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HBV Journal Review

HBV Journal Review
January 1, 2012, Vol 9, no 1
by Christine M. Kukka

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Hepatitis B Doubles the Risk of Death in HIV-Infected
People infected with the human immunodeficiency viruses (HIV) face twice the risk of developing AIDS and death if they are also infected with the hepatitis B virus (HBV), according to a report published in The Journal of Infectious Diseases.

The report underscores the importance of testing, early diagnosis and treatment of hepatitis B in those living with HIV.

Hepatitis B and C viruses only attack the liver, while HIV infection weakens the immune system. Researchers have found that hepatitis C doesn’t appear to worsen HIV infection, but they wanted to investigate if hepatitis B posed a more serious coinfection risk than hepatitis C.

National Naval Medical Center researchers monitored HIV-infected patients treated at Army- and Navy-based facilities nationwide. They zeroed in on 2,352 people who had become HIV-infected within three years and whose HBV status could be identified.

Of the 2,352 patients:

  • 20% had resolved infections (positive for hepatitis B surface antibodies)
  • 3% had active hepatitis B infections (positive for hepatitis B surface antigen-HBsAg)
  • 74% were uninfected
  • 3% were positive for the hepatitis B core antibody but negative for HBsAg, suggesting an occult or mutated infection.

Those coinfected with active, chronic hepatitis B infections were twice as likely to die or develop AIDS, compared to patients with just HIV infections.

Even those with resolved hepatitis B infections had a 35% higher rate of progressing to AIDS or dying than uninfected individuals.

Among those with “occult” hepatitis B, the risk of developing AIDS increased by 54%.

Even when researchers adjusted their data for confounding factors—such as those infected prior to 1996 before more effective AIDS drugs became available—the risk of progressing to AIDS or death was still 80% higher among HIV-HBV coinfected individuals.

Researchers were not able to tease out why HBV infection accelerated AIDS progression in patients. They noted that hepatitis B did not appear to increase HIV viral load levels or lead to lower CD4 cell counts (indicating weakened immune strength). The authors wrote that it is still necessary to determine, “whether hepatitis B is a surrogate of poorer outcome or whether it has a direct harmful impact on HIV disease progression.”

An accompanying editorial stressed the need for increased vaccination efforts and careful use of antiviral drugs in order to avoid causing HBV drug resistance.

“There are undeniable barriers to achieving high rates of HBV vaccination and optimal treatment of HIV-HBV coinfection, both in the United States and internationally,” the authors noted. “However, effective interventions exist and can be integrated into public health practice and clinical care.”

Livers Previously Infected with HBV Can Be Safely Used in Transplants
Because of the scarcity of available livers for organ transplants, researchers have wondered if livers from people with resolved hepatitis B infections could be used.

U.S. researchers studied the outcomes between transplant patients who received uninfected livers to those who received livers that were hepatitis B core antibody-positive (HBcAb) and who additionally were treated with antivirals and hepatitis B antibodies (hepatitis B immune globulin-HBIG) in order to decrease risk of reinfection.

They followed 25 liver transplants with prior infections. Those who received the previously-infected livers tended to have more serious liver disease at the time of the transplant.

However, all patients receiving these livers were treated with long-term antivirals as well as HBIG and none of them developed hepatitis B. Overall survival at 30 days, 1 year and 5 years was 92%, 74% and 74%, respectively, which was comparable to 96%, 89% and 76% in the control group.

Researchers, writing in the January 2021 issue of The International Journal of the Hepato Pancreato Biliary Association, determined that using HBcAb-positive livers was safe.

Transplant Patients Who Keep Viral Loads Low with Antivirals Have High Survival Rates
Researchers, studying the effect of antivirals on hepatitis B liver transplant patients, found that liver cancer patients who maintained low levels of HBV DNA (viral load) during and after the liver transplant had the highest rates of survival.

According to the report published in the December 2011 issue of the Journal of Hepatobiliary Pancreatic Sciences, doctors followed 70 transplant patients. They found the group that had high HBV DNA levels (more than 10,000 copies/mL), and who were not treated with antivirals had worse outcomes.

“Tumor-free survival rate was significantly higher in the antiviral therapy group than in the high viral group,” they wrote. As expected, the presence of multiple tumors prior to the transplant decreased survival rates.

