non-C Hepatocellular Carcinoma Research Articles

Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.

Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC). To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial. A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group). Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a. Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.

Comparative analysis of liver resection in Non-B Non-C and hepatitis virus-associated hepatocellular carcinoma

BackgroundThe incidence of non-hepatitis B and non-hepatitis C hepatocellular carcinoma (NBNC-HCC) is increasing in our country. This study assesses the feasibility of employing an identical surgical treatment strategy for resectable NBNC-HCC as that for hepatitis virus-associated HCC (HV-HCC). MethodsA retrospective analysis (1993–2023) of 1321 curative liver resections for HCC at a single institution was performed. Propensity score matching ensured a balanced comparison of preoperative clinical factors, including tumor status and background liver condition. ResultsThe proportion of NBNC-HCC cases has gradually increased, reaching up to 70 %. After matching, 294 of 473 NBNC-HCC patients and 294 of 848 HV-HCC patients were compared. Operative outcomes, including operation time, blood loss, type of surgical procedure, and morbidity, were comparable. Long-term outcome analysis showed similar recurrence-free survival (HR: 0.86, 95 % CI: 0.70–1.06, P = 0.167) and overall survival (HR: 0.98, 95 % CI: 0.79–1.23, P = 0.865) for NBNC-HCC. Multivariable analysis identified ICGR15 ≥ 15 %, ALBI grade 2 or 3, aspartate aminotransferase ≥40, tumor size > 5 cm, multiple tumors, macrovascular invasion, and microvascular invasion as independent prognostic factors for overall survival, while hepatitis B or C virus status lost significance. ConclusionsDespite the increasing incidence of NBNC-HCC, comparable outcomes were achieved between the two groups of matched cohort.

Impact of MAFLD criteria on postoperative recurrence of non-B, non-C HCC.

This study aimed to clarify the population in whom the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) especially contributes to recurrence after liver resection for non-B, non-C hepatocellular carcinoma (NBNC-HCC). Of the 199 patients who underwent liver resection for NBNC-HCC, those who exceeded Milan criteria and with pathologically proven vascular invasion, intrahepatic metastasis, and positive resection margins were excluded, and the remaining 94 were eligible for this study. We explored factors contributing to postoperative recurrence in populations with and without advanced liver fibrosis. Independent factors contributing to postoperative recurrence in the study population were male sex ( P = 0.023) and presence of type 2 diabetes (DM) ( P = 0.006) and advanced liver fibrosis ( P < 0.001). Factors in cases with advanced liver fibrosis (n = 43) were non-overweight ( P = 0.02), type 2 DM ( P = 0.006), and preoperative alpha-fetoprotein level of 8.2 ng/ml or higher ( P = 0.021). In cases without advanced liver fibrosis (n = 51), only presence of all three MAFLD criteria was related to recurrence. Liver fibrosis is a strong factor contributing to postoperative recurrence of NBNC-HCC, as previously reported. In patients with advanced liver fibrosis, presence of type 2 DM was the only factor associated with recurrence among MAFLD criteria. On the other hand, in patients without advanced liver fibrosis, the combination of all MAFLD criteria, rather than a specific criterion alone, contributed to recurrence. MAFLD criteria were found to have utility as predictors of postoperative recurrence in NBNC-HCC.

Monocyte-to-High-Density Lipoprotein-Cholesterol Ratio Predicts Prognosis of Hepatocellular Carcinoma in Patients with Metabolic-Associated Fatty Liver Disease.

The incidence of non-B and non-C hepatocellular carcinoma (NBNC-HCC) is increasing globally. Metabolically associated fatty liver disease (MAFLD) has been a contributing factor to this rising trend in NBNC-HCC incidence. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) is a new prognostic marker that connects systemic inflammation with disorders of lipid metabolism. Therefore, MHR may be a potential prognostic predictor of patients with MAFLD-related HCC (MAFLD-HCC). This study aims to investigate the relationship between the MHR and prognosis of patients with MAFLD-HCC and construct a novel prognostic prediction tool for MAFLD-HCC. This retrospective study of patients with MAFLD-HCC included training (n = 112) and internal validation (n = 37) cohorts. Univariate and multivariate Cox proportional hazard regression analysis was conducted to identify independent risk factors of survival. A visual nomogram was constructed to assess the performance of the two groups. Furthermore, receiver operating characteristic (ROC) curves and calibration curves were used to verify the prognostic discriminative ability of this nomogram, even in the MHR, ALBI grade, and MHR-ALBI model. Univariate and multivariate analyses revealed that extrahepatic metastases, Vascular invasion, Barcelona staging B, C, D, elevated ALBI Grade 3, C-reactive protein (CRP), and MHR were independent risk factors for the prognosis of MAFLD-HCC. Moreover, calibration plots showed good discrimination and consistency when the significant factors were entered into the nomogram. Meanwhile, the MHR strongly correlated with the prognosis of cancer under a background of MAFLD-HCC, with a sensitivity of 88.89% and a specificity of 79.61%. Importantly, the performance of the MHR alone (AUC = 86.2) was not only superior to the ALBI grade (AUC = 63.8) but was comparable to the combination of MHR and ALBI (AUC = 88.5). The novel nomogram demonstrated good value in predicting the overall survival of patients with MAFLD-HCC. The MHR may be a potential predictor of prognosis.

