The sexual transmission in the epidemiology of HCV

Even before hepatitis C was positively identified, sexual transmission of non-A, non-B hepatitis was suspected. The importance of sexual transmission in the epidemiology of HCV infection is controversial.

– Interspousal and intrafamilial transmission of HCV
– Pregnancy and HCV
– Breast feeding and HCV
– Alcohol and HCV

Interspousal and intrafamilial transmission of HCV

Even before hepatitis C is positively identified, sexual transmission of non-A, non-B hepatitis was suspected. The importance of sexual transmission in the epidemiology of HCV infection is controversial. The “perfect” study has not been done (requiring long term follow-up of monogamous couples, careful selection of index patients, meticulous exclusion of other risk factors, utilizing the latest techniques in virus detection, quantitation and molecular analysis). The early case-controlled studies are somewhat flawed because they used predominantly hemophiliac population, and some only employed first generation antibody testing without RNA analysis (1 – 4). Nonetheless, these studies collectively showed the risk of interspousal transmission to be very low or non-existent.

In 1993, a number of letters published in Lancet documenting sexual transmission of HCV. A carefully studied case of acute hepatitis C following sexual exposure appeared in Gut (5). There are also a number of seemingly conflicting reports. One study in Japan (6) identified 154 viremic HCV index patients (positive HCV by PCR) and found a spousal anti-HCV rate of 27%. 89% of the spouses with positive RNA were infected with HCV of genotypes identical to those of the index patients. It appeared the risk of infection increases with duration of marriage. Those married for less than ten years were not infected. Another study from Taiwan (7) used a second-generation ELISA test for anti-HCV demonstrated spousal positivity rate of 28%. Astonishingly, 54% of the parents of the index patients were tested positive. The authors also concluded prolonged cohabitation is a risk factor. In contrast, another study from Japan analyzed an isolated island where hepatitis C is endemic (8) did not support either vertical or horizontal transmission of the virus. Of the 53 children with anti-HCV positive mothers, only 3 were tested positive for HCV; and both spouses were positive for anti-HCV in 17 of 234 couples. In 11 pairs of spouses in whom HCV genotype was determined, only about half has similar genotype.

One study from United States (9) employed a somewhat different approach, and the patients were recruited from a STD clinic but supposedly non-injection drug user and mostly (95%) African-Americans. Multivariate analysis showed HCV is no different that HIV or HBV, in that risk of infection increased with multiple lifetime sexual partners. Among couples, females whose sexual partners were anti-HCV positive were 3.7 times more likely to have anti-HCV than females whose sex partners were anti-HCV negative. For males, anti-HCV positivity has no relationship to the anti-HCV status of the partners. This suggests male to female transmission is more efficient.

Adding to the controversy include a recent case-controlled study from Egypt, which also has a very high seropositive rates of HCV. Index patients were 65 women identified to be anti-HCV positive at prenatal screening. In comparison with the controlled group, the index group has about 25% of the family (mostly spouses) tested anti-HCV positive (10). Another study with a large number of heterosexual couples from Italy (11) demonstrated apparent effectiveness of prophylatic intramuscular ISG and infection rate of partner at 1% per year.

Pregnancy and HCV

A number of studies are available examining the risk of vertical transmission. Collectively, in HIV negative mothers without active IV drug use, the risk of transmission is less than 18%. This figure was reported from a rather small study from Taiwan. The other studies demonstrated substantially lower risks (0-10%). A summary of the studies is tabled below, modified from Hunt (12).

                                                         Prevalence of                      HCV transmission
                                                           Maternal                              neonate RNA +
Country                    n                  HCVRNA +                        at 6 months                        

Japan                     163                100/163 (61%)                    2/87 (2%)
Japan                      54                    31/54 (57%)                    3/31 (10%)
Italy                        94                    64/116 (55%)                  0/94 (0%)
Italy                        27                    19/27 (70%)                    0/27 (0%)
U.S.A.                     19                    16/19 (84%)                    0/20 (0%)
France                     17                      8/17 (47%)                    0/18 (0%)
France                     13                    10/13 (77%)                    0/13 (0%)
Sweden                   14                    14/14 (100%)                  1/21 (5%)
Taiwan                    15                    15/15 (100%)                  1/15 (7%)
Taiwan                    11                      2/11 (18%)                    2/11 (18%)

Although the numbers are small, studies from Japan and Taiwan suggest that positive transmission to neonate require higher levels HCV RNA, above one million copies/ml. It appears mothers with negative HCV RNA will not transmit the virus. Mothers who are HIV positive are more likely to transmit the virus to neonates. In a review that examined the role of PCR in defining infectiousness of HCV, the pooled risk of vertical transmission was 6.2% in 903 children born to mothers with positive HCV RNA (including a small number of HIV positive mothers), and again no vertical transmission was noted in 735 children born to mothers who are RNA negative (13).

Breastfeeding and HCV

To this date, there is no case report on conclusive evidence that breast feeding can transmit HCV. Lin et al. (14) measured HCV RNA in colostral samples and although it was detectable, the levels were low. There was at least a 3 Рlog difference between serum and clostrum and frequently higher.

