Can type C hepatitis infection be complicated by malignant lymphoma?

HIV-1 status, follow-up was begun at the median HIV-1 seroconversion dates for each geographical and factor-VIII concentrate group.’ Subjects born after their group’s median date were excluded. During a median follow-up of 10-3 years for 1028 subjects, 269 deaths occurred, including 200 among persons with AIDS. There were nine deaths among the 321 HIV-1uninfected subjects, and 260 deaths among the 707 HIV-1infected subjects. 12 year cumulative survival, estimated by the product-limit method, was 96% (SE 3%) for the HIV-1uninfected subjects and 61% (2%) for the HIV-1-infected subjects. Dose of factor VIII concentrate had no effect on survival for either theHIV-1-infected or HIV-1-uninfected groups (figure). Age, however, was important. In a threevariable proportional hazards model for the risk of death, the adjusted relative hazard (RH) was 11-09 (95% CI 5-65-21-77) with HIV-1 infection, 1-50 (1-38-1-64) per decade of age, and 1-04 (0-80-1-36) with high-dose factor VIII concentrate. We previously showed that the use of highpurity or intermediate-purity, viral-inactivated factor VIII concentrate had no effect on mortality among HIV-infected

subjects.’ Darby

al found an excess of mortality with HIV was similar in severe and in mild or moderate haemophilia patients.’ We found no effect on mortality of non-heat-treated factor VIII, but death was 11-fold more likely with HIV. et

infection that

James J Goedert Viral Epidemiology Branch, National Cancer Institute, Rockville, MD 20852, USA

1

2

Darby SC, Ewart DW, Giangrande PLF, et al. Mortality in the complete population of UK haemophiliacs before and after the HIV infection. Nature 1995; 377: 79-82. Goedert JJ, Kessler CM, Aledort LM, et al. A prospective study of

human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. N Engl J Med 1989; 321: 1141-48. 3 Kroner BL, Rosenberg PS, Aledort LM, Alvord WG, Goedert JJ. HIV-1 infection incidence among persons with hemophilia in the United States and Western Europe, 1978-1990. J Acquir Immune Defic Syndr 1994; 7: 279-86. 4 Ehmann WC, Eyster ME, Wilson SE, Andes WA, Goedert JJ. Relationship of CD4 lymphocyte counts to survival in a cohort of hemophiliacs infected with human immunodeficiency virus. J Acquir Immune Defic Syndr 1994; 7: 1095-98. 5 Goedert JJ, Cohen AR, Kessler CM, et al. Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate. Multicenter Hemophilia Cohort Study. Lancet 1994; 344: 791-92.

HIV infection in Cuban

women

SjR—World Health Organization data show that women constitute a group in whom there is the most rapid growth of HIV infection in the past 10 years. In 1994, a million women were affected by HIV and 500 000 had died. In Cuba, between January, 1986, and December, 1994, 1136 persons were diagnosed as infected by HIV, of whom 315 were women-a yearly incidence of 6-3 per 100000 women, with a male/female ratio of 2-5/1-0. 52-2% of men were homosexual or bisexual, which increases the vulnerability of women. In this 9 year period, 52 women have died of AIDS and six by indirect causes.’ 98-7% of these women were infected by the sexual route, with the most important risk factor being sexual relations with a seropositive partner. The predominant virus in these years was HIV-1 subtype B and the most common opportunistic infections were Pneumocystis carinii pneumonia, candidosis, and diarrhoea caused by cytomegalovirus. The number of infected women has increased slowly. In 1986, 23-2% of HIV-positive individuals were women; in 1990, 27’9%; and in 1994 28.6%; but age at detection has 1426

fallen from 29-2 years in 1986 to 25-4 in 1994 (mean 23-9). The greatest number of cases was found in the 20-24 year group (n=105) and the 15-19 year group (96), with an annual incidence of 18-84 and 19-17 per 100000, respectively. Most cases were in the City of Havana, Villa Clara, and Pinar del Rio. During this period 1 627 439 tests for HIV infection were done in pregnant women. 18 women were seropositive-a rate of 0-1 per 10 000 tests. Four cases of perinatal transmission have been notified. Thus, in Cuba there is a low rate of HIV infection in women, but the many consequences are regarded as a serious health problem. *Guillermo Díaz Alonso, Roberto Alvarez Sintes, Rolando Ramírez Fernández Centro Nacional de Información de Ciencias Médicas, Dirección Nacional de Epidemlología, MINSAP, Vedado, Cludad Habana, Cuba CP 10 400.

