Association of graft survival with host response to hepatitis B infection in patients with kidney transplants.

We studied the relation of host response to hepatitis B infection before transplantation with survival of kidney grafts in 79 patients receiving 87 transplants. Antibody to hepatitis B surface antigen (anti-HBs) signaled early graft rejection (median survival congruent to two months), whereas hepatitis B surface antigen (HBsAg) signaled delayed rejection (greater than 22 months). Patients with neither HBsAg nor anti-HBs had graft survival times (median congruent to 16 months) similar to the HBsAg carriers but significantly longer than the anti-HBs-positive patients (p less than 0.01). Similar results were observed when patients who received HLA-identical kidneys or had anti-HLA antibodies before transplantation were excluded. The highest probability of graft rejection was in patients with anti-HBs who received kidneys from male donors. The probability that such grafts would survive for four months was less than 20 per cent. HLA-nonidentical kidneys transplanted into patients with anti-HBs have a poor prognosis, whereas such grafts in HBsAg carriers have as good a prognosis as grafts in uninfected recipients.     

Hepatitis B and delta: the prevalence of seroepidemiological markers in volunteer blood donors and their families]

41 volunteer blood donors and his relatives were studied in order to know about the prevalence of hepatitis B and D virus infections in selected groups. Frequency of HBsAg+ carriers was 0.34 per cent in the Centro Nacional de la Transfusión Sanguínea and 0.15 per cent in the Banco Central de Sangre, IMSS. Most of the HBsAg+ blood donors were 21 to 40 years old (87.8%); 21.9 per cent had IgM antibodies against HBc and just 2.4 per cent were HBeAg positive. Forty one (26.9%) of 152 relatives had one or more of the HBV markers, 3.9 per cent were HBsAg carriers and 1.3 per cent were HBeAg positive. In the infected relatives group 36.6 per cent were ancestory or brothers and just 14.6 per cent of wives were infected. None of the HBsAg+ blood donors or his relatives had antibodies against delta agent. These results support the fact that the frequency of asymptomatic carriers of HBsAg in the volunteer blood donors group is similar to he frequency in the general population and identifies the group of relatives as those with the highest risk to acquire HBV infection.     

Prevalence of delta infection in the western Pacific region

The prevalence of coinfection and superinfection with the delta agent was studied in 2,645 hepatitis B surface antigen (HBsAg)-positive subjects from six countries and nine islands in the Western Pacific region. The study group comprised 262 patients with acute hepatitis B and 2,383 chronic carriers of HBsAg, of whom 278 were suffering from chronic liver disease or primary hepatocellular carcinoma. While major foci of infection were observed in Nauru, Niue, and Western Samoa, delta infection appears to be uncommon in other parts of the region.     

Hepatitis delta virus infections in intravenous drug abusers with hepatitis B in the west of Scotland

The prevalence of delta virus infection was studied in 264 intravenous drug abusers (IVDAs) whose sera were found to be HBsAg positive between 1985 and 1987 and in 15 IVDAs from the period 1971-75, seven from 1976, 15 from 1979, and 37 from 1982. Delta markers were present in 41% of IVDAs with acute hepatitis B and in 65% of those who were chronic HBsAg carriers between 1985-87. The first evidence of delta virus infection was found in 1975. In 1976, 1979, and 1982, respectively, 42, 63, and 5% of IVDAs with acute hepatitis B had delta coinfection. In the West of Scotland, delta infection has been established in the IVDA population since 1975. The very high percentage of IVDA carriers superinfected with the delta virus implies that there will be an excess of patients presenting with severe liver disease in the future.     

Delta agent infection in Melbourne

Evidence of infection with delta agent was sought in 284 patients with acute hepatitis B referred to Fairfield Hospital, Melbourne, between July 1, 1981, and June 30, 1982 and in 127 hepatitis B surface antigen (HBsAg) carriers. Acute and convalescent serum samples from the patients with acute hepatitis B and single or multiple sera from the HBsAg carriers were tested for delta antigen (delta ag) and/or antibody (anti-delta) by solid-phase radioimmunoassay (SPRIA). Evidence of infection was detected in 14.4% of patients with acute hepatitis B and 7.1% of chronic HBsAg carriers. Eighty-eight percent of those in whom delta agent infection was demonstrated were intravenous drug users.     

