HBV Journal Review
July 1, 2011, Vol 8, no 7
by Christine M. Kukka
Undetectable Viral Load
Reduces Liver Cancer Risk
People who are infected with the hepatitis B virus (HBV), but who have undetectable viral load (HBV DNA) in their bloodstream are 72% less likely to develop liver cancer, according to a report published in the June edition of the journal Infectious Disease Special Edition.
The finding underscores the importance of treating people to keep their viral load undetectable or as low as possible, according to Taiwanese and U.S. researchers who collaborated on the study.
The team studied what factors contributed to liver cancer, including viral load, the hepatitis B “e” antigen (HBeAg)–which usually indicates high viral load, and the hepatitis B surface antigen (HBsAg)–which indicates the presence of an HBV infection.
They monitored viral load and presence of the “e” and surface antigens in 1,285 patients with HBV DNA levels exceeding 10,000 copies/mL between 1991 and 2007. During the 16-year study period, 111 patients (8.64%) developed liver cancer. Researchers found that patients with undetectable viral load were 72% less likely to develop cancer than those with detectable HBV DNA.
In contrast, the risk for developing cancer was similar among those with undetectable HBV DNA no matter if they cleared HBeAg or HBsAg.
“Distinguishing between individuals with or without HBsAg seroclearance did not significantly affect the rates of (liver cancer) among those with undetectable HBV DNA levels, with 1.6% of the latter group and 1.9% of the former group developing cancer,” they reported.
Researchers said the study underscores the importance of treating patients with antivirals to suppress viral load in order to prevent liver disease and cancer.
Some Dietary Supplements Cause Liver Damage
According to a review of published studies that examined the impact of dietary supplements on the liver, many supplements such as Herbalife® and Hydroxycut products can cause liver damage, especially in people with pre-existing liver infections such as hepatitis B.
Researchers, reporting in the journal Liver International, conducted a review of studies on dietary supplements and liver health published between 1990 and 2010.
They found that, “Significant liver injury was reported after intake of Herbalife’s
and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others.”
No uniform pattern of liver damage was identified, and liver damage ranged from asymptomatic elevations of liver enzymes, which indicate liver cell damage or death, to liver failure and death.
“Exact estimates on how frequent adverse … reactions occur as a result of dietary supplements cannot be provided,” they noted. However, liver injury from these supplements, which appear to mimic other liver diseases, is being increasingly documented.
Researchers promoted tighter government regulation of dietary supplements, and increased awareness among consumers and health care providers.
Some People Have a Genetic Susceptibility to Cirrhosis
Researchers, writing in the June issue of Hepatology, report that some people may be genetically predisposed to developing cirrhosis. About 5% of patients with cirrhosis have no cause, such as viral hepatitis, fatty liver disease, or alcoholism, for their severe liver scarring.
Now researchers are suggesting that some people are genetically predisposed to cirrhosis, and that their liver cells become cirrhotic because they lack the enzymes and capacity to regenerate properly.
Data from epidemiological studies of people who have cirrhosis with no apparent cause show that when compared to European Americans, this type of cirrhosis is 3.1-fold higher in Hispanic Americans and 3.9-fold lower in African Americans.
This genetic predisposition to cirrhosis may be the reason why some people with hepatitis B advance to cirrhosis so quickly, while others do not experience severe liver damage at all.
Low HBsAg Levels Associated with HBeAg Seroconversion during Interferon Treatment
Researchers followed 399 HBV-infected patients, all positive for HBeAg, treated with pegylated interferon (180 μg/week) alone or with lamivudine (100 mg/day) for 48 weeks to see which patients responded to the treatment.
According to the report published in the journal Hepatology International, the patients with lower levels of HBsAg (around 5,000 IU/mL) tended to clear HBeAg and develop “e” antibodies at higher rates than those whose HBsAg levels were higher, around 50,000 IU/mL.
HBeAg seroconversion rates six months after treatment stopped were significantly higher in patients with HBsAg less than 1,500 IU/mL at weeks 12 and 24 (56.7 and 54.4% respectively) compared to patients with HBsAg levels between 1,500 to 20,000 IU/mL (32.3 and 26.1% respectively).
Antiviral Treatment Markedly Improves Survival after Liver Cancer Surgery
Chinese researchers compared survival rates among 136 liver cancer patients treated with antivirals to those who received no treatment, after all had liver tumors surgically removed.