The diagnostic performance of AFP and PIVKA-II models for non-B non-C hepatocellular carcinoma

ObjectiveThis study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC).ResultsA total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785–0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725–0.791) and 0.866 (95%CI: 0.836–0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients’ age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872–0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1–85.4) and 83.2% (95%CI: 78.9–86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.

Report of the 23rd nationwide follow-up survey of primary liver cancer in Japan (2014-2015).

For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20889 newly registered patients and 42274 previously registered follow-up patients were compiled from 516 institutions over a 2-year period from January 1, 2014 to December 31, 2015. Basic statistics compiled for patients newly registered in the 23rd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 22nd survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2004 and 2015 whose final outcome was survival or death. The median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, Child-Pugh grade, or albumin-bilirubin grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2015 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world.

Comparison of clinicopathologic characteristics among patients with HBV-positive, HCV-positive and Non-B Non-C hepatocellular carcinoma after hepatectomy: a systematic review and meta-analysis

BackgroundThe incidence of HBV-negative and HCV-negative hepatocellular carcinoma (NBNC-HCC) is significantly increasing. However, their clinicopathologic features and prognosis remain elucidated. Our study aimed to compare the clinicopathologic characteristics and survival outcomes of NBNC-HCC with hepatitis virus-related HCC.MethodA literature review was performed in several databases, including PubMed, Embase, Cochrane Library and Web of Science, to identify the studies comparing NBNC-HCC with HBV-positive HCV-negative HCC (B-HCC), HBV-negative HCV-positive (C-HCC) and/or HBV-positive HCV-positive HCC (BC-HCC). The clinicopathologic characteristics and survival outcomes were extracted and pooled to access the difference.ResultsThirty-two studies with 26,297 patients were included: 5390 patients in NBNC-HCC group, 9873 patients in B-HCC group, 10,848 patients in C-HCC group and 186 patients in BC-HCC group. Patients in NBNC-HCC group were more liable to be diagnosed at higher ages, but with better liver functions and lighter liver cirrhosis. Comparing to B-HCC and C-HCC groups, although NBNC-HCC group was prone to have larger tumor sizes, it did not have more advanced tumors. Meanwhile, there were no significant differences in both 5-year and 10-year disease-free survival and overall survival between NBNC-HCC group and B-HCC or C-HCC group.ConclusionsOur meta-analysis revealed patients with NBNC-HCC had as worse prognosis as those with hepatitis virus-related HCC. More attention should be paid on patients with non-alcoholic steatohepatitis or metabolic syndromes to prevent the incidence of NBNC-HCC.

Treatment outcomes after radiofrequency ablation in patients with non-B non-C hepatocellular carcinoma within Milan criteria: comparison with HBV-related hepatocellular carcinoma

Purpose This study aims to evaluate the treatment outcomes of radiofrequency ablation (RFA) for patients with non-B non-C hepatocellular carcinoma (HCC) (NBNC-HCC) within Milan criteria, as well as to compare them with those of patients with hepatitis B virus (HBV)-related HCC (HBV-HCC). Methods From January 2007 to February 2020, 303 patients with primary HCC who underwent RFA were retrospectively reviewed, including 259 patients with HBV-HCC (HBV-HCC group) and 44 patients with NBNC-HCC (NBNC-HCC group). The clinical characteristics and treatment survivals were evaluated and compared. Moreover, the propensity score matching was used to reduce selection bias. Results A significantly lower proportion of cirrhosis was observed in the NBNC-HCC group (p = .048). Before propensity score matching, local tumor progression, disease-free survival, and overall survival after RFA showed no significant differences between the two groups (all p > .05). After matching, the overall survival rates in the NBNC-HCC group were significantly better than those in the HBV-HCC group (p = .042). Moreover, for patients with NBNC-HCC, tumor size (hazard ratio = 8.749, 95% confidence interval, 1.599–47.849; p = .012) was the only independent predictor of local tumor progression. Conclusions Patients with NBNC-HCC within the Milan criteria after RFA had better long-term survival than patients with HBV-HCC, although larger, prospective and multicenter trials are required to validate these results.

