| AASLD 2011 Liver Meeting
HBV Coverage by Christine M. Kukka Hepatitis B experts from around the world, meeting at the 61st annual meeting of the American Association for the Study of Liver Diseases, shared the latest in hepatitis B treatment and research. Here are some of the highlights.
Tenofovir and entecavir updates Long-term tenofovir reverses fibrosis and cirrhosis among Asian Patients:
Asian patients who took the antiviral tenofovir (Viread) over five years had dramatic declines in HBV DNA (viral load) and improvements in fibrosis and cirrhosis—and they experienced no antiviral resistance despite the lengthy treatment period. Liver biopsies before and after five years of treatment found 95% of patients with fibrosis had improvements (or no worsening) in liver health, 86% of cirrhotic patients no longer had cirrhosis and 96% of patients achieved undetectable viral load (less than 400 copies/mL). Surprisingly, no Asian patients lost the hepatitis B surface antigen (HBsAg) during the five-year treatment period. None of the patients had kidney problems or appeared to lose bone mineral density despite the long duration of antiviral treatment. -
1376. Five years of Treatment with Tenofovir DF for Chronic Hepatitis B Infection in Asian Patients is Associated with Sustained Viral Suppression and Significant Regression of Histological Fibrosis and Cirrhosis. -
238. No Detectable Resistance to Tenofovir Disoproxil Fumarate (TDF) Following up to 240 Weeks of Treatment in Patients with HBeAg+ and HBeAg- Chronic Hepatitis B Virus Infection.
Entecavir proves effective:
Several studies involving entecavir treatment showed the antiviral to be effective, although it is less effective in patients who have already developed resistance to lamivudine and adefovir, and it has a slightly higher rate of resistance than tenofovir. In the Korean study cited below, 72 patients (mostly male, average age 49, never before treated) received entecavir for three years. Only one developed resistance. Of the 45 HBeAg-positive and 27 HBeAg-negative patients, 51.1% and 85.2% responded respectively with lowered viral load and healthier livers. About 25% of HBeAg-positive patients seroconverted.
Side effects from antivirals examined Tenofovir and entecavir: No threat to kidneys?:
Increasingly, researchers are reporting that some antivirals cause kidney damage (and harming renal function) and are finding side effects. They followed 212 patients treated with tenofovir and 79 treated with entecavir (most were male, half were African-American, and 24% were Asian-American.) They monitored their renal function at the start of treatment, and six and 12 months later and found no deterioration in renal function in the tenofovir-treated patients, and only a small impact on renal function in the entecavir-treated group. Other doctors find kidney damage from antivirals:
Increasingly, doctors are finding that long-term use of antivirals causes kidney damage, as evidence by reduced renal function. French researchers followed 220 antiviral-treated patients (mostly male, average age 47), including 30% with extensive fibrosis or cirrhosis, who were treated for an average 4.6 years. Researchers found above-average rates of renal impairment among the antiviral-treated patients. Tenofovir and entecavir don’t lower vitamin D levels:
Researchers are also worried about the impact of antivirals on vitamin D levels, which are essential to maintain healthy bone density. A British study of 212 patients treated with tenofovir and 79 treated with entecavir found that while hepatitis B in itself reduces vitamin D levels in patients, “tenofovir and entecavir treatment had no significant effect on vitamin D levels after 12 months of treatment.” Weakened bones found in tenofovir- and adefovir-treated patients:
A National Institutes of Health study found phosphate wasting nephropathy in between 10 and 15% of patients treated for two years with either tenofovir or adefovir. They followed 51 patients treated for an average 6.3 with the two antivirals, and reported that 14% developed phosphate wasting nephropathy, which can lead to bone softening and degeneration, after an average of three years. The problem is, “partially reversible with change to other antivirals,” researchers wrote, “but may result in significant osteomalacia (bone softening) if not recognized and managed promptly. Routine monitoring of serum phosphate, creatinine, uric acid and urinalysis is prudent during long-term adefovir and tenofovir therapy.” A similar study in Italy looked at the bone mineral density of 124 patients treated with lamivudine and/or tenofovir. They found 77% of the patients had no signs of bone weakening, 8% actually had improved bone density, but 15% had suffered bone loss.
