HBV Journal Review
June 1, 2011, Vol 8, no 6
by Christine M. Kukka
HBV-Infected Mothers Receive Little Care or Follow-Up After Giving Birth
Current medical guidelines recommend that infants born to women infected with the hepatitis B virus (HBV) receive immediate immunization and HBIG (hepatitis B antibodies) to prevent infection, but a recent study at Columbia Presbyterian Medical Center shows their mothers rarely receive follow-up care for their chronic infections.
The study, which focused on non-white and immigrant women in the New York City area, found that while all but one infant was properly protected from HBV infection by immunizations and HBIG, nearly 90 percent of the mothers did not receive education about hepatitis B, additional laboratory testing, or subsequent follow-up care and monitoring for liver disease.
The study revealed an unexpectedly high rate of HBV infection among these women, and nearly 75% of those who screened positive were Hispanic, many from the Dominican Republic. This ethnic group has historically not been considered at high risk for hepatitis B.
This group of young, vulnerable, and non-English-speaking patients continued to live with a chronic disease that they know little about, and remained unlikely to receive the standard of care currently recommended.
Prenatal screening for the hepatitis B surface antigen (HBsAg), the antigen that indicates a current HBV infection, is recommended for all pregnant women. The testing is a golden opportunity to identify HBV infection among pregnant women, and should be used to identify and treat people with chronic HBV, the researchers recommend.
This is one of the first studies of its kind to look at the scope—and subsequent failure—of intervention and follow-up care among women who were identified as having HBV during prenatal screening.
The study was unveiled at the annual Digestive Disease Week conference held in early May in Chicago. The conference attracts physicians and researchers who specialize in liver disease from around the world.
Breastfeeding Does Not Increase Risk of Hepatitis B Transmission to Infants
HBV-infected mothers can safely breastfeed their children, according to a recent study by Chinese and American researchers published in the May issue of the Archives of Pediatrics and Adolescent Medicine.
Researchers examined results of 10 research studies, all conducted in China, which compared hepatitis B infection rates in more than 1,300 infants born to HBV-infected women. About half of the mothers breastfed their babies. All of the newborns were immunized against hepatitis B at birth, and received the recommended two additional vaccine doses, and all were also treated with HBIG to prevent infection.
At their first birthday, 31 out of 637 breastfed-babies tested positive for HBsAg. A similar number of babies who were not breastfed also became infected. Thirty-three of 706 babies who were not breast-fed were infected with hepatitis B. Most of the infected infants in both groups were probably infected during pregnancy or at birth from exposure to their mothers’ body fluids.
Researcher did caution that HBV-infected mothers should avoid breastfeeding if they have cracked or bleeding nipples or lesions on their breasts, because blood and body fluids other than breast milk may transmit the virus.
The endorsement of breastfeeding by HBV-infected mothers is welcome news, because breastfed-babies in developing countries receive better nutrition and have higher survival rates.
Pregnant Women at Risk of Liver Failure Benefit from Antiviral Treatment
Some women infected with HBV are at risk of liver failure during pregnancy. Doctors treated 70 pregnant women, who were experiencing liver failure during pregnancy, with antivirals before and after birth to see if the treatment improved their survival and liver health, and reduced the risk of mother-to-child infection.
According to the study published in May by FIGO--the International Federation of Gynecology and Obstetrics, 14 women were treated with the antiviral lamivudine (HBV-Epivir) during their third trimester of pregnancy and after birth, and 26 others were treated with the antivirals lamivudine or entecavir (Baraclude) after giving birth.
Viral load (HBV DNA) and hepatitis B "e" antigen (HBeAg) levels declined significantly after one and two months of treatment with the antivirals, especially when compared to a control group that received no treatment.
Death rates among the women, and the rate of intrauterine HBV infection, which contributes to infection of newborns, were lower in the treated group. No newborns had any apparent abnormalities as a result of the antiviral treatment.
Transplanted Stem Cells
Regenerate Liver Tissue
Johns Hopkins researchers have successfully taken human liver cells and genetically reprogrammed them into embryonic stem cell-like tissue to regenerate liver tissue in mice with liver damage.
According to the report published in the May 11 issue of the journal Science Translational Medicine, researchers found that liver cells derived from “induced-pluripotent stem cells (iPSCs)” could eventually be used as an alternative to liver transplants in patients with serious liver diseases, which would sidestep the long waiting lists for liver transplants.