Detection of hepatitis B virus DNA in the serum of Canadian hepatitis B surface antigen negative,anti-HBc positive individuals,using the polymerase chain reaction

Continuing hepatitis B virus (HBV) infection is normally associated with the presence of hepatitis B surface antigen (HBsAg) in the serum. In spite of sensitive screening assays for HBsAg, rare cases of post-transfusion HBV infection are still observed. Antibody to hepatitis B core antigen (anti-HBc) often indicates remote HBV infection but DNA hybridisation and more sensitive polymerase chain reaction (PCR) assays have demonstrated that some HBsAg negative individuals, positive for anti-HBc, have continuing HBV replication. To determine the incidence of ongoing HBV infection in a Canadian HBsAg negative, anti-HBc positive population we studied three groups with this combination of HBV markers: Group A, 36 patients referred for investigation of raised serum aminotransferases; Group B, 21 Canadian Red Cross blood donors; Group C, seven vaccinees in an Ottawa Health Care Student hepatitis B vaccination programme. The PCR was carried out using a nested PCR reaction with primers specific for the pre-core region of HBV. Seven of 36 (19%) patients in Group A had detectable HBV DNA whereas none of Group B or C were positive. This data indicates that in some HBsAg negative patients with ongoing hepatic inflammation, continuing HBV replication may persist. This was not observed in any healthy blood donors or health care students investigated. Larger studies are required, but this data would suggest that, in Canada, the addition of anti-HBc testing for all blood donors for detection of low level HBV replication would not be indicated. © 1994 Wiley-Liss, Inc.     

Clinical significance of a highly sensitive enzyme immunoassay of hepatitis B surface antigen using a novel electron spin resonance technique.

We developed a highly sensitive enzyme immunoassay (EIA), the p-AP/HHTIO method, that detects serum hepatitis B surface antigen (HBsAg) by measuring stabilized nitroxide radicals using a novel electron spin resonance technique [Matsuo et al. (1998) Free Radic Biol Med 25:929-935]. To demonstrate the clinical significance of this method and to reveal occult hepatitis B virus (HBV) infection in patients, we used the method to analyze serum samples of 30 patients with acute or fulminant hepatitis who were negative for HBsAg by standard EIA, and those of seven chronic HBV carriers who became negative for HBsAg during a follow-up period by standard EIA. We also examined serum HBV DNA by amplification of the HBV S gene, using the polymerase chain reaction (PCR) technique. The p-AP/HHTIO method showed that 9 of 20 (45%) patients with acute hepatitis and 2 of 10 (20%) with fulminant hepatitis were positive for HBsAg; PCR detected HBV DNA in these HBsAg-positive patients. Antibody against hepatitis B core antigen was detected in one patient with fulminant hepatitis. The p-AP/HHTIO method demonstrated prolonged seropositivity of HBsAg even after standard EIA showed a loss of HBsAg in all seven HBV carriers. Our p-AP/HHTIO method is useful for screening and diagnosing HBV infection in patients with liver diseases who are negative for conventional HBV-related serological markers.     

The declining risk of post-transfusion hepatitis C virus infection.

BACKGROUND. The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown. METHODS. From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive. RESULTS. Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 patients receiving transfusions since the addition in May 1990 of screening for antibodies to HCV, the risk was 0.57 percent per patient (0.03 percent per unit). The trend toward decreasing risk with increasingly stringent screening of donors was statistically significant (P less than 0.001). After we controlled for the method of donor screening, the risk of seroconversion was strongly associated (P less than 0.001) with the volume of blood transfused, but not with the use of particular blood components. CONCLUSIONS. The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV. The current risk of post-transfusion hepatitis is about 3 per 10,000 units transfused.     

