Volume 165 Issue 5

A diving fatality due to oxygen toxicity during a "technical" dive Christopher H Lawrence An experienced diver drowned after a generalised seizure caused by oxygen toxicity during a 19-minute "technical" dive to a depth of 47 m. He had used a 50% oxygen/nitrogen gas mixture inappropriately during the dive. This case attests the risk of oxygen toxicity from oxygen-enriched air during deep dives, the shortcomings of the diver's equipment, and the need to examine, with knowledge of diving physiology and practice, both the body and equipment. (MJA 1996; 165: 262-263) Introduction Scuba diving carries the risks of decompression illness and nitrogen narcosis; these risks increase the deeper the dive. Therefore, recreational scuba divers have been encouraged to avoid depths over 40 m. 1 In the past five years, some recreational divers have used highly specialised equipment and techniques to enable diving to greater depths (known as "technical" diving). These techniques include the use of surface supply and rebreather diving apparatuses and gas mixtures with a lower nitrogen concentration than compressed air to reduce the absorbed nitrogen load, allowing a longer bottom time with less decompression. Another technical diving technique uses oxygen-enriched gas mixtures during decompression to accelerate shedding of absorbed nitrogen from the body ("enriched- air", or "nitrox", diving). Unfortunately, higher concentrations of oxygen may have a toxic effect on the brain, causing generalised convulsions which may lead to drowning. The extent of the toxic effect depends on duration of exposure and is increased by exertion and immersion in water. An oxygen tension limit of 161 kPa (1.6 atm) is often adopted in practical diving for exposures of less than 30 min (National Oceanic and Atmospheric Administration guidelines). 2,3,4 However, oxygen toxicity can occur at tensions as low as 121 kPa (1.2 atm). 2 The "safe" level is currently under review and is clearly dependent on duration of exposure. The dangers of "technical" diving have been shown in a report of eight fatalities during technical dives in the United States in 1992. 4 We report the death of an experienced diver in Australia during a technical dive using an oxygen-enriched gas mixture. This case attests the risk of oxygen toxicity from oxygen-enriched air during deep dives, the shortcomings of the equipment used and the importance of an integrated approach to examination of the body and equipment by those experienced in diving practice and physiology. Clinical record A 47-year-old experienced underwater cave diver, with no significant medical history, was diving with two tanks -- one containing compressed air, the other a 50% mixture of oxygen and nitrogen (nitrox). Towards the end of the 47-m, 19-min dive, he was seen floating head down, unresponsive, with his mouthpiece out of his mouth and "his fins [flippers] moving as if he was shivering" (as reported by another diver to the Coroner). The body was carried up to 15 m depth and then allowed to ascend freely as the other divers decompressed. Cardiopulmonary resuscitation was attempted, but abandoned after 43 minutes as there was no response. Autopsy findings Erect postmortem x-rays and autopsy of the body performed 24 hours after death revealed large amounts of gas in the venous system of the trunk and limbs and in both sides of the heart (Figure 1). The heart weighed 380 g and was normal, apart from foamy blood and gas in all chambers. Analysis of gas from the right ventricle showed O 2 (20.6% by volume), and N 2 (75.9%). There was bruising of the tongue and petechiae on the lungs and heart. The brain (1740 g) showed mild cerebral oedema and a microscopic perivascular haemorrhage in the floor of the fourth ventricle. Figure 1: Postmortem erect chest x-ray, showing gas in both sides of the chest and in the neck veins (a combination of postmortem decompression, perimortem barotrauma and, possibly, decomposition). Examination of diving equipment Examination of the subject's diving equipment (Figure 2) re-vealed that he had been breathing the 50% oxygen/nitrogen mixture for most of the dive. Each tank had a separate first stage connected in an unusual fashion by a two-way switch, which the diver had had made by a local engineering shop. This allowed the diver to switch from one tank to another rapidly. This switch supplied a single second-stage mouthpiece. The