Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements

Abstract

Primary liver cancers carry significant morbidity and mortality. Hepatocellular carcinoma (HCC) develops within the hepatic parenchyma and is the most common malignancy originating from the liver. Although 80% of HCCs develop within background cirrhosis, 20% may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC (NCHCC). NCHCC is often diagnosed late due to lack of surveillance. In addition, the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on non-cirrhotic patients. Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC. NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection, signifying the role of Hepatitis B infection in NCHCC. Given the effectiveness of current antiviral therapies, surgical techniques and locoregional treatment options, nowadays such patients have more options and potential for cure. However, these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes. Better understanding of the NCHCC risk factors, tumorigenesis, diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients. In this review, we aim to discuss NCHCC epidemiology, risk factors, and pathogenesis, and elaborate on NCHCC diagnosis and treatment strategies.

Effect of COVID-19 Pandemic on Hepatocellular Carcinoma Diagnosis: Results from a Tertiary Care Center in North-West Italy

“…In our study, the prevalence of cirrhotic patients was slightly higher than that expected from the literature data (about 80% [23]), but compatible with a cohort in which HCV is still the main cause [24], despite a progressive increase in NAFLD as a cause (or a contributing cause) of HCC (from 17% to about 40%). This figure reflects the prediction that NAFLD will be the leading cause of HCC over the next decade [25], but it appears to have even worsened perhaps due to social restrictions and home confinement that limited physical activity; furthermore, we may have been more sensitive to reporting NAFLD as a contributing cause: in fact, its increase is not proportional to the decrease in viral infection, but is added to them.…”

Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy

“…As a result, improper medication withdrawal may result in disease progression. We also speculated whether long-term untreated OBI with positive HBeAg would more likely to result in the occurrence of adverse consequences such as liver cirrhosis and HCC, which has been reported in OBI with HBeAg negativity ( Perisetti et al, 2021 ; Huang et al, 2022 ).…”

Concomitant Gastric Malignancy and Hepatocellular Carcinoma

“…However, one year after treatment, the patient was incidentally found to have a liver lesion consistent with HCC. Classically, HCC occurs in the setting of cirrhosis, but up to 20% of cases occur in non-cirrhotics, most often associated with chronic viral hepatitis (B/C), nonalcoholic fatty liver disease, hemochromatosis, alpha-1 antitrypsin deficiency, aflatoxin exposure, or other toxin exposure [ 8 ]. The incidence of HCC in non-cirrhotic patients with HCV ranges from 4.4%-10.6% [ 9 ].…”

“…The incidence of HCC in non-cirrhotic patients with HCV ranges from 4.4%-10.6% [ 9 ]. Studies have shown that HCC risk is still increased after HCV eradication [ 8 ], implying a direct oncogenic effect of the virus. HCV viral proteins have been shown to inhibit tumor suppressor genes and cell cycle checkpoints, causing the increased cell growth and division seen in cancer [ 10 ].…”