Hepatocellular Carcinoma

Key clinical point: Consider testing for hepatitis D virus in patients receiving nucleoside/nucleotide analogues (NA) for chronic hepatitis B virus infection (HBV).

Major finding: Prevalences of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. Five-year cumulative rates of hepatocellular carcinoma (HCC) were 22.2% among patients with detectable HDV RNA vs 7.3% among patients with undetectable HDV RNA (P = .01).

Study details: This was a single-center retrospective study of 1,349 patients receiving NA for chronic HBV.

Disclosures: The Center for Liquid Biopsy, Center for Cancer Research, Cohort Research Center, Kaohsiung Medical University, and Kaohsiung Medical University Hospital provided funding. Two coinvestigators disclosed ties to Abbott, BMS, Gilead, Merck, AbbVie, Roche, and IPSEN. The other investigators reported having no conflicts of interest.

Source: Jang T-Y et al. Sci Rep. 2021 Apr 14. doi: 10.1038/s41598-021-87679-w

Key clinical point: Consider testing for hepatitis D virus in patients receiving nucleoside/nucleotide analogues (NA) for chronic hepatitis B virus infection (HBV).

Major finding: Prevalences of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. Five-year cumulative rates of hepatocellular carcinoma (HCC) were 22.2% among patients with detectable HDV RNA vs 7.3% among patients with undetectable HDV RNA (P = .01).

Study details: This was a single-center retrospective study of 1,349 patients receiving NA for chronic HBV.

Disclosures: The Center for Liquid Biopsy, Center for Cancer Research, Cohort Research Center, Kaohsiung Medical University, and Kaohsiung Medical University Hospital provided funding. Two coinvestigators disclosed ties to Abbott, BMS, Gilead, Merck, AbbVie, Roche, and IPSEN. The other investigators reported having no conflicts of interest.

Source: Jang T-Y et al. Sci Rep. 2021 Apr 14. doi: 10.1038/s41598-021-87679-w

Key clinical point: Consider testing for hepatitis D virus in patients receiving nucleoside/nucleotide analogues (NA) for chronic hepatitis B virus infection (HBV).

Major finding: Prevalences of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. Five-year cumulative rates of hepatocellular carcinoma (HCC) were 22.2% among patients with detectable HDV RNA vs 7.3% among patients with undetectable HDV RNA (P = .01).

Study details: This was a single-center retrospective study of 1,349 patients receiving NA for chronic HBV.

Disclosures: The Center for Liquid Biopsy, Center for Cancer Research, Cohort Research Center, Kaohsiung Medical University, and Kaohsiung Medical University Hospital provided funding. Two coinvestigators disclosed ties to Abbott, BMS, Gilead, Merck, AbbVie, Roche, and IPSEN. The other investigators reported having no conflicts of interest.

Source: Jang T-Y et al. Sci Rep. 2021 Apr 14. doi: 10.1038/s41598-021-87679-w

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: Compared with lenvatinib alone, triple combination therapy with lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy appeared to demonstrate acceptable safety and improved survival in patients with advanced hepatocellular carcinoma (HCC).

Major finding: Median progression-free survival was 11.1 months with triple combination therapy vs 5.1 months with lenvatinib alone (hazard ratio, 0.48; P less than .001). Compared with lenvatinib alone, triple combination therapy was associated with a significantly higher rate of grade 3-4 neutropenia, thrombocytopenia, and nausea.

Study details: Findings come from a retrospective study of 157 patients with unresectable HCC, of whom 86 received lenvatinib and 71 received lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy with FOLFAX (oxaliplatin, leucovorin, and 5-fluorouracil).

Disclosures: The study was funded by the National Key R&D Program of China, National Natural Science Foundation of China, and National Science and Technology Major Project of China. The researchers reported having no conflicts of interest.

Source:  He M-K et al. Ther Adv Med Oncol. 2021 Mar 25. doi: 10.1177/17588359211002720

Key clinical point: Compared with lenvatinib alone, triple combination therapy with lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy appeared to demonstrate acceptable safety and improved survival in patients with advanced hepatocellular carcinoma (HCC).