two tanks were different colours; the circuit from the black (compressed-air) tank was marked with yellow tape, while the circuit from the yellow (nitrox) tank was unmarked. Figure 2: Equipment used by the diver, showing the 50% oxygen/nitrogen gas tank (yellow, right), compressed-air tank (black, left), yellow tape marking the compressed-air circuit, and two-way valve which controlled the source of the air supply (inset shows close-up of valve). The regulator had a small tear and a bite mark in the mouthpiece. The diver wore a facemask and separate mouthpiece rather than a full facemask, which covers eyes, nose and mouth. Discussion The cause of death, as determined by the Coroner, was drowning after oxygen toxicity. 5 The "shivering" movements and the biting of the tongue and mouthpiece suggested fitting. Using a 50% oxygen/nitrogen mixture at 47 m depth, the diver had been exposed to a partial pressure of oxygen of 291 kPa (2.9 atm), possibly for as long as 19 min. During diving, this gas mixture should be used only at depths less than 14-18 m (depending on the duration of exposure). Cerebral gas embolism and decompression illness were unlikely causes of death, as the subject was unresponsive before ascent. The gas observed at autopsy probably resulted from a combination of postmortem decompression (release of tissue nitrogen), perimortem barotrauma and, possibly, a degree of decomposition. 6 This death resulted from several compounding problems: The diver may have turned the switch to the unmarked nitrox circuit, thinking he was using the circuit to the compressed air in the black tank (the yellow label marked the circuit from the black [compressed-air] tank, not the circuit from the yellow [nitrox] tank). Alternatively, as the two-way valve needed very little pressure to turn, it could have been accidentally switched from a safe to an unsafe gas mix. The diver was using a separate facemask and mouthpiece. During the seizure, the mouthpiece fell out. A full facemask, covering both the mouth and nose, should be worn by divers using oxygen-rich mixtures or carrying out deep diving on compressed air, to reduce the chance of drowning should an oxygen convulsion occur. This technical diving fatality and those reported in the United States in 1992 4 were in experienced divers, who should have understood the dangers. The standard of equipment and of diving practice during technical dives should be that of a commercial operator, with planning of the dive to stay below an appropriate oxygen pressure for the duration of the dive (e.g., below 161 kPa [1.6 atm] for a 19-min dive), 2 use of a full facemask, proper analysis of gas mixtures and access to surface decompression facilities after long deep dives. Use of home-made equipment is not appropriate. During the inquest the New South Wales State Coroner declined to recommend legislation to regulate recreational technical diving, preferring that it remain subject to a voluntary code of conduct. 5 Acknowledgements I thank Sergeant John Marshall, New South Wales Police Divers, for the examination of the equipment. References Moon RE, Vann RD, Bennett PB. The physiology of decompression illness. Sci Am 273: 54-61. Gorman DF. Oxygen and carbon dioxide toxicity. In: Gorman DF, editor. Diving and hyperbaric medicine. 2nd ed. Adelaide: Hyperbaric Medicine Unit, Royal Adelaide Hospital, 1993: 26.2-26.4. Clark JM. Oxygen toxicity. In: Bennett PB, Elliott DH, editors. The physiology and medicine of diving. 4th ed. Philadelphia: WB Saunders, 1993. Menduno M. Safety first, an analysis of recent technical-diving accidents. Technical Diver 1993; 2: 3-10, reproduced in SPUMS J 1993; 23: 177-184. New South Wales State Coroner. Coroner's Court, 1995. File number 94/574. Williamson JA, King GK, Callanan VI, Rich KW. Fatal arterial gas embolism: detection by chest radiography and imaging before autopsy. Med J Aust 1990; 153: 97-100. Author's details NSW Institute of Forensic Medicine, Sydney, NSW. Christopher H Lawrence, BSc(Med), FRCPA, Forensic Pathologist; and Clinical Lecturer in Pathology, University of Sydney, Sydney, NSW. Reprints: Dr C H Lawrence, NSW Institute of Forensic Medicine, PO Box 90, Glebe, NSW 2037. E-mail: IOFM AT OZEMAIL. COM. AU Make a comment - Register to be notified of new articles by email - - To top of article - ©MJA1996 < URL: http://www.mja.com.au/> © 1996 Medical Journal of Australia. We appreciate your comments.