Influence of hepatitis delta virus superinfection on the clearance of hepatitis B virus (HBV) markers in HBV carriers in Japan

To elucidate the influence of hepatitis delta virus (HDV) superinfection on the clearance of hepatitis B virus (HBV) associated antigens in HBV carriers, we examined for antibody to hepatitis delta antigen (anti-HD) serial sera collected from 1,029 HBV carriers in Kure, Japan. Of the 242 HBV carriers with hepatitis B e antigen (HBeAg), 28 became seropositive for anti-HD, of whom 18 (64.3%) cleared HBeAg; 214 did not become seropositive for anti-HD, of whom 70 (32.7%) cleared HBeAg. Thus, HBeAg clearance was observed in a significantly higher proportion of HDV-superinfected carriers as compared with carriers without HDV infection (P less than 0.005). In the 56 HBV carriers who cleared hepatitis B surface antigen (HBsAg), anti-HD was detected in three cases with increased serum alanine aminotransferase activity preceding HBsAg clearance. The duration of anti-HD seropositive state was less than 5 years, and the titer of anti-HD was relatively low in every case. These data suggest that the HDV infection rate in Japan is higher than previously reported, that HDV superinfection can be one of the factors that induce the HBeAg clearance and HBsAg clearance in HBV carriers, and also that the most likely outcome of HDV superinfection in HBV carriers in Japan may be acute self-limited infection.     

Prevalence and clinical significance of hepatitis D virus co-infection in patients with chronic hepatitis B in Korea

Hepatitis D virus (HDV) infection can cause severe acute and chronic liver disease in patients infected with hepatitis B virus (HBV). Despite the significant decline in the global HDV infection, it remains a major health concern in some countries. This study aimed to investigate the prevalence and clinical features of HDV co-infection in patients with chronic HBV infection in Korea, where HBV infection is endemic. Nine hundred forty patients [median age, 48 (18-94) years; men, 64.5%] infected chronically with HBV were enrolled consecutively. All patients who were positive for hepatitis B surface antigen (HBsAg) for at least 6 months and were tested for anti-HDV. A portion of the HDV delta antigen was amplified, sequenced, and subjected to molecular and phylogenetic analysis using sera from the patients who were anti-HDV positive. Clinical features and virologic markers were evaluated. Inactive HBsAg carriers, chronic hepatitis B, cirrhosis and hepatocellular carcinoma accounted for 29.5%, 44.7%, 17.9%, and 8.0%, respectively. Only three patients were positive for anti-HDV, corresponding to a 0.32% positive rate. All patients who were positive for anti-HDV were inactive HBsAg carriers. HDV RNA could be amplified by PCR from the sera of two patients. Phylogenetic analysis showed that both carried HDV genotype 1. In conclusion, the prevalence of HDV infection is very low (0.32%) in Korea. All HDVs were genotype 1 and detected in inactive HBsAg carriers. Therefore, HDV co-infection may not have a significant clinical impact in Korean patients with chronic HBV infection.     

Hepatitis B virus antigens in liver resections from patients with hepatocellular carcinoma

A high rate of hepatitis B virus (HBV) antigen carriers among patients with hepatocellular carcinoma (HCC) has been recorded from areas of endemic HBV infections in Africa and Asia, but there are only rare and contradictory data for Europe. 12 specimens of resected liver tissue were immunohistologically investigated for hepatitis B surface antigen (HBsAg) as well as for hepatitis B core antigen (HBcAg). HBsAg was contained in non-tumorous liver tissue in 66 per cent of these cases. In two cases detection of HBcAg in the liver provided evidence to replication of the virus. HBcAg plus HBsAg were present in tumour tissue in one case. All of the HBV antigen carriers did not have chronic hepatitis. On the other hand, all patients with chronic hepatitis had HBV antigens in their liver tissue. HBV antigens were detectable in 7 non-cirrhotic livers, but were contained in only one of two cirrhotic livers. These results are likely to suggest a possible relevance of HBV infection to the aetiology of HCC even in central Europe without customary liver cirrhosis.     

