Combined Hepatitis Research Articles

Prevention of hepatitis B virus infection from hepatitis B core antibody‐positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation

Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.

Shantha Biotechnics has launched a combination diphtheria, tetanus, pertussis and hepatitis B (DTPH) vaccine [Shantetra] in India.

Shantha Biotechnics has launched a combination diphtheria, tetanus, pertussis and hepatitis B (DTPH) vaccine [Shantetra] in India.

Combination hepatitis C virus antigen and antibody immunoassay as a new tool for early diagnosis of infection

Reduction of the window period of hepatitis C virus (HCV) infection represents an important goal in the transfusional and diagnostic setting. A prototype assay designed to simultaneously detect circulating HCV antigen and anti-HCV, has been developed. Aim of this study was to evaluate the performance of this new assay in terms of specificity and sensitivity and to compare its efficacy with commercial assays. To evaluate the specificity of the assay, 400 samples from the general population and 100 'difficult' sera, negative for anti-HCV, were tested. To assess sensitivity, the new test was used on 76 PCR-positive and anti-HCV negative sera, seven natural or commercial seroconversion panels that included 17 RNA-positive and anti-HCV negative sera and 31 anti-HCV positive sera, 20 weak anti-HCV positive sera, 80 viraemic and anti-HCV-positive sera from patients infected with different subtypes and 10 sera from patients with HBV-HCV or HIV-HCV co-infections. Of 500 anti-HCV negative samples, 499 (99.8%) were negative with a cut-off index <0.5, while one sample was within the grey zone. Of the 93 HCV-RNA positive and anti-HCV negative sera from patients and panels, 85 (91.4%) resulted positive, and one had the cut-off index in the grey zone. The reduction in the diagnostic window period observed with the new test and HCV-RNA assays were equal, on average, to 24 and 34.4 days respectively. All anti-HCV positive sera were positive. The new assay shows high sensitivity and specificity and could be a useful tool not only in the diagnostic setting, where procedures to reduce the window period, such as antigen or HCV-RNA detection, are not currently recommended, but also in the screening of blood donations, when nucleic acid technologies is not feasible because of costs, organization, emergency and/or logistic difficulties.

Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1–11-year-old children

This study was conducted to compare the reactogenicity, immunogenicity and safety of a combined two-dose (0, 6 months) hepatitis A and B vaccine (720 EL U HAV, 20 mcg HBsAg) with the established three-dose (0, 1 and 6 months) hepatitis A and B vaccine (360 EL U HAV, 10 mcg HBsAg). A total of 511 children aged 1–11years who had not previously received a hepatitis A or B vaccine were enrolled in the study. Both vaccines were well tolerated, and were shown to be safe and immunogenic. The analysis, stratified according to two age groups (1–5 year and 6–11-year-old children) demonstrated that the reactogenicity profile of the two-dose schedule was at least as good as that of the established schedule. Both vaccines and schedules provided at least 98% seroprotection against hepatitis B and 100% seroconversion against hepatitis A, 1 month after the end of the vaccination course (Month 7).

Sinovac Biotech has launched its combined hepatitis A-hepatitis B vaccine, Bilive, in China.

Sinovac Biotech has launched its combined hepatitis A-hepatitis B vaccine, Bilive, in China.

Prevalence of hepatitis B surface antigen in vaccinated children and controls in rural Nigeria

To determine the prevalence of hepatitis B surface antigen (HBsAg) amongst vaccinated children and controls aged 1-4 years in a rural community in mid-western Nigeria. The vaccinated children had received at least three doses of hepatitis B vaccine. The vaccines included recombinant hepatitis B vaccine at birth and a combined diphtheria, tetanus, pertussis (whole cell) plus hepatitis B (DTPw-HBV) vaccine. HBsAg was determined by a rapid immunoassay method based on the immunochromatographic sandwich principle. Two hundred and twenty-three children and 219 controls were recruited into the study. The prevalence of HBsAg was significantly lower in the vaccinated group (1.3%) than in the control group (4.6%, p=0.04). The prevalence rates were significantly higher in males (p=0.02) and two-year birth cohort (p=0.01). The controls were estimated to be at a six-fold higher risk of being positive for the surface antigen than the vaccinated children. The vaccine effectiveness was estimated to be approximately 80%. These results confirm that hepatitis B vaccine protects against hepatitis B surface antigen carriage and confirm immunogenicity of the combined DTPw-HBV vaccine.

