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HBV Journal Review

HBV Journal Review
February 1, 2011, Vol 8, no 2
by Christine M. Kukka

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Doctors Push for Changes in Treatment Guidelines to Better Identify and Treat Those at Risk of Liver Cancer
Experts, writing in the January 2011 issue of the Journal of Gastroenterology and Hepatology, have called for changes in the current treatment guidelines for hepatitis B to more effectively treat people at risk for liver cancer.

They argue that the current guidelines do not recommend antiviral treatment for people who are at high risk for liver cancer and death.

Researchers examined the current guidelines’ (shared by European, North American, and Asian medical societies) recommendations for antiviral treatment, which stops the hepatitis B virus (HBV) from replicating, to see if specific patients who later developed liver cancer would have received antiviral drugs.

They used the treatment criteria in the guidelines to determine if 369 hepatitis B surface antigen (HBsAg)-positive patients would have received antivirals to lower their viral load (HBV DNA). Among these patients, 30 developed liver cancer and 37 died of non-cancerous liver-related causes during an 84-month period.

“Using criteria for antiviral therapy as stated (in the) current guidelines, 19-30% of patients who died of non-cancer liver-related complications and 23-53% of patients who developed liver cancer would have been excluded for antiviral therapy,” the researchers wrote.

If the patients’ albumin levels (equal to or greater than 3.5g/dl) or platelet counts (equal to or greater than 130,000 platelets per microliter of blood) had been added to the treatment criteria, then 85% to 94% of patients who developed liver-related complications would have been treated, they noted.

Additionally, if doctors had also screened for certain HBV mutations, which carry a high risk of liver cancer, then more patients would have been identified for treatment.

“[Adding] baseline serum albumin and platelet counts to current criteria would have identified a majority of these patients for antiviral therapy,” they concluded. “These tests should be [added to] hepatitis B treatment strategies.”

Sexual Transmission Increasing the Rates of Genotype A Hepatitis B in Japan
In Japan and other countries, historically HBV infection has spread primarily from mother-to-child, but with the advent of immunization, researchers are now finding that sexual transmission of HBV between men having sex with men is increasing.

Scientists carefully tracked the increasing HBV transmission among men already infected with HIV, and identified the strains or genotypes of HBV involved in the infection.

To their surprise, they found that 80.7% of the 26 men in the study had HBV strain or genotype A, which previously had been rare in Japan. Only 19.3% had genotype C, which had been the more dominant genotype in Japan.

The scientists, writing in the January issue of the Journal of Clinical Microbiology, concluded that genotype A has been recently introduced into this population, and that sexual contacts within this community were more common than expected.

“In addition, we found a lamivudine-resistant mutation (resulting from antiviral treatment) in one naïve (previously untreated) case, suggesting a risk of drug-resistant HBV transmission,” they noted.

Because genotype A HBV carries a higher risk of infectivity and transmission through sexual contact because of its high viral load, the researchers called for immediate implementation of prevention programs among those at risk of infection.

Glutamine Synthetase May Be a New, More Accurate Test for Liver Cancer
Chinese researchers may have found a new, more accurate test for liver cancer in patients with hepatitis B.

Currently, alpha fetoprotein (AFP) tests are used to identify the presence of liver tumors, but this blood test can be unreliable and often catches only advanced liver cancer, when it is too late for treatment.

Researchers focused on glutamine synthetase (GS), a key enzyme that controls the use of nitrogen inside cells. They measured GS levels in more than 300 people, including healthy patients and those with liver cancer, cirrhosis (severe liver scarring), and hepatitis B.

They found GS in 70% of liver cancer patients, 46.7% of chronic hepatitis B patients with severe liver damage, and in 38% of hepatitis B patients with moderate liver damage.

The increased presence of GS levels in liver cancer patients and those with serious liver damage show that GS may be a valuable new tool in the early diagnosis of liver cancer, according to the report published in the journal Hepatology International.

Women with Hepatitis B at Higher Risk of Non-Hodgkin Lymphoma Cancer
Taiwanese researchers compared the rates of non-liver cancers among 1.78 million women who had been screened for hepatitis B during their pregnancies to see if hepatitis B led to any other increased risk of cancer, other than liver cancer.

They specifically looked for rates of intrahepatic cholangiocarcinoma (also called ICC or cancer of the bile duct) and non-Hodgkin lymphoma (also known as NHL or sometimes just lymphoma) among the infected women over a seven-year period after their pregnancies.