Non-B hepatocellular carcinoma: influence of age, sex, alcohol, family clustering, blood transfusion and chronic liver disease

In 144 cases of hepatocellular carcinoma (HCC), 166 cases of cirrhosis without HCC and 142 cases of chronic hepatitis, we examined HBsAg, anti-HBs and anti-HBc in sera and compared the following factors between hepatitis B virus marker-negative and -positive patients: age, sex, alcohol consumption, family clustering of liver diseases, and histories of blood transfusion and post-transfusion hepatitis. Results of this study demonstrated several distinct differences in clinical backgrounds between non-B (negative for HBsAg, anti-HBs and anti-HBc) and B (positive for HBsAg) patients with HCC. Non-B patients were significantly older, had a lower frequency of familial tendencies for liver diseases, and more frequently had cancers other than HCC in their families. Some of these differences were also observed between non-B and B patients with cirrhosis and chronic hepatitis. Among patients with chronic hepatitis, the non-B patients had received blood transfusion or had post-transfusion hepatitis more frequently than the B patients. However, this difference was not apparent in patients with liver cirrhosis or HCC, suggesting that progression of non-A, non-B post-transfusion hepatitis to cirrhosis and HCC may not be as frequent as progression to chronic hepatitis.     

Fulminant hepatitis in asymptomatic hepatitis B surface antigen carriers in Greece

Eleven male fulminant hepatitis (FH) patients (mean age: 47.7 +/- 16 years) positive for hepatitis B surface antigen (HBsAg) but negative for IgM antibody to hepatitis B core antigen (IgM anti-HBc) were admitted consecutively to the Athens Hospital for Infectious Diseases between May 1981 and November 1983. Because of the absence of IgM anti-HBc, determined by an enzyme immunoassay, these patients were considered to be HBsAg carriers with a superimposed acute hepatitis. Three of the 11 patients received immunosuppressive chemotherapy during the six months before the onset of the acute hepatitis. None of the patients was homosexual or a drug addict. Infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis delta virus (HDV) was detected with serologic markers and/or molecular hybridization techniques. Fulminant hepatitis was attributed to spontaneous reactivation of chronic hepatitis B in four patients, chemotherapy-induced reactivation of chronic hepatitis B in three patients, HDV superinfection in one patient and possible superinfection by non-A, non-B agent(s), HDV, or HDV-like agents in three patients. Reactivation of chronic hepatitis B was an important cause of apparent acute hepatitis in heterosexual male HBsAg carriers from an area with a high prevalence of HBV infection.     

Diagnostic value of anti-HBc IgM in high HBV prevalence areas

The diagnostic value of an anti-mu-capture immunoassay for the detection of IgM antibody against hepatitis B core antigen (anti-HBc) was evaluated. Strongly positive results were obtained from the acute phase sera of the 25 acute hepatitis B patients who were hepatitis B surface antigen (HBsAg) positive and of the 18 confirmed acute hepatitis B patients who had already cleared HBsAg when symptoms developed. Negative results were obtained in 5 hepatitis A patients, 20 non-A, non-B acute hepatitis patients serologically susceptible to HBV, 22 patients with chronic hepatitis B liver disease, 15 asymptomatic HBsAg carriers, and 10 healthy patients immune from past HBV infection. Fourteen of the acute hepatitis patients remained HBsAg positive for a follow-up period of at least 6 months, and 12 of these were found consistently anti-HBc IgM negative. These were considered as chronic HBsAg carriers with a superimposed form of acute liver injury. These data show that this assay can differentiate between acute from chronic (HBsAg positive) and recent from old (HBsAg negative) hepatitis B virus infection. Thus, it should be very useful in the complex diagnostic situations encountered commonly in areas with high prevalence of HBV infections.     

