Medicine and the liver: your role in optimizing patients’ liver health
The organ we ignore
The liver is the largest internal organ and handles nearly every critical process in the body, yet it is often overlooked. A January 2025 survey by Liver Canada found that only 9% of Canadians prioritize their liver when thinking about their health—well behind heart, mental, digestive, lung, and even skin health. One in four Canadians is affected by chronic liver disease, yet there is no national strategy to address this largely preventable condition.
Given the prevalence of liver diseases and the rise in liver cancer cases, Liver Canada is working to fill this void by raising awareness, driving prevention, and supporting Canadians through education, advocacy, and research. Pharmacists are uniquely positioned to play a role in promoting liver health and optimizing medication management for patients with liver disease. This article provides practical information for frontline pharmacists on assessing medication appropriateness and safety in various stages of liver dysfunction, determining if a medication may have contributed to liver injury, and understanding the pharmacist’s role in caring for at-risk patients.
Understanding liver function and dysfunction
The liver’s functions can be divided into three basic categories: regulation, synthesis, and secretion of glucose, proteins, bile, lipids, hormones, and clotting factors; storage of glycogen, vitamins, and minerals; and purification, transformation, and clearance of waste products, drugs, and toxins. Typically, the liver’s response to injury is inflammation. Chronic inflammation caused by viral infections, excessive alcohol consumption, or metabolic conditions can trigger progression to an advanced form of liver dysfunction known as cirrhosis.
Cirrhosis is characterized by four distinct elements: extensive hepatic fibrosis, nodularity of the liver, alteration of liver architecture, and disruption of hepatic circulation. Portal hypertension, which manifests from increased resistance to hepatic portal blood flow, is a driver in the development of cirrhosis complications; the greater the degree of portal hypertension, the greater the cirrhosis severity and degree of complications. The risk of hepatocellular carcinoma is significantly heightened in the presence of liver cirrhosis.
Cirrhosis is commonly divided into two stages: compensated (the initial asymptomatic stage) and decompensated (the symptomatic phase associated with complications such as variceal bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome). Decompensated cirrhosis results in frequent hospital admission, impaired quality of life for patients and caregivers, a significant financial burden, and, in the absence of liver transplantation, patient death.
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Risk factors and clinical presentation
Progress has been made in curbing the impact of viral hepatitis in the Canadian population with the arrival of direct-acting antivirals to cure hepatitis C and the availability of more effective antiviral treatments for hepatitis B. However, increased alcohol misuse and the obesity epidemic have recently emerged as major contributors to liver disease in Canada, counteracting much of the progress made by mitigating the impact of viral hepatitis. It is concerning that the number of Canadians affected by metabolic dysfunction-associated steatotic liver disease is projected to increase by 20% between 2019 and 2030.
Initial symptoms in the setting of liver dysfunction often include fatigue, weakness, loss of appetite, right upper quadrant discomfort, and unexplained weight loss. As liver dysfunction progresses and the decompensated cirrhotic state manifests, clinical findings throughout the body become common, including hepatosplenomegaly, ascites, jaundice, sclera icterus, spider nevi, redness on the palms of the hands, pale nailbeds, finger clubbing, gynecomastia, and loss of secondary sexual characteristics.
Assessment and scoring tools
Lab values of interest when conducting a liver-related assessment are included in standard clinical tables. It is important to consider trends in lab values, as isolated abnormal values can be difficult to interpret and may not be a good measure of overall liver health. Cirrhosis assessment is typically done using noninvasive tests, with common validated methods including the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on four factors (FIB-4), and transient elastography. Online calculators exist for the APRI and FIB-4 tools, which use lab values and clinical information.
Child-Pugh and Model for End-Stage Liver Disease (MELD) scores are used to predict the outcomes of cirrhotic patients. The Child-Pugh score classifies the severity of liver cirrhosis based on five variables—each rated using a 1–3-point scale whereby the higher the points assigned, the worse the complication or test derangement. Child-Pugh Class A (5–6 points) indicates well-compensated liver cirrhosis, while Class C (10–15 points) indicates decompensated disease, whereby the patient has an estimated one-year survival of 45%. The Child-Pugh score is also used to dose drugs in hepatic impairment.
The MELD score serves as a predictor of mortality for both end-stage liver disease and acute liver failure. The original MELD scoring system uses only three variables (INR, bilirubin, and creatinine) with scores ranging from 6 to 40. An adapted version called the Na+ MELD score, which incorporates an assessment of serum sodium, is used to prioritize patients awaiting liver transplant.
