Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes

Figures & data

Figure 1 The etiology of Liver cancer diagnosed as new cases based on GLOBOCAN 2020.Reproduced from GLOBOCAN 2020. Available from: https://gco.iarc.fr/.¹ East Asia includes China, Japan, Republic of Korea, Democratic People’s Republic of Korea, and Mongolia. North America includes USA and Canada. Western Europe includes Austria, Belgium, France, Germany, Luxembourg, Switzerland, and Netherlands.

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; ALD, alcohol-related liver disease.

Table 1 Summary of Latest Society Guidelines for Treatment of Chronic Hepatitis B

Guidelines	APASL 2015^Citation38	EASL 2017^Citation17	AASLD 2018^Citation16,Citation36	US Panel Algorithm 2021^Citation37
When to start treatment	ALT level > 2×ULN and HBV DNA level of >2000 IU/mL (HBeAg negative) or >20,000 IU/mL (HBeAg-positive) and/or moderate to severe inflammation or significant fibrosis Compensated cirrhosis with HBV DNA level of >2000 IU/mL or with HBV DNA detectable if elevated ALT Decompensated cirrhosis with detectable HBV DNA	HBV DNA level of >2000 IU/mL, ALT level > ULN^a, and/or at least moderate liver necroinflammation or fibrosis HBV DNA level of >20,000 IU/mL and ALT level > 2×ULN Compensated or decompensated cirrhosis with detectable HBV DNA HBeAg positive, high HBV DNA level, and age >30 yr Family history of HCC or cirrhosis and extrahepatic manifestations	ALT level > 2×ULN ^b and HBV DNA level of >2000 IU/mL (HBeAg negative) or >20,000 IU/mL (HBeAg positive) Compensated or decompensated cirrhosis with detectable HBV DNA Other factors include age >40 yr, family history of HCC, previous treatment, and presence of extrahepatic manifestations	ALT level > ULN ^c, HBV DNA level of >2000 IU/mL Normal ALT with significant fibrosis and detectable HBV DNA Compensated or decompensated cirrhosis with detectable HBV DNA

Notes: ^aThe ULN for ALT is 40 U/liter. ^bThe ULN for ALT in healthy adults is 35 U/liter for males and 25 U/liter for women. ^cThe ULN for ALT in healthy adults is 30 U/liter for males and 19 U/liter for females.

Abbreviations: ALT, alanine aminotransferase; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.

Figure 2 Sustained virologic response (SVR) rate with interferon-free direct-acting antivirals (DAAs) in hepatitis C patients with or without cirrhosis / HCC.

Abbreviations: SVR, Sustained virologic response; DAA, direct-acting antivirals; HCC, hepatocellular carcinoma; SVR, sustained viral response.^62–69

Table 2 Sustained Virologic Response (SVR) with Interferon-Free Direct-Acting Antivirals (DAAs) and Outcome in Patients with HCV-Related HCC Who Have Achieved SVR

Author/Publication Year	Country/Region	DAA-Treated HCC Patients (n)	SVR in HCC Patients	SVR in Patients with Active HCC	SVR in Patients with Inactive HCC	SVR in HCC Patients with LC			SVR in HCC Patients Without LC		5-Year Overall Survival
Beste et al 2017^Citation81	USA	482	74.4% †91.1% in the non-HCC group †94.0% in the HCC/LT group			73.0% †87.9% in non-HCC patients with LC			82.5% †92.4% in non-HCC patients without LC
Ji et al 2019^Citation68	15 countries from USA, Japan, Italy, Egypt, France, China, Spain, United Kingdom, Germany, Switzerland, Romania, Belgium, Australia, Canada, and Poland	2581 *Including active HCC patients (n=277) and inactive HCC patients (n=2304)	89.6% ^†93.3% in the non-HCC group (P=0.0012)	73.1%	92.6%
Ogawa et al 2020^Citation62	Hong Kong, Japan, South Korea, and Taiwan	436 *Including active HCC patients (n=55), inactive HCC patients (n=366) and unknown(n=15)	92.7% ^†95.0% in the non-HCC group (P=0.16)	85.5%	93.7%
Dang et al 2020^Citation92	USA, Japan, South Korea, and Taiwan	321 *All achieved SVR *Propensity Score Matching patients									87.78% †66.05% in DAA-untreated HCC patients (P <0.001)
He et al 2020^Citation90	13 countries from France, Canada, US, Italy, UK, NZ, Spain, Egypt, Germany, Japan, Taiwan, Poland, and China	361	82.5% ^†90.4% in the curative HCC management group
Chen et al 2021^Citation91	Taiwan	1473 *Including active HCC patients (n=328) and inactive HCC patients (n=1145)	96.5% ^†98.5% in the non-HCC group (P <0.001)	93%	97.6%		Active HCC	Inactive HCC	Active HCC	Inactive HCC
						Naïve LC	91.6%	97.7%	96.3%	96.3%
						Prior treatment experience	92.2%	98.2%	98.1%	96.6%

Notes: This table includes only studies with a number of DAA-treated HCC patients > 100. *Comments on study population or/and method, ^†Analysis in subgroup.

Abbreviations: DAA, direct-acting antivirals; SVR, sustained virologic response; HCC, hepatocellular carcinoma; LC, liver cirrhosis; LT, liver transplantation; HR, hazard ratio; CI, confidence interval.

Figure 3 Risk factors and prevention for HCC development in patients with NAFLD.

Abbreviations: HCC, hepatocellular carcinoma; NAFLD, nonalcoholic fatty liver disease; SNPs, Single Nucleotide Polymorphism; PNPLA3, patatin-like phospholipase domain-containing 3 gene; NASH, nonalcoholic steatohepatitis.

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