Drug-induced acute liver failure

Acute liver failure is the most severe expression and represents the first cause of fatalities related to drugs. As a consequence, it is also the first cause of drug withdrawal from the pharmaceutical market. The incidence of drug-induced hepatotoxicity in the general population has been recently estimated to be around 14/100,000 inhabitants in a Western country. Drugs appear to be responsible for 10-52% of all causes of acute liver failure. In Western countries, paracetamol (acetaminophen) represents the first cause of all liver failures. The contribution of non-paracetamol drugs given at normal doses is equivalent to that of combined viral hepatitis A and B. The natural prognosis varies between drugs. The spontaneous mortality rate ranges from 32% to 50% for paracetamol intoxication and more than 75% for other drugs. The preventive occurrence of drug hepatotoxicity and the course to acute liver failure is rather limited. It is recommended to stop the administration of a suspected drug when alanine aminotransferase levels increase to more than 3-5 times the upper limit of normal. In paracetamol intoxication, the rapid administration of N-acetylcysteine is a classical antidote. At the stage of liver failure, treatment is mostly supportive. Since irreversible damage is unpredictable, early transfer to a transplantation centre should be considered.

Efficiency of the incorporation of the hepatitis A vaccine as a combined A + B vaccine to the hepatitis B vaccination programme of preadolescents in schools

In 1998, the Department of Health of Catalonia (Spain) began universal vaccination of preadolescents against hepatitis A by replacing the simple hepatitis B vaccine with a combined hepatitis A + B vaccine. Economic analyses were made of the two alternative strategies: to continue with the simple hepatitis B vaccination or to replace the simple vaccine with a combined hepatitis A + B vaccine. The analysis was made from the societal perspective and the time horizon considered was 25 years. In the base case, (estimated annual hepatitis A incidence of 15 per 100,000 and incremental price of the hepatitis A + B vaccine over the simple hepatitis B vaccine of €1.98) the net present value of the programme was positive (€+533,708) and the benefit-cost ratio was 2.58. If the estimated disease incidence were reduced by half, the programme would still be efficient.

Interleukin (IL)‐4, IL‐10, IL‐18 and IFN‐γ Cytokines Pattern in Patients with Combined Hepatitis C Virus and Schistosoma mansoni Infections‡

Schistosoma mansoni infection is characterized by a strong T-helper type 2 (Th2) cell-associated immune response, but in the case of viral infection, it is associated with interferon-gamma (IFN-gamma) increase and induction of Th1 immune response. Few data are available about the immune response of cases infected with combined hepatitis C virus (HCV) and schistosomiasis. Thus, the investigation of the cytokine pattern in patients coinfected with both HCV and Schistosoma mansoni was our rationale. This study included four patient groups: Group 1 included 20 patients infected with chronic HCV, Group 2 included 15 patients infected with schistosomiasis alone, Group 3 included 20 patients with chronic HCV and schistosomiasis and Group 4 included 15 healthy control individuals with matched age and sex. Serum levels of IFN-gamma, interleukin (IL)-4, IL-10 and IL-18 were measured in all groups by enzyme-linked immunosorbent assay. The results showed that the patients infected with HCV had significantly higher serum levels of IFN-gamma and IL-18 compared with the controls and with the patients with schistosomiasis and coinfection (P < 0.001). On the other hand, serum levels of IL-4 and IL-10 were significantly higher in patients with schistosomiasis and coinfection compared with the control group (P < 0.001 and 0.0001, respectively) and with the HCV patients (P < 0.05 and P < 0.001, respectively). A significant increase in serum levels of IL-4 and IL-10 was also found in HCV patients compared with the control (P < 0.05). Schistosomiasis appears to induce a Th2 cytokine profile, with increase in serum levels of IL-4 and IL-10, even in the presence of HCV coinfection. In conclusion, schistosomiasis may downregulate the stimulatory effect of HCV on Th1 cytokines and this may lead to the chronicity of HCV infection in coinfected patients.

Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles–mumps–rubella or a diphtheria–tetanus–acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12–18 months

Two studies were undertaken to investigate the concomitant administration of combined hepatitis A/B vaccine with a diphtheria–tetanus–acellular pertussis-inactivated poliomyelitis vaccine mixed with Haemophilus influenzae vaccine (DTPa-IPV/Hib), or with a measles–mumps–rubella vaccine (MMR), during the second year of life. On completion of the vaccination course, all subjects were seropositive or seroprotected against all antigens except for one subject who was seronegative for anti-PT. Seropositivity and seroprotection rates for all other antibodies were comparable to reference values for each vaccine component, indicating that the immunogenicity of MMR, DTPa-IPV/Hib and combined hepatitis A/B vaccines is not impaired by co-administration. All vaccines were well tolerated.