Major finding: Median progression-free survival was 11.1 months with triple combination therapy vs 5.1 months with lenvatinib alone (hazard ratio, 0.48; P less than .001). Compared with lenvatinib alone, triple combination therapy was associated with a significantly higher rate of grade 3-4 neutropenia, thrombocytopenia, and nausea.

Study details: Findings come from a retrospective study of 157 patients with unresectable HCC, of whom 86 received lenvatinib and 71 received lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy with FOLFAX (oxaliplatin, leucovorin, and 5-fluorouracil).

Disclosures: The study was funded by the National Key R&D Program of China, National Natural Science Foundation of China, and National Science and Technology Major Project of China. The researchers reported having no conflicts of interest.

Source:  He M-K et al. Ther Adv Med Oncol. 2021 Mar 25. doi: 10.1177/17588359211002720

Key clinical point: Compared with lenvatinib alone, triple combination therapy with lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy appeared to demonstrate acceptable safety and improved survival in patients with advanced hepatocellular carcinoma (HCC).

Major finding: Median progression-free survival was 11.1 months with triple combination therapy vs 5.1 months with lenvatinib alone (hazard ratio, 0.48; P less than .001). Compared with lenvatinib alone, triple combination therapy was associated with a significantly higher rate of grade 3-4 neutropenia, thrombocytopenia, and nausea.

Study details: Findings come from a retrospective study of 157 patients with unresectable HCC, of whom 86 received lenvatinib and 71 received lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy with FOLFAX (oxaliplatin, leucovorin, and 5-fluorouracil).

Disclosures: The study was funded by the National Key R&D Program of China, National Natural Science Foundation of China, and National Science and Technology Major Project of China. The researchers reported having no conflicts of interest.

Source:  He M-K et al. Ther Adv Med Oncol. 2021 Mar 25. doi: 10.1177/17588359211002720

Key clinical point: Among patients receiving liver transplantation for hepatocellular carcinoma (HCC), acute rejection conferred a significantly greater likelihood of HCC recurrence.

Major finding: HCC recurred in 28.6% of patients with acute rejections (defined as occurring within 20 months after transplant) vs 13.0% of patients without acute rejections (P = .002). Acute rejection remained a significant risk factor for recurrence in multivariable analysis (hazard ratio, 2.91).

Study details: Findings come from a retrospective study of 252 patients undergoing liver transplantation for HCC, of whom 91 had histopathologically confirmed acute rejections and 47 had HCC recurrence.

Disclosures: The researchers reported receiving funding for open access publications but no other financial support. The senior author disclosed ties to Merck Serono, Bayer AG, ERBE Elektromedizin, Amgen Inc, Johnson & Johnson, Takeda, Olympus K.K., Medtronic GmbH, and Intuitive Surg. Inc. The other researchers reported having no conflicts.

Source: Gül-Klein S et al. J Hepatocell Carcinoma. 2021 Mar 18. doi: 10.2147/JHC.S292010

Key clinical point: Among patients receiving liver transplantation for hepatocellular carcinoma (HCC), acute rejection conferred a significantly greater likelihood of HCC recurrence.

Major finding: HCC recurred in 28.6% of patients with acute rejections (defined as occurring within 20 months after transplant) vs 13.0% of patients without acute rejections (P = .002). Acute rejection remained a significant risk factor for recurrence in multivariable analysis (hazard ratio, 2.91).

Study details: Findings come from a retrospective study of 252 patients undergoing liver transplantation for HCC, of whom 91 had histopathologically confirmed acute rejections and 47 had HCC recurrence.

Disclosures: The researchers reported receiving funding for open access publications but no other financial support. The senior author disclosed ties to Merck Serono, Bayer AG, ERBE Elektromedizin, Amgen Inc, Johnson & Johnson, Takeda, Olympus K.K., Medtronic GmbH, and Intuitive Surg. Inc. The other researchers reported having no conflicts.

