Prevention and treatment of hepatitis B in patients on hemodialysis and vaccination of hemodialysis health personnel against hepatitis B

The prevalence and incidence of hepatitis B in hemodialysis patients in Croatia have been estimated to 1.3% and 0.03%, respectively. HBV infection in dialysis patients is usually asymptomatic, has a prolonged course, and progresses to chronic HBsAg hepatitis in 50% of cases. Some 15%-40% of HBsAg carriers on dialysis will develop cirrhosis, liver decompensation or hepatocellular carcinoma. Strict adherence to the standard infection prevention measures, continuous monitoring of HBV markers in patients on hemodialysis, patient and personnel immunization and hepatitis B treatment in hemodialyzed patients are mandatory. Each new patient in a dialysis center must be tested for HBV markers irrespective of prior immunization. All patients in the center should be routinely screened every 3-4 months. HBV immunization is mandatory for all patients on dialysis. In patients with uremia the anti-HBs antibody production is decreased (antibodies will develop in 50%-60% of cases after immunization). It is recommended to immunize all patients with progressive kidney disease, preferably in the preterminal stage. Hepatitis B therapy is recommended in all patients with biopsy proven chronic liver disease. Patients should be treated with standard interferon alpha and/or lamivudine, or peginterferon alpha monotherapy. Hepatitis B treatment is most important in kidney and/or liver transplant candidates. HBV immunization is obligatory for all hospital personnel who are in close contact with infected patients and infective materials.     

The management of viral hepatitis in CKD patients: an unresolved problem

Chronic kidney disease (CKD) patients in dialysis (HD) show peculiar, atypical features of clinical presentation and diseases (cardiovascular, metabolic, hematologic). This is also true for viral hepatitis infections, for which CKD patients represent an important risk group. In the past, hepatitis B virus (HBV) was the major cause of viral hepatitis in end-stage renal disease (ESRD). However, the introduction of a rigorous infection-control strategy, routine screening of patients and staff for hepatitis B serologic markers, vaccination of susceptible patients and staff, use of separate rooms and dedicated machines for HD of HbsAg-positive patients have all led to a decline in the spread of HBV infection in dialysis. Despite the prevalence of the antibody-hepatitis C virus (HCV), there has been a marked decrease in HD patients; after the introduction of routine screening for HCV and the use of erythropoietin, its occurrence ranges from 5% to 25% in the United States, with a prevalence of 6.8% in Europe. In CKD and in HD patients, the presence of HBV and HCV is an independent and significant risk factor for death and this risk may be at least partially attributed to chronic liver disease with its attendant complications. Liver disease can progress with modest hepatic inflammation and prominent fibrosis; the natural history of viral hepatitis in these patients is dependent on the immune dysfunction typical of kidney disease. Despite recent advances in antiviral therapy, there are still many uncertainties in regards to the efficacy and long-term outcomes of treatment with antiviral agents.     

HBs-Ag-negative hepatitis in a hemodialysis unit: relation to Epstein-Barr virus.

Eleven of 40 patients in a hemodialysis unit had clinical or biochemical evidence of hepatitis during a five-week period. The clinical disease was mild, being limited solely to dialysis patients. Epidemiologic investigation indicated that the incubation period was between 17 and 35 days and that 10 of 11 patients had been exposed to a single venous-pressure monitor before onset. Dried blood and evidence of blood reflux up the venous-pressure gauge suggested that cross-contamination of the blood of successive patients probably resulted in transmission of disease. No association with the hepatitis B surface antigen or anti-hepatitis B antibody was demonstrated, but 10 of the 11 patients with elevated transaminase levels had evidence of recent exposure, to Epstein-Barr virus as manifested either by Ox-cell hemolysin titers or rises in titers to viral capsid antigen.     

