Seroepidemiology of hepatitis E virus in patients with non-A, non-B, non-C hepatitis in Hungary

Many cases of acute hepatitis remain undiagnosed and the hepatitis E virus (HEV) is emerging in industrialized countries. The aim of this study was to assess the role HEV as causative agent in acute non-A, non-B, and non-C hepatitis patients in Hungary. 10.5% of the 264 acute non-A, non-B, and non-C hepatitis patients tested had anti-HEV IgG and 1.9% had anti-HEV IgM as tested by ELISA. After confirmation by Western blot 6.1% of the acute non-A, non-B, and non-C hepatitis patients had anti-HEV IgG antibodies only and 1.1% of the patients had both IgG and IgM. All 19 patients that were positive for anti-HEV IgG and/or IgM tested negative for HEV RNA by PCR. Only a small proportion of the acute hepatitis cases in the southwest of Hungary are assumed to be attributed to HEV infection, however, hepatitis E should be considered along with hepatitis A, B, and C in the diagnosis of acute hepatitis.     

Hepatitis E virus infection in Japan

Hepatitis E virus (HEV) is the major etiologic agent of enterically transmitted viral hepatitis in many developing countries. Epidemics are primarily waterborne in areas where water supplies are contaminated with HEV of human origin. There is increasing evidence, however, that HEV is also prevalent in very low numbers in non-endemic countries, including Japan. Although the source of HEV in these sporadic cases is unknown, a recently isolated swine virus is the best candidate for causing a zoonotic form of hepatitis E. The virus is serologically cross-reactive with human HEV and genetically very similar, and the human and swine strains seem to be cross-infective. Very recent evidence has also shown that swine HEV, and possibly a deer strain of HEV, may be related to avian HEV and HEV in other hosts and potential reservoirs. We examined the prevalence of anti-HEV IgM and IgG among patients serologically diagnosed with non-A, non-B, non-C acute hepatitis (n = 126) and compared with a matched control group of 76 individuals. Enzyme-linked immunosorbent assay revealed a significant difference in seroprevalence between the two groups for anti-HEV IgM (5.6% versus 0%), whereas there was no difference for anti-HEV IgG (21.4% versus 26.3%). For confirmed cases of anti-HEV IgM we also detected HEV RNA in sera by means of a sensitive polymerase chain reaction (PCR) assay. This study provides evidence of locally acquired hepatitis E in the Chiba area. Therefore, in cases of unexplained acute hepatitis, the diagnosis of hepatitis E should be considered even in the absence of foreign travel.     

Empty virus-like particle-based enzyme-linked immunosorbent assay for antibodies to hepatitis E virus

Hepatitis E, an enterically transmitted non-A, non-B hepatitis, is a serious viral infection that occasionally causes large epidemics in developing countries. In developed countries, the disease only appears sporadically due to the transmission routes, and it is considered to be less important. The hepatitis E virus (HEV) cannot grow in cultured cells and no reliable assay system has ever been developed. In addition, the present diagnostic are not perfect, and actual rates of HEV infection may be underestimated. Highly purified empty virus-like particles (VLPs) of HEV have been produced by the use of a recombinant baculovirus vector in insect cells. Using these VLPs as an antigen, an enzyme-linked immunosorbent assay (ELISA) for antibodies to HEV was developed. A panel of 164 sera that were randomized and coded, and sera collected periodically from three patients with hepatitis E were used for the evaluation. The sensitivity of the assay was shown to be equal to or better than that obtained in previous research that used the same serum panel. The ELISA demonstrated that the serum IgM level of the patients was highest at the onset of the clinical illness and then rapidly decreased. In contrast, a high level of circulating IgG antibody titers lasted for more than 4 years. In Japan, a non-endemic country, the prevalence of the IgG class antibody to HEV in healthy individuals was found to range from 1.9% to 14.1%, depending on the geographical area. Only one out of 900 (0.1%) serum samples was IgM-positive. The IgM class antibody to HEV was detected in 10.8% of non-A, non-B, and non-C acute hepatitis patients in northeast China, whereas none of the patients in Korea had the IgM antibody. The ELISA utilizing the VLPs is sensitive and specific in its detection of the IgM and IgG antibodies to HEV. The ELISA is therefore useful for diagnosing HEV infection and for seroepidemiological study of hepatitis E.     

