Vaccination against hepatitis b in patients with chronic liver disease

The prevalence of chronic liver disease is increasing, while at the same time, many at-risk populations are witnessing a resurgence of hepatitis B virus (HBV) infection. Thus, more patients are likely to have multiple causes of liver disease, as risk factors often overlap. Such patients may develop either acute viral hepatitis superimposed on pre-existing chronic liver disease or chronic infection with two hepatitis viruses. Patients with chronic HBV and hepatitis C virus coinfection have more severe laboratory abnormalities, more hepatic fibrosis, and greater frequency of cirrhosis, in addition to more complications of cirrhosis and a higher incidence of hepatocellular carcinoma. Acute hepatitis B superimposed on chronic hepatitis C may result in fulminant hepatitis, although this outcome is not as well proven as the increased morbidity of chronic hepatitis B and C coinfection. Both acute and chronic coinfection with HBV can be prevented. Vaccines for hepatitis B are safe in patients with chronic liver disease of a variety of causes and are effective, particularly if used early. Early vaccination against hepatitis B, as well as hepatitis A, should be part of the routine management of chronic liver disease.     

Hepatitis B Vaccination: Current and Evolving Recommendations

Hepatitis B virus (HBV) is the leading cause of chronic liver disease worldwide. Antiviral therapy for HBV is a safe and effective strategy for preventing the development of complications of chronic infection, including cirrhosis and hepatocellular carcinoma; however, treatment is expensive and may be required long-term. Thus, prevention of HBV infection with universal vaccination at birth, and after birth in specific unvaccinated risk groups, is a preferred strategy that confers durable life-long protection against HBV and will eliminate a future reservoir of infected individuals. In addition to the traditional at-risk groups for hepatitis B, patients with diabetes mellitus were recently identified as being at increased risk for HBV infection, and they should also be considered for screening and vaccinated if not immune. This short review summarizes current and evolving recommendations for hepatitis B vaccination.     

Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.     

Increased effective immunogenicity to high-dose and short-interval hepatitis B virus vaccination in individuals with chronic hepatitis without cirrhosis

Hepatitis B virus (HBV) vaccination is recommended for individuals with chronic liver disease. However, the response to standard doses of hepatitis B vaccines in such individuals has been poor. The aim of the present study was to assess the response to high-dose short-interval HBV vaccination in individuals with chronic liver disease of different aetiologies. A total two hundred and 24 subjects with chronic liver disease (138 chronic active hepatitis and 86 cirrhosis) and 26 healthy controls were vaccinated using a high-dose (40 μg) short-interval (monthly for 3 consecutive months) HBV vaccination schedule.
One hundred and thirty-eight of the 224 subjects with chronic liver disease (62%) seroconverted to anti-HBs antibody positivity (>10 mIU/mL) after the third dose of vaccine as compared with 24 of the 26 controls (92%) ( P  < 0.01). The response rate was reduced in individuals with cirrhosis (36/86, 42%), particularly in alcohol-induced cirrhosis (2/17, 12%), as compared with individuals with chronic hepatitis (102/138, 74%) ( P  < 0.001). No significant HBV vaccination-related adverse effects were seen in individuals with or without cirrhosis as well as in the controls.
High-dose short-interval HBV vaccination is safe and efficacious in individuals with chronic liver disease. The response to HBV vaccination is reduced in cirrhotics, particularly those with alcoholic cirrhosis. These data suggest that HBV vaccination should be accomplished early in an individual cause of chronic liver disease prior to the development of cirrhosis.     

A review of the case for hepatitis B vaccination of high-risk adults

The sequelae of hepatitis B virus infection include fulminant liver failure, chronic liver disease, hepatocellular carcinoma, and death. The hepatitis B vaccine is efficacious, safe, and cost-effective, but has been consistently underutilized in high-risk adults despite long-standing recommendations. Instituting routine hepatitis B vaccination for high-risk adults in settings such as prisons and jails, sexually transmitted disease clinics, drug treatment centers, and needle exchange programs could prevent up to 800 cases of hepatitis, and 10 deaths from hepatitis, per 10,000 vaccinations, with an overall cost savings. Low rates of completion of the three-dose series and lack of funding for adult immunizations have always been challenges to offering hepatitis B vaccines to high-risk adults. However, there is benefit to an incomplete vaccination series, and high-risk populations are accessible for follow-up vaccination outside of traditional medical settings. A clear national objective and federal funding for vaccinating high-risk adults are needed.     