Prognostication algorithm for non-cirrhotic non-B non-C hepatocellular carcinoma-a multicenter study under the aegis of the French Association of Hepato-Biliary Surgery and liver Transplantation.

Liver resection and local ablation are the only curative treatment for non-cirrhotic hepatocellular carcinoma (HCC). Few data exist concerning the prognosis of patients resected for non-cirrhotic HCC. The objectives of this study were to determine the prognostic factors of recurrence-free survival (RFS) and overall survival (OS) and to develop a prognostication algorithm for non-cirrhotic HCC. French multicenter retrospective study including HCC patients with non-cirrhotic liver without underlying viral hepatitis: F0, F1 or F2 fibrosis. A total of 467 patients were included in 11 centers from 2010 to 2018. Non-cirrhotic liver had a fibrosis score of F0 (n=237, 50.7%), F1 (n=127, 27.2%) or F2 (n=103, 22.1%). OS and RFS at 5 years were 59.2% and 34.5%, respectively. In multivariate analysis, microvascular invasion and HCC differentiation were prognostic factors of OS and RFS and the number and size were prognostic factors of RFS (P<0.005). Stratification based on RFS provided an algorithm based on size (P=0.013) and number (P<0.001): 2 HCC with the largest nodule ≤10 cm (n=271, Group 1); 2 HCC with a nodule >10 cm (n=176, Group 2); >2 HCC regardless of size (n=20, Group 3). The 5-year RFS rates were 52.7% (Group 1), 30.1% (Group 2) and 5% (Group 3). We developed a prognostication algorithm based on the number (≤ or >2) and size (≤ or >10 cm), which could be used as a treatment decision support concerning the need for perioperative therapy. In case of bifocal HCC, surgery should not be a contraindication.

Prognostication Algorithm for Non-cirrhotic Non-B Non-C Hepatocellular Carcinoma - A Multicenter Study under the Aegis of the French Association ACHBT

Prognostication Algorithm for Non-cirrhotic Non-B Non-C Hepatocellular Carcinoma - A Multicenter Study under the Aegis of the French Association ACHBT

Comparison of effectiveness and safety of camrelizumab between HBV-related and non-B, non-C hepatocellular carcinoma: A retrospective study in China.

Purpose: This study aimed to compare the clinical outcomes of camrelizumab in hepatitis B virus-related hepatocellular carcinoma (HBV–HCC) patients and non-HBV, non-HCV hepatocellular carcinoma (NBNC–HCC) patients in China. Materials and methods: A total of 54 patients with hepatocellular carcinoma who received camrelizumab were included in this retrospective study from January 2019 to December 2021. The patients were assigned to the HBV–HCC group (n = 28) and the NBNC–HCC group (n = 26). The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Multivariate analysis using Cox proportional hazard regression was used to identify independent prognostic factors. A nomogram model was subsequently established based on independent prognostic factors. Results: The mean duration of follow-up was 12.7 ± 3.6 months. The median OS was not determined. The median PFS in the HBV–HCC group was significantly longer than that in the NBNC–HCC group (9.2 vs. 6.7 months, p = 0.003). The ORR and DCR in the HBV–HCC group were significantly higher than those in the NBNC–HCC group (ORR, 28.6% vs. 7.7%, p = 0.048; DCR, 71.4% vs. 42.3%, p = 0.031). No significant differences in the total incidence of AEs were found between the HBV–HCC group and the NBNC–HCC group (75.0% vs. 69.2%, p = 0.224). Multivariate regression analysis identified etiology, AFP level, and vascular invasion as independent prognostic factors (all p < 0.05). Conclusion: Our findings demonstrate that camrelizumab is more effective in HBV–HCC patients than in NBNC–HCC patients, with manageable safety.

Current status of liver transplantation for non-B non-C liver cirrhosis and hepatocellular carcinoma.