Case report: Role of hepatitis E virus in the etiology of community-acquired non-A,non-B hepatitis in greece

The aim of this study was to determine the frequency of hepatitis E virus (HEV) infection in a population of Greek adults with community-acquired (sporadic) non-A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus (anti-HCV). All patients admitted to the Liver Unit of Western Attica General Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis between February, 1986, and May, 1990, were enrolled in follow up studies (n = 66). Nineteen patients with HCV infection and 11 patients with acute non-A, non-B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from this patient showed evidence of anti-HEV seroconversion at the fourth week after the onset of hepatitis. The patient had not travelled abroad or within Greece or had not had apparent contact with people from foreign countries for the previous 3 months. These data show that HEV infection is not a major cause of community-acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive seroprevalence studies are needed for an accurate estimation of the extent of HEV infection in the southeastern European countries. © 1994 Wiiey-Liss, Inc.     

Seroepidemiology of hepatitis E in selected Australian populations

The presence of hepatitis E virus-specific antibodies (anti-HEV) was determined in selected Australian groups. Anti-HEV was detected initially using a recombinant antigen-based enzyme immunoassay (EIA). It was found that 1 of 279 (0.4%) blood donors, 14 of 182 (7.7%) Indochinese refugees, 2 of 89 (2.2%) sera submitted for amoebic serology (generally people who had visited developing countries), 1 of 13 (7.7%) patients with non-A, non-B hepatitis, none of 7 (0%) patients with fulminant non-A, non-B hepatitis, and none of 33 (0%) control sera were repeatedly reactive by the HEV EIA. The positive sera were subjected to further testing using a supplemental immunoblot. Preliminary data suggest that while potentially large numbers of people infected with HEV are entering Australia, no compulsive evidence was found in these particular groups for endemic HEV infection in Australia. This is the first seroepidemiological survey of HEV in Australia. © 1995 Wiley-Liss, inc.     

Seroepidemiological studies on a non-A, non-B hepatitis specific antigen/antibody system (SO-antigen/anti-SO)

The patients and staff members of a haemodialysis unit were examined for their serological responses to SO-antigen, which was isolated from the urine of epidemic type non-A, non-B hepatitis patients at Tohoku University Hospital. To understand how SO-antigen or SO-antigen-related aetiology can be incriminated for the hepatitis found in the haemodialysis unit, the prevalence of SO-antigen/anti-SO system and hepatitis A and B virus-related antibodies was compared in the sera of patients and staff members. Although the SO-antigen was rarely detected in the serum, anti-SO antibody was frequently detected in the sera of patients and staff. A significantly higher prevalence was found in the serum of patients (15%, 54 out of 361) than staff members (7.1%, 13 out of 184) and volunteer blood donors (1%, 3 out of 305). The same prevalence percentages of HBV-related antibodies (either positive for anti-HBs or anti-HBc) and anti-HAV were observed among the patients, staff, and volunteer blood donors, irrespective of whether the sera were anti-SO positive or negative. Among the staff, anti-SO antibody was more frequently found in those with a history of acute hepatitis (16.7%, 3 out of 18) than in those without (6%, 10 out of 166). These prevalence ratios conformed with those of HBV-related antibodies, but the same prevalence ratios of antibody to HAV were observed between the staff with and without a history of acute hepatitis. These results indicate that the SO-antigen/anti-SO system or entity related to this immune system is distinct from HBV or HAV, and this immune system was found widely in the haemodialysis unit where type B and non-A, non-B hepatitis were also found frequently.     

Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays.

BACKGROUND. The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. METHODS. We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. RESULTS. Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. CONCLUSIONS. Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).     

Identity of a novel swine hepatitis E virus in Taiwan forming a monophyletic group with Taiwan isolates of human hepatitis E virus

Recently, we found that more than 10% of the cases of acute non-A, non-B, non-C hepatitis in Taiwan were caused by a novel strain of hepatitis E virus (HEV). Since none of these patients had a history of travel to areas where HEV is endemic, the source of transmission remains unclear. The recent discovery of a swine HEV in herd pigs in the United States has led us to speculate that HEV may also circulate in herd pigs in Taiwan and may serve as a reservoir for HEV in Taiwan. Of 275 herd pigs obtained from 10 pig farms in Taiwan, 102 (37%) were seropositive for serum anti-HEV immunoglobulin G (IgG). A 185-bp genomic sequence within the ORF-2 of the HEV genome was amplified and cloned from serum samples of an anti-HEV positive pig and subsequently from serum samples of a patient with acute hepatitis E. Sequence comparison revealed that the swine and human isolates of HEV share 97.3% identity. Phylogenetic analyses further showed that the Taiwan swine and human isolates of HEV form a distinct branch divergent from all other known strains of HEV, including the U.S. swine strain. To examine the potential risk of cross-species transmission of swine HEV to humans, the seroprevalences of anti-HEV IgG in 30 swine handlers, 20 pork dealers, and 50 control subjects were assessed and were found to be 26.7, 15, and 8%, respectively (for swine handlers versus controls, P = 0.048). Our findings may help provide an understanding of the modes of HEV transmission and may also raise potential public health concerns for HEV zoonosis.     

