Hepatitis B Flashcards
What kind of virus is HBV?
HBV is one of a family of animal viruses, hepadnaviridae (hepatotropic DNA viruses), and is classified as hepadnavirus type 1.
What is the prevalence and associated geographic distribution of HBV infection?
The overall prevalence of HBsAg is reported to be 3.6 percent; however, it varies depending upon the geographic area. The prevalence of chronic HBV ranges from <2 percent in low-prevalence areas (eg, United States, Canada, Western Europe) to 2 to 7 percent in intermediate-prevalence areas (eg, Mediterranean countries, Japan, Central Asia, Middle East, and parts of South America) to ≥8 percent in high-prevalence areas (eg, Western Africa, South Sudan).
What is the rate of progression from acute HBV infection to chronic HBV infection?
The rate of progression from acute to chronic HBV infection is approximately 90 percent for perinatally acquired infection, 20 to 50 percent for infections between the age of one and five years, and less than 5 percent for adult-acquired infection.
What are some of the mortality statistics associated with HBV infection?
In 2013, viral hepatitis, primarily due to HBV and hepatitis C virus, was the seventh leading cause of death worldwide. Most mortality was attributable to liver cancer and cirrhosis. Globally, the total number of deaths due to hepatitis B in 2013 was estimated to be 686,000. In the United States, the rate of HBV-related mortality from 2009 to 2013 was 0.5 deaths/100,000 population; among the various subpopulations, HBV-related mortality was highest among Asians and Pacific Islanders at 2.6 deaths/100,000 population. In China, the age-standardized death rate for HBV-related liver cancer and cirrhosis in 2013 was 10.95 and 4.91 per 100,000 people, respectively.
How is HBV transmitted?
The predominant mode of HBV transmission varies in different geographical areas. Mother-to-child transmission is the predominant mode of transmission in high-prevalence areas. In comparison, horizontal transmission, particularly in early childhood, accounts for most cases of chronic HBV infection in intermediate-prevalence areas, while unprotected sexual intercourse and injection drug use in adults are the major routes of spread in low-prevalence areas.
Provide brief notes for the following forms of transmission:
- MTC
- Breastfeeding
- Paternal
- Transfusion
- Sexual
- Percutaneous
- Nosocomial
- Transplant
- Other
- Mother-to-child transmission — The infection rate of infants born to hepatitis B surface antigen (HBsAg)-positive mothers is as high as 90 percent among infants who do not receive hepatitis B immune globulin and hepatitis B vaccination at birth [5]. Mother-to-child transmission may occur in utero, at the time of birth, or after birth. However, most infections occur at or before birth.
- Breastfeeding — Breastfeeding does not appear to increase the risk of transmission.
- Paternal transmission — Transmission of HBV from fathers to their infants is possible based upon genotypic and phylogenetic analysis. In a study conducted in Taiwan, the HBV infection rate was 65 percent among neonates born to HBsAg-negative mothers and HBsAg-positive fathers.
- Transfusion
- Sexual
- Percutaneous transmission usually happens among injection drug users (IDU) who share syringes and needles. In addition to drug use, certain practices such as acupuncture, tattooing, and body piercing have also been associated with transmission of HBV through the use of equipment that is contaminated with HBV-infected blood.
- Nosocomial infection — HBV can be transmitted in the healthcare setting. Transmission generally occurs from patient to patient or from patient to healthcare providers (HCP) via contaminated instruments or an accidental needle stick.
- Transplant recipients — HBV infection can be transmitted from HBsAg-positive donors to HBsAg-negative recipients, with severe clinical consequences when the recipient is nonimmune (ie, anti-HBs-negative). Transmission of HBV infection has been reported after hematopoietic stem cell and solid organ transplantation.
- Other modes of transmission — Adults and children may acquire HBV infection via blood exposure to minor breaks in the skin or mucous membranes. In addition, transmission can occur via exposure to household articles that have been contaminated with blood, such as toothbrushes, razors, and toys, since HBV can survive outside the human body for a prolonged period. Although HBV DNA has been detected in various bodily secretions of hepatitis B carriers, there is no firm evidence of HBV transmission via body fluids other than blood or semen.
Comment on the two major forms of prevention of HBV infection.
