My Thoughts on Assessing HBV Treatment Candidacy in the Setting of Other Host Factors

The progression of chronic hepatitis B (CHB) disease is influenced both by virologic factors and host-related factors. Some patients diagnosed with hepatitis B virus (HBV) have complex medical and social histories. Host factors such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), obesity, diabetes mellitus (DM), current heavy alcohol use, or active tobacco smoking can alter the course of HBV infection and increase a patient’s risk for developing fibrosis, cirrhosis, and/or hepatocellular carcinoma (HCC). These host factors can complicate the treatment course and confound the clinical picture of whether the patient’s HBV disease is improving or worsening. Although the European Association for the Study of the Liver guidelines recommend taking a complete medical history to collect information such as these, the role of host factors in the monitoring and treatment of CHB is an area largely unexplored by the guidelines.

Metabolic Syndrome Parameters
Obesity and DM are often associated with the development of NAFLD or NASH, which can accelerate progression to fibrosis, cirrhosis, and/or HCC in the setting of HBV. Also, obesity and DM can each independently increase a patient’s risk of developing cirrhosis and/or HCC. In combination with harmful alcohol consumption, obesity even further increases a patient’s risk of HCC. The presence of these host factors in a patient with HBV complicates assessment and monitoring of the patient’s risk for these liver complications.

Difficulty Evaluating ALT
Alanine aminotransferase (ALT) levels typically normalize in patients who achieve complete HBV DNA viral suppression under treatment with nucleos(t)ide analogues. When ALT levels remain elevated in the setting of HBV DNA viral suppression, it could be a function of ongoing liver injury due to obesity, DM (sometimes associated with NAFLD or NASH), and/or harmful alcohol consumption. However, transient ALT flares followed by a decrease in HBV DNA may indicate immune reconstitution, which can lead to hepatitis B e antigen (HBeAg) clearance in HBeAg-positive patients and, more exceptionally, to hepatitis B surface antigen loss. On other occasions, in patients treated with nucleos(t)ide analogues who are not adherent to the medication, ALT and HBV DNA levels could increase. Therefore, it is important to categorize these ALT flares as “good flares” associated with a potentially positive outcome related to CHB or “bad flares” that can lead to progression of liver damage and even hepatic decompensation.

Treatment Conundrums
Because many host-related factors may contribute to poor outcomes in a patient with HBV, it brings up the question of whether modifiable host factors (eg, obesity, tobacco smoking, harmful alcohol use) should be addressed before the initiation of drug therapy for CHB. Optimally controlling metabolic comorbidities and encouraging cessation of alcohol consumption and/or tobacco smoking in a patient with HBV can decrease that patient’s risk for developing fibrosis, cirrhosis, and/or HCC. This decreased risk may alter the decision to initiate treatment. If treatment is initiated, better control or even elimination of certain host factors can favorably affect the adverse event profile of first-line CHB treatments, such as peginterferon.

Your Thoughts?
How do you approach treatment candidacy in patients with HBV and other causes of liver disease? Do you address host factors before HBV treatment, or do you address host factors concurrently while treating the HBV? Please share your thoughts in the comments box.