Alcohol consumption is high in most Western countries. According to a survey using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) definition of alcohol use disorder, in 2021, 11.3% of US adults age 18 and older had alcohol use disorder in the past year (see National Institute on Alcohol Abuse and Alcoholism [NIAAA]: Alcohol Use Disorder (AUD) in the United States). The NIAAA reported a 25.5% increase in deaths involving alcohol use, from approximately 79,000 to more than 99,000 per year from 2019 to 2020, up from the 2.2% increase per year over the previous two decades, suggesting an increase due to the COVID-19 pandemic ( 1).
Liver disease may have complex effects on drug clearance, biotransformation, and pharmacokinetics. Pathogenetic factors include alterations in intestinal absorption, plasma protein binding, hepatic extraction ratio, liver blood flow, portal-systemic shunting, biliary excretion, enterohepatic circulation, and renal clearance. Sometimes alterations increase levels of bioavailable drug, causing normal medication doses to have toxic effects. However, levels and effects for an individual drug are unpredictable and do not correlate well with the type of liver injury, its severity, or liver test results. Thus, no general rules are available for modifying drug dosage in patients with liver disease.
Hepatic fibrosis is overly exuberant wound healing in which excessive connective tissue builds up in the liver. The extracellular matrix is overproduced, degraded deficiently, or both. The trigger is chronic injury, especially if there is an inflammatory component. Fibrosis itself causes no symptoms but can lead to portal hypertension (the scarring distorts blood flow through the liver) or cirrhosis (the scarring results in disruption of normal hepatic architecture and liver dysfunction). Diagnosis is based on liver biopsy. Treatment involves correcting the underlying condition when possible.
The liver produces about 500 to 600 mL of bile each day. Bile is isosmotic with plasma and consists primarily of water and electrolytes but also organic compounds: bile salts, phospholipids (mostly lecithin), cholesterol, bilirubin, and other endogenously produced or ingested compounds, such as proteins that regulate gastrointestinal function and drugs or their metabolites. Bilirubin is a degradation product of heme compounds from worn-out red blood cells (RBCs) and is the pigment that gives bile its yellow-green color.
Isolated hepatic cysts are commonly detected incidentally on abdominal ultrasonography or CT ( 1). These cysts are usually asymptomatic and have no clinical significance. The rare congenital polycystic liver is commonly associated with polycystic disease of the kidneys and other organs. It causes progressive nodular hepatomegaly (sometimes massive) in adults. Nevertheless, hepatocellular function is remarkably well preserved, and portal hypertension rarely develops. Occasionally, very large cysts cause pain or symptoms from compression of other organs. In these instances, intervention such as cyst marsupialization or drainage can be considered; however, cysts often recur. Thus, rarely, significant symptoms or quality-of-life issues warrant consideration of liver transplantation.
The liver has a dual blood supply. The portal vein (which is rich in nutrients and relatively high in oxygen) provides two thirds of blood flow to the liver. The hepatic artery (which is oxygen-rich) supplies the rest. The hepatic veins drain the liver into the inferior vena cava. When portal vein blood flow increases, hepatic artery flow decreases and vice versa (the hepatic arterial buffer response). This dual, reciprocally compensatory blood supply provides some protection from hepatic ischemia in healthy people.