Pre-exposure vaccination — Vaccination against hepatitis B virus (HBV) prior to an exposure is the best way to prevent HBV infection. Universal vaccination of newborns is recommended in most countries.
Postexposure prophylaxis — Postexposure prophylaxis to prevent HBV infection should be considered for individuals who have had an exposure that could potentially transmit HBV. These include percutaneous (eg, bite or needlestick) or mucosal exposures to blood or infectious secretions (eg, semen, body fluids that contain blood) of a patient who is HBsAg-positive or whose HBsAg status is unknown.
Briefly discuss the spectrum of clinical manifestations of HBV infection.
The spectrum of clinical manifestations of hepatitis B virus (HBV) infection varies in both acute and chronic disease. During the acute phase, manifestations range from subclinical or anicteric hepatitis to icteric hepatitis and, in some cases, fulminant hepatitis; during the chronic phase, manifestations range from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Extrahepatic manifestations can also occur with both acute and chronic infection.
Describe the acute phase of HBV infection under the following headings:
- Anicteric, icteric and fulminant disease
- The incubation period
- Prodromal features
- Lab abnormalities (excl. HBV serology)
- Outcome
- Approximately 70 percent of patients with acute hepatitis B have subclinical or anicteric hepatitis, while 30 percent develop icteric hepatitis. The disease may be more severe in patients coinfected with other hepatitis viruses or with underlying liver disease.
Fulminant hepatic failure is unusual, occurring in approximately 0.1 to 0.5 percent of patients. Fulminant hepatitis B is believed to be due to massive immune-mediated lysis of infected hepatocytes. This explains why many patients with fulminant hepatitis B have no evidence of HBV replication at presentation.
The reasons that HBV has a fulminant course in some patients are not well-understood.
- The incubation period lasts one to four months.
- A serum sickness-like syndrome may develop during the prodromal period (fever, arthralgia/arthritis, and rash, which is most commonly maculopapular or urticarial), followed by constitutional symptoms, anorexia, nausea, jaundice, and right upper quadrant discomfort. The symptoms and jaundice generally disappear after one to three months, but some patients have prolonged fatigue even after normalization of serum aminotransferase concentrations.
- Laboratory testing during the acute phase reveals elevations in the concentration of alanine and aspartate aminotransferase levels (ALT and AST); values up to 1000 to 2000 int. unit/L are typically seen during the acute phase with ALT being higher than AST. The serum bilirubin concentration may be normal in patients with anicteric hepatitis. The prothrombin time is the best indicator of prognosis. In patients who recover, the normalization of serum aminotransferases usually occurs within one to four months. A persistent elevation of serum ALT for more than six months indicates a progression to chronic hepatitis.
- Among patients who recover from acute hepatitis B, it has been thought that the virus is completely cleared by antiviral antibodies and specific cytotoxic T lymphocytes. Subsequent observations suggest that complete eradication of HBV rarely occurs after recovery from acute HBV infection and that latent infection can maintain the T cell response for decades following clinical recovery, thereby keeping the virus under control. Immunosuppression in such patients can lead to reactivation of the virus.
Describe the chronic phase of HBV infection under the following headings:
- History of previous hepatitis
- Symptoms
- Signs
- Lab abnormalities
- A history of acute hepatitis is elicited in only a small percentage of patients with chronic HBV infection.
- Many patients with chronic hepatitis B are asymptomatic (unless they progress to decompensated cirrhosis or have extrahepatic manifestations), while others have nonspecific symptoms such as fatigue. Some patients experience exacerbations of the infection which may be asymptomatic, mimic acute hepatitis, or manifest as hepatic failure.
- Physical examination may be normal, or there may be stigmata of chronic liver disease. Jaundice, splenomegaly, ascites, peripheral edema, and encephalopathy may be present in patients with decompensated cirrhosis.
- Laboratory tests may be normal, but most patients have a mild to moderate elevation in serum AST and ALT. During exacerbations, the serum ALT concentration may be as high as 50 times the upper limit of normal, and alfa-fetoprotein (AFP) concentrations as high as 1000 ng/mL may be seen. A progression to cirrhosis is suspected when there is evidence of hypersplenism (decreased white blood cell and platelet counts) or impaired hepatic synthetic function (hypoalbuminemia, prolonged prothrombin time, hyperbilirubinemia).