Christopher H Lawrence

The clinical and ethical implications of hepatitis C for organ transplantation in Australia Ian H Kerridge, Peter Saul and Robert G Batey Current Australian policy prohibiting transplantation of organs from hepatitis C-infected donors raises questions about patient autonomy and medical paternalism. MJA 1996; 165: 282-285 Readers may print a single copy for personal use. No further reproduction or distribution of the articles in whole or in part should proceed without the permission of the publisher. For copyright permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Introduction - HCV infection - Transmission of HCV by organ transplantation - Implications of HCV infection after organ transplantation - Ethical issues - Conclusions - Acknowledgements - References - Authors' details - Register to be notified of new articles by email - - ©MJA1996 Case 1 A 42-year-old man presented to a liver clinic for assessment as he had recently been found to be hepatitis C virus antibody (anti-HCV) positive. Liver function test results had been normal in the two years preceding this appointment, and the patient felt perfectly well. There were no signs of chronic liver disease, and a liver biopsy (undertaken at the patient's request) 12 months earlier had shown minimal inflammatory damage and no fibrosis. One of the main points for discussion at the outpatient clinic was that this patient had been rejected as an organ donor by the transplantation service. He was indignant that his offer of organs was rejected, particularly as he felt that it would be appropriate in the event of his death for his liver to be made available to another HCV-positive patient. He asked for advice as to why HCV-positive patients were unable to donate organs for transplantation. Case 2 A 48-year-old man presented with advanced alcohol-related liver disease and is awaiting liver transplantation. His clinical progress had improved slowly after cessation of alcohol intake but his liver function had deteriorated in the preceding six months. He had been advised that liver transplantation might be required within 12 months but had not yet been placed on the active transplantation list. This patient asked if he could have a liver transplant earlier if he agreed to accept an HCV-antibody positive liver. This request was motivated by his frustration at being unable to work and his awareness that patients with hepatitis C were receiving transplants and apparently doing well. He was advised, that at present, there is a policy banning the use of organs from all HCV-positive donors in Australia. He agreed to abide by these rules but insisted that this issue be investigated further. Introduction D uring the past decade, advances in immunosuppression and transplantation technology have increased the demand for organ transplantation without a corresponding increase in the number of donors. In June 1995, 1869 Australians were on waiting lists for solid-organ transplantation, with a further 1435 awaiting corneal transplants. Waiting-list numbers increased by 17% in the first six months of 1995, while the Australian organ donation rate continued to fall. 1 The relative donor shortage and its impact on both waiting lists and the length of time patients wait for transplantation highlights the importance of efficient and effective organ procurement and use. 2 Viruses which may be transmitted by organ transplantation (such as cytomegalovirus, herpes simplex virus, Epstein-Barr virus, human immunodeficiency virus, hepatitis A virus, hepatitis B virus, hepatitis D virus and human T-cell lymphotropic virus type 1) have become one of the major causes of morbidity and mortality in organ transplant recipients. 3 For this reason, potential organ donors are routinely screened for the presence of viral infection. After the identification of the hepatitis C virus, and the recognition that it may be transmitted by organ transplantation, transplantation organisations have restricted the use of organs from anti-HCV-positive organ donors. 