HBV Journal Review
June 1, 2013, Vol 10, no 6
by Christine M. Kukka
DDW 2013 Edition
U.S. Doctors Failing to Treat Patients Who Need Treatment
Fewer than 50% of patients infected with the hepatitis B virus (HBV) who need treatment get antivirals or interferon from their primary care doctors and fewer than 70% of patients who go to university liver clinics get appropriate treatment, according to research presented at the Digestive Disease Week medical conference held in Orlando in May.
Stanford University researchers conducted a real-life study to see what percentage of 1,976 hepatitis B patients treated in various clinical settings over four years received treatment. They used current medical guidelines when evaluating whether patients received appropriate treatment.
In their analysis:
- 329 patients (Group 1) were treated at community primary care clinics
- 1,268 (Group 2) were treated at community gastroenterology clinics, and
- 379 (Group 3) were treated at university liver clinics, where one would expect treatment based on medical guidelines.
All three patient groups were similar in age, gender, and nearly all were Asian-American. Group 2 had slightly higher viral loads (HBV DNA) and Group 3 had significantly higher alanine aminotransferase (ALT) levels, which indicate liver damage.
The patients treated at specialized liver clinics had the highest treatment rates—59% of those eligible for treatment actually received it, compared to 45% at community gastroenterology clinics.
Patients treated at community primary care clinics had the lowest treatment rate—only 25% to 50% of patients who needed treatment received it.
The reasons the doctors gave for not treating patients was that patients did not ask for treatment, or because doctors wanted to continue observing the patients, or they incorrectly decided there was not sufficient liver damage to merit treatment.
Source: "Antiviral Treatment Eligibility and Treatment Rates..." by Kim, Nguyen et al. Digestive Disease Week, May 2013.
Doctors Say Poor Training and Limited Resources Contribute to Substandard Care
Another study finds that obstetricians and nurses are so poorly trained about hepatitis B that they fail to educate even pregnant, HBV-infected women about infection prevention and treatment.
Asian Liver Center researchers at Stanford University interviewed 16 obstetricians and 17 perinatal nurses in Santa Clara County, California, which has one of the highest hepatitis B rates in the U.S., for the study published in the current issue of the Asian Pacific Journal of Cancer Prevention (Vol. 14, 2013, Issue 3).
Treating and educating pregnant women, who are nearly all screened for HBV during prenatal visits, is a high priority because fewer than half of 24,000 infants born to HBV-infected women across the U.S. each year get the proper immunization and prevention treatment to reduce mother-to-child infection. Additionally, if pregnant women with high viral loads are identified during prenatal visits and treated with antivirals, the risk of infecting newborns is dramatically reduced.
But even these doctors and nurses knew little about hepatitis B despite their patients' high risk of infection. Their medical training was inadequate, they reported, and they lacked effective educational materials for patients (especially in multiple languages). As a result, they often failed to teach patients about how the infection occurred, how it could be treated, and how it could be prevented.
If patients knew something about hepatitis B, providers were more willing to talk and educate them about the infection, but they frequently failed to teach those who appeared disinterested or fearful. In one example, a female patient asked the doctor not to mention her infection in front of her husband.
"The obstetricians and nurses perceived a stigma attached to hepatitis B that made patients reluctant to receive information and/or encourage their sexual contacts and family members to be tested for hepatitis B," researchers reported. This sense of stigma made the providers, "wary of openly discussing hepatitis B with their patients, especially if the patients were accompanied by other people."
Nurses also lamented the lack of time they had to share information about hepatitis B with patients—most of their interactions focused on childbirth and how to care and breastfeed the newborn.
This missed opportunity to educate, screen, and treat people with HBV is another example of a healthcare system that fails to address hepatitis B, researchers noted. If the healthcare system could make institutional changes to address HIV infection, it should be able to make the changes and allocate the resources needed to combat hepatitis B, the doctors and nurses noted.
As noted in a recent Institute of Medicine report, "the surveillance system for viral hepatitis in the United States is poorly funded, incomplete, inadequate for follow-up of recently-diagnosed cases, and insufficiently informative for policymakers to best allocate resources for viral hepatitis prevention and control programs."
This study underscores the need for improved provider education and institutional changes to better care for people with hepatitis B, so that "both providers and patients can be empowered with the knowledge, skills and attitudes to prevent perinatal transmission of hepatitis B and promote long-term care of hepatitis B among (infected) women."
Source: "Education and Counseling..." by Yang, Cheung et al. APJPC vol 14.3, 2013
More Proof—Many Patients with Slightly Elevated ALTs Have Fibrosis
A U.S. research team scoured a number of studies to determine how many hepatitis B patients had fibrosis (liver inflammation) even though they had only slightly elevated ALT levels. (ALT levels rise above normal when infected liver cells are damaged or die.)
Historically, doctors have assumed that slightly elevated ALT levels did not signal liver damage. However, increasingly researchers are finding liver damage in patients with moderately elevated levels.
In this study, the team reviewed nine studies involving 683 patients whose ALT levels were twice the normal level and who had biopsies that revealed fibrosis. (Normal ALT levels are 30 IU/L in men and 19 IU/L in women.)