Lymphoma is a cancer that starts in cells called lymphocytes, which are part of the body's immune system. Lymphocytes are in the lymph nodes and other lymphoid tissues (such as the spleen and bone marrow).

Scientists identified 18 cases of ICC and 192 cases of NHL among the women. Incidence rates of ICC were 0.09 and 0.43 per 100,000 person-years, respectively, among HBV-infected women and women without HBV.

The rates of NHL, however, were far higher among HBV-infected women. They are 3.18 per 100,000 person-years for HBV-positive women and 1.23 per 100,000 person-years for uninfected women. The researchers, writing in the journal Hepatology, suggest a link between chronic HBV infection and development of these cancers.

In a separate study published in the Annals of Surgical Oncology, Chinese researchers compared the incidence of ICC in 196 healthy subjects and 98 people with ICC who also had HBV infection and other health issues.

There were higher rates of ICC in people with HBV infection, liver cirrhosis, hepatolithiasis (the presence of gallstones in the biliary ducts of the liver), and liver fluke infestation.

HBV-infected ICC patients were male and younger, and had higher rates of AFP and cirrhosis.

High Rates of Cirrhosis Found in Hepatitis B and C Patients with Liver Cancer
Researchers, searching for common factors among hepatitis B and C patients who had liver cancer, compared the incidence of cirrhosis and liver disease progression in 64 hepatitis B and 118 hepatitis C patients.

Cirrhosis was the common factor shared by the two groups with liver cancer. Cirrhosis was present in 94% of patients with HBV infection and 97% with hepatitis C virus (HCV) infection.

Among HCV patients, 5.2% were negative for HCV RNA after undergoing antiviral treatment, and 63.4% of HBV patients had HBV DNA less than 2,000 IU/mL (with or without treatment). Patients with HBV tended to have received little medical monitoring or treatment, and had more advanced stages of liver cancer, according to the report published in the January 2011 issue of the journal of Clinical Gastroenterology and Hepatology.

20-Year Study Finds Decline in Liver Cancer, with Higher Survival Rates Due to Earlier Detection
The rate of hepatitis B-related liver cancer is declining in Italy over the last 20 years, and those who are diagnosed with liver cancer are having their cancers identified earlier, according to a study published in the February 2011 issue of the journal Liver International.

Researchers followed 2,042 liver cancer patients enrolled in the Italian Liver Cancer database, 346 of whom had chronic HBV infection, between 1987 and 2006 and assessed their clinical and virological health over that period.

While the numbers of people diagnosed with liver cancer increased overall, the proportion of HBV-related cancers decreased over time from 26.7% (47 of 176 patients) in 1987–1991 to 14.7% (127 of 862 patients) in 2002–2006.

In recent years, a greater proportion of patients was diagnosed with non-advanced liver cancer (from 26% in 1987–1991 to 48% in 2002–2006), resulting from more frequent monitoring that increased to twice a year (from 63% in 1987–1991 to 80% in 2002–2006).

Hepatitis B and C Infections Appear to Lower Vitamin B Intake Among Patients
Chinese researchers, writing in the Chemistry and Materials Science European Journal of Nutrition, report that people with HCV and HBV infections appear to process B vitamins faster and may require antioxidant supplements.

Researchers followed the diets and blood levels of B vitamins and oxidative stress–associated biomarkers in 195 healthy people, 132 people infected with HBV, and 114 HCV-infected patients.

HBV-infected patients had significantly higher levels of total cholesterol, free fatty acids (FFA), and lower ghrelin level while HCV-infected patients had significantly higher Ishak inflammation score and lactate dehydrogenase activity. HBV patients had significantly lower red blood cell vitamins B2 and B6 levels, and HCV infection significantly decreased vitamins B2, B6 and folate levels in red blood cell and plasma.

HBV or HCV infection, “enhanced oxidative stress and lowered B vitamins in circulation,” researchers wrote.

“In order to avoid other healthy risk, nutrition status should be monitored and limitation or supplementation of certain nutrients might be helpful for HBV- or HCV-infected patients,” they concluded.

Which to Prescribe First: Pegylated Interferon or Antivirals?
Doctors continue to wrestle with which medication to prescribe first for hepatitis B—pegylated interferon, which can boost the immune system and result in a permanent clearance of infection, or an antiviral, which can quickly lower viral load but may require long-term treatment.