Outbreak of severe hepatitis due to delta and hepatitis B viruses in parenteral drug abusers and their contacts

We investigated an unusually large and severe outbreak of hepatitis B, primarily involving parenteral drug abusers and their sexual contacts, in Worcester, Massachusetts, over a 21-month period from 1983 to 1985. Of 135 patients with drug-related acute hepatitis B, 81 percent were parenteral drug abusers and 19 percent had sexual contact with drug abusers; 13 fulminant cases resulted in 11 deaths. Among the patients with hepatitis B, evidence of delta virus infection was found in 54 percent of drug abusers, 33 percent of their sexual contacts, and 9 percent of other patients with acute hepatitis B (P less than 0.001). Most of the delta infections (86 percent) were coinfections with hepatitis B virus; the balance were superinfections. Delta infection was strongly associated with fulminant hepatitis: 91 percent of patients with a fulminant outcome had delta infection, as compared with 45 percent of less severely ill drug abusers and their contacts (P = 0.0037). Alcohol, other drugs, and other hepatitis viruses could not be implicated as hepatotoxic cofactors for fulminant disease. This outbreak appeared to result from the concurrent spread of hepatitis B and delta viruses among new drug users. Control measures included the distribution to physicians of guidelines on prophylaxis in contacts of patients with hepatitis B, health education for drug abusers, and a hepatitis B vaccination program. Despite these efforts, the outbreak continued unabated until the number of new cases began to decline slowly in late 1986.     

Prevalence and risk factors of hepatitis C and B virus infections in hemodialysis patients and their spouses: A multicenter study in Beijing,China

Hemodialysis patients are at risk for hepatitis C and B virus infections. This study investigated the prevalences and risk factors of HCV and HBV infection and the distribution of HCV genotypes among hemodialysis patients and their spouses. From August to November 2011, a cross‐sectional study was conducted on 20 hemodialysis units in Beijing to investigate prevalences and risk factors for markers of HCV and HBV among 2,120 patients and 409 spouses. In hemodialysis patients, prevalences of anti‐HCV, HCV RNA, and hepatitis B surface antigen (HBsAg) were 6.1%, 4.6%, and 7.0%, respectively. The prevalence of HCV antibodies among spouses was 0.5%, of HCV RNA was 0.2%, and of HBsAg was 4.2%. Risk factors for HCV infection were dialysis duration, blood transfusion, and attending more than one dialysis unit. HBV infection was independently associated with age, family member with hepatitis infection, gender, and surgery. The predominant HCV genotypes were 1b (89.0%) and 2a (7.7%), and genotypes 3a, 3b, and 6a were each 1.1%. A significant decrease in HCV and HBV prevalences in Chinese dialysis units showed that infection control measures were effective. However, because nosocomial transmissions persist, strict adherence to infection control measures should be emphasized to reduce the risk of transmission. J. Med. Virol. 85:425–432, 2013. © 2013 Wiley Periodicals, Inc.     

Prevention of hepatitis B and C

Preventive measures are determined by epidemiological characteristics of HBV and HCV infections. A significant difference between these two infections is in the availability of effective vaccine for hepatitis B. Vaccine against hepatitis C is not available. The vaccination program for hepatitis B in Croatia was initiated in 1994, at first only for high risk groups. The vaccination program for children in the 6th grade of primary school started in 1999. Besides that, all pregnant women are obliged to undergo HBV testing. HBV infection is very rare but not unknown in early childhood. HBV infection in early childhood, most commonly asymptomatic, results in very high prevalence of chronic infection and carries a high risk of late serious consequences of the HBV infection. Since the main aim of vaccination is to prevent serious chronic liver disease, it is very important to protect the youngest children. The prevention of hepatitis C consists of primary prevention, mostly eliminating the risks of the presence and spread of infection. It is recommended to follow instructions regarding prevention of transmission by skin and mucosal contact with blood and body fluids, especially in health institutions and during hemodialysis. Providing due education to high risk persons (i.v. addicts, persons with more than one sexual partner, patients and workers who come in contact with blood and other body fluids) is very important. Early identification of infected persons enables timely treatment. It is not recommended to screen general population but only persons at high risk identified by medical history and other relevant medical information.     

Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group

BACKGROUND: There has been some concern that vaccination may precipitate the onset of multiple sclerosis or lead to relapses. Since the recent hepatitis B vaccination program in France, there have been new reports of an increased risk of active multiple sclerosis after vaccination. METHODS: We conducted a case-crossover study to assess whether vaccinations increase the risk of relapse in multiple sclerosis. The subjects were patients included in the European Database for Multiple Sclerosis who had a relapse between 1993 and 1997. The index relapse was the first relapse confirmed by a visit to a neurologist and preceded by a relapse-free period of at least 12 months. Information on vaccinations was obtained in a standardized telephone interview and confirmed by means of medical records. Exposure to vaccination in the two-month risk period immediately preceding the relapse was compared with that in the four previous two-month control periods for the calculation of relative risks, which were estimated with the use of conditional logistic regression. RESULTS: Of 643 patients with relapses of multiple sclerosis, 15 percent reported having been vaccinated during the preceding 12 months. The reports of 94 percent of these vaccinations were confirmed. Of all the patients, 2.3 percent had been vaccinated during the preceding two-month risk period as compared with 2.8 to 4.0 percent who were vaccinated during one or more of the four control periods. The relative risk of relapse associated with exposure to any vaccination during the previous two months was 0.71 (95 percent confidence interval, 0.40 to 1.26). There was no increase in the specific risk of relapse associated with tetanus, hepatitis B, or influenza vaccination (range of relative risks, 0.22 to 1.08). Analyses based on risk periods of one and three months yielded similar results. CONCLUSIONS: Vaccination does not appear to increase the short-term risk of relapse in multiple sclerosis.     

Seroprevalence of hepatitis B virus infection in children in Taipei, 1989: five years after a mass hepatitis B vaccination program

A nationwide hepatitis B vaccination program was launched in Taiwan in 1984. To study the impact of this ongoing program on hepatitis B virus (HBV) infection, a follow-up seroepidemiologic study was carried out in 1989 in a Taipei district where pre-vaccination seroepidemiology had been studied. HBV markers were studied in 1134 apparently healthy children (619 boys and 515 girls) under 13 years of age between March and July 1989. The prevalence of hepatitis B surface antigen (HBsAg) in children under 5 years of age decreased from 9.3% in 1984 to approximately 2% in 1989. A significant decrease in HBsAg prevalence and hepatitis B core antibody in 5- to 8-year-old children who were not immunized against HBV showed that horizontal infection among the older children had also decreased. Thus, this program not only protected vaccinated subjects; the reduction in numbers of highly infectious young HBV carriers also contributed to a lower prevalence of hepatitis B infection and carrier rates in some older children. This study demonstrates that hepatitis B vaccination is effective in protecting the majority of children in hyperendemic areas from HBV infection and from becoming chronic carriers.     

Antiviral therapy for chronic hepatitis B in China

The vaccination program against hepatitis B virus (HBV) has greatly reduced the incidence of HBV infection. However, almost one-fourth of the HBV infected patients worldwide are still located in China. The healthcare burden from chronic HBV infection is a big challenge for the Chinese government and clinicians. Antiviral therapy plays a central role in controlling chronic HBV infection and preventing the disease progression. However, due to the specific economic and medical system issues, the first-line antiviral agents recommended by the AASLD and EASL have not been widely used for Chinese patients. In this review, we will discuss some key issues in the area of antiviral treatment for chronic hepatitis B in China.     

Interferon system status in hemodialysis patients infected with hepatitis B and C viruses]

The production of alpha- and gamma-interferon (IFN) by peripheral blood cells in vitro and the concentration of serum IFN were studied in patients treated by hemodialysis at the Pelgulinna Tallinn Hospital and compared to controls. Out of 108 patients on hemodialysis, 19.4% were infected with hepatitis B (HBV), and antibodies to hepatitis C virus (HCV) were detected in 7.4%. During 3.5 years of observation, cases of hepatitis B and C infection among patients and medical staff were rare. The production of alpha- and gamma-IFN in 23 patients with HBV and/or HCV markers on hemodialysis and in 38 patients without markers was similarly decreased in comparison with the controls and the titers of serum IFN were similarly increased. Lack of reliable difference between IFN status of two groups of patients may be explained by the absence of clinical symptoms of hepatitis, confirmed by laboratory findings.     

