A B S T R A C T PurposeMost patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade. Patients and MethodsWe developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels. We then tested the model using similar cohorts from other geographical regions (n ϭ 5,097) and other clinical situations (patients undergoing resection [n ϭ 525] or sorafenib treatment for advanced HCC [n ϭ 1,132]). The specificity of the model for liver (dys)function was tested in patients with chronic liver disease but without HCC (n ϭ 501). ResultsThe model, the Albumin-Bilirubin (ALBI) grade, performed at least as well as the C-P grade in all geographic regions. The majority of patients with HCC had C-P grade A disease at presentation, and within this C-P grade, ALBI revealed two classes with clearly different prognoses. Its utility in patients with chronic liver disease alone supported the contention that the ALBI grade was indeed an index of liver (dys)function. ConclusionThe ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting. This new model eliminates the need for subjective variables such as ascites and encephalopathy, a requirement in the conventional C-P grade.

MicroRNAs (miRNAs) are a non-coding family of genes involved in post-transcriptional gene regulation. These transcripts are associated with cell proliferation, cell differentiation, cell death and carcinogenesis. We analysed the miRNA expression profiles in 25 pairs of hepatocellular carcinoma (HCC) and adjacent nontumorous tissue (NT) and nine additional chronic hepatitis (CH) specimens using a human miRNA microarray. Targets and references samples were co-hybridized to a microarray containing whole human mature and precursor miRNA sequences. Whereas three miRNAs exhibited higher expression in the HCC samples than that in the NT samples, five miRNAs demonstrated lower expression in the HCC samples than in the NT samples (Po0.0001). Classification of samples as HCC or NT by using support vector machine algorithms based on these data provided an overall prediction accuracy of 97.8% (45/46). In addition, the expression levels of four miRNAs were inversely correlated with the degree of HCC differentiation (Po0.01). A comparison of CH and liver cirrhosis samples revealed significantly different pattern of miRNA expression (Po0.01). There were no differences, however, between hepatitis B-positive and hepatitis C-positive samples. This information may help clarify the molecular mechanisms involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

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The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.

Background and Aim: The Child-Pugh classification has some non-objective factors, with chronic hepatitis indistinguishable from early liver cirrhosis in Child-Pugh A. We retrospectively evaluated the efficacy of albumin-bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for grading hepatocellular carcinoma (HCC) patients based on hepatic function and predicting their prognosis. Method: From 2000 to 2014, 2584 naïve HCC [69.0 ± 9.8 years old, 1850 men, 734 female, Child-Pugh class A:B:C = 1871:558:155] were enrolled. TNM staging was determined using the classification of the Liver Cancer Study Group of Japan and ALBI grade, instead of Child-Pugh classification (ALBI with TNM score: ALBI-T score) (Table 1), and is similar to the Japan Integrated Staging (JIS) score. We retrospectively compared ALBI-T and JIS scores in these patients. Results: Of patients classified as Child-Pugh A (n = 1871), 1285 with 5 points were divided into 858 with ALBI grade 1 and 427 with grade 2, while 586 with 6 points were divided into 53 with grade 1 and 533 with grade 2. The ratio of ALBI grade 2 patients with a Child-Pugh score of 6 points (91.0%) was similar to that of those with 7 points (91.8%). Patients with a lower ALBI-T score (0-5 points) showed a better median survival time than those with a corresponding lower JIS score [137.7:83.2:53.4:27.4:5.0:1.4 vs 97.6:74.9:39.7:15.0:4.0:1.0 months]. Conclusion: Albumin-bilirubin grade was found to be superior for distinguishing patients with better hepatic function. ALBI-T scoring may be a better total prognostic scoring system for predicting survival of Japanese patients with HCC.