难以评估 ALT
丙氨酸氨基转移酶 (ALT) 水平通常在使用核苷（酸）类似物治疗后完全抑制 HBV DNA 病毒的患者中恢复正常。当 ALT 水平在 HBV DNA 病毒抑制的情况下保持升高时，它可能是由于肥胖、DM（有时与 NAFLD 或 NASH 相关）和/或有害饮酒导致的持续肝损伤的功能。然而，一过性 ALT 突然升高，随后 HBV DNA 下降可能表明免疫重建，这可能导致 HBeAg 阳性患者的乙型肝炎 e 抗原 (HBeAg) 清除，更例外的是，导致乙型肝炎表面抗原丢失。在其他情况下，在接受核苷（酸）类似物治疗但不依从药物的患者中，ALT 和 HBV DNA 水平可能会升高。因此，重要的是将这些 ALT 突发归类为与 CHB 相关的潜在阳性结果相关的“良好突发”或可导致肝损伤进展甚至肝功能失代偿的“不良突发”。
My Thoughts on Assessing HBV Treatment Candidacy in the Setting of Other Host Factors
Maria Buti, MD
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? Click the button below to answer the polling question, post comments, or follow the discussion.