Medication management and drug-induced injury
The liver is essential to the absorption, distribution, metabolism, and elimination of drug products. The presence of cirrhosis affects the selection and dosing of drugs metabolized by the liver. Some medications may need to be avoided or dose-adjusted according to the remaining liver function. This is a major challenge in clinical practice as specific guidelines are lacking. Dosing considerations in liver disease begin with an assessment of the severity of cirrhosis using the Child-Pugh score. Pharmacists may also make dose reductions based on the hepatic extraction of a given drug, which relates to the principle of absorption.
High hepatic-extraction drugs (e.g., statins, antipsychotics) are highly dependent on hepatic blood flow. In patients with reduced hepatic blood flow, drug levels can be significantly increased. Low hepatic-extraction drugs (e.g., pantoprazole, anticonvulsants) are less affected by hepatic blood flow but instead accumulate in the context of reduced metabolic capacity.
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Drug-induced liver injury (DILI) represents a diverse set of responses involving the liver that follow exposure to a manufactured or naturally occurring chemical compound. From a lab test standpoint, DILI is typically defined as meeting one of the following thresholds: ≥ 5 times upper limit of normal (ULN) elevation in alanine aminotransferase (ALT), ≥ 2 times ULN elevation in alkaline phosphatase (ALP) with accompanying elevations in gamma-glutamyltransferase (GGT) in the absence of known bone pathology, or ≥ 3 times ULN elevation in ALT with simultaneous elevation of total bilirubin > 2 times ULN.
The number of drugs associated with adverse liver reactions is extensive, but in practice DILI is predominantly attributed to acetaminophen, antibiotics, and antiseizure medications. Several herbal and dietary supplements have been linked to hepatotoxicity, including black cohosh, kava, green tea extract, and ashwagandha. DILI has traditionally been classified as direct or idiosyncratic, but indirect injury has emerged as a third type. Direct hepatotoxicity is caused by agents intrinsically toxic to the liver when given in high doses. Idiosyncratic hepatotoxicity is caused by agents with little or no intrinsic toxicity and is categorized as hepatocellular, cholestatic, or mixed. Indirect hepatotoxicity is caused by the action of the drug rather than its toxic or idiosyncratic properties, such as when a targeted immunotherapeutic agent reactivates hepatitis B.
Assessing DILI involves a process of elimination of other potential culprits for the presenting liver injury. Use of a causality assessment tool validated for hepatotoxicity, such as the Roussel Uclaf Causality Assessment Method (RUCAM), can provide an organized approach to determining the likelihood that a patient’s liver injury is caused by a given drug. Management of DILI involves discontinuation of the causative agent and supportive care. Very few specific treatments exist for DILI beyond N-acetylcysteine for acetaminophen toxicity, L-carnitine for valproic acid toxicity, and cholestyramine for leflunomide toxicity.
The pharmacist’s role in prevention and management
Pharmacists can promote liver health by educating patients about the impact of alcohol and obesity on the liver. They can screen for these aspects and refer patients to appropriate resources to facilitate early intervention. They can also assist with the pharmacologic management of alcohol use disorder or obesity-related health conditions. Pharmacists can use the Alcohol Use Disorders Inventory Test (AUDIT) or the shorter AUDIT-C questionnaire to identify individuals with hazardous alcohol consumption and potential alcohol use disorders, as well as provide a framework for intervention to assist those with unhealthy alcohol use in reducing or ceasing their alcohol consumption.
Pharmacists can also support initiatives focused on the prevention of viral hepatitis acquisition, whether that be via education about vaccination for hepatitis A and/or B (and by extension of hepatitis B vaccination, vaccination against hepatitis D) or risk reduction measures, such as safe needle and instrument supply to mitigate hepatitis B, C, and D transmission.
Pharmacists have a role to play in assessing the need for medication dose adjustment based on liver cirrhosis severity, as well as in identifying drugs and natural health products that confer a higher risk of hepatotoxicity and counseling patients accordingly. To improve patient care in the liver dysfunction area, pharmacists can use indirect methods such as symptom assessments during medication reviews to explore medication safety considerations. For example, the presence of ascites should prompt pharmacists to suspect significant liver dysfunction and the need to examine the patient’s medication regimen for hepatically-metabolized agents that may warrant closer monitoring or potential dose adjustment.