High prevalence of hepatitis B virus infection among tuberculosis patients with and without HIV in Rio de Janeiro, Brazil

To determine the prevalence and exposure factors associated with hepatitis B infection in tuberculosis patients with and without HIV type 1 coinfection, the presence of hepatitis B virus serological markers was investigated in a retrospective study. The seroprevalence of hepatitis B virus in patients with tuberculosis only was 14.6%, and in tuberculosis patients coinfected with HIV it increased to 35.8%. In patients with HIV and tuberculosis coinfection, homosexuality constituted the principal exposure factor, while in tuberculosis patients without HIV, a gradual increase in hepatitis B virus seroprevalence was noted along with increasing age. The results demonstrate that hepatitis B infection is highly prevalent in tuberculosis patients in Brazil and suggest that a vaccination program for the general population should be considered in order to prevent further hepatitis B infections.     

Blood‐borne virus infections in dialysis units—A review

Hepatitis outbreaks in haemodialysis unit patients and staff were reported in the late 1960s. In 1972, the Rosenheim report in the UK established guidelines which included routine tests for hepatitis B surface antigen and isolation facilities for dialysing patients with hepatitis B virus which resulted in a dramatic fall in cases of hepatitis. However, since these guidelines were introduced, other blood‐borne viruses, notably HCV and HIV have been discovered, and failures of infection control practices still lead to outbreaks of HBV in haemodialysis units. The prevalence of HCV in dialysis patients varies considerably throughout the world, with reported prevalence ranging from 3·9% to 71%. The number of blood transfusions and the length of time on dialysis have consistently been associated with HCV prevalence. Several reports provide evidence of patient‐to‐patient HCV transmission with environmental blood contamination the most significant factor in intra‐unit transmission. There is no evidence that HCV has been transmitted by re‐use of dialysis machines but being dialysed next to an HCV positive patient is associated with a significant risk of HCV acquisition. Several studies have shown that dialysing HCV positive patients in a separate unit or in a defined sector of a dialysis unit significantly reduces nosocomial HCV infection. HGV is prevalent in dialysis units where there is evidence of transmission to patients but no evidence of associated symptoms. HIV is infrequently transmitted in dialysis units and several units treating many HIV‐positive patients have shown no evidence of transmission. Careful attention needs to be paid to infection control procedures and regular virological testing. Copyright © 1999 John Wiley & Sons, Ltd.     

New hepatitis B vaccine formulated with an improved adjuvant system

A new hepatitis B vaccine (FENDrix, GlaxoSmithKline Biologicals) containing as active substance 20 microg of recombinant hepatitis B virus surface antigen produced in Saccharomyces cerevisiae has recently been licensed in Europe. It is prepared with a novel adjuvant system: aluminum phosphate and 3-O-desacyl-4 -monophosphoryl lipid A. It is intended for use in adults from the age of 15 years onwards for active immunization against hepatitis B virus infection for patients with renal insufficiency (including prehemodialysis and hemodialysis patients). It is applied in a four-dose scheme: day 0, month 1, 2 and 6 after day 0. Due to the improved adjuvant system it induces higher antibody concentrations that reach protective levels in a faster fashion. Furthermore, due to higher titers reached after the primary immunization course, protective levels are retained for a longer period of time. Vaccination with FENDrix induces more transient local symptoms, with pain at the injection site being the most frequently reported solicited local symptom. Other symptoms such as fatigue, gastrointestinal disorders and headaches were also frequently observed but resolved without sequelae. The higher risk of hepatitis B transmission in patients with end-stage renal disease and the often immunocompromised status of these patients afford a tailored vaccination strategy that, up to now, has consisted of injecting double doses of ordinary hepatitis B vaccines. With the introduction of FENDrix there now exists an efficient alternative with superior immunogenicity that is, despite comparatively higher reactogenicity, well tolerated.     

