Changing Patterns of Causation and the Use of Transplantation in the United Kingdom

William Bernal

doi:10.1055/s-2003-42640

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2003; 23(3): 227-238
DOI: 10.1055/s-2003-42640

Changing Patterns of Causation and the Use of Transplantation in the United Kingdom

William Bernal

Consultant in Intensive Care Medicine Liver Intensive Therapy Unit Institute of Liver Studies King's College Hospital London,United Kingdom

Abstract

ABSTRACT

Acute liver failure (ALF) is a rare condition in the United Kingdom. Comprehensive supportive intensive care of extra-hepatic organ failure and the early recognition of and use of transplantation for those who will not survive form the cornerstone of its management. Over the last 30 years there has been a reduction in the proportion of cases resulting from viral and seronegative hepatitis, and a progressive rise in those resulting from severe acetaminophen-induced hepatotoxicity. The latter cases mostly result from deliberate self-poisoning and formed the major cause of ALF hospital admissions and indication for emergency liver transplantation. The increasing misuse of acetaminophen has paralleled a rise in sales and greater availability of the drug. Introduction of legislation to restrict sales of acetaminophen has been followed by a fall in hospital admissions resulting from self-poisoning, a 20% reduction in deaths, and a 50% fall in the number of patients undergoing emergency liver transplantation. The reduction in acetaminophen-related ALF has been paralleled by an increase in the number of transplants performed in ALF of nonacetaminophen etiologies.

KEYWORDS

Acute liver failure - acetaminophen - self-poisoning - transplantation - hepatotoxicity