An enzyme-linked immunosorbent assay for an antigen related to non-A, non-B hepatitis and its antibody: partial characterization of the antigen and chimpanzee transmission

An enzyme-linked immunosorbent assay (ELISA) was developed based on sera from patients convalescent from non-A, non-B hepatitis and haemophilia A patients who had been frequently treated with commercial blood products. Using this ELISA, an antigen was detected which appears to be related to non-A, non-B hepatitis. The antigen is provisionally designated as DS-antigen (DS-Ag). The serum of another patient with haemophilia A, which was strongly positive for the DS-Ag, caused a typical case of non-A, non-B hepatitis in a chimpanzee. DS-Ag could be detected in the serum of the chimpanzee during the acute phase of the infection. The ELISA for DS-Ag reacted with neither hepatitis A or B virus antigens, nor Epstein-Barr virus or cytomegalovirus. The assay was provisionally evaluated using sera from different groups of patients. Out of 17 patients with posttransfusion hepatitis non-A, non-B, 11 were found positive in the ELISA for DS-Ag (65%). As expected, a relatively high prevalence of DS-Ag (9%) was found in patients with haemophilia, who are regularly treated with blood-clotting factor-concentrates. Antibodies to DS-Ag were found in 48% of these patients. The DS-Ag was found in 8 of 1400 (0.6%) volunteer blood donors, and antibody to DS-Ag in 3% of the sera. Remarkably, a high incidence (41%) of antibodies to DS-Ag was found in prostitutes, suggesting that this antigen may be transmitted by a sexual route. The DS-Ag was pelleted by ultracentrifugation for four hours at 100,000g and was found to have a buoyant density of 1.32 g/cm3 in a CsCl gradient.     

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children

BACKGROUND AND PURPOSE: Major hepatotropic viruses continue to be important causes of acute viral hepatitis in developing countries. This work was carried out to detect the seroprevalence of hepatitis E virus (HEV) markers in children with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A, non-B, non-C acute hepatitis, and to ascertain the influence of HEV superinfection in individuals infected with hepatitis viruses (A, B and C). METHODS: We studied prospectively 162 children with sporadic acute hepatitis who reported to our hospital. Thirteen healthy controls were also included in the study. Laboratory investigations were performed, including complete liver function tests. Complete serological profiles for hepatitis viruses A, B, C and E were evaluated. RESULTS: HEV immunoglobulin G was detected with highest percentage among patients with hepatitis B (56.7%), followed by patients with hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus patients and in 3.3% of hepatitis B patients. The prevalence of HEV immunoglobulin G and immunoglobulin M correlated with the levels of hepatic aspartate aminotransferase and alanine aminotransferase in patients with dual markers of infection with hepatitis E and other viruses compared to patients with acute hepatitis due to A and C viruses. CONCLUSIONS: HEV serological markers are common among children with acute viral hepatitis, especially from hepatitis C and B viruses. There may be increased sensitivity to HEV coinfection in association with hepatitis B and C infections. Dual infection with HEV and other hepatotropic viruses was associated with greater elevation of aspartate and alanine aminotransferases.     

Serological evidence for hepatitis E virus infection in Israel

Israel is suspected to be endemic for hepatitis E virus (HEV) because of its geographic location and the large-scale immigration from endemic countries. Although no cases of local HEV infection have been diagnosed, a serological survey would provide indirect evidence for such infection. We examined sera from 1,416 healthy subjects, including 1,139 Jews from various regions of Israel and 277 Arabs, most of whom reside in the West Bank of the Jordan River. In addition, we tested 13 non-A, non-B, and non-C viral hepatitis patients. Sera were screened for antibody to hepatitis E virus (anti-HEV) by a newly developed enzyme immunoassay (EIA) and by immuno-blots for both IgG and IgM anti-HEV activity. Positive samples were confirmed by neutralization. The seroprevalence found by EIA was 2.81% and 1.81% in the Jewish and Arab populations, respectively. More than a 2-fold higher prevalence in males compared to females and an increase with age were found in both populations. However, these differences were nonsignificant. The geographical distribution was even throughout the country, except for two clusters of 3 and 4 seropositive individuals possibly reflecting past foci of infection. Eight of 37 ElA-positive sera were positive for IgG, and 3 were positive for IgM by the immunoblot assay. Among hepatitis patients (9 acute and 4 chronic), one patient with chronic hepatitis was positive for both IgG and IgM. Our study provides indirect evidence that Israel is endemic for HEV. The lack of outbreaks may be attributed to generally good hygienic conditions and a controlled potable water supply, while unrecognized sporadic cases may be due to the unavailability of diagnostic tests. © 1995 Wiley-Liss, Inc.     

