Percutanous ethanol injection or percutaneous acetic acid injection for early hepatocellular carcinoma

  • Review
  • Intervention




Hepatocellular carcinoma (HCC) is the fifth most common global cancer. When HCC is detected early, interventions such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), and radiofrequency thermal ablation (RFTA) have curative potential and represent low invasive alternatives to surgery. The role of PEI or PAI has not been addressed in a systematic review.


To evaluate the beneficial and harmful effects of PEI or PAI in adults with early HCC.

Search methods

A systematic search was performed in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and ISI Web of Science in May 2009. Meeting abstracts of six oncological and hepatological societies (ASCO, ESMO, ECCO, AASLD, EASL, APASL) and references of articles were handsearched. Researchers in the field were contacted.

Selection criteria

Randomised trials comparing PEI and PAI with other percutaneous interventions or surgery and trials comparing PEI or PAI with no intervention or sham intervention for the treatment of early HCC were considered regardless of blinding, publication status, or language. Studies comparing RFTA or combination treatments were excluded.

Data collection and analysis

Two authors independently selected trials for inclusion, extracted, and analysed data. The hazard ratios for median overall survival and recurrence-free survival were calculated using the Cox regression model with Parmar's method. Type and number of adverse events were reported descriptively.

Main results

Three randomised trials with a total of 261 patients were eligible for inclusion. The risk of bias was high in all trials. Two of the trials compared PEI with PAI. Overall survival (HR 1.47; 95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95% CI 0.68 to 2.94) were not significantly different. Data on the duration of hospital stay were inconclusive. Data on quality of life were not available. There were only mild adverse events in both treatment modalities.

The other trial compared PEI with surgery. There was no significant difference in overall survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group. Three postoperative deaths occurred in the surgery group.

Authors' conclusions

PEI and PAI do not differ significantly regarding benefits and harms in patients with early HCC, but only a limited number of patients have been examined and the risk of bias was high in all trials. There is also insufficient evidence to determine whether PEI or segmental liver resection is more effective. While some data from the single trial suggested that PEI was safer, the high risk of bias and the lack of any confirmatory evidence make an assessment impossible.




肝細胞癌 (Hepatocellular carcinoma ,HCC) 是世界上第五大常見癌症。當早期檢測出HCC之後,干預療法如肝腫瘤內酒精注射治療 (percutaneous ethanol injection,PEI), 經皮穿刺醋酸注射 (percutaneous acetic acid injection,PAI)和射頻熱燒灼術 (adiofrequency thermal ablation,RFTA) 有機會治療早期肝癌且為手術外微創手術選擇之代表。 PEI或 PAI的功用還沒有在系統性的文獻回顧闡明。


評估PEI 或PAI治療早期肝細胞癌成年人的利弊。


我們進行系統性搜尋,搜索截至2009年5月的The Cochrane HepatoBiliary Group Controlled Trials Register, The Cochrane Library的Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE和ISI Web of Science。6個腫瘤和肝病協會的會議摘要 (ASCO, ESMO, ECCO, AASLD, EASL, APASL) ,手動搜索文章的參考文獻清單。同時聯繫該領域的研究者。


考慮PEI 或PAI 對照無干預法、假干預、其他經皮穿刺干預或外科手術治療早期肝細胞癌的隨機試驗。不受盲法、發表狀態或語言的限制。並排除比較RFTA 或合併治療之研究。


2位作者獨立選擇要收納的試驗,摘錄和分析數據。 使用Cox回歸模式結合Parmar方法,計算總存活率中值和無復發存活率的hazard ratios。不良事件的類型和數量採用描述性說明。


共有3個隨機試驗符合收錄標準,共有 261 位病人。所有試驗具有較高的偏誤風險。其中2個試驗比較PEI 和PAI。總體存活率(HR 1.47; 95%CI0.68 3.19)和無復發存活率(HR 1.42; 95% CI 0.68 2.94)沒有顯著差異。兩者的住院天數無從比較,且無法得知生活品質的變化。2種治療只記錄有輕微的不良事件。另外一次試驗比較PEI和外科手術。 總體存活率(HR 1.57; 95% CI 0.53 4.61) 和無復發存活率(HR 1.35; 95% CI 0.69 2.63)沒有顯著差異。PEI組沒有報導嚴重的不良事件。外科手術組出現三例術後死亡。


PEI 和PAI在治療早期肝細胞癌病人的利弊方面沒有顯著差異,但是只檢查了數量有限的病人,而且所有試驗具有較高的偏誤風險。 同時沒有充足的證據能夠判定PEI 還是部分肝臟切除術更有效,儘管PEI可能更安全。


此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。


肝細胞癌 (肝癌) 位居世界第五大癌症。人們已使用經皮穿刺手術來治療早期肝細胞癌, 例如如肝腫瘤內酒精注射治療經皮穿刺醋酸注射、射頻熱燒灼術、冷凍消融和經肝動脈化療栓塞。儘管手術切割被認為是傳統治療早期幹細胞癌的第一線治療方法,但肝硬化病人仍然會出現極高的發病率和死亡率。本次回顧沒有發現如肝腫瘤內酒精注射注射治療和經皮穿刺醋酸注射治療在早期肝細胞癌病人時,在總體存活率和無復發存活率方面有顯著差異。2種方法皆屬於低侵入性且安全。根據一個隨機試驗,治療早期肝細胞癌的病人手術切割似乎沒有比肝腫瘤內酒精注射治療好。後者的結果受到病人組分佈不均勻,檢驗的病人人數不足,試驗的方法缺陷等因素的限制導致試驗的系統誤差風險較高(偏誤)。

Plain language summary

Percutanous interventions for early hepatocellular carcinoma

Hepatocellular carcinoma (liver cancer) ranks fifth in global cancer burden. Percutaneous techniques such as percutaneous ethanol injection, percutaneous acetic acid injection, and radiofrequency thermal ablation, cryoablation, and transarterial chemoembolisation have been used to treat early hepatocellular carcinoma. While surgical resection has been traditionally considered to be the first-line therapy in early hepatocellular carcinoma, it has considerable morbidity and mortality in patients with liver cirrhosis. The review found no significant difference in overall and recurrence-free survival in patients with early hepatocellular carcinoma treated with percutaneous ethanol injection as compared with percutaneous acetic acid injection. Both methods are minimally invasive and safe. Based on a single randomised trial, surgical resection does not seem to be superior to percutaneous ethanol injection in patients with early hepatocellular carcinoma. The latter result is limited by the inhomogeneous patient group, the paucity of patients examined, and the methodological weaknesses of the trials leading to high risks of systematic errors (bias) in the trials.