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.

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.

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.

We validated the performance of the GALAD and BALAD-2 models for the diagnosis of HCC and predicting patient survival, respectively (based on levels of the serum markers AFP, AFP-L3, and des-γ-carboxyprothrombin), in an international cohort of almost 7000 patients. These systems might be used in HCC surveillance and determination of patient prognosis.

Background/Aim: The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. Materials/Methods: We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, n = 2,357) and validation (validation group: V group, n = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. Results: In the E group, Akaike’s Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. Conclusion: The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.

Background:Application of curative therapy for hepatocellular carcinoma is crucially dependent on underlying liver function. Using the recently described ALBI grade we examined the long-term impact of liver dysfunction on survival of early-stage hepatocellular carcinoma (HCC) patients.Methods:This cohort study comprised 2559 HCC patients from different geographic regions, all treated with curative intent. We also examined the relation between indocyanine green (ICG) clearance and ALBI score. Survival was measured from the date of treatment to the date of death or last follow-up.Results:The ALBI score correlated well with ICG clearance. Among those undergoing surgical resection, patients with ALBI grade-1 (good liver function) survived approximately twice as long as those with ALBI grade-2 (less good liver function), although more than 90% of these patients were classified as Child–Pugh (C-P) grade A. In the cohort receiving ablative therapies, there was a similar difference in survival between ALBI grade-1 and grade-2. Cox regression analysis confirmed that the ALBI score along with age, gender, aetiology and tumour factors (AFP, tumour size/number and vascular invasion) independently influenced survival in HCC patients receiving curative treatments.Conclusions:The ALBI score represents a simple approach to the assessment of liver function in patients with HCC. After potentially curative therapy, those with ALBI grade-1 survived approximately twice as long as those with ALBI grade-2. These data suggest that ALBI grade-1 patients are appropriately treated with surgical resection whereas ALBI grade-2 patients may, where the option exists, be more suitable for liver transplantation or the less invasive curative ablative therapies.

Background/aim We assessed suitable factors indicating newly developed lenvatinib (LEN) treatment for unresectable hepatocellular carcinoma (u‐HCC) by investigating real‐world clinical features of patients. Materials/methods One hundred fifty two u‐HCC patients, who receive LEN treatment from March to December 2018, were enrolled. (Child‐Pugh score [CPS] 5/6/7/8 = 76/61/13/2, modified albumin‐bilirubin grade [mALBI] 1/2a/2b/3 = 53/35/60/4). Clinical features were evaluated retrospectively. Results Overall‐response rate (ORR)/disease control rate (DCR) at 1 month after starting LEN were 38.7%/86.0%, respectively. Estimated median time to progression (TTP) was 7.0 months, while median survival time was not reached within the observation period. CPS (≥7) and past history of tyrosine‐kinase inhibitor (TKI) were not significant prognostic factors. mALBI ≥2b was an only significant prognostic factor (HR 4.632, 95%CI 1.649‐13.02, P = 0.004) in Cox‐hazard multivariate analysis. In patients with Child‐Pugh A, c‐index/Akaike's information criterion (AIC) of prognostic predictive value of mALBI were superior to CPS (0.682/135.6 vs 0.652/138.7), while those of stopping LEN also showed that mALBI was better (0.575/447.3 vs 0.562/447.8). Additional analysis of patients with good mALBI (1/2a) revealed that time to stopping LEN was significantly shorter in those with the adverse event (AE) of appetite loss (any grade) than those without ( P = 0.006) and body mass index (BMI) was also lower in patients with that AE (20.3 ± 3.0 vs 23.6 ± 4.0kg/m 2 , P < 0.001), while patients with a hand‐foot skin reaction (any grade) showed good ORR/DCR (59.1%/86.4%) and longer TTP as compared to patients without ( P = 0.007). Conclusion Good hepatic function (mALBI 1/2a) is the best indication for LEN, while potential appetite loss in association with low BMI should be kept in mind in such cases.

Hypointense nodules with a maximum diameter of at least 15 mm often become hypervascular. Therefore, patients with hypointense nodules characterized by a maximum diameter of 15 mm or greater should be observed carefully because of the high incidence of vascularization.