All of the liver cancers resulted from HBV infection and patients were followed for five years after surgery. Forty-two received antiviral treatment and 94 (the control group) received no treatment after cancerous tumors were removed from their livers.
According to the report published in the June issue of Archives of Surgery, antiviral treatment markedly improved survival. The
1-, 3-, and 5-year survival rates in the treated group were 88.1%, 79.1%, and 71.2% respectively; compared to the control group’s survival rates of 76.5%, 47.5%, and 43.5% respectively.
The 1-, 3-, and 5-year disease-free survival rates in the treatment group were 66.5%, 51.4%, and 51.4% respectively, and in the control group they were 48.9%, 33.8%, and 33.8%.
The researchers recommend that all patients receive antiviral treatment following surgical removal of liver tumors.
Blood Tests May Accurately Identify When Treatment Is Needed –Bypassing Biopsies
Doctors continue to search for a noninvasive blood test that gives a true picture of the health of a patient’s liver so they can know if treatment is needed. While testing alanine aminotransferase (ALT) levels is universally used and usually indicates when severe liver damage is present (elevated ALTs indicate damaged or dying liver cells) doctors know some patients with normal ALT levels also have liver damage and require treatment.
Short of an invasive liver biopsy, doctors want a simple way to determine the health of the liver so they know if treatment is necessary.
Recently, researchers applied a wide range of liver tests to 227 viral hepatitis-infected patients with normal or moderately elevated ALT levels to see which test, or which combination of tests, provided the most accurate snapshot of liver health. Fifty-three of the patients were known to have serious liver inflammation, which was previously identified by a liver biopsy.
Writing in the journal Liver International, researchers described testing the patients’ ALT and aspartate aminotransferase (AST) levels, platelet count, γ-glutamyl transpeptidase, alkaline phosphatase, hyaluronic acid, haptoglobin, apolipoprotein A1 and procollagen III N-terminal peptide levels to assess liver health.
They found that elevated AST and apolipoprotein A1 levels accurately identified liver inflammation or fibrosis in patients, even when the patients’ ALT levels were normal.
These two blood tests, when used together, can potentially identify patients who are experiencing liver damage and require treatment, even when their ALT levels are normal. If proven to be accurate when tested on a larger number of patients, the two tests can help determine when treatment is needed and avoid costly and invasive liver biopsies.
In an unrelated article published in the Journal of Viral Hepatitis, British researchers report that the Enhanced Liver Fibrosis (ELF) test also appears to accurately identify liver fibrosis and damage in patients with hepatitis C, even when ALT levels are normal. The ELF test measures three things to identify the presence of fibrosis–hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metaloproteinase 1.
They used the test in 347 patients, who also had liver biopsies, to determine its accuracy. ELF was able to predict severe fibrosis in 81% of the patients, which means those biopsies could have been avoided.
Biopsy and Treatment When ALT Slightly
Researchers, writing in the June issue of Liver International, recommend liver biopsies for all hepatitis B patients who test negative for HBeAg and have ALT levels that are 1.5-times higher than normal.
Currently, treatment and a liver biopsy are often recommended when ALT levels are twice normal. Normal ALT levels for women are 19 IU/L and 30 IU/L for men.
The researchers followed three groups of 499 hepatitis B patients with detectable viral load over a three-year period and administered liver biopsies to them.
· Group 1 had 181 patients with normal ALT levels.
· Group 2 had 200 patients with ALT levels between normal and twice normal.
· Group 3 had 118 patients with ALT levels that were twice normal or higher.
As expected, patients with highly elevated ALT levels were found to have liver inflammation and fibrosis.
However, in Group 1 among those with positive HBeAg status, 29 (52.7%) had liver damage and five (9.1%) had fibrosis. Among those in Group 1 who were HBeAg-negative, 66 (23.1%) had liver damage and 31 (10.8%) had fibrosis.
In Group 2 with positive HBeAg status, 14 (15.7%) had moderate-to-severe liver damage and 19 (21.2%) had fibrosis. Among those in Group 2 with negative HBeAg, 34 (30.6%) had moderate-to-severe liver damage and 38 (34.2%) had fibrosis.
Additionally, liver damage and fibrosis were significantly greater in patients age 30 and older.
“We recommend liver biopsy in HBeAg-negative (hepatitis B patients) over 30 years of age regardless of ALT level and starting treatment at when ALT is 1.5-times normal instead of twice normal,” they wrote.