1

Torres R, Joanes J, Carrira L, et al. La infección de la inmunodeficiencia humana y la tuberculosis en Cuba. Bol Oficina Sanit Panam 1995; 119: 66-68.

Can type C

hepatitis infection by malignant lymphoma?

be

complicated

SiR-Morris and colleagues (Sept 16, p 754) review the possible role of infection with specific viruses in the pathogenesis of some malignant diseases. In particular, hepatitis C virus (HCV) seems to be correlated with the development of hepatocellular carcinoma even in the absence of cirrhotic lesions.’ This finding suggests a direct oncogenic effect of HCV on chronically infected liver. Since HCV is also a lymphotropic virus/ several autoimmune and lymphoproliferative disorders have been correlated with chronic HCV infection-namely, autoimmune hepatitis, mixed cryoglobulinaemia, and idiopathic B-cell nonHodgkin’s lymphoma (NHL).3 Anecdotal case reports have previously focused on the possible complication of chronic hepatitis type C with lymphoma always being limited to liver and/or spleen .1,5 We report clinical and virological features of a cohort of 14 patients with chronic hepatitis type C complicated by diffuse B-cell NHL (table). The patients belong to our series of 500 with chronic hepatitis type C. The B-cell lymphomas appeared medially after 9 (SD 6) years from onset of disease, and were characterised by low-grade NHL in eight patients, intermediate in five; and high in one (working formulation classification). All patients showed serum anti-HCV (RIBA II, Chiron, Emeryville, CA) and HCV RNA, detected by one-tube nested PCR, as described previously;2 HCV genome was also present in both fresh and cultured peripheral lymphocytes. Analysis of HCV genotypes showed a higher prevalence of type 2 compared with unselected chronic type C (50% vs 15%). Finally, in three patients lymph node and/or bone marrow biopsy specimens showing

WF, working formulation classification; PBMC, fresh and cultured penpheral blood mononuclear cells. *Mean (SD, range). Table: Clinical and virological features of 14 patients with type C hepatitis and complicating lymphoma

neoplastic B-lymphocyte infiltration were available for virological studies. With PCR, HCV genomic sequences were demonstrated in both bone marrow and lymph node specimens in one patient, and in bone marrow in another two; in the same patients HCV RNA was also detected in liver biopsy specimens. HCV RNA cannot be integrated in the host genome; thus, other factors (ie, genetic, infectious, and/or environmental agents) could be involved in the oncogenesis of HCV-related NHL. A similar multifactorial process has been suggested for other virus-induced neoplasias such as African Burkitt’s lymphoma. In this condition Epstein-Barr virus infection and endemic malaria are regarded as cofactors of the disease. In chronically infected individuals, HCV can represent a triggering factor for immune system alterations; the appearance of benign or malignant lymphoproliferation should be regarded as a multistep pathological process with variable clinical expressions. The intimate mechanism(s) involved in the pathogenesis of different clinical patterns deserves further investigation. B-cell NHL can be a harmful complication of chronic hepatitis type C that can change the prognosis of the disease. Since chronic type C is increasingly frequent, the prevalence of complicating lymphoma is probably underestimated. Thus, in patients with such a disorder a careful clinical work-up at diagnosis and during follow-up is especially recommended.

*Clodoveo Ferri, Luca La Civita, Monica Monti, Giovanni Longombardo, Francesco Greco, Giampiero Pasero, Anna Linda Zignego *Istituto Patologia Medica I, University of Pisa, 56126 Pisa, Italy; Istituto di Medicina Interna, University of Florence; and Blood Centre, S Chiara Hospital, Pisa

