HBV Journal Review
October 1, 2011, Vol 8, no 10
by Christine M. Kukka
Young, Hepatitis B Patients Who Smoke Are at Higher Risk of Liver Cancer
Most cases of liver cancer are found in people infected with the hepatitis B virus (HBV) when they are older than age 40 (in men) or 50 (in women.) However, a new study of Asian-Americans suggests that younger people under age 40 may be at increased risk of “early onset” liver cancer if they smoke and have a family history of liver cancer.
This finding may be a wake-up call to doctors to screen younger patients who smoke more often for liver cancer. Current medical guidelines recommend frequent liver cancer screening for older patients—not men under age 40 or women under age 50.
New York researchers examined liver cancer in HBV-infected Asian-Americans of all ages to see what increased the risk of “early onset” liver cancer.
They collected data on all Asian immigrants with hepatitis B treated at Bellevue Hospital Center between 2003 and 2009. They found 168 cases of liver cancer, with 74% found in older patients and 26% in younger patients—men under 40 and women under 50.
Each age group was compared with similarly-aged hepatitis B patients who were cancer-free. They found male gender and the presence of cirrhosis (severe scarring of the liver from the infection), increased the risk of liver cancer in older patients.
When younger liver cancer patients were compared with younger cancer-free patients with hepatitis B, researchers found that a family history of liver cancer and smoking increased liver cancer rates.
Surprisingly, cirrhosis did not lead to cancer in this younger group, as it did among the older patients, according to the report published in the American Journal of Gastroenterology.
The study suggests that younger Asian HBV patients who smoke or have a family history of liver cancer are at higher risk of cancer and should be screened more frequently for liver cancer regardless of their young age.
Your Address, Ethnicity and Drug Use Determine Your HBV Genotype
The U.S. Centers for Disease Control and Prevention analyzed blood samples from 614 patients who experienced acute, or new, hepatitis B infections in six counties nationwide that participate in the Sentinel Counties Study of Acute Viral Hepatitis between 1999 and 2005.
Researchers wanted to know which hepatitis B strains or genotypes were spreading most rapidly in this sample population.
There are eight genotypes (A-H), and each genotype evolved in specific geographic areas of the world. For example, genotype A is prevalent in northwestern Europe, North America, and Africa; genotypes B and C are common in Asia; genotype D is most frequently found in the Mediterranean area; genotype E is prevalent in Africa; genotype F is prevalent in the aboriginal populations of South America; genotype G is found in Europe and the U.S., and genotype H is prevalent in the Amerindian populations of Central America.
As expected, all HBV genotypes are found in the United States, with genotype A commonly found in white and African-American patients and genotypes B and C found in Asian-Americans.
According to the report on new HBV infections, published in the August 2011 issue of the journal of Clinical Infectious Diseases:
- 75% of new HBV infections were genotype A
- 18% were infected with genotype D
Genotype A infections (compared with genotype D) were five times greater among African-Americans than among Hispanics.
The odds of infection with genotype A were 49-, 8-, and 4-times higher in patients from Jefferson County (Alabama), Pinellas County (Florida), and San Francisco (California), respectively, than among those living in Denver County (Colorado).
Genotype A was less common among recent injection drug users than it was among non-injection drug users.
Researchers concluded that ethnicity, geographic residence, and injecting drug use greatly determined a hepatitis B patient’s genotype.
Dramatic Decline in Hepatitis B Evident Due to Universal Immunization
A 20-year study of the impact of universal hepatitis B immunization in newborns in Taiwan, published in the journal Pediatrics, found the vaccine has dramatically reduced the rate of chronic hepatitis B in children. Hepatitis B-related kidney problems fell from 11.6% (1974-1984) to zero (2004-2009).
The researchers monitored the rate of HBV-associated membranous nephropathy (a kidney disorder that occurs when the organ becomes inflamed and can no longer filter waste and fluids) in 471 children. The rate of nephrotic syndrome was
- 11.6% between 1974 and 1984;
- 4.5% between 1984 and 1994;
- 2.1% between 1994 and 2004;
- and 0% between 2004 and 2009.
Similarly, the number of children who were chronically infected with hepatitis B also declined dramatically.
“The vaccine produced a profound decline in hepatitis B virus infection via a reduction in horizontal (mother-to-child) transmission as well as a significant decrease in the overall incidence of hepatitis B virus-associated membranous nephropathy, which is closely related to hepatitis B horizontal infection,” they wrote.