The study suggests that treating hepatitis B transplant patients with antivirals is critical to keep liver cancer from recurring.

Older Age, Low Viral Load Increases Chance of Spontaneous HBsAg Clearance
Each year, between 0.5% and 2.26% of people with chronic hepatitis B are able to get rid of HBsAg spontaneously, without treatment. Researchers have long wondered what predisposes some people to clearing the virus on their own.

South Korean researchers, writing in the December issue of the journal Digestion, followed HBV DNA levels in 880 patients who tested negative for the hepatitis B e antigen (HBeAg), to see which ones cleared HBsAg spontaneously, and what conditions might lead to the event.

They chose HBeAg-negative patients (average age was 50) because they tended to have lower viral loads and had better chances at clearing the virus.

Over 31 months, researchers found 1.8% of the studied patients cleared HBsAg. Those who cleared the virus tended to be older and had lower HBV DNA levels--under 2,000 IU/ml.

Screening Fathers—Not Just Mothers—for STIs Prevents Infection of Newborns
Historically, screening efforts for sexually transmitted infections (STIs), such as HBV, HCV and HIV, focused only on pregnant women to prevent mother-to-child infections.

However, sexual partners of pregnant women can also infect pregnant women. A team of British researchers tried a program where male partners of pregnant women, who were being screened by ultrasounds as part of their regular prenatal treatment, were also offering STI screening.

According to the report published in the December 2011 journal of Sexually Transmitted Infections, 1,243 male partners of 2,400 women who were undergoing ultrasound examinations were offered STI screenings, and 430 (35%) accepted testing.

The screening identified 16 infections (representing 4% of those tested) including two cases of hepatitis C, eight cases of hepatitis B, and six cases of chlamydia—all of which can infect the child or affect the pregnancy. No HIV infections were identified.

The pilot program shows the need for screening partners of pregnant women, according to the report.

As Expected, Getting Hepatitis A on Top of HBV Increases Liver Failure Risk
While experts assume getting a second liver infection on top of a hepatitis B infection is bad, South Korean researchers decided to find out exactly how serious a hepatitis A infection would be on top of a HBV infection. Hepatitis A is generally transmitted through contact with feces or consuming uncooked shellfish exposed to raw sewage.

They scoured the medical records of 449 patients hospitalized for acute hepatitis A, and found 30 who were HBsAg-positive at the time of their hepatitis A infection.

According to their report in the December issue of the journal Gut Liver, the HBsAg-positive group suffered far more liver health problems at their time of their hospitalization for hepatitis A.

They had higher rates of gastrointestinal bleeding, acute renal (kidney) failure, and acute liver failure. In particular, liver failure rates were nine-fold higher in the

HBsAg-positive group than in the HBsAg-negative group (23.3% vs. 3.3%).

Many Drug Users Treated at Methadone Centers Remain at High Risk of Hepatitis
A report presented to the American Public Health Association 139th Annual Meeting in New York City showed that many injecting drug users treated at area methadone centers had been infected with hepatitis A or B, or were at risk of the infection and had not yet been immunized.

As part of the study, researchers evaluated 8,060 patients and found:

  • 35% of patients had not been immunized against HBV
  • 27% had resolved HBV infections
  • Only 23% had been vaccinated against hepatitis B
  • 1% were HBsAg-positive, indicating current infections
  • And 35% were susceptible to hepatitis A, requiring immunization against that infection.

“Overall, 50% were susceptible to hepatitis A, B or both,” the authors wrote.

In addition, of 56% of patients who had been exposed to the hepatitis C virus (HCV), 17% were susceptible to HBV and 22% were susceptible to hepatitis A, representing a very high-risk population.

The study authors promoted immunization of these patients at methadone centers using an accelerated vaccination schedule to reach as many individuals as possible. They suggested patients be vaccinated with the three hepatitis B doses over a two-month period, instead of the recommended six-month dosing because the population is hard to reach.

Even Prednisone Increases Risk of HBV Reactivation
Increasingly, doctors are finding even low-dose medications used to suppress the immune system for common ailments, such as prednisone (similar to cortisone) used to treat arthritis and other allergic conditions, can cause hepatitis B to reactivate, even in people with resolved or inactive HBV infections.

