Diagnostic Approach and Pathophysiological Mechanisms of Anemia in Chronic Liver Disease—An Overview

Abstract

Hematological abnormalities are frequently linked to chronic liver disease of any etiology. About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal tract, malnutrition, an enlarged spleen brought on by portal hypertension, hemolysis, and coagulation issues are the main causes of anemia. Alcohol, a common cause of chronic liver disease, determines anemia through direct toxicity on the bone marrow, with the suppression of hematopoiesis, through vitamin B6, B12, and folate deficiency due to low intake and malabsorption. In patients with chronic hepatitis C virus infection, antiviral drugs such as pegylated interferon and ribavirin can also cause significant anemia. The use of interferon has been linked to bone marrow toxicity, and hemolytic anemia brought on by ribavirin is a well-known dose-dependent side effect. Within six months of the infection with hepatitis B, hepatitis C, and Epstein–Barr viruses, aplastic anemia associated with hepatitis is seen. This anemia is characterized by pancytopenia brought on by hypocellular bone marrow. Esophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia can all cause acute and chronic blood loss. These conditions can progress to iron deficiency anemia, microcytic anemia, and hypochromic anemia. Another common hematologic abnormality in liver cirrhosis is macrocytosis, with multifactorial causes. Vitamin B12 and folate deficiency are frequent in liver cirrhosis, especially of alcoholic etiology, due to increased intestinal permeability, dysbiosis, and malnutrition. Many chronic liver diseases, like viral and autoimmune hepatitis, have a chronic inflammatory substrate. Proinflammatory cytokines, including tumor necrosis factor and interleukin 1, 6, and 10, are the main factors that diminish iron availability in progenitor erythrocytes and subsequent erythropoiesis, leading to the development of chronic inflammatory, normochromic, normocytic anemia.

Keywords

• chronic liver disease
• anemia
• hepcidin
• chronic hepatitis
• liver cirrhosis
• gastrointestinal bleeding