SEN virus infection does not affect the progression of non-A to -E liver disease

SEN virus (SEN V) was discovered recently as a potential causative agent of non-A, non-B, non-C, and non-E (non-A to -E) hepatitis. The aim of this study was to obtain information about the prevalence of this virus in Japan and its association with non-A to -E liver disease. Sixty-seven patients hospitalized for non-A to -E liver disease, including hepatocellular carcinoma (19 patients), cirrhosis (7 patients), chronic hepatitis (18 patients), and acute hepatitis (23 patients), were tested, along with 49 blood donors. The patients were admitted to Nihon University Hospital between 1991 and 1998. SEN V DNA was detected by a nested polymerase chain reaction, targeting the 5' untranslated region. SEN V DNA was detected in 14 of 49 (28.6%) blood donors and in 33 of 67 (49.3%) patients with non-A to -E liver disease. The prevalence of SEN V DNA was similar among patients with various liver diseases, including hepatocellular carcinoma (42.1%), cirrhosis (57.1%), chronic hepatitis (55.6%) and acute hepatitis (47.8%) and among blood donors (28.6%). There were no significant differences in the clinical profiles of patients with SEN V DNA-positive or -negative chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Similarly, there were no significant differences in the clinical profiles between patients with SEN V DNA-positive and -negative acute hepatitis. In conclusion, SEN V infection is present among many blood donors and is common in patients with non-A to -E liver disease. There are insufficient data to prove a causal role for SEN virus infection in non-A to -E liver disease.     

Antibodies to hepatitis E virus among chinese patients with acute hepatitis in Taiwan

The prevalence of antibodies to hepatitis E virus (anti-HEV) was investigated in patients with acute hepatitis, and correlated with the clinical features. Sera from 110 patients with acute hepatitis and 60 healthy controls were tested for anti-HEV, antibody to hepatitis C virus (anti-HCV), and hepatitis B surface antigen (HBsAg). There were significant differences in the prevalence of anti-HEV, anti-HCV, and HBsAg between patients and controls (21.8% vs. 0%, 16.3% vs. 1.6% and 58.1% vs. 18.0%, respectively). Anti-HEV was detected in 6 (25.0%) of 24 patients with anti-HCV, 6 (9.3%) of 64 patients with HBsAg, and another 6 (22.2%) of 27 patients with acute hepatitis non-A, non-B, non-C. Anti-HEV was found in 15 men and three women, whose ages ranged from 34 to 75 (median, 57) years old. The median age of patients with anti-HEV was older than that in patients without this antibody (57 vs. 38 years; P = 0.001). The prevalence of anti-HEV in patients with anti-HCV alone (35.2%) was higher than that (11.1%) in patients with HBsAg alone (P = 0.03). Compared to patients without anti-HEV, HEV-infected patients had a higher frequency of travel to a foreign country (P = 0.0001), had a lower HBsAg rate (P = 0.019), and had higher serum alkaline phosphatase levels (P = 0.04) and gamma-glutamyl transpeptidase levels (P = 0.01). In conclusion, HEV infection occurs in 22.2% of patients with acute hepatitis non-A, non-B, non-C. HEV superinfection may occur in patients with chronic hepatitis B or C virus infection. © 1994 Wiley-Liss, Inc.     

Hepatitis E virus (HEV) capsid antigens derived from viruses of human and swine origin are equally efficient for detecting anti-HEV by enzyme immunoassay

The recombinant truncated ORF2 (capsid) antigen derived from the Meng strain of swine hepatitis E virus (HEV) differs from that of the Sar-55 strain of human HEV by approximately 5% at the amino acid level. Serial serum samples from two chimpanzees and six rhesus monkeys experimentally infected with HEV were tested with one enzyme immunoassay (EIA) based on the Sar-55 antigen and with a second EIA based on the Meng antigen. We obtained 98% agreement (kappa = 0.952) by direct comparison. The virtually identical results obtained with these antigens in detecting seroconversion following infection with HEV suggests that they were reacting with antibodies that detect the same or very similar epitopes of HEV. We then tested human and swine serum samples for anti-HEV in EIAs that utilized one or the other of the two ORF2 antigens and showed that these results were also virtually identical. The specimens tested included swine sera from the United States, Canada, China, Korea, and Thailand and sera from veterinarians, U.S. and non-U.S. volunteer blood donors, and U.S. and non-U.S. animal handlers. We tested 792 swine sera and obtained 93% agreement (kappa = 0.839). We similarly tested 882 human sera and obtained 99% agreement (kappa = 0.938). Moreover, we found virtually no difference in the levels of prevalence of anti-HEV as measured by the two tests, again suggesting that the antigens derived from human and swine HEV contain the same immunodominant epitopes.     

