Changing aetiologic patterns of acute viral hepatitis in Taiwanese children

During 1981-86, 76 children were diagnosed as having acute viral hepatitis at the Department of Pediatrics, National Taiwan University Hospital, which is a major referral centre for hepatitis in children in northern Taiwan. The majority (64%) of children had acute hepatitis B which had occurred mainly during infancy. Perinatal transmission from a hepatitis B e negative surface antigen (HBsAg) carrier mother or infection through blood transfusion from a donor who had escaped notice by a less sensitive screening test (reverse passive haemagglutination test) for HBsAg were the two important modes of transmission of hepatitis B virus. The number of cases of acute hepatitis B declined after 1984, with the beginning of the nation-wide hepatitis B vaccination programme. Due to an outbreak of hepatitis A in northern Taiwan in 1982, the number of cases of hepatitis A peaked that year. Subsequently, cases of acute hepatitis A decreased remarkably. Better socio-economic conditions and improved hygiene might have contributed to the marked decrease of viral hepatitis A. The frequency of non-A, non-B hepatitis remained stable during the study period. It is possible to conclude that the aetiologic pattern of acute hepatitis in Taiwanese children changed during the past 6 years: clinical cases of hepatitis A and B decreased, probably because of more effective control of hepatitis A and B virus infections, whereas the control of non-A, non-B virus apparently requires further efforts.     

New technologies for the inactivation of infectious pathogens in cellular blood components and the development of platelet substitutes

Despite the increased safety of blood components, achieved through improved donor selection and testing, transfusion recipients remain at risk of transfusion-associated diseases. Transfusion of cellular blood components has been implicated in transmission of viral, bacterial and protozoan diseases. While it is commonly recognized that hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), and retroviruses, such as human immunodeficiency virus (HIV) and the human lymphotrophic viruses (HTLV), can be transmitted through cellular components, other pathogens are emerging as potentially significant transfusion-associated infectious agents. For example, transmission of protozoan infections due to trypanosomes and Babesia have been reported. In addition to viral and protozoan infectious agents, cases of bacterial contamination of platelet and red cell concentrates continue to be reported and may be an under-reported transfusion complication. More importantly, new infectious agents continue to enter the donor population, and there is an inherent time delay before the new pathogens are definitively identified and new tests implemented in order to maintain consistent safety of the blood supply. The paradigm for this problem is the HIV pandemic.During the past decade a number of methods for inactivating infectious pathogens in platelet concentrates have been investigated as a strategy to improve the safety of platelet transfusion therapy. One method of treating platelet concentrates to inactive pathogens has now reached the advanced clinical trial phase in the United States and Europe. Similar efforts with a new class of compounds are underway for red cell concentrates, and two of these are in early phase trials. In addition to studies with allogeneic platelets and red cells, a number of laboratories have described methods for developing platelet substitutes or modified platelets to avoid the use of traditional platelet concentrates as a means to improve safety.     

Transfusion of plasma from a blood donor induced hepatitis E in Rhesus monkey

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) infection is normally transmitted via the faeco-oral route. The possibility that the infection might be transmissible by blood has been suggested. Direct evidence of blood-borne transmission of hepatitis E infection is, however, absent. MATERIALS AND METHODS: In this report, 10 ml of plasma obtained from a healthy, but hepatitis E viraemic, blood donor was transfused to a Rhesus monkey. RESULTS: Acute hepatitis E developed following transfusion of blood from the hepatitis E viraemic donor. This was confirmed by virological, immunological, biochemical and histopathological data. CONCLUSIONS: These results, combined with other epidemiological findings previously reported, indicate that transfusion-associated hepatitis E can occur. The risk of transfusion-associated HEV infection in endemic areas should be assessed and strategies developed to reduce it.     

The risks of transfusion-transmitted infection: direct estimation and mathematical modelling

Direct measurement of the risk of transfusion-transmitted infection (TTI) is practical and accurate only if the level of risk is high. Historically, studies that established frozen repositories of transfusion recipient and/or blood donor samples were important in establishing the risk of many TTI agents, including the human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). However, given the current very low risk of TTI, mathematical modelling is necessary to estimate the magnitude of such a risk. For agents for which routine blood donor screening is performed, most of this risk comes from transfusion of units collected in the window period between donor infection and a positive blood screening assay. The incidence/window period model has been used to estimate the magnitude of such risks (of the order of 1:100 000 to 1:1 000 000) and for predicting the extent of risk reduction that can be expected with implementation of new tests. Direct estimation and mathematical modelling approaches are both important tools for future assessment of potential, new or emerging TTI agents.     