Clinical factors associated with hepatitis B screening andvaccination in high-risk adults

BACKGROUND Hepatitis B virus is a viral infection that can lead to acute and/or chronic liver disease, and hepatocellular carcinoma(HCC). Hepatitis B vaccination is 95% effective in preventing infection and the development of chronic liver disease and HCC due to hepatitis B. In 2011, the Centers for Disease Control updated their guidelines recommending that adults at high-risk for hepatitis B infection be vaccinated against hepatitis B including those with diabetes mellitus(DM). We hypothesize that adults at high-risk for hepatitis B infection are not being adequately screened and/or vaccinated for hepatitis B in a large urban healthcare system.AIM To investigate clinical factors associated with Hepatitis B screening and vaccination in patients at high-risk for Hepatitis B infection.METHODS We conducted a retrospective review of 999 patients presenting at a large urban healthcare system from 2012-2017 at high-risk for hepatitis B infection. Patients were considered high-risk for hepatitis B infection based on hepatitis B practice recommendations from the Center for Disease Control. Medical history including hepatitis B serology, concomitant medical diagnoses, demographics, insurance status and social history were extracted from electronic health records.Multivariate logistic regression was used to identify clinical risk factors independently associated with hepatitis B screening and vaccination.RESULTS Among the 999 patients, 556(55.7%) patients were screened for hepatitis B. Of those who were screened, only 242(43.5%) patients were vaccinated against hepatitis B. Multivariate regression analysis revealed end-stage renal disease[odds ratio(OR): 5.122; 2.766-9.483], alcoholic hepatitis(OR: 3.064; 1.020-9.206),and cirrhosis or end-stage liver disease(OR: 1.909; 1.095-3.329); all P 0.05 were associated with hepatitis B screening, while age(OR: 0.785; 0.680-0.906),insurance status(0.690; 0.558-0.854), history of DM(OR: 0.518; 0.364-0.737), and human immunodeficiency virus(OR: 0.443; 0.273-0.718); all P 0.05 were instead not associated with hepatitis B screening. Of the adults vaccinated for hepatitis B,multivariate regression analysis revealed age(OR: 0.755; 0.650-0.878) and DM were not associated with hepatitis B vaccination(OR: 0.620; 0.409-0.941) both P 0.05.CONCLUSION Patients at high-risk for hepatitis B are not being adequately screened and/or vaccinated. Improvements in hepatitis B vaccination should be strongly encouraged by all healthcare systems.     

Chronic hepatitis B virus infection in the Asia-Pacific region and Africa: review of disease progression

Countries in the the Asia-Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia-Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975-2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5-year mortality rates (<4%); rates (>50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co-infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.     

Prospects for hepatitis B virus eradication and control of hepatocellular carcinoma

Hepatitis B virus infection is the most common cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. In areas hyperendemic for HBV infection, the related complications occur mostly during adulthood. However, nearly half of all primary infection in chronic carriers occurs in the perinatal period through maternal transmission, the other half arising from horizontal transmission mainly through intrafamilial spread or injection using unsterilized needles. A universal vaccination programme is better than immunization for at-risk groups. Hepatitis B vaccination should be integrated into the Expanded Programme on Immunization in children. Universal immunization against hepatitis B virus has proved to be effective in reducing the hepatitis B carrier rate to one-tenth of the prevalence before the vaccination programme in highly endemic areas, and the incidence of hepatocellular carcinoma in children has also been shown to be significantly reduced. Continued efforts to implement universal vaccination programmes worldwide will very likely reduce the incidence of hepatitis B virus-related diseases, particularly liver cirrhosis and hepatocellular carcinoma.     

Prevention of virus hepatitis A to E

Infection with hepatitis viruses can lead to acute hepatitis with the risk of developing liver failure. Chronic viral hepatitis may evolve into liver cirrhosis and hepatocellular carcinoma. Thus, prevention of viral hepatitis and its sequels is essential. Vaccination against hepatitis A is successful in almost all individuals. Protective antibodies maintain for at least 20?years. Booster vaccinations are not necessary. Since the introduction of hepatitis A vaccines, the incidence of new HAV-infections has declined significantly. Hepatitis B vaccines are safe and highly effective. Special populations such as dialysis patients or immunocompromised patients require special vaccine schedules. New vaccines with improved adjuvants are currently being tested in clinical trials. So far there is no hepatitis C vaccine on the horizon. Prophylaxis of HCV-infections relies primarily on hygiene measures. Early therapy of acute hepatitis C can prevent chronic hepatitis?C. HDV-infection can only be established if HBsAg is present. Thus, prevention of hepatitis B or elimination of HBsAg means prevention of hepatitis delta. Hepatitis E vaccines have been evaluated in phase III studies. The development of HEV vaccines becomes more relevant since chronic HEV infections have been reported in immunosuppressed individuals.     

Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.     

Hepatitis B and human immunodeficiency virus co-infection

Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.     

Therapeutic management of hepatitis B-related cirrhosis

Hepatitis B virus (HBV) infection has a world-wide distribution, and may lead to cirrhosis, end-stage liver disease and hepatocellular carcinoma. Therapeutic strategies for HBV cirrhosis are changing rapidly. Treatment with interferon (IFN)-α may be hazardous and often can only be administered at low doses. The availability of lamivudine has revolutionized the treatment of chronic hepatitis B and opened up new options for the management of patients with decompensated cirrhosis or recurrent hepatitis B post-liver transplantation. However, lamivudine therapy should be weighed against the risk of selection of resistant mutants and randomized control trials are needed. Hopefully, in the near future, new antiviral drugs such as adefovir dipivoxil which is active on lamivudine-resistant mutants will become available. IFN-α is still the only molecule which may prevent HBV-induced hepatocarcinogenesis in humans. Whether other antivirals will also prove useful warrants further follow-up studies.     

Leberzirrhose: Prävention

Risk factors for the development of liver cirrhosis include toxins, chronic hepatitides and metabolic liver diseases. This knowledge has led to prevention strategies: avoiding exposure, vaccination against hepatitis B, and the early determination of hereditary liver diseases (e.g. hemochromatosis). The early use of effective treatment for chronic liver disease (e.g. immunosuppression, bloodletting, elimination of copper) allow, in part, the avoidance of later, irreversible sequelae such as the development of hepatocellular carcinoma. The therapy for chronic hepatitis B and C is becoming increasingly efficient and individualized. Nevertheless, it leads to complete virus suppression/elimination only in some patients; additional antiviral substances are being examined in clinical studies. In cases of acute HCV infection, contact with a hepatology clinic should be made due to possible involvement in a clinical study. In cases of chronic hepatitis D, the indications for antiviral therapy should only be made in cooperation with such a clinic.     

Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma?

Approximately 75% to 80% of hepatocellular carcinomas (HCC) worldwide are attributed to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Thus, effective prevention of HBV and HCV infection and progression from acute HBV and HCV infection to chronic hepatitis, cirrhosis and HCC might prevent as many as 450,000 deaths from HCC each year. The most effective approach to preventing HCC is to prevent HBV and HCV infection through vaccination. Indeed HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a vaccine for HCV is not available and for persons who are chronically infected with HBV or HCV, antiviral therapy is the only option for preventing HCC. Direct evidence supporting a benefit of antiviral therapy on the prevention of HCC has been shown in a few randomized controlled trials. There is abundant evidence that antiviral therapy, in patients with long-term virological response, can improve liver histology, providing indirect support that antiviral therapy may prevent HCC by slowing progression of liver disease and possibly even reversing liver damage. Nevertheless, the risk of HCC remains in patients with chronic HBV or chronic HCV infection if treatment is initiated after cirrhosis is established. These data indicate that treatment might be of greater benefit if instituted earlier in the course of chronic hepatitis B or C. Safer, more effective, and more affordable antiviral therapies are needed for both hepatitis B and hepatitis C so more patients can benefit from treatment and more HCCs can be prevented.     

Consensus statement on the role of hepatitis A vaccination in patients with chronic liver disease

Hepatitis A virus (HAV) is a ubiquitous, easily transmitted virus that can cause severe hepatitis, particularly in the adult population. Improvements in sanitation and hygiene in the developing world have led to a decline in immunity against HAV. A growing number of adults are now susceptible to infection, with those who have not been vaccinated against hepatitis B virus (HBV) being at risk of dual infection and potentially more severe illness. The symposium, "The role of hepatitis vaccination in patients with chronic liver disease", provided the opportunity to develop a consensus statement. It was concluded that patients with non-viral chronic liver disease (CLD) and certain groups with HBV infection can develop more severe disease in the event of HAV infection. It was identified that patients with CLD should be targeted for hepatitis A vaccination as soon as CLD is diagnosed.     