They found, according to the report presented at the European Study for Liver Disease (EASL) conference, that a substantial proportion of patients with mildly elevated ALT have significant fibrosis, no matter if they are positive or negative for the hepatitis B "e" antigen (HBeAg).
Given the heightened risk of liver damage that results from even moderately elevated ALT levels, researchers suggested that "the threshold for antiviral treatment and the decision to obtain definitive histologic diagnosis (i.e., liver biopsy) must be individualized. Further studies are needed to investigate the proportion of patients with modest ALT elevation who are at risk for progressive liver disease."
Tenofovir Reduces Viral Load in HBeAg-Positive Patients Faster than Entecavir
A Stanford University study presented at the Digestive Disease Week conference found that the antiviral tenofovir (Viread) was more effective than entecavir (Baraclude) at quickly reducing high viral loads in HBeAg-positive patients.
However, both antivirals are equally effective in HBeAg-negative patients.
Both entecavir and tenofovir are highly-rated antivirals and both are recommended as first-line treatment for hepatitis B.
Researchers compared how long it took each antiviral to completely suppress HBV DNA to undetectable levels (less than 60 international units per milliliter – IU/mL) in patients whose viral load exceeded 1 million IU/mL and who had never been treated before.
Sixty-two patients were treated with tenofovir and 199 patients were treated with entecavir. Both groups were fairly similar in age, weight, gender, ALT levels and liver health.
Among HBeAg-negative patients, there was no significant difference in viral suppression rates between the two antivirals.
But among HBeAg-positive patients:
- 16% of those treated with tenofovir achieved viral suppression within six months, compared to 11% of those treated with entecavir.
- After 12 months, 50% of tenofovir-treated patients achieved undetectable HBV DNA compared to 31% of entecavir-treated patients.
- And after 18 months, 71% of tenofovir patients had undetectable viral compared to 39% of entecavir-treated patients.
"Tenofovir is significantly more effective than entecavir for achieving complete viral suppression in HBeAg-positive, treatment-naïve hepatitis B patients with HBV DNA (exceeding) 1 million IU/mL," they wrote. "Moreover, the difference between tenofovir and entecavir becomes more and more pronounced with increasing treatment time. In contrast, for HBeAg-negative patients, there is no significant difference in rates of viral suppression between entecavir and tenofovir."
Source: "Tenofovir Is More Effective Than Entecavir..." by Linhyi, Huy et al. Digestive Disease Week, May 2013.
74% of Patients Get Rid of
Cirrhosis after 5 Years of
A Taiwanese study, published in the May issue of the Journal of Hepatology, showed that tenofovir was able to get rid of cirrhosis in nearly three-quarters of patients treated with the antiviral after five years.
In the study, 348 hepatitis B patients were treated with tenofovir for 240 weeks. Liver biopsies, which had been conducted at the start and end of treatment, showed that 87% had improvements in liver health.
They reported that 51% had regression or reduced fibrosis, and of the 96 with cirrhosis (severe liver scarring), they found that 71 (74%) no longer had cirrhosis after 240 weeks.
"In patients with chronic HBV infection, up to 5 years of treatment with tenofovir was safe and effective," researchers wrote. "Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis."
Source: “Reversal of Cirrhosis,” by Liaw YV. Hepatol. 2013 May.
Researchers Find Tenofovir Does Not Damage Kidneys
People chronically infected with HBV reportedly have higher rates of mild kidney damage, and tenofovir has been linked to kidney damage and reduced renal (kidney) function in HIV patients. Researchers from the University of California San Francisco, Pacific Health Foundation and Stanford monitored hepatitis B patients to see if tenofovir caused kidney problems more so than the antiviral entecavir.
They followed two groups of 72 patients treated with either tenofovir or entecavir. The patient groups were similar in demographics.
Researchers found no significant difference in changed renal function in the two groups. None of the patients experienced any marked decreases in kidney function.
"Tenofovir treatment was not an independent predictor for significant deterioration of renal function but older age and baseline impaired renal function were," researchers noted in their presentation at the Digestive Disease Week conference. "Renal function of HBV patients on antiviral therapy with either tenofovir or entecavir should be monitored, especially in those who are older and/or with known impaired renal function."
Source: "Renal Function in CHB Patients Treated With Tenofovir..." by Ha, Ku et al. Digestive Disease Week, May 2013.
Tenofovir and Entecavir Highly Effective—If Taken as Prescribed
Researchers followed 845 patients treated with antivirals over a 10-year The study, which lasted from 2001 to 2011, followed 93 patients treated with lamivudine (Epivir-HBV), 198 with adefovir (Hepsera), 447 with entecavir and 107 with tenofovir over 12 months.
The majority of patients were Asian-Americans, male and HBeAg-negative with an average age of 47. Viral loads were similar among all participants. The percentage who achieved undetectable viral load after 12 months of treatment varied significantly between groups.
- 39% in the lamivudine group
- 54% in the adefovir group
- 75% in the entecavir group, and
- 81% in the tenofovir group.
