HBV Journal Review
March 1, 2010, Vol 7, no 3
by Christine M. Kukka
Drug-Resistant HBV Strains Found in Newly-Infected Patients with Acute Hepatitis B
Historically, experts assumed that drug-resistant hepatitis B virus (HBV) occurred only in chronically-infected patients who had been treated long-term with antiviral medications.
These drugs make it difficult for most HBV to replicate, except for those with mutations that allow them to "resist" the antiviral's impact. These mutated HBV can be more virulent than their non-mutated cousins.
Recently, Japanese researchers have found patients with acute hepatitis B who were infected with drug-resistant HBV.
They studied 45 patients with acute hepatitis B and found lamivudine-resistant HBV in two of them. In the January 2010 issue of the Journal of Gastroenterology and Hepatology, researchers wrote, “Lamivudine-resistant (HBV) strains are rare, but they are starting to be found in patients with acute hepatitis B. Surveillance for detecting drug-resistant HBV strains would be important for clinical practice.”
Researchers Endorse Only Tenofovir and Entecavir for Antiviral Treatment
U.S. researchers, reporting on Viral Resistance in Hepatitis B: Prevalence and Management in the Journal of Current Gastroenterology Reports, warned about over-use of antiviral medications to treat hepatitis B.
Because viral load is increasingly recognized as linked to cirrhosis and liver cancer, “the impetus increases to offer treatment to those previously not treated,” the physicians noted, and, “with the development of more robust antivirals with reasonable safety profiles, long-term treatment is becoming more common.”
However, they stressed that drug resistance is also emerging as an important public health issue, and the potential exists for developing multi-drug-resistant HBV that could be transmitted to others.
Because current antiviral agents only target one area of HBV’s replication cycle, “it is logical to restrict clinical use to only the most potent agents with the lowest risk for resistance,” which includes tenofovir (Viread) and entecavir (Baraclude). Both of these antivirals have good safety records and low rates of viral resistance.
“Ideally, new targets of drug therapy will allow for true combination studies to maximize viral suppression and inhibit the development of resistance,” they wrote. “In lieu of this, however, the responsible use of current single agents, perhaps the use of two agents in selected settings, and careful monitoring for compliance and viral breakthrough are necessary to minimize viral resistance in HBV infection.”
Entecavir’s Effectiveness Proven in Five-Year Studies of Previously-Untreated Patients
A report published in the January 2010 issue of Hepatology by Taiwanese researchers found that hepatitis B “e” antigen (HBeAg)-positive patients who were treated with the antiviral entecavir for five years did well, and only one patient developed resistance to the antiviral.
At Year 5, 94% (88 of 94 patients) had undetectable HBV DNA (viral load) and 80% (78/98) had normal levels of alanine aminotransferase (ALT). ALT is an enzyme detectable through blood tests that increases when liver cells are damaged or die.
Among patients treated for five or less years in other studies, 23% (33 of 141 patients) achieved HBeAg seroconversion (loss of HBeAg and development of “e” antibodies), and 1.4% (2 out of 145 patients) lost hepatitis B surface antigen (HBsAg) during the study.
In an unrelated entecavir study:
- HBeAg-negative patients, who had never been treated before, all responded the same to the entecavir treatment regardless of their ALT levels at the start of treatment, according to a separate report by Taiwanese researchers published in a recent issue of Hepatology.
- However, entecavir-treated HBeAg-positive patients, who had never been treated before and who had only mildly elevated ALT levels, had lower response rates to the antiviral than those with higher ALT levels.
- Those with slightly elevated ALT rates had lower rates of developing undetectable viral load, ALT normalization, and HBeAg seroconversion than HBeAg-positive patients who began treatment with high ALT levels that were at least twice the normal level.
Occult Hepatitis B Infection Increases Risk of Liver Cancer
Hidden or “occult” hepatitis B infection, which occurs when HBV DNA is present without discernable levels of HBsAg in the blood, can still promote development of liver cancer, according to a report by Italian researchers published in Gastroenterology.
Unlike chronic hepatitis B infection when HBV antigens can be detected in the blood, during an occult infection only HBV DNA can be detected in the blood and the virus is found only in liver tissue. While chronic hepatitis B infection has been linked to liver cancer for years, until this study, it was not clear if an “occult” HBV infection could lead to liver cancer.
