JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan

Abstract

The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term "lipiodol" from the definition of TACE failure/refractoriness.

Keywords: Clinical practice guidelines; Definition of transarterial chemoembolization failure; Hepatocellular carcinoma; Japan Society of Hepatology; Liver Cancer Study Group of Japan.

Fig. 1

Surveillance and Diagnostic Algorithm of HCC (Proposed by the Liver Cancer Study Group of Japan 2014). SPIO=superparamagnetic iron oxide; CTAP=computed tomographic arterial portography; CTHA=computed tomographic hepatic arteriography. ^aCavernous hemangioma may show hypointensity on equilibrium (transitional) phase of dynamic Gd-EOB-DTPA MRI (pseudo-washout). It should be excluded by other sequences of MRI and/or other imaging modalities. ^bCavernous hemangioma usually shows hypointensity on hepatobiliary phase of Gd-EOB-DTPA MRI. It should be excluded by other sequences of MRI and/or other imaging modalities. ^cBiopsy may be considered for confirmation.

Fig. 2

JSH-LCSGJ Consensus-based Treatment Algorithm for Hepatocellular Carcinoma revised in 2014. ^aTreatment should be performed as if extrahepatic spread is negative when extrahepatic spread is not regarded as a prognostic factor. ^bSorafenib is the first choice of treatment in this setting as a standard of care. ^cIntensive follow-up observation is recommended for hypovascular nodules by the Japanese Evidence-Based Clinical Practice Guidelines. However, local ablation therapy is frequently performed in the following cases: 1) when the nodule is diagnosed pathologically as early HCC, 2) when the nodules show decreased uptake on hepatobiliary phase Gd-EOB-DTPA-MRI, 3) when the nodules show decreased portal flow by CTAP or 4) decreased uptake is shown on Kupffer phase of Sonazoid enhanced US, since these nodules are known to frequently progress to the typical hypervascular HCC. ^dEven for HCC nodules exceeding 3 cm in diameter, combination therapy of TACE and ablation is frequently performed when resection is not indicated. ^eTranscatheter arterial chemoembolization (TACE) is the first choice of treatment in this setting. Hepatic arterial infusion chemotherapy (HAIC) using reservoir system is also recommended for TACE refractory patients. The regimen for this treatment is usually low-dose FP (5FU+CDDP) or 5FU infusion combined with systemic interferon therapy. Sorafenib is also a treatment of choice for TACE refractory patients with Child Pugh A liver function. ^fResection is sometimes performed even when the number of nodules is greater than 4. Furthermore, ablation is sometimes performed in combination with TACE. ^gMilan criteria: Tumor size ≤ 3 cm and tumor number ≤ 3; or solitary tumor ≤ 5cm. Even when liver function is good (Child-Pugh A/B), transplantation is sometimes considered for frequently recurring HCC patients. ^hSorafenib and HAIC are recommended for HCC patients with Vp1,2 (minor portal vein invasion) or Vp3 (portal invasion at the 1st portal branch). Sorafenib is not recommended for HCC patients with Vp4 (portal invasion at the main portal branch), whereas HAIC is recommended for such patients with tumor thrombus in the main portal branch. ⁱResection and TACE is frequently performed when portal invasion is minor such as Vp1 (portal invasion at the 3rd or more peripheral portal branch) or Vp2 (portal invasion at the 2nd portal branch). ^jEven in Child-Pugh A/B patients, transplantation is sometimes performed for relatively younger patients with frequently or early recurring HCC after curative treatments. ^kLocal ablation therapy or subsegmental TACE is performed even for Child-Pugh C patients (CP score 10 and 11) within Milan criteria when transplantation is not indicated. In the case, patients with no hepatic encephalopathy, no uncontrollable ascites, and a low bilirubin level (< 3.0mg/dl) are selected for treatment. Although these are well-accepted treatments in the routine clinical setting, there is no high-level evidence of its survival benefit in Child-Pugh C patients. A prospective study is necessary to clarify this issue.