Human iPSCs can be generated from various tissues, including skin, blood and liver cells.
Researchers at the Johns Hopkins Kimmel Cancer Center says the iPSC-derived liver cells can be generated in large amounts, and tailored to individual patients to avoid organ rejection.
Although the liver can regenerate itself, when severely damaged and scarred by HBV infection, it cannot mend itself.
To date, mature liver cells and adult liver stem cells have been difficult to grow in the laboratory, in contrast, iPSCs can be made from a tiny amount of many types of tissue and the iPSCs can grow in laboratory cultures indefinitely.
Researchers say additional studies are needed before clinical trials can begin in humans to make sure the iPSCs don’t cause abnormal cell growth or tumors.
HBeAg-Negative Hepatitis B Increases Risk of Cancer Recurrence after
Korean researchers followed 145 patients (81.4% male) with chronic hepatitis B who had liver tumors removed surgically to see what common factors were present in those who had recurrence of liver cancer within an average 29 months.
Ninety patients (62.1%) had serum HBV DNA greater than 2,000 international units per milliliter (IU/mL) and 63 patients (43.4%) experienced a recurrence of liver tumors.
Researchers, writing in the May issue of the Journal of Gastroenterology and Hepatology, reported that patients who tested negative for HBeAg were at higher risk of a return of liver cancer. Elevated alpha-fetoprotein (AFP) levels (which indicate the presence of cancerous tumors) also increased the risk of tumor recurrence.
Neither the type of surgery performed nor the viral load appeared to have any impact on cancer recurrence.
Entecavir Effective in Lowering Viral Load and Improving Liver Health in Liver Cancer Patients
Researchers followed 231 hepatitis B patients, including 71 with liver cancer, to see how effective the antiviral entecavir was in improving liver health. None of the patients had ever been treated before with an antiviral, which meddles with the HBV’s DNA and impedes replication.
The cancer and the non-cancer groups both experienced similar declines in viral load and HBeAg loss after two years of treatment. Both groups also experienced similar improvements in liver health, indicated by normal alanine aminotransferase (ALT) levels (which can increase when liver cells are damaged or die). After just 12 months, entecavir treatment improved liver health even in those with cirrhosis and liver cancer.
Of the 71 liver cancer patients, 16 underwent surgery while continuing entecavir treatment. Of this group, patients who had undetectable viral load by week 24 had better overall survival, but the rate of cancer recurrence was the same as in the other cancer patients.
“First-line entecavir (treatment) is comparably effective in chronic hepatitis B patients with and without (liver cancer), and improves hepatic function in HBV-related liver cancer patients,” researchers wrote in the May issue of the Journal of Gastroenterology and Hepatology.
Entecavir Should Be Continued, Even If Undetectable HBV DNA Levels Aren’t Achieved by Week 48
Patients who appear not to respond to entecavir treatment even after a year of treatment should still continue to receive the antiviral, according to a report by Dutch researchers published in the May issue of Hepatology.
Researchers followed 333 patients (243 had never been treated with an antiviral before.) They found that at week 48, 96 and 144, respectively, 48%, 76% and 90% of HBeAg-positive patients and 89%, 98% and 99% of HBeAg-negative patients responded.
Thirty-six of 175 (21%) of patients who had never been treated before continued to have detectable viral load at 48 weeks, but as time went by, more and more of them achieved a partial—or lowered—viral load.
Twenty-nine (81%) patients with partial viral response ultimately achieved undetectable viral load after prolonged treatment and none of them developed drug resistance.
“Continuous HBV DNA decline was observed in most patients without viral response during follow-up and in three patients (medication) adherence was suboptimal according to the treating physician,” the researchers noted.
Entecavir can be continued in previously-untreated patients with detectable—but declining—HBV DNA at week 48, they concluded.
Switching from Entecavir to Lamivudine, While Cheaper, Not Effective
Lamivudine is the cheapest antiviral available on the global market today, but it has a high rate of drug resistance—up to 76% after eight years. Hong Kong researchers wondered if patients could first attain undetectable viral load by using the antiviral entecavir (which has a resistance rate of 1% after five years), and then switch to less expensive lamivudine.
Fifty patients took entecavir for six or more months—achieving normal ALT levels and undetectable viral load (less than 60 copies/mL), and then half of them switched to lamivudine, according to the report published in the journal Hepatology.
After 96 weeks, all 25 (100%) who continued to take entecavir still had undetectable viral load, but six of the 25 who switched to lamivudine experienced a viral rebound, with an increase in HBV DNA.
