HBV Journal Review
November 1, 2010, Vol 7, no 11
by Christine M. Kukka
"Occult" HBV Issue
Researchers Assess the Causes, Impact, and Prevalence of Occult Hepatitis B
“Occult” or hidden hepatitis B occurs when a person has been infected with the hepatitis B virus (HBV) in the past, but currently tests negative for the hepatitis B surface antigen (HBsAg), which is the critical lab test that indicates whether a person is infected.
While scientists have known about occult HBV infection since 1978, they have not been able to define how it develops or how widespread it is. In a recent article published in the journal of Digestive Diseases and Sciences, U.S. researchers attempted to define its causes, its impact on liver health, and its prevalence.
Researchers are finding that many people may be infected with occult hepatitis B. One source of this infection is donated blood—which was considered safe because of the absence of HBsAg. Today, labs use highly refined equipment to test blood supplies for even low levels of HBV DNA when HBsAg is absent.
· Occult infection may increase liver damage:
Research suggests that occult HBV may speed the progression of liver fibrosis and increase the risk of liver cancer, especially in people with other immune-suppressing infections, such as HIV or hepatitis C virus (HCV) infection.
· High rates of occult HBV in HCV- and HIV-infected patients:
Many patients are coinfected with hepatitis B and C and HIV. When they have occult HBV, this infection acts to decrease the effectiveness of hepatitis C treatment (pegylated interferon and ribavirin). In a study of 200 HCV-infected patients, who were HBsAg negative, 33% tested positive for HBV DNA, indicating an occult infection.
In another study of 57 HIV-infected patients who tested negative for HBsAg and positive for the core antibody, HBV DNA was detected in 89.5% of them. Another study of 53 HBsAg-negative patients with HIV in India uncovered an occult HBV infection rate of 17% (with detectable HBV DNA).
Among 1,169 healthy blood donors without HIV or HCV, researchers found an occult HBV infection rate of 1% among donors testing positive for the core antibody.
· Unclear what causes occult HBV:
To date, researchers do not know what mutations or immune action leads to occult hepatitis B. Some suspect that even after a patient clears HBsAg and generates surface antibodies, some HBV remain hidden from the immune system in the liver, and appear able to replicate and generate HBV DNA without needing HBsAg for the replication process.
Because occult HBV often occurs simultaneously with a hepatitis C infection, researchers speculate that some gene or antigen in the HCV somehow suppresses HBsAg production during the HBV replication process. As a result, only low levels of HBV DNA can be produced in the presence of HCV. Scientists believe this because often when HBV-HCV coinfected patients clear the hepatitis C infection, their hepatitis B infections tend to reactivate and HBV DNA levels rebound.
· Occult HBV accelerates liver damage:
Patients with occult HBV tend to have more advanced fibrosis and elevated alanine transaminase (ALT) levels, which indicate liver damage when they rise above normal. One study found that 22 of 66 (33%) patients coinfected with HCV and occult hepatitis had cirrhosis, compared to only 26 of 134 (16%) patients infected with only HCV.
· Increased risk of liver cancer:
Researchers believe occult HBV are able to integrate themselves more effectively into liver cells’ DNA, which can lead to abnormal cell growth, tumors, and liver cancer. They suspect that a viral mutation that leads to occult HBV may make them more effective at integrating into the DNA and causing cancer.
· Transplanted organs with HBV core antibody transmit HBV:
HBV can be transmitted when donor livers test positive for the core antibody, even when they are free of HBsAg. Researchers now suspect that occult HBV are present in these transplanted livers and manage to transmit infection to their hosts.
· Chemotherapy can reactivate infection when occult HBV is present:
Given the prevalence of occult HBV in people with resolved hepatitis B infections, it is important that patients are tested for the core antibody before they are given cancer-fighting drugs that suppress the immune system. These patients may experience a resurgence of hepatitis B during cancer treatment unless they are given antiviral medication to suppress the virus during cancer treatment. Some scientists now recommend that any cancer patient who tests positive for the core antibody should also be tested for HBV DNA, and given antivirals if they are found to have occult HBV.
Three-Year Study Shows Tenofovir Highly Effective in HBeAg-Positive and –Negative Patients
A three-year trial of the antiviral tenofovir (Viread) in HBeAg-positive and –negative patients shows it to be highly effective without causing any drug resistance, according to an article in the October issue of the journal of the Gastroenterology.
To date, tenofovir has proven to be more effective than adefovir (Hepsera) in one-year studies. More recent trials that followed patients treated for three years revealed:
- At week 144, 87% of HBeAg-negative and 72% of HBeAg-positive patients had undetectable levels of HBV DNA (less than 400 copies/mL).
- Among patients previously treated with adefovir, 88% of HBeAg-negative and 71% of HBeAg-positive patients had undetectable HBV DNA.
- Overall, 81% of HBeAg-negative and 74% of HBeAg-positive patients maintained normal ALT levels and 34% lost HBeAg. None developed antiviral resistance.
- Additionally, 8% of HBeAg-positive patients lost HBsAg.