Post-Transfusion Hepatitis: Current Risks and Causes

Viral hepatitis which follows transfusions (post-transfusion hepatitis) may be due to those transfusions, i.e., transfusion-transmitted hepatitis (TTH), or may be incident to the reason for the transfusion and, thus, may be transfusion-associated, but not transfusion-transmitted. The current risks of TTH, today, are extremely small, but are still due, primarily, to the hepatitis B virus (HBV) and the hepatitis C virus (HCV), the latter, formerly being known as “non-A, non-B hepatitis.” The residual, now, of TTH which is non-A, non-B, and non-C is extremely small and may be due to a variety of agents. Using volunteer (unpaid), repeat, blood donors, who are carefully screened for hepatitis risk factors and then tested for evidence of HBV infection, the risk of HBV being transmitted by a transfusion today is in the order of 1 per 63,000 units of blood. For transfusion-transmitted HCV, with the same repeat, volunteer (unpaid) donors, careful screening and a sensitive assay for anti-HCV, the risk is in the order of 1 in 125,000 units. These risks of HBV and HCV due to transfusions are so small that other means of acquiring these viruses should be sought when patients develop hepatitis following blood transfusions. However, efforts to further reduce the current risks of HBV and HCV transmission by transfusions should continue; these include restricting transfusions to those which are necessary or appropriate, utilizing alternatives to transfusion, employing novel assays to detect viral nucleic acids, and, finally, implementing various microbial inactivation techniques on blood, blood components and plasma derivatives.     

Prospective controlled study of posttransfusion hepatitis after cardiac surgery in a large referral hospital in India

ABSTRACT— We studied the risk of post-transfusion hepatitis (PTH) in recipients of blood collected from voluntary donors screened for HBsAg. Two hundred and fifty patients without any previous history of liver disease or transfusion were followed up for 12 months subsequent to cardiac surgery. Thirty-five of them had closed-heart surgery without receiving transfusion and served as controls. The remaining 215 patients received single-point transfusions (mean 4 ± 2.4 units). None of the controls and 15 (6.9%) blood recipients developed PTH. Three (20%) patients had hepatitis-B-virus-induced hepatitis while the remainder (80%) had non A, non B (NANB) hepatitis. The number of units of blood transfused and surrogate markers for development of PTH (donor alanine aminotransferase, anti-HBc and anti-HBs antibody) were not associated with the occurrence of PTH (p>0.05). Nine (60%) of the 15 patients developing PTH were asymptomatic. All the patients recovered from the PTH, except one who died of fulminant hepatitis. At the end of 1 year of follow-up, none of the patients had evidence of chronic hepatitis. Only three (25%) of the patients with NANB-PTH developed anti-hepatitis C virus (HCV) antibody during the follow-up. We conclude that the incidence of PTH in India is similar to other parts of the world and NANB virus was the major cause of the PTH. The absence of chronicity and lack of seroconversion to anti-HCV antibody in the majority of the patients after 1 year of follow-up may suggest the possibility of a NANB virus other than HCV as the major cause of PTH in India.     

Prevalence and screening costs of hepatitis C virus among Ugandan blood donors

BACKGROUND: Screening donated blood for hepatitis C virus (HCV) is important for HCV prevention and is routinely practiced in North America and Europe. However, in many African countries little is known about HCV prevalence or cost-effectiveness of HCV antibody (anti-HCV) screening. METHODS: We investigated 2592 plasma specimens collected consecutively from blood donors in central Uganda in 1999. Routine screening by the blood bank included human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and syphilis. To assess HCV prevalence and cost-effectiveness of testing, specimens were additionally tested for anti-HCV IgG by enzyme immunosorbent assay (EIA). Specimens repeatedly reactive (RR) on EIA were tested with a recombinant immunoblot assay (RIBA). RESULTS: Overall, 107 (4.1%) specimens were HCV EIA RR. Fifteen EIA RR specimens (0.6%, 95% confidence interval = 0.3-0.9%) were RIBA positive and 47 (1.8%) were RIBA indeterminate. Most (80%) RIBA-positive specimens were non-reactive for HIV, HBsAg, and syphilis. RIBA positivity was not associated with donor age, sex, number of donations, HIV, or HBsAg positivity. Costs of screening donors for anti-HCV by using EIA were estimated at US Dollars 782 per potential transfusion-associated HCV infection (exposure to RIBA-positive blood) averted. CONCLUSIONS: Current screening tests for other infections are ineffective in removing HCV-positive donations. Testing costs are considerable; cost-effectiveness of identifying HCV-infected donors will be critical in decision making about HCV screening in Uganda.     