Volltext

Referenzen

REFERENCES

1 Mortality Statistics: cause. National Statistics. London: The Stationery Office; 1999
2 Williams R. Classification, etiology, and considerations of outcome in acute liver failure. Semin Liver Dis . 1996; 16 343-348
3 O'Grady J. Acute liver failure. In: O'Grady J, Lake J, Howdle P, eds. Comprehensive Clinical Hepatology, 1st ed London: Mosby 2000 : 30.1-30.20
4 Hartley P, Petruckvitch A, Reeves B. et al . The national liver transplantation audit: an overview of patients presenting for liver transplantation from 1994 to 1998. Br J Surg . 2001; 88 52-58
5 Statistics prepared by UK Transplant from the National Transplant Database maintained on behalf of transplant services in the UK and Republic of Ireland. October 2002
6 Dhiman R, Seth A, Jain S. et al . Prognostic evaluation of early indicators in fulminat hepatic failure by multivariate analysis. Dig Dis Sci . 1998; 43 1311-1316
7 Ellis A, Rhodes A, Jackson N. et al . Acute liver failure (ALF) in a specialist intensive care unit; a 7 year experience. Crit Care . 1998; 2(Suppl 1) P150
8 Ostapowicz G, Fontana R, Sciodt F. et al . Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med . 2002; 137 947-954
9 Trigo P, Lendoire J, Braslavsky G. et al . Etiology and outcome of 83 patients with fulminant hepatic failure in adults. Experience of an Argentinian liver transplant unit. Hepatology . 2001; 34 657A
10 O'Grady J, Schalm S, Williams R. Acute liver failure; redefining the syndromes. Lancet . 1993; 342 273-275
11 O'Grady J, Alexander G, Hayllar K, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology . 1989; 97 439-445
12 Anand A, Nightingale P, Neuberger J. Early indicators of prognosis in fulminant hepatic failure: an assessment of the Kings's criteria. J Hepatol . 1997; 26 62-68
13 Bernal W, Wendon J, Rela M. et al . Use and outcome of liver transplantation in acetaminophen induced acute liver failure. Hepatology . 1998; 27 1050-1055
14 O'Grady J, Wendon J, Tan K. et al . Liver transplantation after paracetomol overdose. BMJ . 1991; 303 221-223
15 Mitchell I, Bihari D, Chang R. et al . Earlier identification of patients at risk from acetaminophen induced acute liver failure. Crit Care Med . 1998; 26 279-284
16 Bernal W, Donaldson N, Wyncoll D, Wendon J. Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure. Lancet . 2002; 359 558-563
17 Pereira L M, Langley P G, Hayllar K M. et al . Coagulation factor V and VIII/V ratio as predictors of outcome in paracetamol induced fulminant hepatic failure: relation to other prognostic indicators. Gut . 1992; 33 98-102
18 Izumi S, Langley P G, Wendon J. et al . Coagulation factor V levels as a prognostic indicator in fulminant hepatic failure. Hepatology . 1996; 23 1507-1511
19 Sizer E, Bernal W, Wendon J. Acute liver failure in the intensive care unit. In: Vincent J, ed. 2003 Yearbook of Intensive Care and Emergency Medicine Berlin: Springer 2003
20 Rivers E, Nguyen B, Havstad S. et al . Goal-directed therapy for severe sepsis and septic shock. N Engl J Med . 2001; 345 1368-1377
21 Makin A, Wendon J, Williams R. A seven year experience of severe acetominophen-induced hepatotoxicity (1987-1993). Gastroenterology . 1995; 109 1907-1916
22 Bihari D, Gimson A, Lindridge J, Williams R. Lactic acidosis in fulminant hepatic failure: some aspects of pathogenesis and prognosis. J Hepatol . 1985; 1 405-416
23 Harry R, Ausinger G, Wendon J. Clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology . 2002; 36 395-402
24 Annane D, Sebille V, Charpentier C. et al . Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA . 2002; 288 862-871
25 Davenport A, Will E J, Davidson A M. Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med . 1993; 21 328-338
26 Davenport A, Will E J, Davison A M. et al . Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy. Nephron . 1989; 53 142-146
27 Forni L, Hilton P. Current concepts: continuous hemofiltration in the treatment of acute renal failure. N Engl J Med . 1997; 336 1303-1309
28 Bellomo R, Baldwin I, Ronco C. High volume hemofiltration. Curr Opin Crit Care . 2000; 6 442-445
29 Ronco C, Bellomo R, Homel P. et al . Effects of different doses in continuous veno-venous hemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet . 2000; 355 26-30
30 Ede R, Gimson A, Bihari D, Williams R. Controlled hyperventilation in the prevention of cerebral odema in fulminant hepatic failure. J Hepatol . 1986; 2 43-51
31 Wendon J A, Harrison P M, Keays R, Williams R. Cerebral blood flow and metabolism in fulminant liver failure. Hepatology . 1994; 19 1407-1413
32 Strauss G, Hogh P, Knudsen G. et al . Regional cerebral blood flow during mechanical hyperventilation in patients with fulminant hepatic failure. Hepatology . 1999; 30 1368-1373
33 Cordoba J, Gottstein J, Blei A. Chronic hyponatraemia exacerbates ammonia induced brain edema in rats after portocaval anastamosis. J Hepatol . 1998; 29 589-594
34 Murphy N, Wendon J. Serum sodium is inversely proportional to intracranial pressure in acute liver failure (Abst). Crit Care . 1999; 3(Suppl 1) 110