Patients Fare Slightly Better When Treated with Interferon Than Adefovir
Researchers treated HBeAg-positive patients, who had developed resistance to the antiviral lamivudine (Epivir-HBV) with either pegylated interferon (Pegasys) or adefovir (Hepsera) to see which drug worked best.
Adefovir, an antiviral like lamivudine, prevents the virus from replicating by disrupting its reproductive capabilities. Interferon boosts the immune system to fight the infection. Antivirals are used over an indefinite period, while interferon injections can span six to 12 months.
The researchers, reporting in the June 2011 issue of the journal Alimentary Pharmacology and Therapeutics, reported that the 55 patients treated with interferon had a higher HBeAg seroconversion rate (loss of HBeAg and development of “e” antibodies) of 14.6% compared to a 3.8% seroconversion rate among 80 adefovir-treated patients.
At week 72, interferon-treated patients who had a steep decline in HBsAg during the first 24 weeks of treatment had the highest rate of HBeAg seroconversion compared to patients who did not have such a decline (25.5% versus 7.7%.)
However, after 72 weeks of continuous adefovir treatment, 22.5% of patients achieved undetectable HBV DNA (viral load) compared with 10.6% in interferon-treated patients.
Overall, the response to interferon treatment remained disappointing, researchers noted, with a response rate of only 14.6%. However, monitoring HBsAg levels during the early weeks of treatment can help to predict who will ultimately respond to interferon.
Entecavir Fails in an Immune-Compromised Patient
Doctors, writing in the June issue of the journal Infection, described successfully treating a hepatitis B patient who had failed to respond to treatment with the antiviral entecavir (Baraclude.)
What puzzled doctors was that even though the patient had a weakened immune system, he had not developed any drug resistance to the antiviral entecavir. Yet, the antiviral was ineffective in lowering his high viral load (HBV DNA).
Doctors next treated him with tenofovir (Viread), an antiviral that is known for its potency and its low rate of drug resistance. Within weeks, the patient achieved undetectable viral load
“This case highlights the difficulty in choosing an optimal therapy in such specific conditions and supports the concept of tailoring therapy (including combination regimens) on the basis of the particular conditions of each individual patient,” they wrote.
Researchers Urge CDC to Screen More Adults for Hepatitis B
Current U.S. Centers for Disease Control and Prevention and Public Health Service guidelines recommend that doctors screen adults for hepatitis B only if they are from high-risk groups (including immigrants from high prevalence areas, injecting drug users, or men who have sex with men) that have HBV infection rates exceeding 2%.
However, an article published in the July issue of the journal of Clinical Infectious Diseases argues it is cost-effective to screen nearly all adults, even those from lower-risk populations.
Researchers factored the costs of screening and then treating a 35-year-old man in a region with low HBV infection rate to assess if screening would be cost effective. They evaluated the cost of not screening the patient compared with the cost of screening, followed by treatment.
Researchers determined that even if the prevalence of hepatitis B was as low as 0.3%, it would still be cost-effective to screen and treat adults, and avoid more costly treatment when the disease has progressed, and therefore the current screening policy, “should be reconsidered” to include a larger population.
Screening Immigrants for HBV Would Save Lives
Current Canadian health policy does not recommend screening immigrants for hepatitis B. Chronic hepatitis B infection among immigrants to North America ranges from 2% to 15%. Forty percent of those with chronic HBV infection will develop advanced liver disease.
Researchers assessed the cost effectiveness of a variety of strategies to determine if not screening is economically advisable.
They studied the cost effectiveness of not screening, screening and then treating (instead of waiting for advanced liver disease to develop), and screening, treating, and then vaccinating uninfected family members of immigrants age 20 to 65.
They measured predicted HBV-related deaths, cost of treatment, quality-adjusted life years, and cost effectiveness.
“Our results show that screening all immigrants will prevent 59 HBV-related deaths per 10,000 persons screened over the lifetime of the (group),” researchers wrote in the journal Liver International. Screening produced an increase in quality of life and a cost savings (in avoided medical costs) of $1,665 per person when compared with no screening.
The “screen, treat, and vaccinate” approach initially costs the government an additional $81 per person, but it also increases length and quality of life among those infected with HBV, and it saves $3,648 per person, compared with the screen and treat approach.
“We show that a selective hepatitis B screening program targeted at all immigrants in Canada is likely to be moderately cost-effective,” they added. “Identification of silent chronic hepatitis B infection with the offer of treatment when appropriate can extend the lives of immigrants at reasonable cost.”
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