Effect of hepatitis C antibody screening in blood donors on post-transfusion hepatitis in Taiwan

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients in Japan

Hepatitis B surface antigen is widely used in hepatitis B virus surveillance; patients who test negative for the antigen are judged to be uninfected. However, occult hepatitis B virus infection has been confirmed with hepatitis B virus DNA at low levels in the liver and peripheral blood in patients positive for hepatitis B core antibody or hepatitis B surface antibody, even if they test negative for hepatitis B surface antigen. To investigate the prevalence of occult hepatitis B virus in hemodialysis patients, we performed cross‐sectional analysis of 161 hemodialysis patients in two related institutions for hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody. Hepatitis B surface antigen, hepatitis B core antibody, or hepatitis B surface antibody was present in 45 patients (28.0%). Hepatitis B virus DNA was present in six patients (3.7%), all of whom also tested positive for hepatitis B core antibody. Hepatitis B surface antibody positivity was unrelated in only one of the six patients. Four of the six patients were positive for hepatitis B surface antigen; however, two (1.3%) of these with occult hepatitis B virus infection were found to be hepatitis B surface antigen negative. Occult hepatitis B virus infection may be missed in hepatitis B virus surveillance using hepatitis B surface antigen alone; therefore, routine hepatitis B core antibody screening is necessary. Patients who test positive for hepatitis B core antibody should undergo further hepatitis B virus DNA testing to enable accurate hepatitis B virus screening.     

Clinical features and etiology of hepatocellular carcinoma arising in patients with membranous obstruction of the inferior vena cava: in reference to hepatitis viral infection

BACKGROUND AND AIMS: Budd-Chiari syndrome (BCS) comprises hepatic vein thrombosis and inferior vena cava (IVC) obstruction known as membranous obstruction of the IVC (MOVC). The latter is frequently complicated by hepatocellular carcinoma (HCC).The etiology of MOVC-associated HCC in relation to hepatitis viral infection is not known. In this study, we investigated the clinical features and etiology of HCC in MOVC. METHODS: Membranous obstruction of IVC and HCC were diagnosed and studied by using imaging techniques. Sera from patients with MOVC, complicated by HCC, were examined for hepatitis viral antigens and antibodies (hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to hepatitis B core antigen (anti-HBc) and third generation antibody to hepatitis C virus (anti-HCV)) and for hepatitis viral nucleic acids (hepatitis B virus (HBV)-DNA, hepatitis C virus (HCV)-RNA, hepatitis G virus (HGV)-RNA and TT virus DNA). RESULTS: We studied 12 patients with BCS who were seen between April 1968 and February 1999. All of them had MOVC. Hepatocellular carcinoma developed in three (25%) of them. There were no obvious differences in the clinical features and imaging findings concerning MOVC between patients with and without HCC. Hepatocellular carcinoma in these three patients showed no clear trend in clinical features and imaging findings. Of the hepatitis viral markers examined, HBsAg, anti-HBc and HBV-DNA were positive in only one of three patients with HCC and all of the viral markers were negative in the other two patients. CONCLUSIONS: Chronic congestion in the liver, caused by an outflow block of hepatic veins and subsequent histopathologic change, must have led to HCC in two patients without any hepatitis viral markers. Patients with MOVC should be followed closely as a high-risk group for HCC.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

Pilot study for hepatitis virus screening among employees as an effective approach to encourage employees who screened positive to receive medical care in Japan

Aim

Countermeasures against hepatitis B and C virus (HBV, HCV) infection at work sites in Japan have not yet been implemented. This study aimed to determine the status of viral hepatitis infection among employees in Japan.

Methods

We undertook a workplace‐based cross‐sectional study from 2011 to 2016 in Hiroshima, Japan. Hepatitis B virus and HCV markers were identified during a routine checkup of employees in 15 enterprises. The screening results were sent to employees directly and not to employers. A thorough examination of the participants who screened positive was encouraged by forwarding to them a referral letter by our research group to specialized medical institutions.