4 There is no international consensus about the use of HCV-positive organs in transplantation. Three recent studies from the United States highlight the variation in policies for the transplantation of organs from HCV-positive donors. Milfred et al. 5 found that, for heart and lung transplantation, 22% of the centres studied would accept organs from anti-HCV-positive donors irrespective of recipient HCV status, 45% would accept such donors only for anti-HCV-positive recipients, 27% would never accept these donors, 2% did not screen donors, and 4% did not have a defined policy. 5 By contrast, studies by Ramos et al. 6 and Schweitzer et al. 7 found that most US transplant centres would not accept organs from anti-HCV-positive donors for renal transplantation. Part of the reason for the lack of consensus is that the consequences of transplantation of organs from anti-HCV donors (including the degree of HCV transmission, the prevalence of liver disease and the impact of HCV infection on survival) remain unclear. 8-11 Furthermore, any guidelines must incorporate ethical considerations relating to resource allocation, prognostic uncertainty, medical paternalism and limitation of patient autonomy. In New South Wales, the Transplant Advisory Committee policy currently excludes transplant of all HCV-positive organs and tissues, including transplant to known HCV-positive recipients. The implications are that one in 50 potential organ donors are lost to the transplant program and that certain individuals therefore lose the right to choose potentially life-sustaining organ transplantation with an organ they know to be infected with HCV. These cases raise questions about the current Australian policy of excluding transplantation of HCV-positive organs and whether this constitutes unjustifiable paternalism. As with many questions of ethics in clinical practice, further understanding depends upon a number of factual issues concerning the transmission of HCV during transplantation and the consequences of HCV infection for the graft recipient. HCV infection HCV infection is now the most frequently reported notifiable disease in Australia. 12 Its true prevalence is unknown, but studies of Australian blood donors demonstrate a prevalence of 0.3%-0.7%. 13,14 Most estimates suggest that there are at least 100 000 cases in Australia. International studies reporting the incidence of HCV in cadaveric organ donors have shown wide variation (1.5%-16.7%), 15-17 probably reflecting both geographical variation in HCV prevalence and the different testing methods used for HCV identification. Second generation enzyme-immunoassays used to detect anti-HCV have a sensitivity and specificity of about 90% and 99%, respectively, resulting in a positive predictive value in Australian blood and organ donors of less than 50%. 18 Confirmatory assays (e.g., radioimmunoblot assay [RIBA-2] and polymerase chain reaction techniques) can provide further evidence of actual HCV infection but may also give false positive or false negative results. 19 Genotyping assays are now available and may prove to be important for prognosis, determining epidemiological research and monitoring response to treatment. Most cases of hepatitis C in Australia can be traced to a history of parenteral exposure through intravenous drug use (50% of cases) 20 or blood products (10%-15% of cases). 21 Since the introduction of routine donor screening for hepatitis C, the risk of transmission by infected blood products has reduced substantially. 22 Accurate information about the natural history of hepatitis C is extremely limited because diagnoses of acute hepatitis are rarely made, serum transaminase levels are poor predictors of liver disease and most studies of long-term outcome are limited to a 10-year follow-up. It is estimated that 50%-80% of infected patients develop chronic hepatitis C and 20%-30% of these will progress to cirrhosis. An unknown number (varying from 10%-75%) will develop hepatocellular carcinoma (HCC). 23 The mean interval between infection and diagnosis of cirrhosis is estimated to be 20 years. The cornerstones of managing hepatitis C virus infection are education about its natural history and counselling to prevent transmission or worsening of the disease (e.g., avoiding the sharing of needles, restricting alcohol intake and practising "safe-sex"). Interferon alfa is available for treatment of chronic HCV under the Pharmaceutical Benefits Scheme but is extremely expensive; the long term response rate after a standard six-month course is approximately 20%-25%. 