Describe the extra-hepatic manifestations of HBV infection. Please include the reason why these conditions are important to recognize and a sentence or two on their pathogenesis.
Extrahepatic manifestations, which are thought to be mediated by circulating immune complexes, occur in 10 to 20 percent of patients with chronic HBV infection. They are important to recognize because they may occur without clinically apparent liver disease and may be mistaken for other independent disease processes in other organ systems. The two major extrahepatic complications of chronic HBV are polyarteritis nodosa and glomerular disease.
- Arthritis-Dermatitis: The constellation of fever, arthralgias, rash, angioneurotic oedema, and, less commonly, haematuria and proteinuria is seen as a prodromal manifestation of acute HBV and rarely in patients with chronic HBV. The proximal interphanageal joints, knees, ankles, shoulders and wrists are the joints most commonly affected. During the period of acute joint symptoms, HBsAg titers in the blood are high and complement levels are low.
- PAN: Develops in <1% of patients with HBV; acute < chronic HBV. Clinical features are the same in PAN with no HBV infection. No apparent relationship exists between the severity of the vasculitis and the severity of the hepatic disease, and the hepatic disease is often relatively mild despite high levels of viral replication.
- GN: HBV can induce both membranous nephropathy and, less often, membranoproliferative glomerulonephritis. Most cases of HBV-related glomerulonephropathy occur in children. The typical presentation is with nephrotic range proteinuria. A progression to renal failure can occur, particularly in adults.
- Cryoglobulinaemia: Type II and III cryoglobulinaemia have been associated with HBV but the association is uncommon. Cryoglobulinaemia may be associated with systemic vasculitis (purpura, arthralgias, PN, and GN) but is often pauci-symptomatic or asymptomatic.
- Aplastic anemia has been described in association with HBV infection, although most cases of post-hepatitis aplastic anemia are not due to HBV.
Give a brief overview of the natural history of chronic HBV infection and the factors that may play a role in its progression.
The natural course of chronic hepatitis B virus (HBV) infection is determined by the interplay between virus replication and the host immune response. Other factors that may play a role in the progression of HBV-related liver disease include gender, alcohol consumption, and concomitant infection with other hepatitis virus(es). The outcome of chronic HBV infection depends upon the severity of liver disease at the time HBV replication is arrested.
What are the 2 phases of chronic HBV infection?
Chronic HBV infection generally consists of two phases: an early replicative phase with active liver disease, and a later phase with low replication and remission of liver disease. In some patients, reactivation of HBV replication occurs after a varying period of quiescence.
Discuss the immune tolerance phase of chronic HBV infection.
In patients with a perinatally acquired HBV infection, the initial phase is characterized by high levels of HBV replication—the presence of hepatitis B e antigen (HBeAg) and high levels of HBV DNA in serum—but no evidence of active liver disease as manifested by lack of symptoms, normal serum ALT concentrations, and minimal changes on liver biopsy. The lack of liver disease despite high levels of HBV replication has typically been attributed to immune tolerance to HBV. The immune tolerance phase usually lasts 10 to 30 years, during which there is a very low rate of spontaneous HBeAg clearance.
Discuss the immune clearance phase of chronic HBV infection.
The transition from the immune tolerance to the immune clearance phase occurs during the second and third decades in patients with perinatally acquired HBV infection. During the immune clearance phase, spontaneous HBeAg clearance increases to an annual rate of 10 to 20 percent.
HBeAg seroconversion is frequently, but not always, accompanied by biochemical exacerbations (abrupt increases in serum ALT). Exacerbations are believed to be due to a sudden increase in immune-mediated lysis of infected hepatocytes. They are often preceded by an increase in serum HBV DNA and a shift of HBcAg (hepatitis B core antigen) from nuclear to cytoplasmic sites within hepatocytes.
Most exacerbations are asymptomatic and are discovered during routine follow-up. However, some are accompanied by symptoms of acute hepatitis and may lead to the incorrect diagnosis of acute hepatitis B in patients who are not previously known to have chronic HBV infection. Exacerbations may be associated with an elevation in the IgM anti-HBc titer, which may lead to misdiagnosis of acute HBV infection and an increase in the serum alpha-fetoprotein concentration, which may raise concerns about the diagnosis of HCC. As noted above, exacerbations are more commonly observed in men than in women. In a small percentage of patients, exacerbations result in hepatic decompensation and rarely death from hepatic failure. Patients with severe exacerbations should be referred to specialized centers for liver transplantation and receive treatment with nucleos/tide analogues. Interferon is not indicated in this setting since it can cause further exacerbation of the disease.