Italian researchers tested for HBV in liver tissue from 107 patients with liver cancer and 192 patients with other liver diseases. None of the patients had evidence of HBsAg in their blood.
HBV was detected in the livers of 64% of liver cancer patients compared with just 33% of patients with other liver diseases. Moreover, the apparent link between liver HBV and cancer held even after accounting for age, sex, and co-infection with the hepatitis C virus (HCV).
Researchers recommend that doctors who treat patients with liver disease but no evidence of HBV in their blood should be tested for occult HBV infection.
Liver Cancer Is Still a Risk in Patients Who Clear HBsAg
U.S. researchers who followed Alaskan natives infected with hepatitis B over many years, report that liver cancer can still occur in people even after they’ve cleared HBsAg and show no signs of severe liver inflammation and scarring (cirrhosis).
To date, many doctors assume that once patients clear HBsAg they are at low risk of liver damage because their immune systems have successfully “fought off” the HBV and reduced the virus to very low levels. Some doctors no longer regularly monitor these patients for liver damage.
Researchers in Alaska followed 1,271 Alaska Native persons with chronic HBV for an average of 19.6 years to assess their risk of liver cancer after losing HBsAg.
HBsAg loss occurred in 158 persons, many were older and HBsAg loss occurred in men and women equally. HBV strain or genotype played no role in who lost HBsAg. Patients were followed for an average 108.9 months after HBsAg loss.
Six patients--two with cirrhosis and four without-- developed liver cancer an average 7.3 years after HBsAg clearance.
The incidence of liver cancer in those who cleared HBsAg was much lower than those who remained HBsAg-positive, researchers noted.
Interesting, after loss of HBsAg, HBV DNA continued to be detected in the bloodstream of 28 (18%) of patients even 3.6 years after clearing HBsAg.
The researchers recommended that doctors continue to monitor patients who have cleared HBsAg with periodic liver ultrasounds to detect liver cancer in their report published in Hepatology.
HBV Genotype C Associated with Higher Rates of Cirrhosis
Chinese researchers followed 634 HBsAg-positive patients and compared their HBV strain or genotype with the patients’ incidence of high viral load and cirrhosis.
Cirrhosis was only found in the HBeAg-negative patients, and was most common in those with genotype C than in those with genotype B (14.8% vs. 8.0% respectively).
In HBeAg-negative patients, high viral load was frequently associated with elevated ALT levels, and high ALT levels were more commonly found in those with suspected cirrhosis than those without (19.5% vs. 7.8% respectively).
Researchers, writing in the January 2010 issue of the World Journal of Gastroenterology, reported that HBV genotype C, older age, male gender and elevated ALT levels were related to occurrence of cirrhosis.
More Than 26% of Patients with Liver Disease Use Alternative Medicine
U.S. researchers surveyed 1,040 patients with liver disease to determine how many of them used complementary and alternative medicine (CAM), which includes vitamins, supplements, or herbal medicine.
Patients were asked about their use of CAM specifically for liver disease and 284 (27.3%) reported current use of at least one of three common CAM therapies. Vitamins or other dietary supplements were the most commonly used, reported by 188 (18.1%) patients, followed by herbal medicine (175 patients, 16.8%) and homeopathy (16 patients, 1.5%).
Patients using CAM tended to have higher levels of income and education, and were infected with viral hepatitis or had abused alcohol.
“Use of CAM therapies that have the potential to interact with conventional treatments for chronic liver disease was quite common among this population-based sample of patients,” researchers wrote in the February 2010 issue of the Journal of Clinical Gastroenterology. “There is a need for patient and practitioner education and communication regarding CAM use in the context of chronic liver disease.”
Viral Mutations and Genotype B Increase Risk of Liver Failure
Researchers compared the HBV for mutations from patients who had chronic hepatitis B against those with chronic hepatitis B who experienced acute liver failure. Neither patient group had signs of cirrhosis.
Researchers reported in the January 2010 issue of the Journal of Viral Hepatitis that the 75 patients who developed liver failure, without any pre-existing liver cirrhosis, had a higher incidence of having genotype B than the control group, and they had a higher rate of basal core promoter and precore mutations (BCP/PC) in their HBV.
