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Humanity and Health Medical Group
Hong Kong, China
Chair, Professor, and Co-Director
Liver Diseases & Transplant Centre
The Fifth Medical Centre of Chinese PLA General Hospital,
George Lau MBBS (HKU), MD (HKU), FRCP (Edin, Lond), FAASLD (USA), has no relevant financial relationships to disclose.
Hepatitis B guidelines aim to define “older age” when it comes to those with chronic hepatitis B (CHB), but what it means to be “older” should be defined at an individual level. People who are defined as “older” based on biological age actually may be mentally and physiologically younger than their stated age. Indeed, the current quoted “natural history of CHB” was structured at a time when there was no effective treatment for CHB and the only virologic assays were an insensitive semiquantitative hepatitis B virus (HBV) DNA test and qualitative serologic assay. Only recently was a noninvasive test of liver fibrosis—the most important determinant of prognosis in CHB—made available. In short, the definition is fluid, and therefore we should be proactive in our approach to monitoring and treating all patients with CHB, regardless of age.
Should Age Be a Factor in CHB Treatment Decisions?
Defining “older” by age alone is not serving the best interests of patients with CHB, including immune-tolerant patients who have high viral replication. Many years ago, we thought that immune-tolerant patients did not need treatment. Our current view has changed. The definition of elevated alanine aminotransferase (ALT) has changed; 30 years ago, the upper limit of normal for ALT was 60-70 U/L, and now it’s in the 20s (eg, 20-29 U/L). Time has shown us that we need to be more aggressive in monitoring and treating all patients with CHB and striving for HBV DNA suppression in patients of all ages. We also need to have a good surveillance program for all patients, with a goal of early detection of hepatocellular carcinoma (HCC), and thus enable a reduction of morbidity and mortality of CHB, which is the ultimate goal of CHB treatment.
Personally, I think we should not set age cutoff points for CHB treatment or use age as a parameter to define the natural history of CHB. Younger patients who were diagnosed at 13 years of age may have ALT values that double by the time they are 18 years of age. Although their current ALT value may be within the range defined as normal, it is the increase that is worrisome. The same ALT phenomena also can occur in older patients, so we should be treating the individual rather than the age.
My Approach to CHB Treatment
A treatment hurdle to overcome is simply getting patients on treatment and suppressing their HBV DNA. In my opinion, too much time is spent trying to decipher which patients to treat and which nucleoside/nucleotide analog is best to use. To me, even when there are differences between the drugs, those differences are minor, and all patients with CHB with detectable viral replication should be treated.
My primary concern when treating patients with CHB is to get them on drug therapy to reduce viral replication. This is key because the higher the replication, the higher the chance of necroinflammation when the immune system mounts a response in an effort to curtail the HBV infection. Also important to consider is the higher chance of HBV DNA integration throughout the host genome with high levels of replication. HBV DNA integration is one of the drivers for mutational changes that lead to the development of HCC. Conceptually, you want to decrease or stop HBV DNA replication to reduce integration and, therefore, decrease the risk of HCC. Given all of this, age should not be a concern. The focus should be on treating anyone with high levels of HBV DNA replication.
Duration and Cost of CHB Treatment
When it comes to treatment of a chronic disease state like CHB, there are patients who do not want to be on therapy forever. However, the drugs we use nowadays are better tolerated, with virtually no adverse events and no toxicity. In terms of cost, in my country entecavir costs less than a bottle of water; in US dollars, it’s only approximately $2 per month. It’s not like years ago when I tried to get tenofovir to my lamivudine-resistant patients. At that time, the cost of 1 bottle of tenofovir was equivalent to almost $1,500.
We are fortunate that the current CHB treatment is affordable, but we must keep in mind that liver cancer is very costly. Even if HCC is treated in early stages and cured with resection, the cost incurred is tremendously more than the treatment of CHB.
Barriers to CHB Care at Any Age
Patients with CHB who develop HCC have in common that most—if not all—never received an antiviral treatment, irrespective of age. It’s always the same story: These patients never received any CHB surveillance, including simple monitoring such as ultrasounds and alpha-fetoprotein tests.
In my opinion, there should no longer be an older age designation in CHB risk stratification. I’m confident that at least 95% of patients can achieve complete resolution of necroinflammation and normalization of ALT with appropriate treatment. Treatment, coupled with ongoing surveillance, can drastically reduce the occurrence of HCC.
Should we remove age as a factor in our treatment decisions for patients with CHB? Join the discussion by posting a comment below.