Not all exacerbations lead to HBeAg seroconversion and clearance of HBV DNA from the serum, a phenomenon termed abortive immune clearance. These patients may develop recurrent exacerbations with an intermittent disappearance of serum HBV DNA with or without a transient loss of HBeAg. Such repeated episodes of hepatitis may increase the risk of developing cirrhosis and hepatocellular carcinoma (HCC).
Describe the inactive carrier state.
Patients in the low or nonreplicating phase/inactive carrier state are HBeAg negative and anti-HBe positive. In some patients, HBV DNA is undetectable in serum, even when tested by polymerase chain reaction assays, and liver disease is in remission as evidenced by normal serum ALT concentrations and the resolution of necroinflammation in liver biopsies. One study found that about 40 percent of inactive carriers had HBV DNA levels of 10(4) copies/mL or greater.
Significant liver disease can be found in patients with HBeAg-negative chronic HBV, but this is rare in those with truly persistent normal ALT defined by at least three normal ALT over a 12-month period and HBV DNA <4 log10 copies/mL (<2000 int. unit/mL).
Because of the fluctuating nature of chronic HBV infection, patients should not be categorized as inactive carriers unless there are at least three ALT levels and two to three HBV DNA levels over a 12-month period of observation. Studies suggest that combined quantification of HBsAg level and HBV DNA at a single time point may help in differentiating inactive carrier phase versus HBeAg-negative chronic hepatitis. HBsAg <1000 int. units/mL in an HBeAg-negative patient with serum HBV DNA <2000 int. units/mL identifies the inactive carrier phase with a high diagnostic accuracy (94 percent).
Describe HBeAg-negative hepatitis.
Some patients continue to have moderate levels of HBV replication and active liver disease (elevated serum ALT and chronic inflammation on liver biopsies), but remain HBeAg negative. Such patients are said to have HBeAg-negative chronic hepatitis. They have a residual wild-type virus or HBV variants that cannot produce HBeAg due to precore or core promoter genetic variations.
Patients with HBeAg-negative chronic hepatitis are older and have more advanced liver disease. They also tend to have fluctuations in HBV DNA and ALT levels.
Discuss briefly the resolution of chronic HBV infection.
Some patients with chronic HBV infection become HBsAg negative. The annual rate of delayed clearance of HBsAg has been estimated to be 0.5 to 2 percent in Western patients and much lower (0.1 to 0.8 percent) in Asian countries.
In most reports, patients without cirrhosis who cleared HBsAg appeared to have a good prognosis. Despite a generally favorable prognosis, clearance of HBsAg does not preclude the development of cirrhosis or hepatocellular carcinoma. Many patients who cleared HBsAg remained HBV DNA positive when tested by PCR assays, particularly during the first 10 years of HBsAg clearance.
What is the spectrum of sequelae following chronic HBV infection?
The sequelae of chronic hepatitis B virus (HBV) infection vary from an inactive carrier state to the development of cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), extrahepatic manifestations, and death.
What are the 5-yr rates of progression from:
- Chronic HBV to cirrhosis?
- Compensated cirrhosis to decompensated disease?
- Compensated cirrhosis to HCC?
- Chronic hepatitis to cirrhosis – 12 to 20 percent
- Compensated cirrhosis to hepatic decompensation – 20 to 23 percent
- Compensated cirrhosis to HCC – 6 to 15 percent
(It should be noted that the rates of progression and rates of survival cited above were based on data in the pre-nucleos/tide analogue era and prognosis of patients with chronic hepatitis B have improved markedly in the last 10 years.)
What are the 5-yr survival rates for:
- Compensated cirrhosis?
- Decompensated cirrhosis?
- Compensated cirrhosis – 85 percent at five years.
- Decompensated cirrhosis – 55 to 70 percent at one year and 14 to 35 percent at five years.