Alcohol and HCV

It has been reported that the prevalence of HCV antibody is higher in chronic alcoholic; and the amount of alcohol consumed is proportional to the severity of liver injury (15). Significant intake of alcohol has also been deemed to negatively influence the possibility of successful treatment of HCV with interferon (16). The level of HCV RNA also appears to be higher in habitual drinkers (17). Experimentally, alcohol also inhibits cellular immune response in mice when challenged by HCV core protein-expressing plasmid constructs (18). It is well known that both alcohol and HCV predispose to hepatocellular carcinoma, and a paper from Japan suggests following resection of small hepatomas (<3 cm) in HCV patients, significant prior consumption of alcohol resulted in poorer survival (19).

Summary

Sexual transmission of HCV does exist. However, it is still difficult to define the risk adequately to help with counselling. Some has advocated against routine testing the spouses of infected individuals. It appears the risk of transmission of HCV increases with anal intercourse, sex during menstrual cycles and years of marriage. Should one suggest universal barrier contraceptives?

One can now provide some reassurance for expectant mothers who are infected with HCV. If they are HIV and HCV RNA negative, then their babies will not be infected. There is some suggestion the route of delivery may be important (vaginal has higher chance of transmitting the virus vs C-section). Can a mother who has positive HCV RNA reasonably asks for elective C-section? Breast-feeding should not be discouraged based on the data available in HIV negative patients.

It is obvious HCV patients should not habitually consume alcohol. Although the data is limited, should we consider prior significant consumption of alcohol is a negative factor in weighing the decision regarding interferon therapy?

Reference

1. Everhart JE, Di BA, Murray LM et al. Risk for non-A, non-B (type c) hepatitis through sexual or household contact with chronic carriers. Ann Intern Med 1990; 112:544-5.

2. Eyster ME, Alter HJ, Aledort LM et al. Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficieency virus (HIV) Ann Intern Med 1991; 115:746-8.

3. Bresters D, Mause BE, Reesink HW et al. Sexual transmission of hepatitis C. Lancet 1993; 342:210-1.

4. Hallam NF, Feltcher ML, Read SJ et al. Low risk of sexual transmission of heaptitis C virus. J Med Virol 1993; 40:251-3.

5. Healey CJ, Smith DB, Walker JL et al. Acute hepatitis C infection after sexual exposure. Gut 1995; 36:148-50.

6. Akahane Y, Kojima M, Sugai Y et al. Hepatitis C virus infection in spouses of patients with type C chronic liver disease. Ann Intern Med 1994; 120:749-52.

7. Chang TT, Liou TC, Young KC et al. Intrafamilial transmission of hepatitis C virus: The important role of inapparent transmission. J Med Virol 1994; 42:91-6.

8. Nakashima K, Ikematsu H, Hayashi J et al. Intrafamilial transmission of hepatitis C vvirus among the population of an endemic area of Japan. JAMA 1995; 274:1459-61.

9. Thomas DL, Zenilman JM, Alter HJ et al. Sexual transmission of hepatitis C among patients attending sexually transmitted diseases clinic in Baltimore Рan analysis of 309 sex partners. J Infect Dis 1995; 171:768-75.

10. Jumar RM. Interspousal and intrafamilial transmission of hepatitis virus: A myth or a concern? Ob Gyn 1998; 91:426-30.

11. Paizza M, Sagliocfcca L, Tosone G et al. Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin Arch Intern Med 1997; 157:1537-44.

12. Hunt CM, Carson KL, Sharara AI. Hepatitis C in pregnancy. Ob Gyn 1997; 89(5 pt 2):883-890.

13. Dore GJ, Kaldor JM, McCaughan W. Systematic review of role of Polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus. Br Med J 1997; 315:333-337.

14. Lin HH, Kao JH, Hsu HY et al. Absence of infection in breast-fed infants born to hepatitis C virus-infected mothers. J Pediatr 1995; 126:589-591.

15. Pares A, Barrera JM, Caballeria J et al. Hepatitis C virus antibodies in chronic alcoholic patients: association with severity of liver injury. Hepatology 1990; 12:1295-9.

16. Oshita M. Hayashi N, Kasahara A. et al. Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C. Hepatology 1994; 20:1115-20.

17. Ohnishi K, Matsuo S, Matsutani K. et al. Interferon therapy for chronic hepatitis C in habitual drinkers: comparison with chronic hepatitis C in infrequent drinkers. Am J Gastroenterol 1996; 91:1374-9.

18. Geissler M, Gesien A, Wands JR. Inhibitory effects of chronic ethanol consumption on cellular immune responses to hepatitis C virus core protein are reversed by genetic immunization augmented with Cytokine-expressing plasmids. J Immunol 1997; 159:5107-13.

19. Kubo S, Kinoshita H, Hirohashi K, et al. High malignancy of hepatoccellular carcinoma in alcoholic patients with hepatitis C virus. Surgery 1997; 121:425-9.

Peter Kwan May 1998

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