Epidemiology of hepatitis B and C in Croatia

The incidence of HBV and HCV infection is hard to determine because of the high number of asymptomatic infections. According to data of the Croatian Institute of Public Health, there are 200 newly infected persons with hepatitis B and approximately the same number of newly identified HBsAg carriers occur each year. Accordingly, Croatia is among the countries with less than 2% of HBsAg carriers in the general population. In these circumstances, HBV infection is most often spread among adolescents and younger adults. The route of transmission is most often sexual (semen) or through the skin in high-risk groups. An increased risk of infection is found in newborns of HBsAg positive mothers, i.v. addicts, promiscuous individuals, male homosexuals, person in close contact with acutely ill or chronic HBsAg carriers, persons that come in contact with blood and other potentially contaminated body fluids, dialysis patients, patients with multiple blood transfusions, patients with transplanted organ or tissue, patients treated for hematologic malignancies and hemophilia, and persons who undergo acupuncture, tattooing or piercing, or travel to areas with a high prevalence of HBV infection. The estimated prevalence of HCV infection marker (anti-HCV) in the Croatian general population is more than 1% and the number of yearly infected with hepatitis C reported to the Croatian Institute of Public Health is around 200 cases. The highest incidence is found in the 20-40 age groups at a high risk of infection by the use of drug injection. At risk are persons who received transfusion of blood or blood products prior to the availability of blood screening of voluntary blood donors.     

Kidney transplantation in hepatitis B surface antigen carriers

Chronic hepatitis B surface antigen (HBsAg) carriers run a high risk of developing chronic liver disease after renal transplantation. To determine the impact of liver disease on long-term morbidity and mortality of HBsAg carriers following kidney transplantation we analyzed 1977 patients, including 76 HBsAg carriers, who underwent renal transplantation during the period 1968–1992. Although the HBsAg carriers had a better 5-year patient and graft survival rate (94% and 83%) than HBsAg-negative patients (87% and 61%), the prognosis was poor after the tenth year of transplantation. Transplant loss is more frequently caused by death of the HBsAg carriers, in contrast to the total population (34% vs 17% for HBsAg-negative patients). Death occurs in 73% of cases due to complications of hepatitis B. In the HBsAg-negative patients, the predominant cause of death is cardiovascular failure (51% vs 11% in HBsAg carriers), whereas only 2% died of liver disease. Kidney transplantation in HBsAg carriers with normal liver function appears to be justified because of rare graft loss due to acute rejection, low early morbidity and mortality, and late onset of fatal hepatic deterioration.Abbreviations HBsAg hepatitis B surface antigen - HBV hepatitis B virus - HBeAg hepatitis B e antigen - GOT glutamic oxaloacetic transaminase - GPT glutamic pyruvate transaminase - GLDH glutamate dehydrogenase - AP alkaline phosphatase - GGT gamma-glutamyl transferase - CHE buturyl cholinesterase - LDH lactate dehydrogenase - HBc hepatitis B core - HDV hepatitis delta virus - HCV hepatitis C virus - CsA cyclosporine A - Aza azathioprine - RIA radioimmunoassay - HD haemodialysis - KTx kidney transplantation - LTx liver transplantation - CMV cytomegalovirus Correspondence to: V Kliem     

Hepatitis B virus concentrations in serum determined by sensitive quantitative assays in patients with established chronic hepatitis delta virus infection.

To clarify the correlation between hepatitis B virus (HBV) DNA levels and serum alanine aminotransferase (ALT) levels in patients with established chronic hepatitis delta virus (HDV) infection, sensitive HBV quantitative assays were used for the study. Thirty-four consecutive patients with chronic liver disease who were positive for both hepatitis B surface antigen (HBsAg) and antibody to HDV (anti-HDV), including 19 patients with chronic hepatitis, 8 patients with liver cirrhosis and 7 patients with hepatocellular carcinoma. All were negative for hepatitis Be antigen (HBeAg) and positive for antibody to HBeAg. HBV DNA was detected in 25 (73.5%) of the 34 patients using real-time detection PCR, and the HBV DNA levels of these patients were significantly lower compared with HBeAg status and ALT level-matched patients with chronic liver disease positive for HBsAg but negative for anti-HDV. There was no correlation between serum HBV DNA and ALT levels among the 34 patients with chronic liver disease positive for anti-HDV. Whereas serum ALT levels in anti-HDV-positive HBsAg carriers with HDV RNA were significantly higher than those without HDV RNA. Liver damage in patients with established chronic HDV infection may be caused mainly by ongoing HDV infection not by HBV replication.     

