AASLD2020[738]可持久檢測的血清HBV DNA和PGRNA 與HCC的後續發展有

StephenW

738
PERSISTENTLY DETECTABLE SERUM HBV DNA AND PGRNA
IS ASSOCIATED WITH SUBSEQUENT HCC DEVELOPMENT IN
CHRONIC HEPATITIS B PATIENTS RECEIVING CHRONIC NRTI
TREATMENT
Lung Yi Mak1, Qi Huang2, Ka Ho Danny Wong3, Ran Yan2,
Lea Ouyang2, James Fung3, Wai Kay Walter Seto4 and Man
Fung Yuen3, (1)State Key Laboratory for Liver Research,
The University of Hong Kong, (2)Assembly Biosciences,
(3)Medicine, The University of Hong Kong, (4)State Key
Laboratory of Liver Research, The University of Hong Kong
Background: Although antiviral therapy reduces the risk
of hepatocellular carcinoma (HCC) in chronic hepatitis B
(CHB) patients, HCC risk is not eliminated in those achieving
undetectable serum hepatitis B virus (HBV) DNA by standard
assays We aimed to assess whether HBV DNA and pgRNA
detected by highly sensitive assays are associated with HCC
development in a retrospective case-control study Methods:
A total of 104 patients [52 HCC cases and 52 non-HCC
controls (matched with age, gender and treatment duration)
on ≥3 years of entecavir (ETV) with undetectable HBV DNA
by Cobas Taqman assay version 2 0 (Roche Diagnostics;
lower limit of detection [LLOD] 20 IU/mL) were included
Stored serum from 3 (-3 years), 2 (-2 years) and 1 (-1 year)
prior to HCC diagnosis or last follow-up (LFU) were assessed
using highly sensitive HBV DNA and pgRNA assays Total
viral nucleic acid was extracted and subjected to HBV DNA
and total nucleic acid (HBV DNA + pgRNA) measurements,
Detection of HBV DNA was performed using a semiquantitative
PCR assay with LLOD of 10 IU/mL Quantitation
of pgRNA was derived from the difference between the total
nucleic acid levels and HBV DNA levels, with a lower limit of
quantification (LLOQ) of 300 copies/mL and LLOD of 10 IU/
mL Results: Among the 104 patients (59 6% male, median
age 61 2 years old, duration of ETV 45 5 months), 93 and 96
had retrievable samples at -3 and -2 years prior to HCC or
LFU, respectively For HCC patients, only 34 1%, 38 5% and
38 5% had undetectable HBV DNA and only 4 3%, 10 3% and
9 6% had undetectable pgRNA by the highly sensitive assays
at time -3, -2 and -1 year, respectively For non-HCC patients,
only 43 9%, 51% and 65 4% had undetectable HBV DNA and
only 11 1%, 22 4% and 36 5% had undetectable pgRNA by the
highly sensitive assays at time -3, -2 and -1 year, respectively
(Figure 1). The median pgRNA was significantly higher in
patients with HCC compared to those without HCC at -3 years
[(1857 (IQR 300 – 172500) vs 300 (IQR 300 – 1819) copies/
mL, p=0 005) Detectable viral nucleic acid at all 3 time points
was significantly associated with HCC development (log rank
P<0 05 for all 3 comparisons) Conclusion: More than half of
CHB patients on ETV with HBV DNA < LLOQ by a standard
assay had persistent HBV DNA and pgRNA detected by highly
sensitive assays which was associated with subsequent HCC
development More profound viral suppression is needed for
further reduction of HCC risk in CHB patients.

StephenW

738
可持久檢測的血清HBV DNA和PGRNA
與HCC的後續發展有關
接受慢性NRTI的慢性乙型肝炎患者
治療
麥龍儀1，齊煌2，黃嘉豪3，冉艷2，
Lea Ouyang2，James Fung3，Wai Kay Walter Seto4和Man
馮遠3，（1）肝臟研究國家重點實驗室，
香港大學，（2）彙編生物科學，
（3）香港大學醫學，（4）國家重點
香港大學肝臟研究實驗室
背景：儘管抗病毒治療降低了風險
慢性乙型肝炎的肝細胞癌的診斷
（CHB）患者，在達到
標準檢測不到血清乙型肝炎病毒（HBV）DNA
分析我們旨在評估HBV DNA和pgRNA是否
通過高度敏感的檢測方法檢測到的肝癌
回顧性病例對照研究的發展方法：
共有104例患者[52例HCC病例和52例非HCC
對照（與年齡，性別和治療時間相匹配）
恩替卡韋（ETV）≥3年且未檢測到HBV DNA
由Cobas Taqman分析版本2 0（Roche Diagnostics;
最低檢測限[LLOD] 20 IU / mL）
3（-3年），2（-2年）和1（-1年）儲存的血清
評估HCC診斷之前或最後一次隨訪（LFU）
使用高度敏感的HBV DNA和pgRNA分析合計
提取病毒核酸並進行HBV DNA
和總核酸（HBV DNA + pgRNA）測量，
使用半定量檢測HBV DNA
LLOD為10 IU / mL定量的PCR檢測
pgRNA的總和之間存在差異
核酸水平和HBV DNA水平，下限為
定量（LLOQ）為300拷貝/ mL，LLOD為10 IU /
毫升結果：在104例患者中（59 6％男性，中位數
61歲2歲，ETV持續時間45 5個月），93和96
在HCC之前-3和-2年有可檢索的樣本，或者
LFU分別對於HCC患者而言只有34 1％，38 5％和
38 5％的患者檢測不到HBV DNA，只有4 3％，10 3％和
9％的人通過高敏感度檢測法檢測不到pgRNA
對於非HCC患者，分別在-3，-2和-1年的時間
只有43 9％，51％和65 4％的患者檢測不到HBV DNA，
僅有11 1％，22 4％和36 5％的pgRNA被
在-3，-2和-1年分別進行高度敏感的測定
（圖1）。 pgRNA的中位數顯著高於
-3年時有HCC的患者與沒有HCC的患者相比
[（（1857（IQR 300 – 172500）vs 300（IQR 300 – 1819）副本/
mL，p = 0 005）在所有3個時間點均可檢測到病毒核酸
與肝癌的發展顯著相關（對數等級
對於所有3個比較，P <0 05）結論：超過一半的
ETV上CHB患者的HBV DNA <LLOQ標準
檢測持續HBV DNA和pgRNA的高度檢測。
與隨後的HCC相關的敏感測定
發展需要更深刻的病毒抑制
進一步降低CHB患者的HCC風險。