24 End-stage liver disease in patients with HCV can be managed medically or by liver transplantation. Reinfection of the graft is almost universal. Despite the need for immunosuppressive therapy, the resultant liver disease is generally benign and graft survival in the medium term (up to five years) is equivalent to that of other causes of liver disease requiring transplantation. Hepatitis C is now the most frequent indication for liver transplantation in Australia. 25 Transmission of HCV by organ transplantation There is conflicting evidence about the risk of transmission of HCV with organ transplantation. 26-30 Retrospective studies indicate that hepatitis is evident in approximately 50% of recipients of HCV-antibody-positive kidney transplants. 31 The type of solid organ transplanted (heart, lung, liver or kidney) does not appear to influence the transmission of HCV from an infected donor to a recipient. Recent studies have also demonstrated the transmission of HCV through bone marrow transplantation 32 and bone, ligament and tendon allografts. 33 Given the likely high degree of HCV transmission by organ transplantation, there is considerable interest in the work of Zucker et al., which suggests that washing donated kidneys can remove 99% of the viral burden. It is not known whether this has any significant impact on the transmission of HCV. 34 Implications of HCV infection after organ transplantation There is evidence that liver disease is more frequent in recipients of anti-HCV-positive organs, 35 that immunosuppression may enhance HCV replication 36 and that immunocompromised patients infected with HCV may have a more aggressive course of infection. 37 A number of studies have also shown that, when HCV infection develops after renal transplantation, it will become chronic in approximately 85% of recipients and may progress to cirrhosis. 38 There is also evidence to suggest that HCV infection may increase the risk of rejection and infection; 39,40 however, no study has consistently demonstrated a significantly increased rate of mortality or graft loss in recipients of anti-HCV-positive organs. 41 The effects of HCV infection on transplanted livers in immunocompromised hosts can be partly surmised by examination of HCV-positive patients who receive HCV-negative liver transplants -- early reinfection occurs almost uniformly 42 and may range in severity from asymptomatic viraemia to cirrhosis and hepatic failure. A small number of patients develop fulminant hepatic failure after organ transplantation, but reinfection is usually not clinically significant, producing only mild inflammation. In general, primary infection with HCV and reinfection in a transplanted patient follow a similar course. 43 Growing awareness of the heterogeneous nature of HCV genotypes has led to suggestions that anti-HCV-positive organs could be safely made available for transplantation into anti-HCV-positive recipients. 44 Unfortunately, a number of studies have suggested that patients may become infected with multiple viral genotypes, 45 and there may not be sufficient cross-immunity between different HCV subtypes. 46 Furthermore, there is some evidence to suggest that repeated exposure to the virus may result in repeated bouts of hepatitis. 47,48 Thus, host seropositivity for HCV may provide no absolute assurance that a patient receiving an HCV-positive organ will have less risk of infection and liver disease. In general terms it seems likely that transplant-related infection may follow a similar course to primary infection with hepatitis, 43 but the long term implications of HCV infection after organ transplantation remain unclear. Importantly, the use of interferon alfa for chronic hepatitis C does not appear to increase the risk of graft rejection. 49 Ethical issues With the increasing scarcity of organs, maximum use of donors is essential to realise the full potential of organ transplantation. However, in attempting to meet the health needs of both individuals and society, all attempts must be made to maximise the benefit and minimise the risks of transplantation to the recipient. The high probability of transmitting HCV by organ transplantation and the uncertain long term consequences of HCV infection in immunocompromised hosts have led the Transplantation Advisory Committee to ban the transplant of HCV-positive organs in New South Wales. This policy is clearly medical paternalism; the question is, is it justifiable paternalism? Should informed patients be able to request transplantation of HCV-positive organs, in the light of their own wishes, beliefs and values, or do policies such as these constitute justifiable limits of autonomy? The uncertain risks of HCV may add to the mortality and morbidity associated with organ transplantation, but this is not in itself sufficient reason for preventing patients from choosing an HCV-positive organ. It is well accepted that competent patients may have the right to choose medical interventions which have significant or uncertain side effects, provided they are aware of the nature and likelihood of such complications. This is especially the case when alternative forms of therapy are associated with high rates of morbidity and mortality. For example, young patients with acute myeloid leukaemia will always be offered bone-marrow transplantation, despite its significant risks, because other treatments for this condition have such poor outcomes. This is not to suggest that patient autonomy is, or should be, unrestricted. Patients may not request treatment that is ineffective, that endangers others, or that is judged by health care professionals and, ultimately, by society to be of insufficient value to be allocated scarce health resources. It may well be that current policy should continue for non-life-threatening conditions (such as renal transplantation in chronic renal failure) because of the uncertain long-term consequences of HCV infection and the small number of donor organs that would be gained from relaxing the prohibition on the use of HCV-positive organs. On the other hand, for patients awaiting heart, lung or liver transplantation, the risk of liver disease after organ transplantation from an HCV-positive donor may well be more acceptable than the risk of death or poor quality of life without transplantation. A further difficulty is that, whereas the transplantation of an HCV-positive organ may benefit the individual, this may be to the detriment of the wider community. The use of HCV-positive organs would clearly generate a potential source of preventable infection which may impact significantly on the lives of others (such as sexual partners) and inevitably demand further expensive treatment. The cost of a six-month course of interferon alfa is $3200 and the cost of liver transplantation for end-stage liver disease is $120 000, plus $7000-$10 000 per annum postoperatively. A conservative estimate of the cost of treating a patient with chronic hepatitis C (including hospitalisations) over five years is approximately $100 000. The effects on the present system of waiting-lists of a separate pool of "sub-standard" HCV-positive organs may also become increasingly complicated. Should a patient be able to "jump the queue" to a position higher up the waiting list if they are willing to accept such an organ? Should a patient at the top of the queue have the right to refuse an HCV-infected organ? Should there be a separate list of patients who are eligible only for HCV-infected organs? Conclusions Much of the uncertainty about the significance of hepatitis C infection in organ transplantation will only be resolved by further research. Until then, the obligations suggested by the ethical principles of autonomy, non-maleficence, beneficence and justice suggest a number of alternative approaches to the management of HCV-positive donors, shown in the Box. The decision to transplant an HCV-infected organ remains a complex issue in which benefit must be weighed against harm and individual choice against the wider demands of society and scarce health resources. Ultimately, such issues may only be resolved through an approach based on shared and informed decision-making between doctors and patients, recognising the many clinical and epidemiological uncertainties involved in these circumstances. That there are organ recipients willing to accept HCV-positive organs, but prevented from doing so by current policy, reflects tension between professional guidelines and individual needs or between medical paternalism and patient autonomy. We believe that there are circumstances in which transplantation of HCV-infected organs may be indicated, particularly