Infection with hepatitis B virus and/or hepatitis C virus is the major cause of liver cirrhosis and liver cancer. Although there are periodical physical and clinical assessments, liver function tests and ultrasonography, it often becomes difficult for accurate diagnosis of the above mentioned liver diseases. The present review discusses a non-invasive simple test based on glycosylation change in serum glycoproteins viz., alpha - fetoprotein (AFP), alphal-acid glycoprotein (AGP) for differential diagnosis among chronic hepatitis B (HBV), HBV with cirrhosis (HBV-LC j, hepatitis C cirrhosis (HCV-LC) and alcoholic cirrhosis (ALC) patients using lectin-based sandwich ELISA. Although, in general, hyperfucosylation, increased level, increased branching and sialylation including variation of sialic acid linkages have been observed in AFP and AGP in all patient groups, there has been subtle changes among these parameters. ALC showed highest level of AFP whereas HBV- LC showed highly/increased branching in both AFP and AGP/AFP in HCV-LC expressed predominantly a 2,3- linked sialic acid whereas AFP in HBV showed the predominance of α 2,6 linked sialic acid. Addition of these results to the conventional liver function markers significantly aid in differential diagnosis among hepatitis and liver cirrhosis.