(It should be noted that the rates of progression and rates of survival cited above were based on data in the pre-nucleos/tide analogue era and prognosis of patients with chronic hepatitis B have improved markedly in the last 10 years.)
Which virological and non-virological factors influence disease progression and survival in chronic HBV infection?
Factors related to HBV infection include the individual’s HBeAg status, the HBV DNA and HBsAg levels, and the HBV genotype. The HBV DNA level is the most important virologic predictor of disease progression in patients with a high HBV viral load (≥2000 IU/mL), whereas the HBsAg level helps determine the risk of progression in those with a HBV DNA <2000 IU/mL.
Factors not associated with HBV include those related to the host (gender, age, diabetes) and environment (alcohol, smoking, carcinogens) as well as coinfection with other viruses (eg, HCV, HDV, HIV).
Write short notes on acute flares in chronic HBV infection.
Chronic HBV is often punctuated by sudden flares of disease activity that are reflected by a rise in serum aminotransferases. Although a uniform definition is lacking, a flare has frequently been described as a rise in serum ALT levels to at least two times the baseline value. Spontaneous flares are an important part of the natural history of HBV infection because when they occur repeatedly, they lead to histologic progression. Most flares result from a change in the balance between immunologic responses to HBV and the level of virasl proliferation.
Causes:
- Spontaneous
- Immunosuppressive therapy-induced
- Antiviral therapy-induced
- Flares associated with genotypic variation
- Flares caused by infection with other viruses (viz. HAV, HCV, HDV and/or HEV).
Describe spontaneous flares in chronic HBV infection.
Spontaneous flares of chronic HBV often result from reactivated infection, and an increase in serum HBV DNA levels often precedes an increase in serum aminotransferase levels.
The reasons for reactivated infection are unknown but likely relate to subtle changes in the immunological control of viral replication.
Fatigue may be reported during flares of chronic HBV but in many instances, patients remain asymptomatic. Occasionally symptoms and signs of frank liver failure become apparent, particularly when the flare is superimposed on advanced chronic HBV.
Most clinically recognizable flares occur in patients who are in the non-replicative phase of HBV infection (ie. initially testing positive for for anti-HBe and negative for serum HBV DNA). During such flares, serum HBV DNA levels increase, and HBeAg often re-appears in serum (seroconversion). HBV DNA and HBeAg are often detectable in the serum when the patient is first seen, but if the flare has been ongoing for several weeks or longer, the accompanying enhancement of the immune response may make it difficult to detect a rise in serum HBV DNA levels. Frequently, subsidence of these flares of hepatitis is accompanied by loss of HBV DNA and HBeAg in serum.
Flares can also occur in patients who are in the replicative phase of infection (i.e., already positive for HBV DNA and HBeAg in serum). In these instances, HBV replication intensifies, serum HBV DNA levels rise, and liver biochemical deterioration occurs, often without the subsequent loss of HBeAg. Multiple episodes of reactivation and remission have been shown to accelerate the progression of chronic HBV and are particularly likely to occur in patients infected with the precore mutant form of chronic HBV.
What is the mechanism of flare in those on antivirals?
Either withdrawal of medication or development of resistance.
Is surveillance for HCC necessary in chronic HBV infected patients?
Yes.
Comment on the relationship between alcoholism and HBV infection. Mention:
- Prevalence in alcoholics
- Risk of chronic infection
- Influence on liver disease
- The prevalence of serum HBV markers among alcoholics has been estimated to be two- to fourfold higher than a corresponding control population, suggesting an increased rate of HBV infection.
- There is no clear evidence that alcoholics have an enhanced risk of chronic HBV infection.
- However, HBV DNA has been detected in the sera and liver tissues in some HBsAg negative alcoholics who present with liver disease, implying that occult HBV infection may have contributed to liver disease in these patients. Alcoholics with HBV infection have been reported to have accelerated liver injury, increased risk of developing cirrhosis and hepatocellular carcinoma (HCC), and reduced survival compared with alcoholics who are not HBV-infected.
Write short notes on HCV coinfection.
Acute coinfection with HBV and HCV may shorten the duration of HBs antigenemia and lower the peak serum aminotransferase concentration compared with acute HBV infection alone. These findings suggest that HCV coinfection may interfere with the replication of HBV, leading to attenuation of liver damage. However, acute coinfection of HCV and HBV, or acute HCV on preexisting chronic HBV have also been reported to increase the risk of severe hepatitis and fulminant hepatic failure. Similarly, acute HBV in patients with chronic HCV can lead to severe hepatitis, but may also lead to clearance of HCV.