Three of the six patients who experienced HBV DNA rebound, achieved undetectable viral load again after switching back to entecavir. Three patients who received lamivudine developed resistance to the antiviral drug, while none of the entecavir-treated patients developed resistance.
Entecavir Ineffective in Patients with Lamivudine and
Adefovir Drug Resistance
Researchers treated 33 patients with high HBV DNA levels—despite earlier treatment with lamivudine and the antiviral adefovir (Hepsera)—with entecavir to see if the drug would be effective against multi-drug-resistant HBV.
According to their report in the Journal of Viral Hepatitis, after 48 weeks of entecavir treatment 67% achieved normal ALT, and only 24% had undetectable HBV DNA.
After 96 weeks of entecavir, 79% had normal ALT levels, but only 17% had undetectable HBV DNA, showing that entecavir was ineffective in this drug-resistant group of patients.
Common Arthritis Drug Helps Chemotherapy Drugs Kill
Cancerous Liver Cells
The common anti-inflammatory drug celecoxib (Celebrex), when used in combination with a chemotherapy drug, appears to be highly effective in reducing cancerous liver cell growth, by causing the tumor cells to “commit suicide.”
The drug appears to react with a protein in the liver cancer cell, which triggers the cell to die. U.S. researchers have experimented with using two conventional chemotherapy drugs to decrease these cancerous cells, but they found that both drugs become much more effective when used in combination with celecoxib. To date, the experiments have occurred in cell cultures in laboratories.
Celecoxib acts on STAT3, a gene inside liver cancer cells that, when activated, allows those cancer cells to resist the effects of chemotherapy drugs. The researchers determined that the celecoxib molecule binds to STAT3 and effectively blocks its ability to function.
Celecoxib is most commonly prescribed to treat arthritis pain.
Few patients survive liver cancer for more than five years. Researchers hope that because celecoxib and the two chemotherapy drugs are already approved by the U.S. Food and Drug Administration (FDA) that clinical use of the combination can begin soon.
The study was made available online in May and is scheduled to be printed in the journal Cancer Prevention Research.
6 Per Cent of Health Care Providers Re-Use Equipment and Put Patients at Risk of Blood-Borne Infections
The U.S. Centers for Disease Control and Prevention and safe injection organizations have issued a report that shows that 6% of U.S. health care workers re-use injection vials—removing the needle and replacing it with a new one—which still puts patients at risk of blood-borne infections, such as hepatitis B.
Even though only the needle enters a patient, blood and body fluids from the patient can enter the vial containing the medication even if the needle is replaced.
The education effort to improve safe injection practices was highlighted in a recent article in the Wall Street Journal. It pointed out that failure to follow safe practices in delivering intravenous medications and injections has resulted in more than 30 outbreaks of infectious disease including hepatitis C, and the notification of more than 125,000 patients about potential exposure just in the last decade.
A survey of 5,446 health care providers in hospitals and other facilities found:
• 6% reported they “sometimes or always” use single-dose/single-use medication vials for more than one patient
• 0.9% “sometimes or always” reuse a syringe while changing only the needle for use on another patient
• And 15.1 percent reuse a syringe to enter a multidose vial and then 6.5 percent save that vial for use on another patient (1.1 percent overall).
Cost-savings was most commonly cited as a motive.
A CDC study of 68 US ambulatory surgical centers in three states found infection-control lapses were common. It cited in particular the use of single-dose medication vials for more than one patient; non-adherence to equipment-reprocessing recommendations; and mishandling of blood glucose monitoring equipment.
Patients Receiving Chemotherapy Appear at Risk of HBV
Nearly 5% of the U.S. population has been infected with HBV. The vast majority cleared the infection and test negative for HBsAg, but these people remain at risk of hepatitis B reactivation if they are ever treated with immune-suppressing drugs, such as chemotherapy used to treat cancer.
Researchers followed 62 cancer patients who tested negative for HBsAg who were treated with rituximab—a medication used in chemotherapy that is known to cause reactivation of hepatitis B—to see if they developed a resurgence of HBV DNA.
According to the report published in the Annals of Hematology, two of the patients experienced an HBV reactivation--both were age 70 or older.
While the reactivation risk is low, researchers say older patients and those who have not yet developed HBsAg antibodies appear to be at higher risk. Current guidelines recommend preventive use of antivirals during chemotherapy in those who currently test positive for HBsAg.
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