Seroepidemiological study of hepatitis delta virus infection in Okinawa,Japan

A seroepidemiological study on hepatitis delta virus (HDV) infection was conducted in the Oki-nawan islands, the area of Japan where hepatitis B virus infection is most prevalent. The subjects of this study included 116 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 48 patients with chronic hepatitis (CH), 19 with liver cirrhosis (LC), and 11 with hepatocellular carcinoma (HCC). Among the 194 serum samples examined, a total of 10 (5.2%) were anti-HDV sero-positive. Anti-HDV was detected in 2 (1.7%) of the 116 asymptomatic HBsAg carriers, in 3 (6.3%) of the 48 patients with CH, and in 5 (26.3%) of the 19 with LC. However, none of the patients with HCC had detectable anti-HDV. Eight of the 10 were born in the Miyako island group and the remaining 2 on the main island of Okinawa. Since the subjects included 34 individuals who were living and/or born in the Miyako islands, the positive rate of anti-HDV in the islands was 23.5%. This study demonstrates the existence of an endemic area of HDV infection in Japan. © 1995Wiley-Liss, Inc.     

The serology of delta hepatitis and the detection of IgM anti-HD by EIA using serum derived delta antigen

A sensitive and specific capture assay for IgM antibody to hepatitis D virus (HDV) was developed employing serum-derived delta antigen (HDAg). In a retrospective and prospective study of an outbreak of hepatitis B (HB), 135 hepatitis B surface antigen (HBsAg) positive drug-abusers with acute hepatitis and 18 HBsAg carriers, attending various hospitals and clinics in Dublin, were found to be infected with HDV. Serological follow-up was available from 24 of those with acute hepatitis allowing a comparison of the duration and level of IgM anti-HD with the more commonly used markers, HDAg and anti-delta (anti-HD), and an assessment of the usefulness of each. HDV and HB serology was grossly altered by human immunodeficiency virus (HIV) in two patients, with severe clinical manifestation in one. All 135 patients with HDV co-infection had delta antigenaemia. In co-infections with optimum sampling times, the mean duration of delta antigenaemia was 21 days. IgM anti-HD was always found between HDAg and sero-conversion to anti-delta and was the only 'window' marker present in five cases. The mean duration of IgM anti-HD was four weeks (optimum at 2.8 weeks) and was of moderate or low titre and occurred simultaneously with HDAg in 78%. In HDV-infected HBsAg carriers, high-titre IgM anti-HD (greater than 1/10,000) persisted for the duration of the study and is a useful indicator of chronic HDV infection. IgM anti-HD was not found in 202 random blood donors nor in 205 patients with non-B hepatitis or other disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection

Although occult hepatitis B virus (HBV) infection (HBV-DNA in serum in the absence of hepatitis B surface antigen [HBsAg]) is common in chronic hepatitis C, its characteristics are not well known. In this work, the presence of HBV-DNA (by polymerase chain reaction; PCR) and its distribution (by in situ hybridization) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 32 patients with chronic hepatitis C and occult HBV infection and in 20 HBsAg chronic carriers were determined. The results showed that serum HBV-DNA levels were statistically lower (P = 0.001) in patients with occult HBV infection than in HBsAg chronic carriers. The HBV infection pattern in liver cells was identical between patients with occult HBV infection and those with chronic hepatitis B. However, the mean percentage of HBV-infected hepatocytes was significantly lower (P = 0.001) in patients with occult HBV infection (5 +/- 4.44%) than in HBsAg chronic carriers (17.99 +/- 11.58%). All patients with chronic hepatitis B have HBV-DNA in their PBMCs while this occurred in 50% of the cases with occult HBV infection. In conclusion, patients with occult HBV infection have a low number of HBV-infected hepatocytes and this fact could explain the lack of HBsAg detection and low viremia levels found in these cases.