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

Abstract

Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCCrelated deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.

Discovery of novel FGFR4 inhibitors through a build-up fragment strategy

“…Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which is the sixth most common cause of cancer-related death in 2022 1 . HCC is reported to be typically developed due to chronic liver inflammation caused by hepatitis B or C infection or non-alcoholic steatohepatitis (NASH) or cirrhosis 2–3 . Regarding therapies for advanced HCC, multi-kinase inhibitors (TKIs), sorafenib 4 and regorafenib 5 have been approved for clinical use.…”

Comprehensive analysis of differentially expressed miRNAs in hepatocellular carcinoma: Prognostic, predictive significance and pathway insights

“…Hepatocellular carcinoma (HCC) is the most common histology identified in primary liver cancers. HCC prognosis is primarily determined by stage, liver function, patient conditions and, indirectly, by HCC aetiology [ 2 ]. The five-year survival ranges from more than 50% in operable diseases to less than 5% in the most advanced stages [ 3 ].…”

Recent Insights into the Biomarkers, Molecular Targets and Mechanisms of Non-Alcoholic Steatohepatitis-Driven Hepatocarcinogenesis

“…Recent epidemiological evidence shows that non-alcoholic fatty liver disease (NAFLD), recently termed metabolic dysfunction-associated steatotic liver disease (MASLD), and steatohepatitis (NASH) have rapidly become leading etiologies predisposing to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) development due to the rapid increase in metabolic syndrome and obesity in the past decades and newly available therapies for hepatitis C (HCV) and B virus (HBV)-associated HCC [ 1 , 2 , 3 , 4 ] ( Figure 1 ). NAFLD/NASH-HCC is known to have even lower survival rates than viral hepatitis HCC and is generally developed based on metabolic syndrome, hyperinsulinemia, insulin resistance, and dyslipidemia, and is characterized by fat accumulation in the liver, either due to the increased inflow of free fatty acids or de novo lipogenesis [ 3 , 4 ]. NAFLD, a hepatic manifestation of insulin resistance, is very important in the pathophysiology of type 2 diabetes (T2DM).…”