Tenofovir Alone or Combined with Emtricitabine Equally Effective in Adefovir- and Lamivudine-Resistant Patients
A multinational team of researchers followed 105 lamivudine- and adefovir-resistant patients who were treated with emtricitabine (FTC) combined with tenofovir or with just tenofovir alone. (Currently, the combination of emtricitabine and tenofovir is not approved for treatment of hepatitis B in the U.S.)
The patients all had high viral load, and had either developed resistance or failed to respond to earlier antiviral treatment.
At week 24, declines in viral load (HBV DNA) were equal. At week 48, 81% of both patient groups had undetectable viral loads, according to the report in the October issue of Gastroenterology.
Moderate Coffee Consumption Reduces Liver Cancer Risk
Recent studies have shown that coffee confers moderate protection against cirrhosis and liver cancer in HBV-infected people. To test that theory, Hong Kong researchers compared the incidence of liver cancer in 109 hepatitis B patients who drank a moderate amount of coffee to that of 125 HBV-infected non-coffee drinkers over an 18-month period.
Researchers found that moderate coffee consumption significantly reduced the risk of liver cancer by 59%.
“The findings provided evidence to support the protective effect of coffee consumption in moderate quantities in HBV chronic carriers,” they wrote in the Journal of Epidemiology and Community Health.
Quality of Hepatitis B Treatment in Canada Depends on Patient’s DrugInsurance
Varying insurance coverage of drugs is resulting in inconsistent treatment of hepatitis B by Canadian physicians, according to a study spearheaded by the Canadian Association for the Study of the Liver, and published in the September 2010 issue of the Canadian Journal of Gastroenterology.
Rising AFP Levels Indicate Cirrhosis and Risk of Liver Cancer
Alpha-fetoprotein (AFP), when found to be above normal in blood tests, can indicate the presence of liver cancer tumors and it can also indicate fibrosis or cirrhosis in advanced hepatitis B.
Chinese researchers monitored AFP levels in 101 patients with liver damage who were treated with entecavir or pegylated interferon. They found entecavir was more effective in reducing AFP levels—successfully knocking down AFP levels within 12 weeks, in contrast to the interferon-treated group which required 22 weeks of treatment before AFP levels declined.
Another group of 93 patients with cirrhosis and elevated AFP levels, were treated with entecavir and monitored. Liver cancer developed in 16 (17.2%) of these patients—all of whom experienced continuously rising AFP levels despite the treatment.
Researchers concluded that cirrhotic patients with rising AFP levels were at very high risk of liver cancer, and that, “early detection of minute lesions may be possible by monitoring AFP levels,” in conjunction with enhanced computed tomography examination,” in their article published in the Journal of Viral Hepatology.
Genotype C Mutation Linked to Higher Liver Cancer Risk
Taiwanese researchers have identified a mutation in HBV genotype or strain C that may increase the risk of liver cancer.
Writing in the October 2010 issue of the Journal of Virology, researchers reported that genotype C patients with the mutation called F141L had a higher rate of liver cancer than patients without the mutation, even when those patients had cirrhosis.
The mutation appears to induce abnormal cell growth associated with liver cancer.
Accelerated Hepatitis B Vaccination in Drug Users Moderately Effective
University of Texas and U.S. Centers for Disease Control and Prevention researchers tried an enhanced community intervention program to see if drug users would accept hepatitis B immunization.
The Drugs, AIDS, STDs, and Hepatitis (DASH) project conducted a randomized controlled trial among current drug users in two urban neighborhoods. The control group participated in a conventional intervention and received information on HIV, while the enhanced intervention was designed to also promote hepatitis B vaccination.
Participants who tested negative for HBV and HIV received either the standard three-dose hepatitis B vaccination schedule (at 0, 1, and 6 months) or an accelerated vaccination schedule (at 0, 1, and 2 months).
Of those in the two programs, 77% agreed to be immunized, and 75% received all three doses.
Injection drug users on the accelerated immunization schedule were significantly more likely to receive all three doses (76%) than those on the standard schedule (66% ), however when all drug users were assessed, the rates were smaller at 77% and 73% respectively.
Those who completed the immunizations were older, African-American, in stable housing, and also used alcohol.
Of those receiving the three doses, 65% achieved protection from HBV, according to the report published in the Journal of Infectious Diseases.
Taking Antiviral Medications As Prescribed Important to Prevent Resistance
Hepatitis B patients who take antiviral medications, which make it difficult for HBV to replicate, are already at risk of developing drug resistance. Over time, HBV with mutations that allow them to replicate despite antiviral treatment increase in number and the infection rebounds.
When patients skip doses, the risk of resistance increases because the antiviral’s strength is weakened.
University of Michigan researchers followed three groups of patients who were prescribed four different antivirals to see how compliant the patients were.
Researchers followed 11,100 patients who were taking either lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir, or tenofovir. The average medication adherence rate (determined by continued renewal of prescriptions) was 87.8%, and was higher among existing patients than among new patients or younger patients (88% vs. 84.6%).
The researchers, writing in the Journal of Hepatology, recommended that counseling of young and/or new patients on the importance of medication adherence may decrease the rate of antiviral drug resistance.
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