The researchers said their data mirror other studies that found a sharp decline in liver cancer after implementation of universal hepatitis vaccination in Taiwan.
Another study of universal hepatitis B immunization, published in the journal Hepatology, assessed the impact of universal immunization and large-scale screening among Alaska Native people, who historically have had high rates of HBV infection and liver cancer. The 25-year study began in 1984.
The rate of HBV infections in people under age 20 fell from 19 cases per 100,000 in 1981-1982 to zero in 1993-1994. No cases of acute HBV (indicating new infections) have occurred in children since 1992.
Liver cancer rates in children decreased from 3 per 100,000 in 1984-1988 to zero in 1995-1999, and no cases have occurred since 1999. The number of identified HBsAg-positive Alaska Native children dropped from 657 in 1987 to two in 2008.
“Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Natives has eliminated (liver cancer) and (new) HBV infections among Alaska Native children and this approach is the best way to prevent HBV-related disease in children,” the researchers reported.
Hospital Policies Dictate Whether Newborns Are Immunized
Which newborns receive the hepatitis B immunization at birth, as recommended by federal health guidelines? It depends on which hospital they are born at, and the education and income of their mothers, according to a study published in the September issue of the Pediatric Infectious Diseases Journal.
University of Colorado researchers and state epidemiologists tracked 64,425 infants born in 2008 to see which infants received the hepatitis B vaccine within 12 hours of birth, which decreases the risk of hepatitis B infection by about 90%.
They found that only 61.6% received the birth dose of HBV (the first of three vaccine doses). Ironically, the higher the mother’s income and education, the lower the child’s chances of getting vaccinated at birth.
Contributing to the lack of immunization was the lack of a hospital policy stipulating that all newborns receive the immunization at birth.
“To effectively reduce risk of perinatal (mother-to-child) hepatitis B transmission, hospitals should stipulate that all infants are offered HBV and ensure that these policies are implemented and followed,” the researchers noted.
Treatment and Monitoring Recommendations for Asian-Americans Published
A group of Asian-American experts have recommended a set of guidelines for monitoring and treatment of Asian-American patients with hepatitis B in the September publication of the journal of Digestive Diseases and Sciences.
Asian-Americans are at high risk of hepatitis B due to its prevalence in Asia and there has been poor screening and immunization among immigrants and their descendants. Currently, experts estimate between 7% to 16% of Asian-Americans have chronic hepatitis B and test positive for the hepatitis B surface antigen (HBsAg). The experts recommend that patients at risk for liver damage from the infection should be treated with antivirals—either entecavir (Baraclude) and tenofovir (Viread). The primary goal of treatment is to suppress viral replication, keep viral load (HBV DNA) as low as possible, and reverse any existing fibrosis. Antiviral treatment has also been found to greatly reduce the risk of cirrhosis and liver cancer.
Patients who are candidates for treatment include those with high viral load and elevated alanine aminotransferase (ALT) levels, which indicate liver cell damage.
- Other indicators for treatment include having testing positive for the hepatitis B e antigen (HBeAg-positive) along with high viral loads, and testing negative for HBeAg if the patient’s HBV DNA levels exceed 10,000 copies/mL (or 2,000 IU/mL).
- Also benefitting from treatment are HBeAg-negative patients with HBV DNA greater than 10,000 copies/mL and normal ALT levels, but who have either serum albumin less than or equal to 3.5 g/dL or platelet count less than or equal to 130,000 mm, or basal core promoter mutations.
- Anyone with close relatives who have had liver cancer should also be offered treatment.
- Patients with cirrhosis and detectable HBV DNA must receive antiviral therapy.
- Antiviral treatment should also be offered to pregnant women with high viral load, to prevent mother-to-child infection, and to those requiring immunosuppressive therapy for cancer or other diseases. Drugs or chemotherapy that suppresses the immune system enables the infection to rebound.
- In HBsAg-positive patients with risk factors, lifelong surveillance for liver cancer with alpha-fetoprotein testing and abdominal ultrasound examination at six-month intervals is required.
High Doses of Lamivudine Effective in Patients with HBV-Related Cirrhosis
The antiviral lamivudine (Epivir-HBV) has fallen out of favor as an antiviral treatment for hepatitis B because it causes drug resistance.
However, a study reported in the Digestive Diseases and Sciences found the antiviral was effective when administered in high doses in patients with cirrhosis.
Researchers treated six people with HBV-related cirrhosis with lamivudine doses raised from the normal dose of 100 mg daily to 200 or 300 mg daily, based on their viral load. Previously, nearly all of these patients had developed lamivudine resistance at the lower, 100 mg-dose, and had failed to improve even after the antiviral adefovir (Hepsera) (10 mg daily) was added to their ongoing lamivudine treatment.
The HBeAg-negative patients continued to receive adefovir, but the lamivudine dose was hiked for 12 months. All achieved a “significant” decrease in HBV DNA, three of the patients achieved undetectable viral load within six months. All achieved normal ALT levels, indicating no liver damage. The higher dose did not adversely impact their kidney function, nor were any other side effects noted.
The researchers suggested that increased doses of any antiviral—not just lamivudine—may be effective in hard-to-treat patients with life-threatening cirrhosis or liver damage.
New Tests Effective in Identifying Liver Inflammation
ALT levels—measured in a blood sample—can reveal if there is liver damage occurring, but scientists are finding this test can give an unreliable picture of your liver’s health. The test gives only a momentary “snapshot” of your liver, and does not show previous damage or fibrosis.
Now researchers think they may have two more reliable tests to show if a liver is inflammed. Scientists, writing in the journal Liver International, report that aspartate aminotransferase(AST) and apolipoprotein A1 levels, measured in a blood sample, can be used to predict moderate liver damage and inflammation, which if untreated over time can lead to cirrhosis or liver cancer.
They performed these two tests on 227 patients with either hepatitis B or C, who had normal or only mildly elevated ALT levels, and then performed liver biopsies to confirm their findings.
They found that 48 (21.1%) and eight patients (3.5%) had serious grade 3 and 4 inflammation respectively. They conducted a wide variety of tests on the patients and found that the AST and apolipoprotein A1 levels measures most accurately indicated if serious inflammation was present – even more so than ALT.
“Using AST and apolipoprotein cut-off values of 44 IU/L or higher and 00ng/ml or higher, respectively, the presence of significant inflammation was predicted with high specificity (of 96.5%),” they wrote.
Entecavir Ineffective in Patients with Lamivudine and Adefovir Resistance
Korean researchers assessed the performance of the antiviral entecavir in 55 patients who had already developed resistance to lamivudine and adefovir.
Ten of the patients had liver cirrhosis and 46 patients were HBeAg-positive with high viral loads. Initially most patients did well on entecavir, but within a few months entecavir lost its effectiveness and most patients developed resistance to the antiviral. Viral load “breakthrough” rates at 6, 12, 24 and 36 months of treatment were 0%, 15%, 45% and 73%, respectively, according to the report in the October issue of the Journal of Viral Hepatology.
Patients with Core Antibody—But No Surface Antigen or Antibodies—May Have Hidden Infections
Because the hepatitis B virus and its antigens mutate so easily, scientists are finding that lab tests they once relied upon to indicate whether an infection was “active” or “resolved” may not be accurate.
For example, historically doctors believed that if patients tested positive for the hepatitis B core antibody, that they had been infected at some point and had either cleared the infection and developed surface antibodies, or they had a chronic infection and tested positive for surface antigen (HBsAg).
But as tests become more refined, researchers are finding patients who test positive for the core antibody but have neither the surface antigen nor the surface antibody.
French researchers took on this challenge and screened 6,431 patients for surface antigens and antibodies and core antibodies. They identified 362 (5.6%) patients who had only the core antibody without either surface antigens or antibodies. (This group represented 24.8% of all patients who were core antibody-positive.)
HBV DNA was found in 10 of the 362 (2.8%) patients, indicating an active infection, and six of them had viral loads exceeding 10,000 copies/mL.
The researchers, writing in the October issue of the Journal of Viral Hepatitis, concluded that the presence of only the core antibody is an indicator that the patient may have HBV that can replicate without large amounts of detectable surface antigen, which is called “occult” or hidden hepatitis B.
Breastfeeding by HBV-Infected Mothers Pose No Risk to Babies
A study published in the Archives of Pediatrics and Adolescent Medicine confirms that breastfeeding by HBV-infected mothers does not transmit the infection to their babies.
Researchers reviewed 10 studies of 751 infants, born to HBV-infected mothers, who were breastfed and 873 infants who were not breastfed. All babies were immunized at birth.
They concluded that, “Breastfeeding after proper immunoprophylaxis (immunization) did not contribute to mother-to-child transmission of HBV.”
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