Recently, non-B non-C chronic liver diseases, including alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), have markedly increased worldwide. Liver transplantation (LT) is an effective curative therapy for hepatocellular carcinoma (HCC) as well as decompensated liver cirrhosis. In Japan, where the source of liver grafts is strongly dependent on living donors, efforts have been made to unify the indications for eligibility of HCC patients for LT, leading to the development of 5-5-500 criteria. Along with the expansion of eligibility for LT, the current changing trends in underlying liver diseases of LT recipients, which are related to the rising tide of non-B non-C cirrhosis and HCC, are highlighting the importance of peri-transplant management of patients with various comorbidities. The post-LT prognosis of patients with ALD is significantly affected by de novo malignancies and metabolic syndrome-related complications as well as posttransplant alcohol relapse. NAFLD/NASH patients often suffer from obesity, type 2 diabetes mellitus, and other metabolic syndrome-related disorders, and nonneoplastic factors such as cardiovascular events and recurrence of NAFLD/NASH have a significant impact on post-LT outcomes. Patient management in the peri-transplant period as well as risk assessment for LT are key to improving post-LT outcomes in the era of a growing number of cases of LT for non-B non-C liver diseases.

Non-B, Non-C Hepatocellular Carcinoma in an HBV- and HCV-Endemic Area: A Community-Based Prospective Longitudinal Study.

A large community cohort of adults who participated in a health screening program from 2003 to 2013 were prospectively analyzed for the risk factors of non-B, non-C (NBNC) hepatocellular carcinoma (HCC). The serostatus of hepatitis B and C of 52,642 participants was linked to the mortality and cancer registration data of the Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan. During a median follow-up of 6 years, 35 of the 43,545 participants who were negative for both HBsAg and anti-HCV antibody developed HCC. Multivariate Cox regression analysis revealed that old age (hazard ratio, 95% CI: 1.058, 1.019–1.098, p = 0.003); male sex (2.446, 1.200–4.985, p = 0.014); high aspartate aminotransferase levels (6.816, 2.945–15.779, p < 0.001); fibrosis index based on four factor score (1.262, 1.154–1.381, p < 0.001); blood sugar (1.009, 1.002–1.015, p = 0.006); and alpha-fetoprotein ≥15 ng/mL (143.938, 43.094–480.760, p < 0.001) were independent risk factors for HCC. By contrast, triglyceride >150 mg/dL was associated with a decreased risk of HCC (0.216, 0.074–0.625, p = 0.005). This prospective community-based study provided insights into the potential HCC risk factors which may shed some light in HCC prevention and screening.

Metabolic Risks Are Increasing in Non-B Non-C Early-Stage Hepatocellular Carcinoma: A 10-Year Follow-Up Study.

BackgroundNon-B, non-C hepatocellular carcinoma (NBNC-HCC) may be related to metabolic syndrome, and the incidence of this tumor type is increasing annually. The definition of metabolic-associated fatty liver disease (MAFLD) proposed in 2020 may help to more accuratelyassess the association between metabolic syndrome and NBNC-HCC. However, this new concept has not yet been applied in NBNC-HCC research. Therefore, this study aimed to compare the clinicopathological characteristics of patients with NBNC-HCC and CHB-HCC diagnosed between 2009-13 and 2014-18, focusing on metabolic risk factors and the new concept of MAFLD.MethodPatients with BCLC-0/A-HCC who received curative hepatectomy between January 2009 and December 2018 were retrospectively assessed; the associations between clinicopathological characteristics and clinical outcomes of NBNC-HCC and CHB-HCC were analyzed by multivariate analysis.ResultCompared to patients diagnosed in 2009-13, the frequency of metabolic disorders in NBNC-HCC was significantly higher in 2014-18 [DM (p=0.049), HTN (p=0.004), BMI (p=0.017) and MAFLD (p=0.003)]; there was no significant change in patients with CHB-HCC. Moreover, CHB-HCC was an independent risk factor for HCC recurrence (HR, 1.339; 95% CI, 1.010-1.775, p=0.043) and death (HR, 1.700; 95% CI, 1.017-2.842, p=0.043) compared to NBNC-HCC.ConclusionsTherisk of MAFLD, obesity, DM, and hypertension in patients with early-stage NBNC have significantly increased in recent years, thus metabolic syndrome should be monitored in this special population. Moreover, NBNC-HCC tend to had a better prognosis than CHB-HCC, probably due to their distinct clinicopathological features.

Report of the 22nd nationwide follow-up Survey of Primary Liver Cancer in Japan (2012-2013).

In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 155 newly registered patients and 43 041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from January 1, 2012 to December 31, 2013. Basic statistics compiled for patients newly registered in the 22nd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathologic diagnosis, recurrence status and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, more patients with non-B non-C HCC, smaller tumor diameter and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer worldwide.

