LIVER DISEASE OVERVIEW

Liver disease is a significant cause of morbidity and mortality in the United States. It affects persons of all ages, but most frequently individuals in the productive years of life, between the ages of 40 and 60 years. Liver disease also disproportionately affects minority individuals and the economically disadvantaged (NCHS, 2021). 

Liver disease is a broad term that includes any genetic or acquired condition which impairs normal liver function.  Some common forms of liver diseases include: viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, drug induced liver injury, cholelithiasis and Wilson's disease.

The liver has tremendous functional reserve which often masks minor liver damage. Liver disease becomes apparent when injury exceeds the liver's capacity to compensate. Liver injury can result from a variety of causes, including: toxins, infectious agents, diet, ischemic events, inherited conditions or medical treatment.

The liver responds to injury in several ways:

1. Accumulation of: bile, fat (steatosis), proteinaceous debris (mallory bodies), minerals (iron-hemochromatosis) (copper-Wilson disease). The accumulation my be due to obstruction of bile outflow, fat deposition, metabolic compromise, etc.
   
2. Inflammation (hepatitis) is initiated when stressed, or dead hepatocytes, spill contents, causing the release of proinflammatory cytokines and chemokines.
3. Necrosis
   • Apoptosis describes the programmed death of individual cells. Under physiological conditions it is a well-regulated, slow process that leads to cell renewal and tissue remodeling. In pathological conditions, the process is less controlled and often more rapidly progressive (pathological apoptosis). (Krishna 2017)
   • Zonal necrosis refers to necrosis involving a particular zone of the acinus (the functional unit of the liver.) resulting from ischemic or drug-related injury. (Krishna 2017)
   • Confluent necrosis describes necrosis involving multiple lobules. The process may be localized in conditions such as localized ischemic injury or as collateral injury with targeted treatment for tumors (e.g., transarterial chemotherapy or radioembolization). (Krishna 2017)
4. Regeneration differs depending on the type of injury
   • regeneration following massive acute necrosis depends on proliferation and differentiation of stem cells originating in the canals of Hering
   • regeneration following partial surgical hepatectomy or submassive necrosis results from proliferation of remaining hepatocytes.  After a 70% partial hepatectomy, the remnant liver can recover its original mass and function.
5. Chronic liver injury results in prolonged activation of hepatic stellate cells (HSC) and provokes fiber deposition. Fibrosis and cirrhosis are common results of most chronic liver diseases.
   • Fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs when the healing process is out of balance. Acute hepatocyte death or injury causes inflammatory mediators to activate hepatic stellate cells (HSC). Activated HSCs secrete collagen, elastin, glycoproteins, proteoglycans and hyaluronan to replace or strengthen areas of extracellular matrix (ECM) damaged by necrosis. The fibers provide a scaffolding that holds sinusoidal endothelial cells (SEC) together and close to the remaining hepatocytes. SECs secrete Hepatocyte Growth Factor (HGF) which stimulates regeneration of hepatocytes. Proliferating hepatocytes produce protease, which degrades excess ECM. Chronic injury results in prolonged activation of HSCs and their fiber deposition. Fibrosis is the overgrowth of the scaffolding.
   • Cirrhosis is a late-stage liver disease when fibrosis exceeds hepatocytes regeneration and the liver is permanently damaged. Scar tissue distorts the circulatory architecure and impairs the liver's ability to process nutrients, hormones, drugs and clear toxins. It also reduces the production of proteins and other substances made by the liver. Cirrhosis diminishes liver function and can be life-threatening.

Reference

Krishna, M. (2017). Patterns of necrosis in liver disease. Clinical Liver Disease (Malden, Mass.), 10(2), 53–56. https://doi.org/10.1002/cld.653

National Vital Statistics Reports (NVSS) - cdc.gov. (2021). Retrieved November 15, 2021, from https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-09-508.pdf.

© RnCeus.com