Liver disease is usually more severe than in patients infected by HBV alone. Patients with dual HBV and HCV infection may also have a higher rate of HCC compared with patients infected by either virus alone, particularly those who are anti-HCV and HBeAg positive.
Should patients with chronic liver disease get vaccinated against HAV?
Yes.
Which patients should be screened for HBV infection?
●Individuals who have signs and symptoms of acute hepatitis;
●Individuals with chronic liver disease (eg, chronically elevated ALT or AST);
●Pregnant women;
●Those requiring immunosuppressive therapy;
●Persons with HIV or HCV;
●Injection drug users;
●Men who have sex with men;
●Individuals with multiple sexual partners and/or a history of sexually transmitted diseases;
●Patients undergoing hemodialysis;
●Household and sexual contacts of HBV infected persons;
●Inmates of correctional facilities.
Which tests are used in screening?
We test for hepatitis B virus infection using HBsAg, hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) in certain groups of patients.
Write short notes on hepatits B antigens and antibodies.
Hepatitis B surface antigen (HBsAg) is the serologic hallmark of HBV infection.
HBsAg appears in serum 1 to 10 weeks after an acute exposure to HBV, prior to the onset of hepatitic symptoms or elevation of serum alanine aminotransferase (ALT). In patients who subsequently recover, HBsAg usually becomes undetectable after four to six months. Persistence of HBsAg for more than six months implies chronic infection. It is estimated that less than 5 percent of immunocompetent adult patients with genuine acute hepatitis B progress to chronic infection. Among patients with chronic HBV infection, the rate of clearance of HBsAg is approximately 0.5 percent per year.
The disappearance of HBsAg is followed by the appearance of hepatitis B surface antibody (anti-HBs). In most patients, anti-HBs persists for life, thereby conferring long-term immunity. In some patients, however, anti-HBs may not be detectable until after a window period of several weeks to months, during which neither HBsAg nor anti-HBs can be detected. At this time, the serologic diagnosis may be made by the detection of IgM antibodies against hepatitis B core antigen (IgM anti-HBc).
Coexistence of HBsAg and anti-HBs has been reported in 5 to 30 percent of HBsAg positive individuals. In most instances, the antibodies are unable to neutralize the circulating virions. These individuals should therefore be regarded as carriers of the hepatitis B virus.
Write short notes on hep B core antigen and antibody.
Hepatitis B core antigen (HBcAg) is an intracellular antigen that is expressed in infected hepatocytes. It is not detectable in serum. Anti-HBc can be detected throughout the course of HBV infection.
The detection of IgM anti-HBc is usually regarded as an indication of acute HBV infection. However, IgM anti-HBc may remain detectable up to two years after the acute infection. Furthermore, the titer of IgM anti-HBc may increase to detectable levels during exacerbations of chronic hepatitis B.
IgG anti-HBc persists along with anti-HBs in patients who recover from acute hepatitis B. It also persists in association with HBsAg in those who progress to chronic HBV infection.
Describe the entity of isolated anti-HepBc.
Isolated detection of anti-HBc can occur in three settings: during the window period of acute hepatitis B when the anti-HBc is predominantly IgM class; many years after recovery from acute hepatitis B when anti-HBs has fallen to undetectable levels; and after many years of chronic HBV infection when the HBsAg titer has decreased below the cutoff level for detection.
In some cases, isolated anti-HBc may be due to a false positive test result. Thus, the evaluation of individuals with isolated anti-HBc should include repeat testing for anti-HBc, HBsAg, anti-HBe, and anti-HBs. In addition:
●Patients who remain positive for isolated anti-HBc IgG, have evidence of a recent HBV exposure, have symptoms of acute hepatitis, and/or have markedly elevated ALT levels should be tested for the presence of anti-HBc IgM to rule out recent HBV infection.
●Individuals with evidence of chronic liver disease should be tested for HBV DNA to exclude low level chronic HBV infection. HBV DNA has been detected in the serum of individuals with isolated anti-HBc when tested by PCR assays; however, the frequency of detection varies from 0 to 20 percent with most studies showing <5 percent detection.
