在其他宿主因素的情况下评估 HBV 治疗候选者的我的想法

StephenW

在其他宿主因素的情况下评估 HBV 治疗候选者的我的想法


玛丽亚·布蒂，医学博士

慢性乙型肝炎 (CHB) 疾病的进展受病毒学因素和宿主相关因素的影响。一些被诊断出患有乙型肝炎病毒 (HBV) 的患者具有复杂的病史和社会史。宿主因素，如非酒精性脂肪性肝病 (NAFLD)、非酒精性脂肪性肝炎 (NASH)、肥胖、糖尿病 (DM)、目前大量饮酒或主动吸烟，可以改变 HBV 感染的进程并增加患者发生纤维化的风险、肝硬化和/或肝细胞癌 (HCC)。这些宿主因素会使治疗过程复杂化，并混淆患者 HBV 疾病是改善还是恶化的临床表现。尽管欧洲肝脏研究协会指南建议收集完整的病史以收集此类信息，但宿主因素在 CHB 监测和治疗中的作用是指南未探索的领域。

代谢综合征参数
肥胖和 DM 通常与 NAFLD 或 NASH 的发展有关，在 HBV 的情况下，NAFLD 或 NASH 会加速进展为纤维化、肝硬化和/或 HCC。此外，肥胖和 DM 可以各自独立地增加患者发生肝硬化和/或 HCC 的风险。与有害饮酒相结合，肥胖甚至会进一步增加患者患 HCC 的风险。 HBV 患者中这些宿主因素的存在使评估和监测患者发生这些肝脏并发症的风险变得复杂。

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”。

治疗难题
由于许多宿主相关因素可能导致 HBV 患者的不良结局，因此提出了一个问题，即是否应在开始 CHB 药物治疗之前解决可改变的宿主因素（例如，肥胖、吸烟、有害饮酒） .优化控制代谢合并症并鼓励 HBV 患者戒酒和/或吸烟可以降低该患者发生纤维化、肝硬化和/或 HCC 的风险。这种降低的风险可能会改变开始治疗的决定。如果开始治疗，更好地控制甚至消除某些宿主因素可以有利地影响一线 CHB 治疗（如聚乙二醇干扰素）的不良事件特征。

你的意见？
您如何处理 HBV 和其他原因肝病患者的治疗候选资格？您是在治疗 HBV 之前解决宿主因素，还是在治疗 HBV 的同时解决宿主因素？单击下面的按钮回答投票问题、发表评论或关注讨论。

StephenW

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.