35 Schell R, Cole D. Cerebral monitoring: jugular venous oximetry. Anesth Analg . 2000; 90 559-566
36 Rolando N, Philpott-Howard J, Williams R. Bacterial and fungal infections in acute liver failure. Semin Liver Dis . 1996; 16 389-402
37 Rolando N, Wade J, Davalos M. et al . The systemic inflammatory response in acute liver failure. Hepatology . 2000; 32 734-739
38 O'Grady J. Fulminant hepatitis in patients with chronic liver disease. J Viral Hepat . 2000; 7(Suppl 1) 9-10
39 Sallie R, Silva A E, Purdy M. et al . Hepatitis C and E in non-A non-B fulminant hepatic failure: a polymerase chain reaction and serological study. J Hepatol . 1994; 20 580-588
40 Jackson N, Ellis A, Rhodes A. et al . Non-paracetamol drug induced acute liver failure in a specialist liver intensive care unit: a seven year experience. Hepatology . 1998; 28 496A
41 Henry J A, Jeffreys K J, Dawling S. Toxicity and deaths from 3,4-methylenedioxymethamphetamine (“ecstasy”). Lancet . 1992; 340 384-387
42 Ellis A J, Wendon J A, Portmann B, Williams R. Acute liver damage and ecstasy ingestion. Gut . 1996; 38 454-458
43 Andreu V, Mas A, Bruguera M. et al . Ecstacy: a common cause of severe acute hepatotoxicity. J Hepatol . 1998; 29 394-397
44 Crowcroft N, Walsh B, Davidson K. et al . Guidelines for the control of hepatitis A infection. Communicable Disease and Public Health . 2001; 4 213-227
45 Goldberg D, McMenamin J. The United Kingdom's hepatitis B immunisation strategy-where now?. Communicable Disease and Public Health . 1998; 1 79-83
46 Melnick J. History and epidemiology of hepatitis A virus. J Infect Dis . 1995; 171(Suppl 1) S2-S8
47 Damme P V, Tormans G, Beutels P, Doorslaer E V. Hepatitis B prevention in Europe: a preliminary economic evaluation. Vaccine . 1995; 13 S54-S57
48 Kyrlagkitsis I, Cramp M, Smith H. et al . Acute hepatitis A virus infection: a review of prognostic factors from 25 years experience in a tertiary referral center. Hepatogastroenterology . 2002; 49 524-528
49 Gow P, Mutimer D. Non-A, non-B fulminant hepatic failure. Arch Intern Med . 2001; 161 1013-1014
50 Williams R, Riordan S. Acute liver failure: established and putatative hepatitis viruses and therapeutic implications. J Gastroenterol Hepatol . 2000; 15 G17-G25
51 McCrudden R, O'Connell S, Farrant T. et al . Sporadic acute hepatitis E in the United Kingdom: an underdiagnosed phenomenon?. Gut . 2000; 46 732-733
52 Wilkinson S, Taylor G, Templeton L. et al . Admissions to hospital for deliberate self-harm in England 1995-2000; an analysis of Hospital Episode Statistics. J Public Health Med . 2002; 24 179-183
53 Hawton K, Fagg J, Simkin S. et al . Trends in deliberate self harm in oxford, 1985-1995. Br J Psychiatry . 1997; 171 556-560
54 Shah R, Uren Z, Baker A, Majeed A. Trends in suicide from drug overdose in the elderly in England and Wales 1993-1999. Int J Geriatr Psychiatry . 2002; 17 416-421
55 McLoone P, Crombie I K. Hospitalisation for deliberate self-poisoning in Scotland from 1981 to 1993; trends in rates and types of drugs used. Br J Psychiatry . 1996; 169 81-85
56 Prescott L. Paracetamol overdose. In: Paracetamol (Acetaminophen) a Critical Bibliographic Review London: Taylor and Francis 1996: 401-473
57 Makin A J, Williams R. Acetaminophen-induced hepatotoxicity: predisposing factors and treatments. Adv Intern Med . 1997; 42 453-483
58 Deaths related to drug poisoning results for England and Wales, 1993 to 2000. Health Statistic Quarterly 2002; 13:76-82 www.statistics.gov.uk/downloads/theme health/ HSQ13 v4.pdf .
59 Makin A, Williams R. Paracetamol hepatotoxicity and alcohol consumption in deliberate and accidental overdose. QJM . 2000; 93 341-349
60 Townsend E, Hawton K, Harriss L. et al . Substances used in deliberate self poisoning 1985-1997; trend and associations with age, gender, repetition and suicidal intent. Soc Psychiatry Psychiatric Epidemiol . 2001; 36 228-234
61 Gunnell D, Hawton K, Murray V. et al . Use of paracetamol for suicide and non-fatal self poisoning in the UK and France: are restrictions on availability justified?. J Epidemiol Community Health . 1997; 51 175-179
62 Hawton K, Ware C, Mistry H. et al . Why patients choose paracetamol for self poisoning and their knowledge of its dangers. BMJ . 1995; 310 69-73
63 Hawton K, Ware C, Mistry H. et al . Paracetamol self-poisoning. Characteristics, prevention and harm reduction. Br J Psychiatry . 1996; 168 43-48
64 Newson P, Bathgate A, Henderson N. et al . Referral patterns and social deprivation in paracetamol-induced liver injury in Scotland. Lancet . 2001; 358 1612-1613
65 Hawton K, Harriss L, Hodder K. et al . The influence of economic and social environment on deliberate self-harm and suicide: an ecological and person-based study. Psychol Med . 2001; 31 827-836
66 Neeleman J, Wessely S. Drugs taken in fatal and non-fatal self poisoning a study in south London. Acta Psychiatr Scand . 1997; 95 283-287
67 Prescott L. Paracetamol, alcohol and the liver. Br J Clin Pharmacol . 2000; 49 291-301
68 Schmidt L, Dalhoff K, Poulsen H. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity. Hepatology . 2002; 35 876-882
