Charatcharoenwitthaya Phunchai, Phisalprapa Pochamana, Pausawasdi Nonthalee, Rungkaew Pimpattana, Kajornvuthidej Sorrayut, Bandidniyamanon Wimolrak, Chotiyaputta Watcharasak, Chainuvati Siwaporn, Tanwandee Tawesak
Division of Gastroenterology, Department of Medicine.
Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Hepatol Res. 2016 Dec;46(13):1347-1357. doi: 10.1111/hepr.12693. Epub 2016 Apr 5.
To evaluate the utility of the combination of alanine aminotransferase (ALT) course, hepatitis B virus (HBV) DNA level, and liver stiffness measurement (LSM) for determining significant liver disease in hepatitis B e antigen (HBeAg)-negative patients.
Three hundred and ninety nine consecutive HBeAg-negative patients with HBV DNA >2000 IU/mL and documented serial measurements of ALT were enrolled to undergo LSM followed by liver biopsy.
Using ALT <40 IU/L as a normal value, 142 patients had persistently normal ALT (PNALT), whereas 257 had persistently or intermittently elevated ALT (PIEALT) in the prior year. Among patients with HBV DNA of 2000-19 999, 20 000-199 999, and ≥200 000 IU/mL, significant pathological lesions defined as the presence of moderate to severe necroinflammation and/or significant fibrosis by METAVIR scoring was present in 40%, 45%, and 71% of the PIEALT group, and 15%, 31%, and 36% of the PNALT group, respectively. In PNALT patients with HBV DNA <20 000 IU/mL, liver biopsy could be avoided in 88% when LSM <7 kPa is used as an indicator of non-significant liver histology but 12% of those who indeed had significant pathological lesions would be missed. In PIEALT patients with HBV DNA ≥20 000 IU/mL, the need for liver biopsy could be reduced by 53% with a false positive rate of 14% when LSM ≥7 kPa is used as a predictor of significant pathological lesions.
The combination of serial ALT, viral load, and LSM appears to be a promising non-invasive tool. A management algorithm for HBeAg-negative patients comprising these non-invasive measures is proposed with liver biopsy being pursued in selected cases.
评估丙氨酸氨基转移酶(ALT)病程、乙型肝炎病毒(HBV)DNA水平和肝脏硬度值测定(LSM)联合应用于确定乙肝e抗原(HBeAg)阴性患者严重肝脏疾病的效用。
连续纳入399例HBV DNA>2000 IU/mL且有ALT系列测量记录的HBeAg阴性患者,进行LSM检查,随后进行肝活检。
以ALT<40 IU/L作为正常值,142例患者ALT持续正常(PNALT),而257例患者上一年ALT持续或间歇性升高(PIEALT)。在HBV DNA为2000 - 19999、20000 - 199999和≥200000 IU/mL的患者中,根据METAVIR评分定义的中度至重度坏死性炎症和/或显著纤维化等显著病理病变在PIEALT组中的比例分别为40%、45%和71%,在PNALT组中分别为15%、31%和36%。在HBV DNA<20000 IU/mL的PNALT患者中,当LSM<7 kPa作为无显著肝脏组织学的指标时,88%的患者可避免肝活检,但12%确实有显著病理病变的患者会被漏诊。在HBV DNA≥20000 IU/mL的PIEALT患者中,当LSM≥7 kPa作为显著病理病变的预测指标时,肝活检需求可减少53%,假阳性率为14%。
ALT系列、病毒载量和LSM联合应用似乎是一种有前景的非侵入性工具。提出了一种针对HBeAg阴性患者的管理算法,包括这些非侵入性措施,在特定情况下进行肝活检。