Low dose intradermal versus high dose intramuscular hepatitis B vaccination in patients on chronic hemodialysis

Patients with end-stage renal disease on hemodialysis (HD) are at high risk for hepatitis B infection. We randomly assigned 86 new patients on HD to receive either 40 microg intramuscular (group 1) or 20 microg intradermal (group 2) recombinant hepatitis B vaccine, in three doses at 0, 1, and 4 months. All patients were seronegative at baseline for hepatitis B surface antigen (HBs-Ag), hepatitis B surface antibody (HBs-Ab), and hepatitis B core antibody (HBc-Ab). HBs-Ab seroconversion rate and antibody titer (ELISA assay) were compared in 27 patients of group 1 and 35 patients of group 2 at 1 month, and in 20 patients of group 1 and 26 patients of group 2 at 6 months after the last vaccine dose. The seroconversion rates (HBs-Ab titer >10 IU/L) were 55.6% and 50% in group 1, and 54.3% and 50% in group 2, at 1 and 6 months, respectively (p = NS). Patients' age, body mass index, serum albumin concentration, and sex distribution were similar in the responders and nonresponders. Intradermal hepatitis B vaccination used at half dose may be a cost saving alternative to intramuscular vaccination in patients on HD. However, the low overall seroconversion rate mandates seeking alternative ways of vaccination in this patient population.     

Nosocomial transmission in simultaneous outbreaks of hepatitis C and B virus infections in a hemodialysis center

Reported here are details of a simultaneous outbreak of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections that occurred in a hemodialysis centre in northern Italy, with three patients seroconverting for HBsAg and four patients seroconverting for HCV antibodies. Phylogenetic analysis of the E2 region of the isolates from HCV-seroconverted patients showed the sequences were grouped in the same distinct branch as in a chronically HCV-infected patient, suggesting that the chronically infected patient was the index case. For the patients with HBV infection, phylogenetic analysis showed strong clustering among the sequences of the three patients who seroconverted to HBsAg and no relatedness between them and the sequences of patients chronically infected with HBV. For one of the patients who seroconverted to HBsAg, the last test with negative results for HBV markers had been performed 18 months prior to HBsAg seroconversion. This patient may have been previously infected with HBV and is presumed to be the source of the outbreak. This report emphasizes the importance of using universal precaution measures and HBV vaccination to prevent the transmission of viral hepatitis among chronic hemodialysis patients.     

High prevalence of hepatitis C in patients with thalassemia and patients with liver diseases in Myanmar (Burma)

We conducted Myanmar-Japan cooperation studies on hepatitis B and hepatitis C virus markers in patients with thalassemias and those with liver diseases. Among the 102 patients with liver diseases, 92% had a history of hepatitis B virus infection (antibody to hepatitis B core antigen positive), 35% were hepatitis B surface antigen positive, 39% were positive for anti-HCV. Among 28 patients with hepatocellular carcinoma, 46% had hepatitis B surface antigen, 21.4% had antibody to hepatitis C virus, and 7% were positive for both hepatitis B surface antigen and anti hepatitis C virus. The history of HCV infection among blood recipients at the Haematology Department of the Yangon General Hospital and at the Yangon Children's Hospital was found to be 55.5% and 46.7%, respectively, which is comparable to the history of hepatitis B infection (66.7% and 46.7%, respectively). This preliminary survey also encountered 2 cases positive for anti-HCV among 34 voluntary blood donors. This survey is the first one to report that hepatitis C is at the epidemic stage in Myanmar. As there is no effective treatment for hepatitis C in this country, a screening program for blood used in transfusion should be started immediately.     

Hepatitis C in a Hemodialysis Unit: Molecular Evidence for Nosocomial Transmission

This study reports four cases of transmission of the rare hepatitis C virus genotype 4 which occurred in a hemodialysis unit and originated from a single source of infection. Phylogenetic analyses performed with the NS5b domain showed that all four patients with secondary infections were infected with virus strains very similar to that of the index patient. Cross infections probably resulted from breaches in safety precautions and lack of dialysis machine sterilization.     