Immunogenicity of hepatitis A vaccine in decompensated liver disease

OBJECTIVE: Hepatitis A can cause decompensation and death in patients with previous liver injury. The hepatitis A vaccine is recommended for patients with chronic liver disease. The aim of this study was to screen, immunize, and measure the safety and antibody response of the hepatitis A vaccine in liver failure and liver transplant patients. METHODS: This was a prospective immunization trial at a referral center for liver disease and liver transplantation. A total of 193 patients with severe chronic liver disease were screened and 24 patients were vaccinated. Sixteen end stage liver disease patients were compared with eight liver transplant patients. Hepatitis A vaccinations using 1440 ELISA units were given at 0 and 2 months. Serum hepatitis A antibody titers were measured after each vaccine dose. An antibody response > or = 33 mIU/ml was considered protective. RESULTS: Screening seropositive rate was 70 of 193 (36%) and 24 patients were available for vaccination. The median antibody titer was markedly lower in liver transplant patients, 0.0 mIU/ml compared to liver failure patients 34.7 mIU/ml (p < 0.001). Liver transplant recipients did not respond to the vaccine (0 of eight patients) compared with seven of 14 liver failure patients (seroconversion rate 50%, p = 0.02). CONCLUSIONS: Liver failure significantly reduces the antibody response to hepatitis A vaccine, and liver transplant recipients were unable to respond to the vaccine. Although this study was small, immunization should be considered early for susceptible patients with chronic liver disease because the development of liver failure may blunt the immunogenicity of the vaccine.     

A Case Report of Hepatocellular Carcinoma 5 Years After HBsAg Loss in Chronic Hepatitis Delta: How Long Surveillance is Required?

BackgroundHepatitis delta virus infection occurs as acute coinfection or as superinfection in patients with preexisting chronic hepatitis B. Chronic hepatitis delta leads to more severe disease than chronic hepatitis B, with more rapid progression of fibrosis and increased risk of hepatocelullar carcinoma.Case reportWe report a case of hepatocelullar carcinoma 5 years after spontaneous clearance of Hepatitis B surface antigen in a patient with previous chronic hepatitis delta. He had been diagnosed with acute hepatitis delta superinfection 30 years ago which evolved to chronic delta infection and subsequently development of liver cirrhosis. Despite no specific antiviral treatment, he lost HBsAg persistently with later regression of cirrhosis.ConclusionsIn patients with cirrhosis due to chronic hepatitis delta who cleared HBsAg with improvement of liver fibrosis by non invasive techniques, it remains unknown how long hepatocelullar carcinoma surveillance has to be maintained.     

Risks associated with hepatitis A and hepatitis B in patients with hepatitis C.

Individuals with hepatitis C virus (HCV) are at risk for acquiring hepatitis A virus (HAV) or hepatitis B virus (HBV) because of shared risk factors. A number of organizations recommend vaccination against HAV and HBV for patients with HCV. The rationale for vaccinating these patients is to prevent hepatic superinfections. Acute HAV superinfection causes more severe disease, acute hepatic failure, and higher fatality rates in patients with underlying chronic liver disease, specifically chronic HBV infection and chronic HCV infection. Available data, although limited, suggest that HBV coinfection with HAV and HCV causes more severe hepatic injury than infection with HAV or HCV alone. At standard doses, hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild-to-moderate hepatitis C or chronic liver disease. Regardless of disease severity, vaccination should be routinely administered to patients upon diagnosis of HCV infection. Early vaccination is important because response to vaccination is reduced as liver disease progresses. Prevaccination and postvaccination serology testing is recommended in specific populations. A new combination hepatitis A and hepatitis B vaccine has been shown to be as safe and effective as monovalent hepatitis A and B vaccines and is currently under review by the United States Food and Drug Administration. A combination vaccine would offer ease of administration and convenience and could increase compliance in patients with hepatitis C or other chronic liver disease: two groups that should be more aggressively targeted by healthcare professionals.     

Role of viral factors in the natural course and therapy of chronic hepatitis B

Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.     

Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements

Primary liver cancers carry significant morbidity and mortality. Hepatocellular carcinoma (HCC) develops within the hepatic parenchyma and is the most common malignancy originating from the liver. Although 80% of HCCs develop within background cirrhosis, 20% may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC (NCHCC). NCHCC is often diagnosed late due to lack of surveillance. In addition, the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on non-cirrhotic patients. Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC. NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection, signifying the role of Hepatitis B infection in NCHCC. Given the effectiveness of current antiviral therapies, surgical techniques and locoregional treatment options, nowadays such patients have more options and potential for cure. However, these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes. Better understanding of the NCHCC risk factors, tumorigenesis, diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients. In this review, we aim to discuss NCHCC epidemiology, risk factors, and pathogenesis, and elaborate on NCHCC diagnosis and treatment strategies.