The clinical significance of isolated anti-HBc is unclear. Occult HBV infection (ie, isolated anti-HBc with a detectable HBV DNA) has been associated with chronic liver disease and hepatocellular carcinoma.
In addition, transmission of HBV infection has been reported from blood and organ donors with isolated anti-HBc. Reactivation of HBV replication with reverse seroconversion (ie, reappearance of HBsAg) can also occur in patients with isolated anti-HBc in the setting of intense immunosuppression. Prophylactic antiviral therapy may reduce the risk of reactivation in certain patients.
Write short notes on Hep B e antigen and antibody.
Hepatitis B e antigen (HBeAg) is a secretory protein that is processed from the precore protein. It is generally considered to be a marker of HBV replication and infectivity. The presence of HBeAg is usually associated with high levels of HBV DNA in serum and higher rates of transmission of HBV infection from carrier mothers to their babies and from patients to health care workers.
HBeAg to anti-HBe seroconversion occurs early in patients with acute infection, prior to HBsAg to anti-HBs seroconversion. However, HBeAg seroconversion may be delayed for years to decades in patients with chronic HBV infection. In such patients, the presence of HBeAg is usually associated with the detection of high levels of HBV DNA in serum and active liver disease.
Seroconversion from HBeAg to anti-HBe is usually associated with a decrease in serum HBV DNA and remission of liver disease. However, some patients continue to have active liver disease after HBeAg seroconversion.
Write short notes on the use of HBV DNA assays.
Mention:
* Levels in acute infection
* Levels in HBeAg-negative chronic infection
* Use in chronic HBV infection
* Use in HBsAg-negative liver disease
Recovery from acute hepatitis B is usually accompanied by the disappearance of HBV DNA in serum as determined by hybridization or bDNA assays. However, HBV DNA may remain detectable in serum for many years if tested by PCR assays. This observation suggests that the virus persists after “recovery” but is controlled by the immune system.
HBV DNA levels are also detectable in patients with HBeAg-negative chronic hepatitis, although levels are generally lower than in patients with HBeAg positive chronic hepatitis. A serum HBV DNA level of >2,000 int. unit/mL has been proposed as a cutoff level to differentiate patients with HBeAg-negative chronic hepatitis from those in an inactive carrier state (ie, HBeAg-negative, persistently normal ALT).
Clinical use — The major clinical role of serum HBV DNA assays in patients with chronic HBV infection is to assess HBV replication and candidacy for antiviral therapy. Indications for HBV treatment are based upon the presence of active liver disease and high HBV DNA levels. A cutoff of 20,000 int. unit/mL has been proposed for treatment initiation in HBeAg positive patients, and a lower threshold 2000 int. unit/mL for HBeAg-negative patients.
Patients with high pretreatment serum HBV DNA levels are less likely to respond to interferon. In contrast, pretreatment serum HBV DNA levels do not appear to predict response to nucleos/tide analogue therapy. However, it may take longer for the HBV DNA to become undetectable in patients treated with nucleos/tide analogue therapy if pretreatment levels are high.
Suppression of serum HBV DNA is also used as one of the end-points in assessing response to antiviral treatment and to detect virologic breakthrough. With the availability of potent antiviral agents, suppression of HBV DNA to undetectable levels by PCR is the goal. Monitoring of serum HBV DNA using sensitive quantitative assays such as real time PCR assays with lower limit of detection of <20 int. unit/mL will identify patients who have suboptimal response that may benefit from additional therapy, and patients who have virologic breakthrough (>1 log increase in HBV DNA from nadir while on treatment).
Rarely, tests for HBV DNA in serum help to identify HBV as the etiology of liver disease in HBsAg-negative patients. This is especially important in patients with fulminant hepatitis B, who may have cleared HBsAg by the time they present.
How is acute HBV infection diagnosed?
The diagnosis of acute hepatitis B is based upon the detection of HBsAg and IgM anti-HBc. During the initial phase of infection, markers of HBV replication, HBeAg and HBV DNA, are also present. Recovery is accompanied by the disappearance of HBV DNA, HBeAg to anti-HBe seroconversion, and subsequently HBsAg to anti-HBs seroconversion.