A two-dose schedule for combined hepatitis A and B vaccination in children aged 6–15 years

A combined hepatitis A and B vaccine, Twinrix, in a paediatric formulation for ages 1–15 years and in an adult formulation for those ages 16 years and older, became commercially available in Turkey as well as in many countries. It is administered according to a three-dose schedule (0, 1 and 6 months). A reduction in the number of doses would improve the compliance rate and reduce administration costs. Therefore, we planned a trial evaluation of the immunogenicity, safety and reactogenicity profile of a high-dose combined hepatitis A and B vaccine, administered in two doses, compared with the profile of a paediatric-dose combined vaccine, administered in three doses, in healthy children aged 6–15 years. One hundred children were randomly attributed to the two study groups. The first group (paediatric-dose vaccine group) received the licensed Twinrix Paediatric, at months 0, 1 and 6; the second group (high-dose vaccine group) received the high-dose vaccine, following a 0, 6 months schedule. The reactogenicity was assessed after each vaccine dose. The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. Both formulations of the combined vaccine were well tolerated. The high-dose combined vaccine administered in two doses, elicits satisfactory immunogenicity profiles, similar to those elicited by the paediatric vaccine administered in three doses. On completion of the vaccination schedule in the two groups all children were protected against hepatitis B and immune for hepatitis A. Anti-HAV GMTs after completion of the vaccination schedule were 7163 ml U/ml in the paediatric-dose group, 8241 ml U/ml in the high-dose group; anti-HBs GMTs were 8679 and 4583 ml U/ml, respectively. These results indicate that a two-dose schedule, compared with the standard three-dose schedule, offers fewer injections for satisfactory protection against the two infections. This means fewer clinic visits, lower administration costs, better compliance, and higher coverage rate. Therefore, this two-dose schedule can be considered an appropriate regimen for the immunization of children and adolescents against hepatitis A and B infection, in the context of school-based immunization programmes.

Reactogenicity profile of a combined hepatitis A and B vaccine in clinical practice: a naturalistic study in adult travellers

A prospective observational naturalistic study was conducted to assess the reactogenicity of the combined hepatitis A and hepatitis B (HAB) vaccine in a real-life setting. All healthy candidates for HAB vaccination attending an adult vaccination centre between October 1998 and February 2000 were invited to participate in the study. A follow-up diary card was provided to subjects to record local and general symptoms during a 4-day follow-up. Intensity was graded from 1 to 3. Redness was recorded as presence or absence. Fever was defined as axillar temperature ≥37.5 °C and grade 3 >39.0 °C. For all other symptoms, grade 3 was defined as an adverse reaction preventing normal everyday activities; 998 subjects (74% females), mean age (±S.D.) of 23 years (±4.5) (range: 11–54 years) agreed to participate. At first immunization 92% were <30 years old. Grade 3 pain and swelling was recorded in 1.2% and 0.3% of local symptom sheets completed, respectively; 438 subjects received the HAB vaccine alone (group 1) whereas 560 received at least one concomitant vaccine (group 2). In 45%, 27%, 18% and 10% of subjects the HAB vaccine was coadministered with 1, 2, 3 or 4 to 6 vaccines (mainly Td adult-type, typhoid, MMR and IPV vaccine). Grade 3 pain and swelling were recorded in 1.2% & 0.3% of symptom sheets (SS), respectively. In group 1, any fever and grade 3 fever was recorded in 3.5% and 0.1% of SS. Group 1 versus 2 had a lower risk for any fatigue ( p = 0.0002; OR = 0.617) and any malaise ( p = 0.0076; OR = 0.693) but not for grade 3 symptoms. In conclusion, our study showed that the HAB vaccine is well tolerated in adults either alone or coadministered with other vaccines in the routine clinical practice.