Interferon and antiviral treatment combinations Historically, researchers have had little success treating patients with a combination of antivirals and pegylated interferon. However, new studies unveiled at the conference show that first lowering a patient’s viral load with antivirals, and then adding interferon to activate the immune system may be a more successful strategy. 40% of patients treated with sequential antiviral and interferon treatment lose HBsAg:
Researchers explored the impact of adding up to 96 weeks of pegylated interferon to ongoing antiviral treatment in 10 patients who had undetectable viral load, as a result of antiviral treatment, when the interferon treatment began. The antivirals used included lamivudine, adefovir, entecavir, or a combination of them. Ultimately 40% of the patients lost HBsAg and one patient developed surface antibodies. Hard-to-treat HBeAg-positive patients also appear to benefit from antiviral-interferon treatment:
Researchers compared one group of HBeAg-positive patients who used only entecavir to a second group who added interferon to their ongoing entecavir regimen. In the second group, there was an eight-week overlap where patients received both interferon and entecavir, after which patients were treated with only interferon. Seven of 53 interferon-treated patients (13%) had HBsAg clearance (compared to 0% in the entecavir-only group). Three of the 53 (6%) cleared the infection, losing HBsAg and developing surface antibodies. Patients with HBsAg levels less than 3,000 IU/mL and who were HBeAg-negative at the start of treatment had the highest chance of clearing HBsAg. Another study compared 218 HBeAg-positive patients who received just pegylated interferon against patients who received varying sequences of entecavir and interferon. The groups were then followed for six months after treatment ended. At the end of the follow-up: The interferon-only group had a HBeAg seroconversion rate of 30.6%, higher than the 24.7% and 26% rates scored by the two groups that did sequential interferon and entecavir treatment. However, 2.4% of the interferon group lost HBsAg, compared to 6.8% rate in the group receiving interferon and then entecavir. Another study focusing on HBeAg-patients followed 266 patients treated with interferon for one year and 91 treated with only entecavir. Those receiving interferon had higher rates of HBeAg seroconversion, and 30 (8%) of patients even cleared HBsAg, most of whom received interferon. “This shows that (interferon) remains an important treatment option in HBeAg-positive patients to achieve serological response,” they wrote. A Vietnamese research team tried switching both HBeAg-positive and –negative patients who had been taking antivirals to interferon. Of the 13 HBeAg-positive patients, 7 (54%) responded and 6 had HBeAg seroconversion and 3 cleared HBsAg. The remaining did not respond and were placed back on antivirals. Of the 10 HBeAg-negative patients, 50% responded and 4 even cleared HBsAg.
Preventing mother-to-child infection Tenofovir may be best antiviral to lower viral load in pregnant women:
An Australian study suggests that tenofovir may be the best antiviral to lower a pregnant woman’s viral load to prevent mother-to-child transmission of HBV infection. Starting at week 32 of pregnancy, they treated 8 women with tenofovir and 44 women with lamivudine, and compared their viral loads prior to treatment and at delivery, and then tested the babies at age 9 months. Women receiving tenofovir had much lower viral loads when treatment stopped, and none of the babies in either group contracted hepatitis B (compared to two in a control group where there was no antiviral treatment.) “Lamivudine is effective but failed to achieve adequate viral suppression in 20% of women treated,” researchers noted. Because researchers believe some babies become infected while in utero, tenofovir may be the more effective drug because of its more effective reduction in viral load in the mother during pregnancy. Another study suggests that waiting until the third trimester of pregnancy to start antiviral treatment is just as effective as starting it during the second trimester in pregnant women with high viral loads. Study finds need for clear practice guidelines for treating HBV-infected pregnant women:
A study that followed how doctors in a NYC public health clinic treated HBV-infected pregnant women found that doctors are slowly changing their practices and are increasingly using antivirals to prevent mother-to-child infection. However, currently there are no clear practice guidelines for managing these patients, and the U.S. Food and Drug Administration has not yet approved antiviral use in pregnant women. Researchers wrote, “Guidelines for the management of pregnant women chronically infected with HBV should be standardized to establish ongoing monitoring for HBV-related complications, provide HBV-specific treatment and decrease the risk of immunoprophylaxis failure in their infants.” Telbivudine also appears effective in preventing infection:
A Chinese study followed 36 pregnant women with high viral load, who were treated with telbivudine prior to delivery. None of the children developed hepatitis B, in contrast an untreated control group had a perinatal infection rate of 17.6%.