Reverse transcriptase/polymerase chain reaction analyses of hemodialysis ultrafiltrates and sera of hepatitis C virus positive patients

The hepatitis C virus is a highly prevalent infection among chronic dialysis patients and represents one of the major problems of hemodialysis units. Hepatitis C virus transmission occurs either by blood transfusion or nosocomially. One of the proposed pathways of nosocomial transmission of the hepatitis C virus is cross-contamination through the dialysis procedure. In an effort to elucidate whether the hepatitis C virus may pass across the hemodialysis membrane, we have performed analyses of ultrafiltrates collected in different stages of hemodialysis treatments, using different types of hemodialysis membranes and different types of dialysis machines. Samples collected from the dialysis compartment during the rinsing of the blood compartment at the end of the hemodialysis treatment were also analyzed. The hepatitis C virus was found in 17 out of 58 ultrafiltrate samples taken at different times of the hemodialysis treatment. Moreover, the hepatitis C virus was present in 15 out of 17 samples collected from the dialysate compartment during the saline solution rinsing step of the blood compartment. The presence of the hepatitis C virus had no strict correlation with the type of dialysis membrane or with the type of dialysis machine. Although the results suggest that the passage of the hepatitis C virus during the hemodialysis treatment is multi-factorial and case- specific, the most critical point is when the blood is flushed out with physiological saline.     

High prevalence and incidence of hepatitis C virus infections among dialysis patients in the East-Centre of Tunisia

Hemodialysed patients are recognised as a group at increased risk of infection with hepatitis C virus (HCV). The aim of this study was to determine the prevalence and incidence of HCV infection among dialysis patients of the east-centre part of Tunisia. Two hundred and seventy-six patients dialysed until 2001 were recruited within seven hemodialysis units located in the cities of Sousse, Monastir and Mahdia. The serum markers of HCV infection were tested over the period of March 2000-December 2002, by a 3rd generation ELISA test for antibodies and by qualitative RT-PCR technique for viral RNA. The prevalence of anti-HCV antibodies and of HCV RNA was 32.6% (90 patients) and 25.7% (71 patients), respectively. Between 1998 and 2002, 20 new infections were documented in five of the seven dialysis units corresponding to an incidence of 2.34% per year, with an average time of contamination after the beginning of dialysis of 4.6 years. If all the infections are assessed to have occurred during dialysis, the density of incidence of HCV contamination was 4.4% per year of dialysis. A high correlation was noticed between the presence of HCV markers in serum and the duration of dialysis (F = 34.15, P < 0.0001). In the absence of other risk factors (transfusion, drug-addiction), these results plead for the nosocomial transmission of the observed HCV infections. A phylogenetic analysis of the E2 hypervariable region of the viral genome is in progress to confirm this assumption.     

Hepatitis B vaccination in patients with chronic hepatitis C.

The aim of the study was to evaluate the safety, immunogenicity, and possible therapeutic effect of hepatitis B vaccine in patients with chronic hepatitis C. The subjects studied included three groups: group I, 26 patients with chronic hepatitis C who were susceptible to hepatitis B virus infection; group II, 35 healthy subjects who were susceptible to both hepatitis B and hepatitis C virus infection; and group III, 30 patients with chronic hepatitis C receiving no hepatitis B vaccination as controls. Three 20 microg/dose of recombinant hepatitis B vaccines were given to subjects of groups I and II in months 0, 1, and 6. Blood samples from the subjects were collected before and 1 month after each dose of vaccination for serological testing. The subjects of groups I and II had similar antibody to hepatitis B surface antigen (anti-HBs) response rates after the first (30.8% vs. 17.1%), second (61.5% vs. 60.0%), and third (88.5% vs. 91.4%) doses of vaccination. Also, their geometric mean titers of anti-HBs did not differ much when vaccination completed in 7 months (360 vs. 581 mIU/ml). During vaccination period, patients with chronic hepatitis C demonstrated no significant change of serum cytokines and HCV RNA levels, but significantly lowered ALT levels after three doses of vaccination. Hepatitis B vaccination is safe and immunogenic in patients with chronic hepatitis C. It did not significantly affect their levels of HCV RNA, but tended to lower ALT levels.