Prevention of hepatitis B virus recurrence after living donor liver transplantation

The emergence of lamivudine-resistant hepatitis B mutations is a major complication during pretransplantation treatment. The proper time to begin Lamivudine before transplantation is not yet known. Twenty-six patients received preoperative lamivudine treatment followed by combined lamivudine and hepatitis B immunoglobulin after transplantation up to December 2002. The length of preoperative lamivudine treatment ranged from 13 to 200 days (mean, 52 ± 37 days). Hepatitis B virus–DNA was positive in 22 of 26 (84.6%) patients before preoperative lamivudine prophylaxis and persistently positive among only 4 of 22 patients (18%) who at transplantation did not show a viral mutation. In all patients, hepatitis B virus–DNA became negative immediately after transplantation. At a median follow-up of 34 months, neither a hepatitis B recurrence nor a mutation had occurred in any patient. The ability to schedule the proper time for preoperative lamivudine prophylaxis is an advantage of living donor liver transplantation.

Manifestations cutanéomuqueuses des affections hépatobiliaires et pancréatiques

Hepatobiliary and pancreatic affections may result in numerous cutaneous manifestations; these have often an indication value that makes them highly interesting for the dermatologist. Their frequency is variable and, in some of them, the evolution is progressive. The frequency of combined hepatitis B + disseminated necrotizing periarteritis which was estimated to be from 30% to 45% has been lowered to about 7% as a result of vaccination campaigns. Conversely, the frequency of the affections related to hepatitis C, in particular cryoglobulinaemia-induced angeitis, has increased. In France, hepatitis C seroprevalence is close to 1%, which indicates 500,000 to 600,000 infected individuals. However, over a half of them are not aware of such seropositivity, which contributes to virus dissemination, particularly in drug-addicted populations. Alcoholic cirrhosis induces numerous dermatologic signs well known by hepatologists. However, the frequently associated isolated or combined deficiency syndromes may be disconcerting, such as the pseudo-glucagonoma syndrome that is observed in severe zinc deficiency. The cutaneous signs observed with other types of cirrhoses are of later occurrence, except for the pruritus related to the primitive biliary cirrhosis that precedes cholestatic jaundice. In pancreatic diseases, cutaneous manifestations are common and, most of the time, indicative. Some of them are frequent but they are observed most of the time by surgeons and gastroenterologists; this is the case with the subcutaneous haemorrhage related to severe acute pancreatitis. Others, such as the panniculites and paraneoplastic syndromes, are rare but have to be detected. This is why a close collaboration between organ specialists is necessary, for the affections of the digestive tract as well as for the liver and pancreas diseases.

Immunogenicity, reactogenicity and adherence to a combined hepatitis A and B vaccine in illicit drug users

The use of illegal drugs is associated with an increase in infective risk for the hepatitis viruses, against which the vaccination of drug users (DUs) is recommended unanimously. The aim of the study was to determine tolerability, adherence and immune response of a combined vaccine providing dual protection against hepatitis A virus (HAV) and hepatitis B virus (HBV). The vaccine was administered to 38 DU, attending three public health centres for drug users in northern Italy, with a three-dose schedule (at 0, 1 and 6 months). The vaccine was well tolerated: only one adverse reaction (fever) was recorded after the 110 doses administered (0.9%). The vaccine schedule was completed successfully in 35 cases (92.1%). At month 8, in 34 subjects (89.5%) antibody response was evaluated: all showed seroprotection for HAV and in 33 subjects (97.1%) for HBV. The vaccine, studied for the first time in DUs, proved to be safe, well accepted and immunogenic; anti-HAV response was 1272 mIU/ml and 1726 mIU/ml for anti-HBV, titres lower than reported in literature for the general population. This study suggests that DUs who are HAV/HBV-negative could be vaccinated with combined vaccine.

Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8–10-year-old children

Hepatitis A and B vaccines are highly immunogenic in three-dose schedules. To obtain an equivalent result in children with two paediatric doses would be of significant benefit. The purpose of this study was to measure the immunogenicity of a two-dose schedule in children with two licensed recombinant HBsAg containing vaccines given at paediatric doses, one of them combined with hepatitis A. Seven-hundred and four healthy school children aged 8–10 years were recruited in an open label study to receive either Twinrix Pediatric (360 El.U HAV antigen; 10 μg HBsAg) or Recombivax (2.5 μg HBsAg) vaccine intramuscularly 6 months apart. The seroconversion (≥1 mIU/ml for anti-HBs antibodies and ≥33 mIU/ml for anti-HAV antibodies), seroprotection (anti-HBs ≥10 mIU/ml) rates and the geometric mean titers (GMTs) were determined 4–8 weeks after the second dose. The anti-HBs seroconversion rate was 97.1% with Twinrix and 97.2% with Recombivax. The seroprotection rates were 96.5 and 94.4%, respectively ( P = 0.17). The GMT was higher with Twinrix than with Recombivax (3248 mIU/ml versus 742 mIU/ml, P < 0.0001). All the children vaccinated with Twinrix seroconverted to HAV and the GMT was 5168 mIU/ml. The obtained results suggest that two paediatric doses of hepatitis vaccines are highly immunogenic in 8–10-year-old children. This schedule could facilitate a greater vaccine acceptance and the addition of hepatitis A vaccine to existing adolescent universal hepatitis B virus immunization programs.