Pegylated interferon benefits: Pegylated interferon is costly, requires weekly injections, and causes side effects such as fatigue, body aches, and depression. But, researchers noted in their article published in the journal of Alimentary Pharmacology & Therapeutics, interferon offers a higher rate of sustained response in patients with certain genotypes, elevated alanine aminotransferase (ALT) levels, and lower HBV DNA levels.

Additionally, doctors can monitor HBsAg levels during interferon treatment, and can within weeks identify which patients will respond to treatment.

Antiviral treatment: Antivirals, which prevent the virus from replicating, can suppress HBV DNA over many months and years. Additionally, the antivirals tenofovir (Viread) and entecavir (Baraclude) have very low rates of drug resistance. However, once patients go off antivirals, the infection usually returns.

Both antivirals and interferon should be considered as front-line treatments, the researchers concluded; “[h]owever, interferon should only be considered for patients with a high chance of response based on pre-treatment and on-treatment factors,” such as ALT levels and genotype.

Even Infants Born to Mothers with Low Viral Loads Have the Virus at Birth
Researchers took blood samples from 109 infants born to HBsAg-positive mothers, before preventive efforts such as immunization and HBIG (hepatitis B immune globulin) were administered, to see the relationship between a mother’s viral load and whether the newborns had HBV in their bloodstream.

According to the findings published in the Journal of Clinical Virology, even newborns born to women with low viral loads had HBV in their blood when they were born and were at risk of infection.

In the study, 92.7% of the mothers were negative for the hepatitis B “e” antigen (HBeAg), but 73.4% of them had detectable HBV DNA at time of delivery. Normally, HBeAg-negative patients have lower viral loads than HBeAg-positive patients.

HBV was detected in three out of eight (37.5%) infants born to HBeAg-positive women and in 24 of 101 (23.8%) born to HBeAg-negative women. None of the newborns developed chronic HBV infections as a result of the preventive immunization and HBIG.

Patients with HBV Genotype A Tend to Have Higher Viral Loads
A large study of hepatitis B patients with genotypes A-G, found that patients with genotype A had markedly higher viral loads, according to the report presented at the Association for Molecular Pathology 2010 Annual Meeting in December.

Researchers from the Laboratory Corporation of America in Research Triangle Park, North Carolina, analyzed viral load in 227 genotype A patients (28% of study participants), 244 genotype B patients (30%), 207 genotype C patients (25.7%), 61 genotype D (7.6%), 39 genotype E (4.9%), 10 genotypes F and G (1.2%), and 16 patients with mixed genotypes (2%).

Researchers found that on average, genotype A had significantly higher viral loads (23 million IU/mL) than the others: genotype B had 13 million IU/mL, genotype C had 13 million IU/mL, genotype D had 14 million IU/mL, and genotypes E to H had 15 million IU/mL.

This is the first study of its kind that looked at so many patients and tracked viral load, which affects disease progression and treatment responses.

Long-Term Tenofovir Treatment Effective in HIV-HBV Coinfected Patients
Dutch researchers followed 102 people coinfected with HBV and HIV who were treated for more than five years with tenofovir, and found the antiviral to be safe and effective, without causing kidney problems, according to the report published in the journal Gastroenterology.

When treatment began, 80% of patients had a detectable viral load and 82 were HBeAg-positive. After five years of treatment, 92% of them had low to undetectable viral load.

All patients responded, even those who had developed resistance to the antiviral lamivudine (Epivir-HBV).

Loss of HBeAg and HBsAg were 46% and 12%, respectively over the five years. All 15 HBeAg-negative patients responded to treatment after four years of treatment and two (13%) lost HBsAg.

Among the 102 patients, only one patient acquired a combination of resistant mutations to antivirals and experienced a resurgence in HBV infection.

Three (3%) patients discontinued tenofovir because of increased creatinine levels, indicating kidney problems. However, overall the treatment was safe and effective in this difficult-to-treat patient group.

Liver Disease a Possible Contributor to and Predictor of Stroke
People suffering from fatty liver disease may be three times more likely to suffer a stroke than individuals without fatty liver, according to a study by researchers in London. The study is the first to find a link between nonalcoholic fatty liver disease—where there is an accumulation of fat in the liver due to over-eating or obesity—and stroke.

In a letter to the editor in the journal Epidemiology, doctors detailed their discovery of high levels of ALT in adults who experienced strokes.

The study showed a strong link between stroke and fatty liver. This is a concern to people with hepatitis B who often have high rates of fatty liver disease and diabetes.

This study suggests that liver enzyme tests may be used to predict the risk of stroke.

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