Screening and treatment programs are inadequate Studies find poor screening for hepatitis B among Asian-Americans:
In several studies, U.S. researchers continued to identify a lack of accurate information among health care providers and Asian-Americans. One study found many with the infection had no idea how they acquired it, and listed food, street vendors, and a dirty wound as possible causes. Many were not vaccinated, and many were unaware that parents or siblings were infected and that they were at high risk of hepatitis B. NYC screening program uncovers need for screening and treatment:
A NYC-based screening initiative targeting foreign-born Korean and Chinese communities found a chronic hepatitis B infection rate of 9%. “This establishes the importance of ethnic urban screening programs that partner with public and community providers to ensure detection of disease and linkage to care,” researchers wrote. Despite guidelines mandating HBV screening for Asian-Americans, only half are tested Researchers scoured the records of more than 300,000 adult Asian-American patients enrolled in the Northern California Kaiser Permanente Medical Care Program to see what percentage of this group, which is at high risk of HBV infection, were screened for the infection, and what care those with diagnosed chronic hepatitis B received. Only 52% of Asian adults were screened, according to their medical records. Screening rates ranged from 47% (Filipino) to more than 60% (Chinese and Vietnamese). Women were more likely screened than men, likely a result of prenatal care. Older adults, over age 60, had the lowest screening rates. Chronic hepatitis B rates among patients were 4.1% for Filipinos, 6% for Korean, 9.1% for Chinese, and 11.8% for Vietnamese. All (11,128) Asian patients with known chronic infections were studied. Rates of ever receiving antiviral therapy ranged from 12% (Filipino) to 28% (Korean). While over 42% of Chinese, Korean, and Vietnamese patients had HBV DNA testing done in the year 2009, only 29% of Filipino patients had such testing. Liver imaging rates for those at risk for cirrhosis and liver cancer ranged from 41% (Filipino) to 63% (Korean), and alpha fetoprotein testing for liver cancer ranged from 38% (Filipino) to 54% (Chinese). “Improvements in hepatitis B screening coverage and disease management are crucial to assuring health equity among Asian-American ethnic groups,” researchers wrote. “Programs that are tailored to patient ethnicity and associated cultural factors may be essential to success.” Community outreach programs vital:
Nationwide, health educators are trying a series of community outreach programs in order reach Asian-Americans who do not regularly interact with health care providers due to lack of insurance and cultural differences. One project in the Dallas-Fort Worth area offered free testing and education to the Vietnamese-American community, and then invited participants back three weeks later to review test results and get free immunization where needed. Most were born in Vietnam, 35% were college-educated, only 32% had health insurance, and 70% had heard about hepatitis B but only 37% had ever been tested. Test results showed 61% of attendees were immune (had either been immunized or had a resolved infection), 24% had not been exposed to the infection and required immunization, and 15% were infected with HBV. Community outreach programs are an effective tool to increase HBV awareness and link patients to appropriate care, researchers noted. Primary care physicians need more education about hepatitis B:
As found in other studies, primary care physicians often fail to screen, immunize and treat people for hepatitis B. Multiple education programs and interventions are needed to improve HBV knowledge and screening practices among these physicians. Lack of health insurance hinders access to care:
A large study of Asian-Americans in Los Angeles found that a lack of medical insurance played a role in preventing 40% of those with hepatitis B from receiving treatment and adequate follow-up care. | 
发表于 2011-11-22 19:54