69 Kuffner E, Dart R, Bogdan G. et al . Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients. Arch Intern Med . 2001; 161 2247-2252
70 Whitcomb D, Block G. Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA . 1994; 272 1845-1850
71 Read R B, Tredger J M, Williams R. Analysis of factors responsible for continuing mortality after paracetamol overdose. Hum Toxicol . 1986; 5 201-206
72 Foster T. Dying for a drink. BMJ . 2001; 323 817-818
73 Galanos A, Pieper C, Kussin P. et al . Relationship of body mass index to subsequent mortality among seriously ill hospitalised patients. Crit Care Med . 1997; 25 1962-1968
74 Sheen C, Dillon J, Bateman D. et al . Paracetamol toxicity: epidemiology, prevention and costs to the health-care system. QJM . 2002; 95 609-619
75 Jones A, Hayes P, Proudfoot A. et al . Should methionine be added to every paracetamol tablet?. BMJ . 1997; 315 301-304
76 Gunnell D, Murray V, Hawton K. Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse. Suicide Life Threat Behav . 2000; 30 313-326
77 WHO. The world health report 2001. Mental health: new understanding, new hope. Geneva: World Health Organization 2001
78 Proudfoot A T, Park J. Changing pattern of drugs used for self-poisoning. BMJ . 1978; 1 90-93
79 Bowles J. Suicide prevention in western Samoa: an example of a suicide prevention program in a developing country. In: Diekstra R, Gulbinat W, Kienhorst I, Leo D, eds. Preventative Strategies on Suicide Leiden: EJ Brill 1995: 173-206
80 Oliver R, Hetzel B. An analysis of recent trends in suicide rates in Australia. Int J Epidemiol . 1973; 2 91-101
81 Ott P, Dalhoff K, Hansen P B. et al . Consumption, overdose and death from analgesics during a period of over-the-counter availability of paracetamol in Denmark. J Int Med . 1990; 227 423-428
82 Committee on Safety of Medicines, Medicines Control Agency. Paracetamol and aspirin. Current Problems in Pharmacovigilance . 1997; 23 9
83 Fagan E, Wannan G. Reducing paracetomol overdoses. BMJ . 1996; 313 1417-1418
84 Laffoy M, Byrne G, Scallan E. Paracetamol availability and overdose in Ireland. Irish Med J . 2001; 94 7
85 Thomas M, Jowett N. Restriction has not reduced admissions with self poisoning. BMJ . 2001; 322 553
86 Balit C, Isbister G, Peat J. et al . Paracetamol recall: a natural experiment influencing analgesic poisoning. Med J Aust . 2002; 176 163-166
87 Hawton K, Townsend E, Deeks J. et al . Effects of legislation restricting pack sizes of paracetamol and salycilate poisoning in the United Kingdom; before and after study. BMJ . 2001; 322 1203-1207
88 Prince M, Thomas S, James O, Hudson M. Reduction in incidence of severe paracetamol poisoning. Lancet . 2000; 355 2047-2048
89 Turvill J, Burroughs A, Moore K. Change in occurrence of paracetamol overdose in UK after introduction of blister packs. Lancet . 2000; 355 2048-2049
90 Sheen C, Dillon J, Bateman D. et al . Paracetamol pack size restriction: the impact on paracetamol poisoning and over-the-counter supply of paracetamol, asprin and ibuprofen. Pharmacoepidemiology and Drug Safety . 2002; 11 329-331
91 Spooner J, Harvey J. Paracetamol overdose; Facts not misconceptions. Pharmaceutical Journal . 1993; 252 706-707
92 Robinson D, Smith A, Johnston G. Severity of overdose after restriction of paracetamol availability: retrospective study. BMJ . 2000; 321 926-927
93 Sheen C, Dillon J, Bateman D. et al . The effect on toxicity on reducing the size of available paracetamol pack sizes. Gut . 2001; 48(Suppl 1) A105
94 Poulin C. Prevention of paracetamol poisoning. Lancet . 2000; 355 2009-2010
95 Hill A. The environment and disease: association or causation?. Proc R Soc Med . 1965; 295-300
96 Altman D. Practical Statistics for Medical Research. London: Chapman and Hall; 1991
97 Bond G R, Hite L. Population-based incidence and outcome of acetaminophen poisoning by type of ingestion. Acad Emerg Med . 1999; 6 1115-1120
98 Nourjah P, Willey M. Epidemiology of acetaminophen-related overdose. Department of Health and Human Services, Center for Drug Evaluation and Research, Food and Drug Administration, 2002. www.fda.gov/ohrms/dockets/ac/02/ briefing/3882b1.htm
99 Ahmad S. OPDRA safety review: review of acetaminophen poisoning exposures in Toxic Exposure Surveillance System (TESS). Department of Health and Human Services, Center for Drug Evaluation and Research, Food and Drug Administration, 2002. www.fda.gov/ohrms/dockets/ac/02 /briefing/3882b1.htm
100 Schiodt F, Atillasoy E, Shakil A. et al . Etiology and prognosis for 295 patients with acute liver failure in the US Liver Transplantation and Surgery . 1999; 5 29-34
101 Gyamlani G, Parikh C. Acetaminophen toxicity: suicidal versus accidental. Critical Care . 2002; 6 155-169
102 Prescott L. Therapeutic misadventure with paracetamol: fact or fiction?. American Journal of Therapeutics . 2000; 7 99-114
103 Food and Drug Administration. September 2002.fdaadvisorycommittee.com/FDC/AdvisoryCommittee/Committees/Nonprescription+Drugs/091902 acetaminophen/091902 AcetaminophenR.htm#.