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

Table 1 Key differences between non cirrhotic hepatocellular carcinoma and hepatocellular carcinoma

	HCC	NCHCC
Epidemiology	Eighty percent of HCC develops with a cirrhotic background. A unimodal age distribution (peak in 7th decade) noted. Male:female ratio - 3:2	Twenty percent of tumors develop in non-cirrhotic liver. A bimodal age distribution (peak in 2nd and 7th decade) noted. Male:female ratio-2:1
Risk factors	Development of cirrhosis from any etiology can progress to HCC. Hepatotropic viruses, environmental and life-style factors (alcohol, tobacco), metabolic conditions (nonalcoholic fatty liver disease, diabetes mellitus, obesity) play a predominant role	NCHCC develops without a background of underlying cirrhosis. Viral (HBV, HCV infection) and non-viral risk factors (obesity, diabetes mellitus, toxin exposure, germline mutations and genetic disorders) noted
Clinical features	Symptoms could be related to underlying cirrhosis (from portal hypertension) or HCC (early satiety, upper abdominal pain) itself. Paraneoplastic signs such as hypercalcemia, hypoglycemia have been reported	Generalized fatigue, abdominal pain and weight loss are common symptoms. Can present at late stage with large tumor burden, extrahepatic metastasis
Diagnosis	High quality cross-sectional imaging (CT/MRI) are used with typical arterial phase hyper-enhancement and portal venous washout. LI-RADS classification is used in classification of radiological findings in HCC	Although CT and MRI are increasingly utilized for diagnosis, liver biopsy are utilized in patients when cross-sectional imaging is equivocal. LI-RADS classification cannot be utilized for NCHCC and instead tumor characteristics (size, imaging features) are utilized for staging
Treatment	Given the underlying cirrhosis, liver transplant candidacy need to be evaluated for HCC patients. Resectability of the lesion, amount of liver reserve, vascular invasion, performance status determines the treatment outcomes	Antiviral treatment recommended when etiology of NCHCC is HBV/HCV. Surgery remains the main treatment modality. Systemic and local therapy options are increasingly being utilized for NCHCC

Key differences in epidemiology, risk factors, clinical presentations, diagnosis and treatment for non-cirrhotic hepatocellular carcinoma and hepatocellular carcinoma. A multidisciplinary team evaluation is frequently utilized for diagnosis and treatment. CT: Computed tomography; MRI: Magnetic resonance; HCC: Hepatocellular carcinoma; NCHCC: Non cirrhotic hepatocellular carcinoma; LI-RADS: Liver Reporting and Data System; HBV: Hepatitis B; HCV: Hepatitis C.