Clinicopathological Analysis of Non-B Non-C Hepatocellular Carcinoma Focusing on Cellular Proliferation.

Non-B non-C hepatocellular carcinomas (NBNC-HCCs) are larger than hepatitis virus-related HCCs. We conducted a clinicopathological study of patients who underwent curative NBNC-HCC resection, including proliferative activity assessments, such as nuclear grade and Ki-67 labelling index (LI). Histopathological findings of 197 patients were examined, including 56 NBNC-HCCs, 45 hepatitis B virus (HBV)-related HCCs (HBV-HCC), and 96 hepatitis C virus (HCV)-related HCCs (HCV-HCC). NBNC-HCCs were significantly larger than HCV-HCCs, but not significantly different from HBV-HCCs. Mitotic counts, nuclear grade, and Ki-67 LI of NBNC-HCCs were not significantly different from those of HCV-HCCs, but were significantly lower than those of HBV-HCCs. Recurrence-free survival was significantly better in the NBNC-HCC group than in the HBV-HCC group in cases with mild liver fibrosis. NBNC-HCCs were significantly larger in diameter, but their nuclear grade or Ki-67 LI were not significantly different from those of other HCCs, suggesting that they do not have a higher proliferative activity.

MAFLD enhances clinical practice for liver disease in the Asia-Pacific region.

Fatty liver is now a major cause of liver disease in the Asia-Pacific region. Liver diseases in this region have distinctive characteristics. First, fatty liver is frequently observed in lean/normal-weight individuals. However, there is no standard definition of this unique phenotype. Second, fatty liver is often observed in patients with concomitant viral hepatitis. The exclusion of viral hepatitis from non-alcoholic fatty liver disease limits its value and detracts from the investigation and holistic management of coexisting fatty liver in patients with viral hepatitis. Third, fatty liver-associated hepatocellular carcinoma (HCC) is generally categorized as non-B non-C HCC. Fourth, the population is aging rapidly, and it is imperative to develop a practicable, low-intensity exercise program for elderly patients. Fifth, most patients and non-specialized healthcare professionals still lack an awareness of the significance of fatty liver both in terms of intrahepatic and extrahepatic disease and cancer. Recently, an international expert panel proposed a new definition of fatty liver: metabolic dysfunction-associated fatty liver disease (MAFLD). One feature of MAFLD is that metabolic dysfunction is a prerequisite for diagnosis. Pertinent to regional issues, MAFLD also provides its diagnostic criteria in lean/normal-weight individuals. Furthermore, MAFLD is independent of any concomitant liver disease, including viral hepatitis. Therefore, MAFLD may be a more suitable definition for fatty liver in the Asia-Pacific region. In this review, we introduce the regional characteristics of fatty liver and discuss the advantages of MAFLD for improving clinical practice for liver disease in the region.

Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing primary curative resection

BackgroundThe albumin–bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery.AimThis study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection.MethodFrom January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis.ResultsThere were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child–Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS.ConclusionThe preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.

Increased Visceral Adipose Tissue and Hyperinsulinemia Raise the Risk for Recurrence of Non-B Non-C Hepatocellular Carcinoma after Curative Treatment.

Simple SummaryWith the increasing prevalence of obesity and diabetes in most countries, the increase in hepatocellular carcinoma (HCC) associated with these factors has recently become a serious healthcare problem. HCC can often emerge in the non-cirrhotic liver among obese patients, and it might suggest that the conventional surveillance strategies for HCC, which is mainly targeted at cirrhotic patients with hepatitis B or C virus, might be insufficient in the overnutrition era. We tried to extract factors that affect recurrence-free survival in patients with non-viral HCC, among obesity and diabetes factors, together with the established recurrence risk factors, using a decision-tree analysis.We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors—visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm2/m2), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191–5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156–8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550–7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm2/m2) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm2/m2 are prone to recurrence after curative treatment.

Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011).

In the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 22,134 new patients and 41,956 previously followed patients were compiled from 546 institutions over a 2-year period from 1 January 2010 to 31 December 2011. Basic statistics compiled for patients newly registered in the 21st survey were cause of death, medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 20th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy and with radiofrequency ablation. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 1998 and 2011 whose final outcome was survival or death (excluding unknown). Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment type (hepatectomy, local ablation therapy, transcatheter arterial chemoembolization, and hepatic arterial infusion chemotherapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2011 into four time-period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer.