Hep B Blog

Perspective on the Liver Biopsy – “The Gold Standard”


Have you noticed fewer patients living with chronic HBV seem to get liver biopsies to assess liver damage?  Here is a perspective on the Liver Biopsy, known as the “gold standard”, by William Carey, MD, Division of Gastroenterology and Hepatology of the Cleveland Clinic.

Published in Healio , July 14, 2014 

Liver biopsy is referred to as the “gold standard” in assessing both the activity and degree of fibrosis in many chronic liver diseases including hepatitis B. It is not likely to retain this lofty status much longer. Liver biopsy has several important drawbacks. Among them are cost, risk for complications, need for additional health care resources, patient and physician aversion to the procedure, inadequate specimen size and the lack of specific findings.

Liver biopsy adds between $2,500 to $3,500 to the cost of an evaluation (even higher for transvenous liver biopsy). Approximately 20% of patients will experience significant pain following percutaneous liver biopsy. More severe complications include pneumothorax, major bleeding, inadvertent biopsy of the kidney or colon, and perforation of the gallbladder. Death, most often due to uncontrolled bleeding, may occur in up to 1 in 1,000 biopsies. Underappreciated is the risk of no-representative sampling, either because of the small size of biopsy specimen or patchy distribution of fibrosis.

Noninvasive measures to assess hepatic fibrosis have been around for a generation and are increasingly used as a substitute for liver biopsy. The 2014 medley of noninvasive estimates of hepatic fibrosis includes FibroTest/FibroSure, APRI, FIB-4, other serum based test combinations, and elastography (either ultrasound- or MRI-based). Noninvasive tests have potential both for determination of current liver damage and for monitoring disease progression. They can be done at a fraction of the cost of a liver biopsy. Salkic and colleagues have reported the results of an exquisitely performed meta-analysis of peer reviewed published reports and confirmed the value of FibroTest/FibroSure in hepatitis B — mainly in excluding the diagnosis of cirrhosis. The findings of this review are restricted to hepatitis B, but others have shown similar findings in hepatitis C and alcoholic liver disease.

While there is growing consensus that noninvasive markers provide valuable information, allowing the clinician to make important decisions about treatment, screening for varices and hepatocellular carcinoma, it is essential to understand limitations of FibroTest, including distortions in results in individuals with Gilbert’s syndrome and in those with hemolysis. This study reiterates the relative insensitivity of noninvasive tests in discriminating between lesser degrees of fibrosis (F0, F1, and F2).

Data are accumulating to suggest noninvasive markers (combining a noninvasive test plus ultrasound-based elastrography, for example) are powerful tools in assessing natural history of individuals with many chronic liver diseases including hepatitis B, providing indices of disease activity, progression and fibrosis regression after treatment. Convenience, lower cost, and ease of repeated measurements over time favor widespread acceptance of these tools in clinical practice.

HBV Journal Review – August 2014

ChrisKHBF is pleased to connect our blog readers to Christine Kukka’s monthly HBV Journal Review that she writes for the HBV Advocate. The journal presents the
 latest in hepatitis B research, treatment, and prevention from recent academic and medical journals. This month, the following topics are explored:

  • Health Concerns Grow as Researchers Uncover the Risks of “Occult”
  • Are Current Hepatitis B Tests Missing Some Infections?
  • First Case of Tenofovir Resistance Found in Patient with Prior Entecavir Resistance
  • Even Specialists Fail to Treat Hepatitis in Patients Who Qualify for Treatment
  • No Benefit Found from Antiviral Treatment after Liver Cancer Surgery
  • Another Study Confirms Success of Sequential Antiviral and Interferon Treatment
  • Snapshot of Hepatitis B in the United States
  • Metformin Safe and Effective in Cirrhotic Patients with Diabetes Type 2

HBV Journal Review

August 1, 2014
Volume 11, Issue 8
by Christine M. Kukka

Health Concerns Grow as Researchers Uncover the Risks of “Occult” Hepatitis B
Researchers studying the health effects of “occult” hepatitis B are finding that this infection that can “hide” from conventional lab tests carries a higher risk of liver cancer and poses a risk to the general population when undiagnosed.

This type of hepatitis B occurs when a mutation in the virus’ outer coat, made up of the hepatitis B surface antigen (HBsAg), makes it impossible for common lab tests that look for that protein to identify an active HBV infection. The HBsAg lab test is commonly used to identify hepatitis B in patients and even blood supplies.

When lab tests fail to identity HBV infection, people can unknowingly spread the infection to their partners, family members and newborns. And when occult HBV infection goes untreated, a patient’s risk of liver cancer is 3.7-fold higher than in patients with “regular” or non-occult hepatitis B, according to a recent report in the August issue of the Journal of Hepatology.

HBsAg has three proteins and in the case of occult HBV, the immune system attacks one of the three surface proteins–the same protein that lab tests look for when screening blood for HBsAg.

Most vaccines contain this exact same HBsAg protein in order to spur production of surface antibodies to fight off an actual infection. In most cases, the vaccine is very effective, but when occult hepatitis B occurs, the vaccine-induced antibodies are powerless against the remaining two surface proteins and viral reproduction and infection can continue.

This concern has grown recently as scientists find a number of children born to HBV-infected mothers, who were immunized at birth, have developed “occult” hepatitis B. Additionally, people with occult hepatitis B can transmit the mutated, “occult” version of HBV to partners and close contacts (even if they’re vaccinated), adding to the spread of this hard-to-identify viral hepatitis infection.