Results

Of the 3015 employees, 2420 (80.3%) underwent hepatitis virus screening. Of these, 13.8% had been screened for hepatitis virus before this survey. The prevalence of hepatitis B surface antigen was 0.95% (n = 23; 95% confidence interval, 0.6–1.3%). The prevalence of hepatitis B core antibody was as high as 31.5% at age 60–69 years, and 41.5% at age 70 years and over. The HCV carrier rate was 0.45% (n = 11; 0.2–0.7%) and 54.5% of them had genotype 2. Thirty‐four carriers were detected, and 44.1% of them were detected for the first time; 53.3% of the newly detected carriers visited medical institutions with the referral, and underwent a periodic follow‐up or treatment.

Conclusion

Promoting hepatitis virus screening for employees may help detect carriers who are unaware of their infection and require treatment. Submitting the results to employees with a referral letter to medical institutions at the time of positive diagnosis may be effective.     

Update on the management and treatment of viral hepatitis

This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.     

Sensitivity of individual donor nucleic acid testing (NAT) for the detection of hepatitis B infection by studying diluted NAT yield samples

BackgroundScreening blood donors for the presence of hepatitis B virus surface antigen (HBsAg) has been the backbone of blood safety. However, occult hepatitis B infection (OBI) in donors can be missed when only HBsAg screening is used. Nucleic acid testing (NAT) is capable of detecting OBI among donors. The aim of our study was to analyse the sensitivity of NAT for detecting OBI.ResultsOf the 18 samples studied, nine were NAT-reactive at a dilution of <1:4 and five out of these showed presence of antibody to core antigen (IgG+IgM). Antibody to surface antigen was present in only two of the nine NAT-reactive samples, one with antibody to core antigen and the other without. Six had a viral load in the range from <10 to 38 IU/mL whereas the viral load in the remaining three samples was not determined. Among the other nine samples which were NAT-reactive at dilutions ≥1:4, antibody to core antigen (IgG+IgM) was present in seven.DiscussionOur study showed that ID-NAT testing along with HBsAg screening could detect most potentially HBV infectious donors (including those with OBI). NAT screening for HBV on diluted samples could compromise blood safety because samples with a low viral load will escape detection.     

Progression of the proportion of hepatitis B virus precore stop mutant following acute superinfection of hepatitis C

To examine the progression of the proportion of hepatitis B virus (HBV) precore stop mutant (codon 28 of precore sequence; TGG to TAG) in the viral population of patients with dual hepatitis virus (B and C) infection, a series of serum samples obtained from six cases with chronic hepatitis B with acute hepatitis C superinfection were analysed by the method of amplification-created restriction site. At the time of superinfection, all patients included in the study were negative for hepatitis B e antigen and positive for its antibody. During the follow up of 30-90 months, in five of the six patients, three different patterns were observed: (i) the proportion of precore stop mutant increased in the first 20 months after acute hepatitis C virus superinfection and then decreased progressively thereafter (two cases); (ii) the proportion of precore stop mutant decreased progressively after superinfection (two cases); and (iii) no precore stop mutant was found during the course (one case).The remaining patient showed a progressive increase in the proportion of precore stop mutant over a period of 9 months after superinfection. Rather than the progressive increase in the proportion of precore stop mutants during the natural course of chronic HBV infection alone, the results of the present study showed a reverse course of progression following acute hepatitis C virus superinfection. This observation raised the possibility of a preferential or accumulative suppression on precore stop mutant by hepatitis C virus in the later stage of dual infection.     

Epidemiology and Prevention of Transfusion-Associated Human Immunodeficiency Virus Transmission in Sub-Saharan Africa

Background and objectives: Compared to industrialised nations, countries in sub-Saharan Africa experience a greater amount of transfusion-associated HIV transmission due to high rates of transfusion in some groups of patients, a higher incidence and prevalence of HIV infection in donor populations, a lack of HIV antibody screening in some areas, and a higher residual risk of contamination in blood supplies despite antibody screening. Materials and methods: Epidemiologic review. Results: Epidemiologic evidence supports the effectiveness of three relatively inexpensive strategies to prevent transfusion-associated HIV transmission in sub-Saharan Africa: HIV antibody screening, avoidance of unnecessary use of blood products, and exclusion of donors at high risk of infection. Such prevention strategies have not been universally implemented. Conclusions: International aid to establish and maintain HIV antibody screening programmes, implementation of sound criteria for transfusion, and the search for HIV risk factors to use as donor exclusion criteria must be expanded in the region.