Hepatocellular carcinoma (HCC) accounts for the third most common cancer related deaths worldwide and is the most common primary liver cancer seen in adults. Age adjusted incidence rate of HCC in India for women 1.2 to 2.2 and for men ranges from 4 to 7.5 and per 100,000 population per year while the female:male ratio for HCC in India is 1:4 and the age of presentation varies from 40 to 70 years. 90 % of the time HCC develops in cirrhotics due to chronic viral infections like Hepatitis B and C, alcoholism, metabolic causes like hemochromatosis, wilsons disease and non alcoholic liver diseases (MAFLD- Metabolic dysfunction-associated fatty liver disease).
The risk of HCC is greater in type 2 diabetes mellitus. Cirrhotics need to be screened every six monthly with imaging and serum AFP (Alpha Feto Protein) levels to assess development of HCC. Mostly they present with sudden decompensation in liver function in cirrhotics with jaundice, hemetemesis, ascites or with non specific symptoms like abdominal pain, fever, loss of appetite, fatigueness or incidentally detected. Immune activation due to repeated inflammations in liver due to various risk factors causes for increased DNA damage and lead to carcinogenic gene mutations.
Triple phase Contrast enhanced CT scan or MR imaging can be diagnostic in most cases with enhancement in arterial phase and characteristic venous wash out. In inconclusive situations image guided biopsy helps in diagnosing HCC. Single tumor < 5cm or 3 tumors- all < 3 cm (Milan Criteria) are the best candidates for liver transplantation, which offers cure for both HCC and cirrhosis with a 5 year survival of around 70 %. Safe major hepatectomy is feasible without liver failure when remnant volume > 30 % in non cirrhotics and > 40 % in early cirrhotics. < 3 cm tumors are curable with ablative therapies like Radio-frequency ablation (RFA) or Micro-wave ablation (MVA) and can produce almost equivalent results with surgery in cirrhotics. Embolization procedures gives the best palliative results with survival advantage. Trans-arterial Chemo embolization(TACE) can give excellent results in larger tumors not amenable to ablative treatments, sometimes in multiple sitting. When portal vein tumour thrombosis(PVTT) is present, Trans arterial Radio embolization (TARE) is preferred over TACE using beta emitter Yttrium-90 via resin or glass micro spheres. Local control of HCC is now feasible with newer external radiotherapy techniques using Stero-tactic body radiotherapy (SBRT). Most of these procedures are feasible in early Child A cirrhosis, preferably in MELD Na <18 and serum bilirubin <3 mg/dl, otherwise hepatic decompensation may occur. In decompensated late Child B and C cirrhosis, those who are outside transplant criteria could be managed only in palliative setting . Immunotherapy is a promising option nowadays, with Atezolizumab (Humanized IgG antibody that binds PD-L1) and Bevacizumab (Antiangiogenic- against Vascular Endothelial Growth factor- VEGF) becoming the standard therapy for unresectable early Child A HCC, replacing Tyrosine kinase inhibitors (TKI) like Sorafenib and Lenvatinib. Size > 5 cm, PVTT, elevated C- Reactive protein (CRP), elevated Neutrophil-Lymphocyte ratio (NLR) and elevated tumour markers like AFP and PIVKA -2 (Protein induced by vitamin k absence) and AFP L3 fraction are high risk for recurrence and metastasis.
5 year relative survival rate is 21.6 % and by stage it is 37.3%, 14.3% and 3.5% in those with localized disease, regional disease and distant disease respectively with multi-disciplinary treatment approach. Those with high risk for HCC should be screened with AFP and USG abdomen 3-6 monthly and appropriate treatment options should be taken as per modified Barcelona Clinic Liver Cancer staging (BCLC) system.