Source: Gül-Klein S et al. J Hepatocell Carcinoma. 2021 Mar 18. doi: 10.2147/JHC.S292010

Key clinical point: Among patients receiving liver transplantation for hepatocellular carcinoma (HCC), acute rejection conferred a significantly greater likelihood of HCC recurrence.

Major finding: HCC recurred in 28.6% of patients with acute rejections (defined as occurring within 20 months after transplant) vs 13.0% of patients without acute rejections (P = .002). Acute rejection remained a significant risk factor for recurrence in multivariable analysis (hazard ratio, 2.91).

Study details: Findings come from a retrospective study of 252 patients undergoing liver transplantation for HCC, of whom 91 had histopathologically confirmed acute rejections and 47 had HCC recurrence.

Disclosures: The researchers reported receiving funding for open access publications but no other financial support. The senior author disclosed ties to Merck Serono, Bayer AG, ERBE Elektromedizin, Amgen Inc, Johnson & Johnson, Takeda, Olympus K.K., Medtronic GmbH, and Intuitive Surg. Inc. The other researchers reported having no conflicts.

Source: Gül-Klein S et al. J Hepatocell Carcinoma. 2021 Mar 18. doi: 10.2147/JHC.S292010

Key clinical point: High serum levels of angiopoietin 2 (Ang2) levels identified patients with hepatocellular carcinoma (HCC) and predicted a shorter time to recurrence after treatment with curative intent.

Major finding: Serum Ang2 levels were significantly higher in patients with HCC vs controls (P less than .001) and patients with chronic liver disease (P less than .001). At the optimal threshold (3.5 ng/mL), sensitivity, specificity, and accuracy were 51%, 84%, and 59.5%, respectively. Higher serum Ang2 levels correlated with significantly shorter recurrence-free survival after ablation therapy, even after controlling for other prognostic factors.

Study details: The researchers reviewed medical charts and used sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ang2 levels in stored serum from 275 patients with HCC, 98 patients with chronic liver disease, and 20 controls.

Disclosures: Partial funding came from the Japan Society for the Promotion of Science and the Program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development. The researchers reported having no conflicts of interest.

Source: J Ao et al. J Cancer. 2021 Mar 5. doi: 10.7150/jca.56436

Key clinical point: High serum levels of angiopoietin 2 (Ang2) levels identified patients with hepatocellular carcinoma (HCC) and predicted a shorter time to recurrence after treatment with curative intent.

Major finding: Serum Ang2 levels were significantly higher in patients with HCC vs controls (P less than .001) and patients with chronic liver disease (P less than .001). At the optimal threshold (3.5 ng/mL), sensitivity, specificity, and accuracy were 51%, 84%, and 59.5%, respectively. Higher serum Ang2 levels correlated with significantly shorter recurrence-free survival after ablation therapy, even after controlling for other prognostic factors.

Study details: The researchers reviewed medical charts and used sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ang2 levels in stored serum from 275 patients with HCC, 98 patients with chronic liver disease, and 20 controls.

Disclosures: Partial funding came from the Japan Society for the Promotion of Science and the Program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development. The researchers reported having no conflicts of interest.

Source: J Ao et al. J Cancer. 2021 Mar 5. doi: 10.7150/jca.56436

Key clinical point: High serum levels of angiopoietin 2 (Ang2) levels identified patients with hepatocellular carcinoma (HCC) and predicted a shorter time to recurrence after treatment with curative intent.

Major finding: Serum Ang2 levels were significantly higher in patients with HCC vs controls (P less than .001) and patients with chronic liver disease (P less than .001). At the optimal threshold (3.5 ng/mL), sensitivity, specificity, and accuracy were 51%, 84%, and 59.5%, respectively. Higher serum Ang2 levels correlated with significantly shorter recurrence-free survival after ablation therapy, even after controlling for other prognostic factors.

Study details: The researchers reviewed medical charts and used sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ang2 levels in stored serum from 275 patients with HCC, 98 patients with chronic liver disease, and 20 controls.