The patients with BCP/PC mutations also had higher rates of HBeAg negativity, higher ALT and lower HBV DNA levels.
New Guidelines Say Viral Load Dictates What Medical Procedures HBV-Infected Health Care Workers Can Perform
The National Institutes for Health and the Society for Healthcare Epidemiology of America (SHEA) has issued guidelines regulating what medical procedures that health care workers infected with HBV, HCV and/or HIV can perform.
Health care workers are at high risk of contracting these infections, and to date there have been no national guidelines defining which medical procedures these infected workers can perform.
Writing in the March 2010 issue of the journal of Infection Control & Hospital Epidemiology, the experts issued the following guidelines for practitioners infected with HBV:
- Those with HBV DNA levels less than 10,000 genome equivalents per millimeter of blood (GE/mL): SHEA recommends no restrictions on their practice, and this includes surgery, as long as the infected healthcare provider has not infected a patient in the past, receives advice from his/her facility’s Expert Review Panel, undergoes follow-up routinely by occupational medicine staff (or an appropriate public health official), and is tested twice a year to monitor viral load. The provider must also be treated by a personal physician with expertise in hepatitis B who is authorized to communicate results to the Expert Review Panel.
The infected practitioner must also consult with an expert about optimal infection control procedures and strictly adheres to the recommended procedures, including the routine use of double-gloving for more high-risk procedures and frequent glove changes during procedures, particularly if performing technical tasks known to compromise glove integrity, such as placing sternal wires.
- Those with HBV DNA levels greater than 10,000 GE/mL: SHEA recommends that HBV-infected health care providers who test either positive for HBeAg or negative for HBeAg but who have circulating HBV burdens of greater than or equal to 10,000 GE/mL routinely use double-gloving for all invasive procedures, for all contact with mucous membranes or nonintact skin, and for all instances in patient care for which gloving is recommended, and that they not perform the Category III procedures that are associated with a risk for provider-to-patient HBV transmission despite the use of appropriate infection control procedures.
The Category III restricted procedures include general surgery, oral surgery, cardiothoracic surgery, open head and neck surgery involving bones, neurosurgery, open resuscitation efforts, obstetrical or gynecological surgery, orthopedic procedures, plastic surgery, transplantation surgery, trauma surgery, and lengthy open surgical procedures. SHEA also cautioned infected practitioners against interacting with violent or seizure-prone patients who might bite the physician.
SHEA recommends that infected healthcare providers should not be totally prohibited from participating in patient-care activities solely on the basis of their infections, and that each case should be independently considered.
Use of HBIG in HBV-Infected Pregnant Women May Reduce Infection of Newborns
Currently, doctors use hepatitis B immunoglobulin (HIBG), which contains hepatitis B antibodies, to prevent infection in adults and in infants born to HBV-infected mothers.
Chinese researchers, reporting in the January 2010 issue of the International Journal of Infectious Diseases, reviewed several trials to see if administering HBIG in HBV-infected pregnant women who had high viral loads would suppress transmission of the infection to their newborns.
According to their review of studies involving 5,900 newborns, those born to HBsAg-positive mothers who were given HBIG had a lower infection rate at birth and several months after birth. The practice appeared safe, though there were some reported adverse effects.
Researcher concluded that, “Multiple injections of HBIG in HBV-carrier mothers with a high degree of infectiousness in late pregnancy, effectively and safely prevent HBV intrauterine transmission.”
HBV May Become Undetectable in Semen When Antivirals Render Viral Load Undetectable
A report presented at the 17th Conference on Retroviruses and Opportunistic Infection held in February 2010 in San Francisco found that men with undetectable HBV DNA levels as a result of antiviral treatment also had undetectable levels of the virus in their semen.
HBV is transmitted through body fluids, especially semen, and researchers had assumed that antiviral treatment was not effective in suppressing the virus in the male genital “compartment.”
The study, involving a small number of men (20), one of whom were also coinfected with HIV, found that the antivirals they were taking (tenofovir or adefovir) were effective in clearing the virus from their semen. But, they noted, this finding could result from ineffective or insensitive testing of semen, and the findings should be retested in a larger study.
Back to News Review