1 De Mitri MS, Poussin K, Baccarini P, et al. HCV-associated liver cancer without cirrhosis. Lancet 1995; 345: 413-15. 2 Ferri C, Monti M, La Civita L, et al. Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed cryoglobulinaemia. Blood 1993; 82: 3701-04. 3 Ferri C, Caracciolo F, Zignego AL, et al. Hepatitis C virus infection in patients with non-Hodgkin’s lymphoma. Br J Haematol 1994; 88: 392-94. 4 Kizawa K, Tsuneyama K, Terada T. An autopsied case of primary hepatic malignant lymphoma associated with chronic active hepatitis C. Nippon Shokakibyo Gakkai Zasshi 1993; 90: 2147-51. 5 Naschitz JE, Zuckerman E, Elias N, Yeshurun D. Primary hepatosplenic lymphoma of the B-cell variety in a patient with hepatitis C liver cirrhosis. Am J Gastroenterol 1994; 89: 1915-16.

and acute asthma in

children SIR-In late 1994, the air of Singapore was affected by a of pollutants originating from forest fires and agricultural burning in south Sumatra, and carried by southwest monsoon winds more than 500 km to Singapore. We examined the effect of the haze on asthma in children less than 12 years old, by the methods of Sunyer et al.’1 Between September and October, 1994, atmospheric concentration of particulate matter less than 10 )im in aerodynamic diameter (PM1o) was 20% higher than the year’s average moving trend. An increase in emergency room attendances for acute childhood asthma was observed in two large general hospitals in Singapore (National University and Singapore General) (table). This association was further substantiated by multiple regression analysis where meterological and other factors were also taken into consideration. The association was strengthened when PMIO

haze

data was logged. Exclusion analysis, which was carried out by sequential removal of data with the highest PMIO levels, showed that the model remained significant up to a threshold of 158 flg/m-3. Our data provides support for the PMIO threshold recommended by the US Environment Protection Agency, which was set at 150 flg/m-3for short term (24 h) exposure. Our study also emphasises the fact that air pollution knows no political boundaries, and its control effort.

cannot

be effective without

a

concerted international

F T Chew, B C Ooi, J KS Hui, R Saharom, D Y T Goh, *B W Lee *Department of Paediatrics, National University of Singapore, Lower Kent Ridge Road, Singapore 0511; Department of Paediatrics. Singapore General Hospital: and Department of Strategic Planning and Research, Ministry of the Environment, Singapore

1

Sunyer J, Anto JM, Murillo C,

Saez M. Effects of urban air pollution admissions for chronic obstructive pulmonary disease. Am J Epidemiol 1991; 134: 277-86. US Environmental Protection Agency: revisions to the National Ambient Air Quality Standards for Particulate Matter. Federal Register on

We thank Dr M A Cagianelli, Dr R Cecchetti, Dr F Caracciolo, and Dr M La Corte for their contributions.

Singapore’s haze

Table: Association between daily asthma attendances and their corresponding mean PM10 levels

2

emergency

room

July 1987; 52: 24634-69.

Hydroquinone and hepatitis SiR-Nowak et al report hepatitis with hydroquinone exposure.’ Their letter describes hydroquinone as a volatile aromatic hydrocarbon; however, hydroquinone is essentially nonvolatile in solid form or when dissolved in developer solution. It has a low vapour pressure (2-3X10’’’ Pa at 25°C), a low Henry’s law constant (3-84X10’" atmm3/mole), and a high relative vapour density (3-81 where air=l), all of which limit its volatility. As the solubility of in it is temperature,

increases with increasing that unlikely operating radiographic processing equipment at normal or elevated temperatures would volatilise hydroquinone. We have sampled air around hydroquinone-containing black-and-white aqueous developer solutions and found that hydroquinone air concentrations were below the analytical limit of detection (<0-02 mg/m3) confirming the lack of volatility under use conditions. Nowak et al also describe "crystals of developing medium" on the stationary rollers of the processor and suggests that when crushed these crystals might be a source of exposure to hydroquinone. Although deposits may form in radiographic processors, depending on operating conditions and maintenance levels, the deposits are typically associated with the fixer tank. The deposits that are usually observed are ammonium thiosulphate, which may appear in the developer tank if the developer replenisher solution becomes contaminated with fixer solution. Although very unlikely, if deposits were to form on the developer tank (other than ammonium thiosulfate) they would most likely be potassium sulphite. Neither ammonium thiosulphate nor potassium sulphite are considered to be hepatotoxic. Because exposure to high levels of hydroquinone dust and p-benzoquinone vapour led to cases of corneal pigmentation and damage during the 1940s, employees of the largest US manufacturer of hydroquinone have been under regular

hydroquinone

water

1427