Disclosures: Partial funding came from the Japan Society for the Promotion of Science and the Program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development. The researchers reported having no conflicts of interest.

Source: J Ao et al. J Cancer. 2021 Mar 5. doi: 10.7150/jca.56436

Key clinical point: Among patients with hepatocellular carcinoma, overexpression of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC) was linked to more aggressive disease and worse survival.

Major finding: PIGC mRNA was overexpressed in cancerous vs normal liver (P less than .0001). Among patients with liver cancer, higher PIGC expression correlated with worse overall survival (37.8 vs 71.0 months; hazard ratio [HR], 1.7, P = .003) and disease-free survival (48.4 vs 68.6 months; HR, 1.5, P = .007), and with higher tumor grade and stage, lymphatic metastasis, and TP53 mutation. In addition, liver cancer cell migration and proliferation were significantly higher in PIGC-upregulated cells, and significantly lower in PIGC-silenced cells. The PIGC mutation rate was 10%; PIGC mutation was significantly associated with higher T and M stages.

Study details: The researchers searched and analyzed bioinformatic databases and websites, such as UALCAN and cBioPortal , and performed Western blot, transwell migration assays, CCK-8 assays, and flow cytometry of cancerous and normal liver cells.

Disclosures: The Fundamental Research Funds of Wuhan University provided funding. The investigators reported having no conflicts of interest.

Source: Guo X et al. J Hepatocell Carcinoma. 2021 Apr 6. doi: 10.2147/JHC.S297601.
 

Key clinical point: Among patients with hepatocellular carcinoma, overexpression of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC) was linked to more aggressive disease and worse survival.

Major finding: PIGC mRNA was overexpressed in cancerous vs normal liver (P less than .0001). Among patients with liver cancer, higher PIGC expression correlated with worse overall survival (37.8 vs 71.0 months; hazard ratio [HR], 1.7, P = .003) and disease-free survival (48.4 vs 68.6 months; HR, 1.5, P = .007), and with higher tumor grade and stage, lymphatic metastasis, and TP53 mutation. In addition, liver cancer cell migration and proliferation were significantly higher in PIGC-upregulated cells, and significantly lower in PIGC-silenced cells. The PIGC mutation rate was 10%; PIGC mutation was significantly associated with higher T and M stages.

Study details: The researchers searched and analyzed bioinformatic databases and websites, such as UALCAN and cBioPortal , and performed Western blot, transwell migration assays, CCK-8 assays, and flow cytometry of cancerous and normal liver cells.

Disclosures: The Fundamental Research Funds of Wuhan University provided funding. The investigators reported having no conflicts of interest.

Source: Guo X et al. J Hepatocell Carcinoma. 2021 Apr 6. doi: 10.2147/JHC.S297601.
 

Key clinical point: Among patients with hepatocellular carcinoma, overexpression of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC) was linked to more aggressive disease and worse survival.

Major finding: PIGC mRNA was overexpressed in cancerous vs normal liver (P less than .0001). Among patients with liver cancer, higher PIGC expression correlated with worse overall survival (37.8 vs 71.0 months; hazard ratio [HR], 1.7, P = .003) and disease-free survival (48.4 vs 68.6 months; HR, 1.5, P = .007), and with higher tumor grade and stage, lymphatic metastasis, and TP53 mutation. In addition, liver cancer cell migration and proliferation were significantly higher in PIGC-upregulated cells, and significantly lower in PIGC-silenced cells. The PIGC mutation rate was 10%; PIGC mutation was significantly associated with higher T and M stages.

Study details: The researchers searched and analyzed bioinformatic databases and websites, such as UALCAN and cBioPortal , and performed Western blot, transwell migration assays, CCK-8 assays, and flow cytometry of cancerous and normal liver cells.

Disclosures: The Fundamental Research Funds of Wuhan University provided funding. The investigators reported having no conflicts of interest.

Source: Guo X et al. J Hepatocell Carcinoma. 2021 Apr 6. doi: 10.2147/JHC.S297601.
 

The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.

Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.

The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.

Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.

The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.

Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.