- Email: [email protected]
Detection of hepatocellular damage
CORRESPONDENCE
Authors’ reply Sir—In the letter to which Jacques Bernuau and colleagues refer we wanted to call attention to the additional benefits of measuring plasma GSTA1-1 concentrations in patients with hepatic damage. We did not plead for GSTA1-1 to be used as a marker for hepatic damage in routine practice. We are fully aware of the fact that, even when solely based on logistic or cost-effective arguments, assessment of GSTA1-1 cannot replace assessment of aminotransferases in most cases. We stated that GSTA1-1 is a superior marker for acute hepatocellular damage, when compared with aminotransferase measurements. We did not even suggest that either GSTA1-1 or the aminotransferases are indicators of hepatic function. We are fully aware of the difficulty of testing liver function. Bernuau and colleagues argue that our comments concerning zonal distribution of GSTA1-1 and aminotransferases are not correct. We agree that our statement “in contrast to the periportal location of the aminotransferases” may suggest that aminotransferases are solely located in this region, but this is not correct.1 Bernuau and colleagues refer to the review paper of Beckett and Hayes2 as evidence that out statement on the primary location of GSTA1-1 in the centrilobular region is incorrect. However, the only paper that indirectly quotes work on GSTA1-1 in the review by Beckett and Hayes is an immunohistochemical study by Hiley and colleagues,3 who states that they find no evidence for a zonal distribution of GSTA1-1. However, immunohistochemistry at best is only semi-quantitative. Bernuau and colleagues apparently overlooked the paper by El Mouelhi and Kauffman,4 wherein a predominant centrilobular distribution was found using quantitative GST enzyme activity measurements in periportal and pericentral hepatocytes from adults, isolated by microdissection. We disagree with Bernuau and colleagues when they say that “serum GSTA1-1 measurement could help clinicians when serum aminotransferase activity is within the normal range”. They then give the examples of chronic infection and very uncommon cases of HELLP syndrome. We have shown that in chronic liver disease GSTA1-1 measurements added little when compared with the information gained by assessing the aminotransferases.1 Also, the HELLP syndrome, which is
1030
seen in up to 20% of women with severe pre-eclampsia,5 should not be classified as very uncommon. Maarten F C M Knapen, Eric A P Steegers, Theo P J Mulder, *Wilbert H M Peters Departments of Obstetrics and Gynaecology, and *Gastroenterology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands (e-mail: [email protected]) 1
2
3
4
5
Mulder TPJ, Janssens AR, de Bruin WCC, Peters WHM, Cooreman MP, Jansen JBMJ. Plasma glutathione S-transferase alpha 1-1 levels in patients with chronic liver disorders. Clin Chim Acta 1997; 258: 69–77. Beckett GJ, Hayes JD. Glutathione S-transferases: biomedical applications. Adv Clin Chem 1993; 30: 281–380. Hiley C, Fryer A, Bell J, Hume R, Strange RC. The human glutathione S-transferases. Immunohistochemical studies of the developmental expression of Alpha- and Pi-class isoenzymes in liver. Biochem J 1988; 254: 255–59. El Mouelhi M, Kauffman FC. Sublobular distribution of transferases and hydrolases associated with glucuronide, sulfate and glutathione conjugation in human liver. Hepatology 1986; 6: 450–56. Geary M. The HELLP syndrome. Br J Obstet Gynaecol 1997; 104: 887–91.
thought to be an important component in tuberculosis control,3 whether tuberculosis DOT should be routinely used for all patients or only in selected circumstances has been and remains a controversy, and its acceptance by patients with tuberculosis is poorly studied. Our programme used prospective inpatient surveillance to identify all patients with known or presumed tuberculosis, who were offered the choice of voluntary participation in tuberculosis DOT (with weekly provision of transportation tokens or food vouchers, with a cash value of US $25 dependent on adherence to treatment and medical follow-up visits) or selfadministered therapy; the two groups received access to concrete social support services. Overall, 85% of eligible patients voluntarily chose DOT.2 We agree with the conclusions of Jimmy Volmink and colleagues that multiple programme components might contribute to the success of tuberculosis DOT in improving treatment completion, and add that such models could be acceptable to patients with tuberculosis on a voluntary basis. *David C Perlman, Nadim Salomon
Directly observed therapy and treatment adherence
Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003, USA (e-mail: [email protected])
Sir—Jimmy Volmink and colleagues (April 15, p 1345)1 provide a valuable review of recent data on tuberculosis directly observed therapy (DOT), and appropriately highlight the potential importance of programme components, such as incentives, outreach efforts, and attention to individual patients’ issues. However, since Cochrane reviews are intended to be exhaustive, we wish to make the researchers aware of our paper published during the study period employed.2 We assessed the adherence of 101 patients with active tuberculosis treated by outpatient DOT, to a programme model that used intermittent (two or three times weekly) treatment regimens, food voucher or transportation token incentives, outreach interventions, and access to social services as needed. With such a model, in a population with a high prevalence of illicit drug use, unstable housing, and unemployment, only 1% of the cohort was lost to follow-up and the overall treatment completion index was 98%.2 Nonetheless, although DOT (irrespective of the programme components used in addition to observation of drug ingestion) is
1
2
3
Volmink J, Malchaba P, Garner P. Directly observed therapy and treatment adherence. Lancet 2000; 355: 1345–50. Salomon N, Perlman DC, Rubenstein A, Mandelman D, McKinley FW, Yancovitz SR. Implementation of universal directly observed therapy at a New York City hospital and evaluation of an out-patient directly observed therapy program. Int J Tuberc Lung Dis 1997; 1: 397–404. Treatment of tuberculosis: guidelines for national programmes, 2nd edn. Geneva: WHO/TB/97, 220, 1997.
Sir—Jimmy Volmink and colleagues1 introduce a timely and important sense of realism to the difficulties in organising a successful programme of tuberculosis control with the DOTS They describe two strategy.2 characteristics of successful DOT programmes that are insufficiently stressed. These are that programmes require the leadership of highly motivated individuals working in a government-funded system, or external support in the form of technical expertise and financial leverage. Our experiences in rural South Africa and conversations with colleagues around the world suggest that these observations are accurate. Following the DOTS strategy requires a high degree of knowledge and motivation. Complex decisions on treatment regimens and doses have to THE LANCET • Vol 356 • September 16, 2000
For personal use only. Not to be reproduced without permission of The Lancet.
Authors’ reply Sir—In the letter to which Jacques Bernuau and colleagues refer we wanted to call attention to the additional benefits of measuring plasma GSTA1-1 concentrations in patients with hepatic damage. We did not plead for GSTA1-1 to be used as a marker for hepatic damage in routine practice. We are fully aware of the fact that, even when solely based on logistic or cost-effective arguments, assessment of GSTA1-1 cannot replace assessment of aminotransferases in most cases. We stated that GSTA1-1 is a superior marker for acute hepatocellular damage, when compared with aminotransferase measurements. We did not even suggest that either GSTA1-1 or the aminotransferases are indicators of hepatic function. We are fully aware of the difficulty of testing liver function. Bernuau and colleagues argue that our comments concerning zonal distribution of GSTA1-1 and aminotransferases are not correct. We agree that our statement “in contrast to the periportal location of the aminotransferases” may suggest that aminotransferases are solely located in this region, but this is not correct.1 Bernuau and colleagues refer to the review paper of Beckett and Hayes2 as evidence that out statement on the primary location of GSTA1-1 in the centrilobular region is incorrect. However, the only paper that indirectly quotes work on GSTA1-1 in the review by Beckett and Hayes is an immunohistochemical study by Hiley and colleagues,3 who states that they find no evidence for a zonal distribution of GSTA1-1. However, immunohistochemistry at best is only semi-quantitative. Bernuau and colleagues apparently overlooked the paper by El Mouelhi and Kauffman,4 wherein a predominant centrilobular distribution was found using quantitative GST enzyme activity measurements in periportal and pericentral hepatocytes from adults, isolated by microdissection. We disagree with Bernuau and colleagues when they say that “serum GSTA1-1 measurement could help clinicians when serum aminotransferase activity is within the normal range”. They then give the examples of chronic infection and very uncommon cases of HELLP syndrome. We have shown that in chronic liver disease GSTA1-1 measurements added little when compared with the information gained by assessing the aminotransferases.1 Also, the HELLP syndrome, which is
1030
seen in up to 20% of women with severe pre-eclampsia,5 should not be classified as very uncommon. Maarten F C M Knapen, Eric A P Steegers, Theo P J Mulder, *Wilbert H M Peters Departments of Obstetrics and Gynaecology, and *Gastroenterology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands (e-mail: [email protected]) 1
2
3
4
5
Mulder TPJ, Janssens AR, de Bruin WCC, Peters WHM, Cooreman MP, Jansen JBMJ. Plasma glutathione S-transferase alpha 1-1 levels in patients with chronic liver disorders. Clin Chim Acta 1997; 258: 69–77. Beckett GJ, Hayes JD. Glutathione S-transferases: biomedical applications. Adv Clin Chem 1993; 30: 281–380. Hiley C, Fryer A, Bell J, Hume R, Strange RC. The human glutathione S-transferases. Immunohistochemical studies of the developmental expression of Alpha- and Pi-class isoenzymes in liver. Biochem J 1988; 254: 255–59. El Mouelhi M, Kauffman FC. Sublobular distribution of transferases and hydrolases associated with glucuronide, sulfate and glutathione conjugation in human liver. Hepatology 1986; 6: 450–56. Geary M. The HELLP syndrome. Br J Obstet Gynaecol 1997; 104: 887–91.
thought to be an important component in tuberculosis control,3 whether tuberculosis DOT should be routinely used for all patients or only in selected circumstances has been and remains a controversy, and its acceptance by patients with tuberculosis is poorly studied. Our programme used prospective inpatient surveillance to identify all patients with known or presumed tuberculosis, who were offered the choice of voluntary participation in tuberculosis DOT (with weekly provision of transportation tokens or food vouchers, with a cash value of US $25 dependent on adherence to treatment and medical follow-up visits) or selfadministered therapy; the two groups received access to concrete social support services. Overall, 85% of eligible patients voluntarily chose DOT.2 We agree with the conclusions of Jimmy Volmink and colleagues that multiple programme components might contribute to the success of tuberculosis DOT in improving treatment completion, and add that such models could be acceptable to patients with tuberculosis on a voluntary basis. *David C Perlman, Nadim Salomon
Directly observed therapy and treatment adherence
Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003, USA (e-mail: [email protected])
Sir—Jimmy Volmink and colleagues (April 15, p 1345)1 provide a valuable review of recent data on tuberculosis directly observed therapy (DOT), and appropriately highlight the potential importance of programme components, such as incentives, outreach efforts, and attention to individual patients’ issues. However, since Cochrane reviews are intended to be exhaustive, we wish to make the researchers aware of our paper published during the study period employed.2 We assessed the adherence of 101 patients with active tuberculosis treated by outpatient DOT, to a programme model that used intermittent (two or three times weekly) treatment regimens, food voucher or transportation token incentives, outreach interventions, and access to social services as needed. With such a model, in a population with a high prevalence of illicit drug use, unstable housing, and unemployment, only 1% of the cohort was lost to follow-up and the overall treatment completion index was 98%.2 Nonetheless, although DOT (irrespective of the programme components used in addition to observation of drug ingestion) is
1
2
3
Volmink J, Malchaba P, Garner P. Directly observed therapy and treatment adherence. Lancet 2000; 355: 1345–50. Salomon N, Perlman DC, Rubenstein A, Mandelman D, McKinley FW, Yancovitz SR. Implementation of universal directly observed therapy at a New York City hospital and evaluation of an out-patient directly observed therapy program. Int J Tuberc Lung Dis 1997; 1: 397–404. Treatment of tuberculosis: guidelines for national programmes, 2nd edn. Geneva: WHO/TB/97, 220, 1997.
Sir—Jimmy Volmink and colleagues1 introduce a timely and important sense of realism to the difficulties in organising a successful programme of tuberculosis control with the DOTS They describe two strategy.2 characteristics of successful DOT programmes that are insufficiently stressed. These are that programmes require the leadership of highly motivated individuals working in a government-funded system, or external support in the form of technical expertise and financial leverage. Our experiences in rural South Africa and conversations with colleagues around the world suggest that these observations are accurate. Following the DOTS strategy requires a high degree of knowledge and motivation. Complex decisions on treatment regimens and doses have to THE LANCET • Vol 356 • September 16, 2000
For personal use only. Not to be reproduced without permission of The Lancet.