Journal of Cellular Signaling

Liver fibrosis is a reversible wound-healing response in which a variety of cells and factors are involved in and results in excessive deposition of extracellular matrix (ECM). Cirrhosis is one of the significant causes of portal hypertension and end-stage liver disease, and it is the 14th most common cause of death around the world. Approximately 1.03 million people worldwide die from liver cirrhosis every year.

There is growing body of literature to identify novel prognostic markers in hepatocellular carcinoma (HCC), including serum ferritin (SF), transferrin levels, alfa fetoprotein (AFP), and neutrophil to lymphocyte ratio (NLR). Chronic inflammation and fibrogenesis are considered quite essential in the oncogenesis of HCC. The trigger for this inflammation could range from viral hepatitis, alcoholic cirrhosis, to non-alcoholic fatty liver disease. Also, iron overload as in hereditary hemochromatosis is linked to one of the factors for HCC oncogenesis.

Since the discovery of the hepatitis B virus (HBV) by Blumberg et al., great progress has been made in understanding the pathogenesis of the virus and its role in hepatocellular carcinoma (HCC). It is estimated that hepatitis B is responsible for about 50% of the HCC cases worldwide. Because of geographic variations in HBV incidence, the burden of HBV-related HCC (HBV-HCC) is highest in endemic areas such as Asian-Pacific and sub- Saharan Africa and lowest in the United States and the West. The hepatitis B vaccines, developed in the 1980s, transformed the evolution of hepatitis B in the modern era. This was followed by high effective anti-viral that reduced HBV infections and HBV-HCC.

Fatty liver (FL) is the most common wide-world liver disease that is nowadays demonstrating an increasing prevalence trend. In sharp contrast, the most common causes of liver diseases, such as viral causes, are decreasing thanks to advances in antiviral therapies. Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation, often associated with insulin resistance (IR), and defined by the presence of steatosis in at least 5% of hepatocytes in absence of relevant alcohol intake.

Multidisciplinary treatment is widely applied for hepatocellular carcinoma (HCC) using liver resection/ transplantation, local ablation therapy, transarterial chemoembolization (TACE), and systemic therapy. Systemic therapy is recommended and can provide a modest prognosis for HCC in Barcelona Clinic Liver Cancer (BCLC) staging C.