The percentage of patients who had a resurgence (viral breakthrough) in HBV DNA after 12 months of treatment was 2.5% in the entecavir group and 8.6% in the tenofovir group. However, these breakthroughs were due to failure to take the antiviral pills as prescribed, according to the report presented at Digestive Disease Week.
"Antiviral therapy with either entecavir or tenofovir is highly effective in suppressing HBV viral replication, and non-adherence is the primary cause of treatment failure, not viral resistance, up to 8-9% after only 12 months," researchers wrote.
Education stressing the importance of taking medications as prescribed and close clinical monitoring are needed to improve patient medication adherence, they added.
Source: "Effectiveness of Oral Antiviral Therapy ..." by Nguyen, Huy et al." Disease Week, May 2013
Family History of Liver Cancer Boosts Cancer Risk to 15.8% Among HBV-Infected
How much does having a family member with liver cancer increase the chance that you will develop cancer if you have hepatitis B?
Researchers from the University of California at San Diego tried to answer that question by studying cancer rates among 22,472 people from seven towns in Taiwan who had been treated for liver disease. They found 374 cases of liver cancer in the population and examined the cumulative rates of liver cancer among family members. They found:
- People with neither hepatitis B nor a family history of liver cancer had liver cancer risks of 0.62%.
- In those with a family history of liver cancer—but no HBV—the risk was 0.65%.
- In HBV-infected people without a family history of liver cancer the risk was 7.5%
- But among HBV-infected people with family histories of liver cancer, the cancer risk was 15.8%.
"Family history of liver cancer multiplies the risk of (cancer) at each stage of HBV infection," researchers wrote in the May issue of the journal of Clinical Gastroenterology and Hepatology. "Patients with a family history of liver cancer require more intensive management of HBV infection and surveillance for liver cancer."
Source: “Synergistic Effects of Family History of Hepatocellular Carcinoma,” by Loomba, Liu et al. Clin Gastroenterol Hepatol. 2013 May 10.
Vitamin D Deficiencies Found in People with High Viral Loads
Research shows that vitamin D appears to play an important role in keeping livers healthy, and a report in the May issue of the journal Hepatology finds that people with high viral loads have low levels of vitamin D.
German researchers monitored vitamin D levels in 203 untreated hepatitis B patients and found that 34% had severe vitamin D deficiency, 47% had moderate insufficiency, and only 19% had adequate vitamin D levels.
The higher the viral load, the less vitamin D was present, researchers reported.
Source: “Low vitamin D serum concentration,” by Farnik, Bojunga et al. Hepatology. 2013 May 22.
More Evidence Shows Breastfeeding Does Not Transmit HBV Infection
A study, published in the May issue of the Journal of Maternal-Fetal and Neonatal Medicine, confirms earlier findings that breastfeeding does not transmit hepatitis B to infants.
Chinese researchers compared mother-to-child infection rates in 1,186 HBV-infected women over a four-year period based on who did and didn't breastfeed. All infants had received immunization at birth to prevent infection.
Of the 1,186 infants, 39 became infected. All were born to HBeAg-positive mothers with high HBV DNA levels.
Researchers reported that among HBeAg-positive women, 9% of their breast-fed infants became infected compared to 9.2% of their formula-fed babies. Clearly, breast feeding did not increase the rate of mother-to-child HBV infection.
Source: “Breast feeding and immunoprophylaxis,” by Zhang, Gui et al. J Matern Fetal Neonatal Med. 2013 May 20.
Cesareans Do Not Reduce Mother-to-Child HBV Infection
Chinese researchers compared infection rates in 546 children born to HBV-infected mothers who had either cesareans or vaginal delivery to see if cesareans decreased risk of infection.
According to their report published in the May issue of the journal of BMC Pregnancy Childbirth, cesareans did not reduce risk of mother-to-child infection.
The infection rate among children delivered vaginally to HBV-infected mothers was 2.3% and the infection rate among those delivered by cesareans was 2.5%.
When the recommended immunization and prevention treatment is used on newborns, there is no advantage gained by choosing cesarean delivery, the authors concluded.
Source: “Effect of elective cesarean section,” by Hu, Chen et al. BMC Pregnancy Childbirth. 2013 May 24;13(1):119.
2% of HBV Genotype D Adults Lose HBsAg
A nine-year study of 2,413 people with the HBV strain or genotype D who were HBeAg-negative found that 2% of them lose the hepatitis B surface antigen annually and develop "inactive" hepatitis B.
Genotype D is a strain found across the Mediterranean-Middle East region into India. Iranian researchers studied Iranian researchers followed the hepatitis B patients as part of a larger study on cancers in Northeastern Iran.
Of the 290 patients who without treatment cleared HBsAg, 24.5% developed surface antibodies during the study period. "HBe Ag-negative, HBV genotype D-infected adults in our cohort had six-year survival rate of 92.8% with 12% chance of spontaneous loss of HBsAg," they reported at the Digestive Disease Week conference.
Source: "Spontaneous Surface Antigen Loss in Hepatitis B E Antigen Negative Genotype D..." by Poustchi, Ostovaneh et al. Digestive Disease Week, May 2013.
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