Because of the unique genetic make-up of this mutated HBsAg and how it interacts with liver cells, this mutation appears to cause more rapid liver damage and cancer.

Scientists suggest that drug resistance, especially to the antiviral lamivudine (Epivir-HBV), may contribute to development of this mutation.

“Recent studies have reported that (surface mutations) tend to (emerge) with the drug resistance-associated mutations in lamivudine-treated patients, and that the (mutations) …. play a supportive role in the replication of lamivudine-resistant viruses,” Italian researchers wrote in the report.

“Therefore it appears of the utmost importance that patients with chronic hepatitis B are screened for the presence of (surface antigen) mutant infection,” they recommended. “The detection of these specific HBV variants may indeed be useful for the identification of those patients requiring a preventive and appropriate treatment and a more intensive follow-up strategy for early detection of liver cancer.”

Source: www.journal-of-hepatology.eu/article/S0168-8278(14)00304-3/fulltext

Are Current Hepatitis B Tests Missing Some Infections?
When do hepatitis B tests miss true infections?A number of confounding factors, ranging from “occult” hepatitis B increase (see above article), failure of lab tests to pick up extremely low levels of HBsAg, immunizations, and the rapidly changing progression of HBV infection can all conspire to mask the infection from conventional laboratory tests.

Read the HBV Journal Review in its entirety 

Hepatitis is Still the Silent Killer


Great way to wrap up World Hepatitis Day events with a commentary from our viral hepatitis champions on Capitol Hill. A big thank you to Senator Mazie K. Hirono and Representatives, Michael M. Honda, Hank Johnson, and Bill Cassidy for their tireless efforts. Viral Hepatitis is a problem we cannot ignore!

Roll Call (online) By Sen. Mazie K. Hirono, and Reps. Michael M. Honda, Hank Johnson, and Bill Cassidy. July 31, 2014, 5 a.m.

Although the price of a revolutionary new hepatitis C treatment has made headlines recently, the real hepatitis crisis continues largely unreported. A more immediate problem for many Americans is not how much one hepatitis C treatment might cost; it is how many Americans are infected with viral hepatitis and do not even know it.

World Hepatitis Day, July 28, reminds us that more than 5 million Americans — or 2 percent of the population — are living with viral hepatitis. Yet the Centers for Disease Control and Prevention (CDC) estimates as many as 75 percent of these Americans are unaware they have the virus. This “silent killer” goes undetected because the virus often remains asymptomatic until it has already wreaked havoc on the liver, causing cirrhosis, end-stage liver disease, or liver cancer. According to the CDC, more than 30 percent of infected individuals will develop one of these conditions.

Meanwhile, since the majority of infected individuals don’t realize they have hepatitis, they do not take the necessary precautions and can unknowingly transmit the virus to others. More Americans die every year from hepatitis C than HIV.

Without effective intervention, it is estimated that deaths due to the hepatitis C virus will double, or even triple, in the next 20 years. Baby boomers — Americans born between 1945 and 1965 — make up 75 percent of Americans with hepatitis C, and are five times more likely to have the virus than the general population.

Hepatitis disproportionately affects communities of color. One in 12 Asian-Americans has chronic hepatitis B, and rates are increasing in African immigrant and Latino populations as well. Hepatitis C is twice as prevalent in African-Americans as in the general U.S. population. Despite the pervasiveness of viral hepatitis, and its potentially deleterious consequences for those infected, testing is not nearly as prevalent as it should be.

The Viral Hepatitis Testing Act, introduced both in the House of Representatives and the Senate, would create the first coordinated national system to address and combat viral hepatitis. It would expand hepatitis education, testing and care, with the priority of reaching those most at-risk. Most importantly, the legislation would help to halt the spread of viral hepatitis by strengthening health care coordination to ensure that patients who test positive are connected with the counseling they need to control their disease and prevent transmission. Through the Viral Hepatitis Testing Act, we can increase the number of individuals who are aware of their status from 25 percent to 75 percent in just two years.

Awareness is the antidote to this silent epidemic. Early diagnosis, determined through a simple blood test, can reduce the spread of viral hepatitis simply by making individuals aware of the infection and helping to connect them with education about the risks of transmission. Organizing our outreach and prevention to be culturally competent and available in different languages will help us reach those communities that are disproportionately affected. The CDC estimates that one-time testing of baby boomers alone would identify 800,000 undiagnosed hepatitis C cases nationwide, and prevent more than 120,000 deaths. We need action at the federal level to make viral hepatitis testing a national priority.

The true cost of viral hepatitis is not measured in the cost of one drug. It is how this epidemic will continue to grow if policymakers do nothing. We urge our fellow lawmakers to enact the Viral Hepatitis Testing Act and establish hepatitis awareness as a national priority.

We cannot ignore this problem.

Mazie Hirono is a Democratic United States Senator from Hawaii. Michael M. Honda is a seven-term Democratic congressman representing the 17th District of California, better known as Silicon Valley. Hank Johnson is five-term Democratic Congressman representing Georgia’s 4th District in the suburbs of Atlanta. Dr. Bill Cassidy is a three-term Republican Congressman representing the 6th District of Louisiana, including Baton Rouge and Houma.