Researchers, writing in the Dutch medical journal Ned Tijdschr Geneeskd, reported on two patients—a 55-year-old woman and 71-year-old man—treated with prednisone for facial paralysis and rheumatoid arthritis.

Experts recommended that all such patients identified for prednisone treatment be screened for hepatitis B and then treated with antivirals during steroid treatment to prevent liver damage resulting from hepatitis B reactivation.

Widespread Pegylated Interferon Treatment Confirms Drug’s Effectiveness
While pegylated interferon (Pegasys) has been studied in clinical trials, Australian researchers checked on the effectiveness of the drug in real life treatment centers to see if the treatment success found in clinical studies would be duplicated in the field.

Pegylated interferon is a time-release interferon, requiring a weekly injection, which boosts the immune system to fight HBV infection. Generally, it is give for about 48 weeks, and unlike oral antivirals, the treatment does not have to continue indefinitely and it does not lead to drug resistance. It is one of the first treatment options recommended to people newly diagnosed with hepatitis B.

In this study, published in the Journal of Gastroenterology and Hepatology, researchers followed 29 HBeAg-negative patients and 63 HBeAg-positive patients treated with interferon at five medical centers. Most had high viral loads and signs of liver damage.

After six months of interferon treatment, among those who were HBeAg-positive:

  • 46% achieved normal alanine aminotransferase (ALT), which indicates no liver damage
  • 16% had undetectable viral loads
  • And 32% lost HBeAg and developed “e” antibodies (called HBeAg seroconversion)

Among the 29 HBeAg-negative patients treated, 48% had high viral loads and 24% had advanced fibrosis. Six months after treatment ended:

55% and 36% respectively maintained normal ALT levels and undetectable viral loads.

Between 50% to 75% of all patients maintained low viral loads and healthy ALT levels over the two-year follow-up period.

The researchers concluded that even in everyday clinical practice, pegylated interferon was effective and well-tolerated, with only 6% stopping treatment because of side effects from the medication, which can include body aches and depression.

Extending Treatment or Adding Antivirals Increases Interferon’s Effectiveness
Chinese researchers followed 92 patients treated with pegylated interferon who initially did not respond to interferon treatment to see if extending treatment or adding antivirals boosted its effectiveness.

According to the report published in the Chinese medical journal, Zhonghua Gan Zang Bing Za Zhi, researchers tried:

  • Extending interferon treatment from 48 to 72 weeks
  • Adding antivirals—either entecavir (Baraclude) or adefovir (Hepsera)—to the ongoing interferon treatment.

Researchers reported that patients with extended interferon treatment had a significantly higher response rate (78.3%) than patients who received only 48 weeks of treatment.

Patients who received antivirals in addition to interferon experienced three-fold reductions in viral load.

“Individualizing therapy by prolonging the duration of (interferon) treatment to 72 weeks or adding (antivirals) such as entecavir and adefovir in patients without early response may substantially increase the sustained viral response rate and lead to the decrease of HBsAg,” they wrote.

Interferon Treatment Appears to Be Safe in Pregnant Women
A team of Canadian researchers have found that interferon alpha treatment in women who have liver disease from hepatitis B or C, or thrombocythemia (ET)—the presence of high platelet counts in the blood—is safe.

The University of Toronto researchers examined reports on 63 pregnant women who were treated with interferon during their pregnancy. No cases of malformations or stillbirths were reported. There was one miscarriage and 13 premature deliveries (20% of all cases).

“The results of our systematic review suggest that interferon does not significantly increase the risk of major malformation, miscarriage, stillbirth or preterm delivery above general population rates,” researchers wrote in the December 2011 issue of the journal of Reproductive Toxicology.

Plant Ribosomes May Help Halt HBV Replication One Day
Ribosomes--tiny structures in cells that convert RNA into protein—from plants may be useful in combating HBV and HIV infections one day, according to a report by Indian researchers published in the December issue of the Chinese medical journal Virologica Sinica.

The researchers found that the ribosome inactivating proteins (RIPs) inhibit replication of HIV, HBV and even herpes simplex viruses.

“Recently, Phase I/II clinical trials have demonstrated the potential use of RIPs for treating patients with HIV disease,” they noted.

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