT
Initial AP
Final ALT
Eosinophils
Initial ALT
Other Meds
Symptoms
Drug Name
Re-challenge
Liver Biopsy
IgM anti-HAV
Date Jaundice
IgM anti-HBc
Final Bilirubin
Liver Imaging
Date Stop Drug
Initial Protime
Date Start Drug
Serial Bilirubin
Date Symptoms
Time Final Labs
Initial Bilirubin
Primary Disease
Duration Therapy
Date Abnormal Labs
History Risk Factors
History Alcohol Use
History Drug Reaction
History Liver Disease
Labs Before Exposure
Concomitant Diseases
Previous Drug Exposure
Relevant Physical Exam
Percent Cases 20
Serial AP
Anti-HCV
Serial ALT
Initial AP
Final ALT
Eosinophils
Initial ALT
Symptoms
Liver Biopsy
Drug Name
Other Meds
IgM anti-HAV
Re-challenge
Previous Drug
Date Jaundice
IgM anti-HBc
Liver Imaging
Initial Protime
Final Bilirubin
Date Start Drug
Date Stop Drug
Serial Bilirubin
Date Symptoms
Time Final Fabs
Initial Bilirubin
Primary Disease
Duration Therapy
Date Abnormal Labs
History Risk Factors
History Alcohol Use
History Drug Reaction
Concomitant Diseases
History Liver Disease
Labs Before Exposure
Relevant Physical Exam
Percent Cases
Date Stop
Serial ALT
Final ALT
Serial AP
Anti-HCV
Initial ALT
Initial AP
Symptoms
Liver Biopsy
Eosinophils
Other Meds
Drug Name
Final Bilirubin
IgM anti-HBc
IgM anti-HAV
Re-challenge
Initial Protime
Previous Drug
Liver Imaging
Date Start Drug
Time Final Labs
Serial Bilirubin
Date Jaundice
Date Symptoms
Initial Bilirubin
Primary Disease
Duration Therapy
Date Abnormal Labs
History Alcohol Use
History Risk Factors
Labs Before Exposure
Concomitant Diseases
History Drug Reaction
History Liver Disease
Relevant Physical Exam

Source: https://dilin.dcri.duke.edu/ancillary-studies/publications_xps/manuscript/Minimal%20Data%20Elements%20for%20DILI%20Case.pdf

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Operation vid Dupuytren’s kontraktur Dupuytren’s kontraktur Dupuytren’s kontraktur är en sjukdom som drabbar den bindvävsplatta som finns i handflatan. Av okänd anledning börjar cellerna bilda ny bindväv som gör att vävnaden förkortas så att fingret/fingrarna böjs och man får därför svårt att sträcka på fingrarna. Sjukdomen drabbar mest medelålders och äldre

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