A combined dual-chamber typhoid/hepatitis A vaccine as a booster dose in hepatitis A primed adults

Vivaxim™ is a combined hepatitis A/typhoid fever vaccine (HA/Vi) licensed for vaccination of travellers, but long-term protection against hepatitis A requires two immunisations at least 6 months apart. A randomised, controlled study was performed in 116 healthy adults primed with hepatitis A vaccine (Avaxim™) to compare immune responses to HA/Vi and Avaxim™ given as booster doses 6 months later. Both vaccines elicited marked booster responses achieving antibody geometric mean titres (GMTs) of 4576 and 3760 mIU/ml in the HA/Vi and Avaxim™ groups, respectively. Although twice as frequent in the HA/Vi group, local reactions (mostly pain) were mainly mild and transient, probably reflecting the larger volume injected (1 ml). Vivaxim™ offers a convenient means of administering both HA and typhoid fever vaccines in subjects already primed for hepatitis A.

A review of combined hepatitis A and hepatitis B vaccination for travelers

Background: Hepatitis A virus (HAV) and hepatitis B virus (HBV) are the 2 most common vaccine-preventable diseases for which travelers are at risk. These viruses are a significant public health concern, as both HAV and HBV cause substantial morbidity and both can be fatal. Objective: This article provides the practitioner with the facts about hepatitis and travel, including why travelers are at risk, which travelers are at greatest risk, and how travelers can protect themselves from both HAV and HBV through vaccination. Methods: A review of the English-language literature published from 1966 to 2002 was conducted through the PreMedline and MEDLINE databases with the search terms hepatitis A, hepatitis B, and travelers. Reference lists from relevant articles were also searched, and abstracts presented at recent conferences were evaluated. Articles containing information from the past 2 decades were used to reference this article. Results: Travelers need protection against both hepatitis A and B. In addition to making travelers aware of a number of behavior modifications, vaccination should be provided. Tolerable and effective monovalent vaccines are available that can prevent these viruses. In addition, a combination HAV/HBV vaccine is available that is well tolerated and decreases the time to immunity. Conclusions: Travelers are often unaware of the risk factors for acquiring hepatitis A and B while traveling, such as the degree of endemicity at the travel destination, the length of stay in the endemic area, and the extent and frequency of contact with the local population. Because these risk factors and areas for endemicity of both hepatitis A and hepatitis B overlap, health care providers can protect travelers from both of these diseases by providing a combination vaccine, thus affording a lifetime of protection against both diseases.

Impact of the introduction of a combined Haemophilus B conjugate vaccine and hepatitis B recombinant vaccine on vaccine coverage rates in a large west coast health maintenance organization

We evaluated the effect of introduction of a combined hepatitis B-Haemophilus influenzae b vaccine on vaccine coverage rates in a large health maintenance organization and found a modest improvement in up-to-date immunization status.

Immunogenicity of combined hepatitis A and B vaccine in elderly persons

More and more elderly people travel to areas where hepatitis A and B are endemic. Their immune system is less effective than in young persons. Therefore, it has to be insured that these travelers have protective immunity after vaccination.In a retrospective study we measured anti hepatitis virus (anti-HAV) and anti-HBs in elderly persons (N=104, mean age 54 years) after combined hepatitis A/B vaccination under every-day conditions. After complete vaccination only 36 (34.6%) had antibodies against both viruses. Only 23 (29%) of 80 vaccinees older than 40 years were protected against hepatitis B and 52 (65%) against hepatitis A.The response to the vaccination decreased with increasing age. Vaccination against hepatitis B—but not against hepatitis A—was also influenced by the presence of chronic disease.After one booster 87% of the anti-HAV negative vaccinees developed protective anti-HAV antibodies. Anti-HBs can be expected in about 50% of the HBV negative vaccinees with every single booster.These results indicate that combined hepatitis A/B vaccination is not very effective in elderly persons. After complete vaccination their anti-HAV and anti-HBs antibodies have to be controlled to insure protection. In case of vaccination-failure boosters are very effective.