Spectrum of hepatitis E virus infection in India

A solid phase enzyme linked immunosorbent assay (ELISA) that detects IgM and IgG to hepatitis E virus (HEV) was used to study seroepidemiology in 40 healthy subjects and 227 consecutive patients with liver diseases in an endemic area. Fifty-two of the liver diseases patients (22.9 percent) had acute hepatitis E. In contrast, none of the 40 healthy subjects were positive for IgM anti-HEV, validating the ELISA assay. Twenty-three of 25 (92%) patients with epidemic non-A, non-B hepatitis were confirmed as having acute hepatitis E. Only 1 of the 10 patients with sporadic, fulminant hepatic failuire of non-A, non-B, non-C etiology was positive for IgM anti-HEV. Five (31.2%) of the 16 patients with acute hepatitis in HBsAg carriers were positive for IgM anti-HEV. One patient with acute hepatitis B wascoinfected with acute hepatitis E. Acute hepatitis was a disease of the adult population, with peak attack rates in the second and third decades of life. This disease was seen in only 4 (16%) of the 25 patients with acute viral hepatitis occurring below 14 years of age. Cholestasis was predominant in 25% of patients, enzyme elevation was monophasic, and all patients had clinical and biochemical recovery from the disease. The data suggest that the majority of patients with acute sporadic non-A, non-B, non-C hepatitis in India have hepatitis E. However, fulminant hepatic failure to sporadic nature is rarely from hepatitis E. © 1994 Wiley-Liss, Inc.     

Seroprevalence of antibodies to hepatitis E virus in the normal blood donor population and two aboriginal communities in Malaysia.

The prevalence of antibodies to hepatitis E virus (HEV) has been examined in many countries, but such studies have generally been limited to majority populations such as those represented in healthy blood donors or cross sections of urban populations. Due to its major route of enteric transmission, large differences in HEV prevalence might be expected between populations in the same country but with different living conditions. Using an ELISA based on GST-ORF2.1 antigen, the prevalence of IgG-class antibodies to HEV was examined in three distinct populations in Malaysia: the normal (urban) blood donor population and two aboriginal communities located at Betau, Pahang and Parit Tanjung, Perak. IgG anti-HEV was detected in 45 (44%) of 102 samples from Betau and 15 (50%) of 30 samples from Parit Tanjung, compared to only 2 (2%) of 100 normal blood donors. The distribution of sample ELISA reactivities was also consistent with ongoing sporadic infection in the aboriginal communities, while there was no significant relationship between HEV exposure and age, sex, or malaria infection. The high prevalence of antibodies to HEV in the two aboriginal communities indicates that this group of people are at high risk of exposure to HEV compared to the general blood donors, and the results suggest that studies of HEV seroprevalence within countries must take into account the possibility of widely varying infection rates between populations with marked differences in living conditions.     

Hepatitis E virus infection in hemophiliacs

Israel is endemic for hepatitis E virus (HEV), the causative agent of enteric non-A, non-B hepatitis. Transmission is via the feco-oral route but the possibility of transmission through blood transfusion has been raised. This question was addressed by examining sera from 188 hemophilic patients in Israel. screening was performed with an enzyme immunoassay (EIA) for antibody against hepatitis E virus (anti-HEV) and confirmed with a neutralization test. Sixteen patients (9%) were seropositive for anti-HEV. A statistically significant difference was not found between the seroprevalence in this group and that of a healthy Israeli control population, matched for sex and age. The anti-HEV-seropositive hemophiliacs had the same seroprevalence of antibodies to hepatitis B and C virus and to HIV and the same number of cases with chronic hepatitis as among the anti-HEV-seronegative patients. The seroprevalence of antibodies to hepatitis A virus (anti-HAV) was, on the other hand, higher in the anti-HEV-seropositive group. This study indicates that HEV is not transmitted by cryopre-cipitate or lyophilized factor concentrates. High prevalence of coinfection with hepatitis A supports our conclusion that HEV infection in Israeli hemophiliacs was due mainly to feco-oral transmission. © 1995 Wiley-Liss, Inc.