in the case of life-saving transplantation. Decisions that deny choice to informed, competent patients are the subject of increasing scrutiny by the medical and legal professions and the community at large. If patients who are aware of the risks and complications are to be denied the choice of an HCV-infected organ, such denial must be carefully considered and explicitly justified. Acknowledgements We acknowledge the contributions of Dr Michael Lowe for his editorial assistance and of members of the John Hunter Hospital Clinical Ethics Committee for advice on the formulation of this paper. References Australian Coordinating Committee on Organ Registries and Donation (Gladesville, Sydney, NSW). Newsletter, October 1995 (distributed to all intensive care and renal transplant units). Shiener PA, Mor E, Schwartz ME, Miller CM. Use of hepatitis C-positive donors in liver transplantation. Transplant Proc 1993; 25: 3071. Aswad S, Mendez R, Weingart RG, Mendez R. Expanding organ availability by using hepatitis C antibody-positive donors. Transplant Proc 1993; 25: 2270-2271. Public Health Service inter-agency guidelines for screening donors of blood, plasma, organs, tissues and semen for evidence of hepatitis B and hepatitis C. MMWR Morb Mortal Wkly Rep 1991; 40: 1-17. Milfred SK, Lake KD, Anderson DJ, et al. Practices of cardiothoracic transplant centers regarding hepatitis C seropositive candidates and donors. Transplantation 1994; 57: 568-572. Ramos EL, Kaiske BL, Alexander SR, et al. The evaluation of candidates for renal transplantation: the current practice of US transplant centers. Transplantation 1994; 57: 490-497. Schweitzer EJ, Bartlett ST, Keay S, et al. Impact of hepatitis B or C infection on the practice of kidney transplantation in the United States. Transplant Proc 1993; 25: 1456-1457. Tesi RJ, Waller K, Morgan CJ, et al. Transmission of hepatitits C by kidney transplantation -- the risks. Transplantation 1994; 57: 826-831. Aeder MI, Shield CF, Tegtmeier GE, et al. The incidence and clinical impact of hepatitis C virus (HCV) positive donors in cadaveric transplantation. Transplant Proc 1993; 25: 1469-1471. Diethelm AG, Roth D, Ferguson RM, et al. Transmission of HCV by organ transplantation. N Engl J Med 1992; 326: 410-411. Triolo G, Squiccimarro G, Baldi M, et al. Antibodies to hepatitis C virus in kidney transplantation. Nephron 1992; 61: 276-277. Commonwealth Department of Human Services and Health. Hepatitis C. Commun Dis Intell 1994; 18: 533. Archer GT, Buring ML, Clark B, et al. Prevalence of hepatitis C virus antibodies in Sydney blood donors. Med J Aust 1992; 157: 225-227. McGuinness PH, Bishop GA, Lien A, et al. Detection of serum hepatitis C virus RNA in anti-HCV seropositive (RIBA positive) volunteer blood donors with normal ALT levels. Hepatology 1993; 18: 485-490. Aeder MI, Shield CF, Tegtmeier GE, et al. Incidence and clinical impact of hepatitis C virus-positive donors in cadaveric transplantation. Transplant Proc 1993; 25: 1469-1471. Pereira BJ, Wright RL, Schmid CH, et al. Screening and confirmatory testing of cadaveric organ donors for hepatitis C virus infection: a US National Collaborative Study. Kidney Int 1994; 46: 886-892. Candinas D, Joller-Jemelka HI, Schlumpf R, et al. Hepatitis C RNA prevalence in a Western European organ donor pool and virus transmission by organ transplantation. J Med Microbiol 1994; 41: 220-223. Talley NJ. Internal medicine. Sydney: Maclennan and Petty, 1990: 288. Strasser SI, Desmond PV, Watson KJR, et al. The value of routine hepatitis C PCR in clinical practice. Gastroenterology 1994; 106: A991. Bell J, Batey RG, Farrell GC, et al. Hepatitis C virus in intravenous drug users. Med J Aust 1990; 153: 274-276. Strasser SI, Watson KJR, Lee CS, et al. Risk factors and predictors of outcome in an Australian cohort with hepatitis C infection. Med J Aust 1995; 162: 355-358. Donahue JG, Munoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med 1992; 327: 369-373. Ikeda K, Saitoh S, Koida I, et al. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 1993; 18: 47-53. David GI, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicentre randomised controlled trial. N Engl J Med 1989; 321: 1501-1506. Ascher NL, Lake JR, Emond K, Roberts J. Liver transplantation for hepatitis C virus related cirrhosis. Hepatology 1994; 20: 245-275. Roth D, Fernandez JA, Babischkin S, et al. Detection of hepatitis C virus infection among cadaver organ donors: evidence for low transmission disease. Ann Intern Med 1992; 117: 470-475. Pereira BJ, Milford EL, Kirkman RL, Levey AS. Transmission of hepatitis C virus by organ transplantation. N Engl J Med 1991; 325: 454-460. Wreghitt TG, Gray JJ, Allain JP, et al. Transmission of hepatitis C virus by organ transplantation in the United Kingdom. J Hepatol 1994; 20: 768-772. Maple PA, McKee T, Desselberger V, Wreghitt TG. Hepatitis C virus infections in transplant patients: serological and virological investigations. J Med Virol 1994; 44: 43-48. McDonnell WM, Lucey MR. Hepatitis C virus transmission during organ transplantation. Hepatology 1993; 17: 162-164. Morales JM, Munoz MA, Castellano G, et al. Impact of hepatitis C in long-functioning renal transplants: a clinicopathological follow-up. Transplant Proc 1993; 25: 1450-1453. Shuhart MC, Myerson D, Childs BH, et al. Marrow transplantation from hepatitis C virus seropositive donors: transmission rate and clinical course. Blood 1994; 84: 3229-3235. Conrad EV, Gretch DR, Obermeyer KR, et al. Transmission of the hepatitis-C virus by tissue transplantation. J Bone Joint Surg Am 1995; 77: 214-224. Zucker K, Cirocco R, Roth D, et al. Depletion of hepatitis C virus from procured kidneys using pulsatile perfusion preservation. Transplantation 1994; 57: 832-840. Weir MR, Kirkman RL, Strom TB, Tilney NL. Liver disease in recipients of long-surviving renal allografts. Kidney Int 1985; 28: 839-844. Chazouilleres O, Kim M, Combs C, et al. Quantitation of hepatitis C virus RNA in liver transplant recipients. Gastroenterology 1994; 106: 994. Pereira BJG, Milford RL, Kirkman RL, et al. Liver disease and HCV infection after transplantation of organs from hepatitis C antibody-positive donors. Transplant Proc 1993; 25: 1458-1459. Huang CC, Lai MK, Lin MW, et al. Transmission of hepatitis C virus by renal transplantation. Transplant Proc 1993; 25: 1474-1475. Roth D, Zucker K, Cirocco R, et al. The impact of hepatitis C virus infection on renal allograft recipients. Kidney Int 1994; 45: 238-244. Fritsche C, Brandes JC, Delaney SR, et al. Hepatitis C is a poor prognostic indicator in black kidney transplant recipients. Transplantation 1993; 55: 1283-1287. Ynares C, Johnson HK, Kerlin T, et al. Impact of pretransplant hepatitis C antibody status upon long-term patient and renal allograft survival -- a 5 and 10-year follow-up. Transplant Proc 1993; 25: 1466-1468. K"nig V, Bauditz J, Neuhaus P, et al. Follow-up of hepatitis C virus (HCV) reinfection in liver allograft recipients. J Hepatol 1991; 13: 540. Wright TL, Ferell L, Donegan E, et al. Impact of hepatitis C viral (HCV) infection on the allograft following liver transplantation. J Hepatol 1991; 14: 51A. Morales JM, Andres A, Campistol JM. Hepatitis C virus and organ transplantation. N Engl J Med 1993; 328: 511-513. Preston FE, Jarvis LM, Markis M, et al. Heterogeneity of hepatitis C virus genotypes in haemophilia: relationship with chronic liver disease. Blood 1995; 85: 1259-1262. Farci P, Alter HJ, Govindarajan S, et al. Lack of protective immunity against reinfection with hepatitis C virus. Science 1992; 258: 135-140. King P. Renal transplantation. N Engl J Med 1994; 331: 1719. FŽray C, Gigou M, Samuel D, et al. Direct evidence for a more pathogenic effect of HCV type II: the model of liver transplantation. J Hepatol 1993; 28 Suppl 1: 54. Shorrock C, Neuberger J. The changing face of liver transplantation. Gut 1993; 34: 295-298. Authors' details Faculty of Medicine and Health Sciences, The University of Newcastle, NSW. Ian H Kerridge, BMed(Hons), MPhil, Lecturer in Clinical Ethics, Health Law and Ethics Programme, and Haematology Registrar, John Hunter Hospital. John Hunter Hospital, Newcastle, NSW. Peter Saul, FANZCA, FFICANZCA, Intensive Care Specialist; Robert G Batey, MD, FRACP, Associate Professor and Director, Department of Gastroenterology. No reprints will be available. Correspondence: Dr I H Kerridge, John Hunter Hospital, Lookout Road, New Lambton Heights, NSW 2305. - Register to be notified of new articles by email - - To top of article - ©MJA1996 < URL: http://www.mja.com.au/> © 1996 Medical Journal of Australia.

Ian H Kerridge · Peter Saul · Robert G Batey