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A quick guide for healthcare providers on chronic liver disease

 

The condition commonly referred to as “fatty liver” is more accurately termed Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) or Metabolic Dysfunction-Associated Steatohepatitis (MASH) when liver inflammation is present. MASLD is the most prevalent form of chronic liver disease, with its incidence steadily increasing due to rising rates of obesity, diabetes, and metabolic syndrome.

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This guide outlines the management of patients with chronic liver disease. In addition to MASLD, other leading causes of chronic liver disease in Nova Scotia include Alcohol-Associated Liver Disease (ALD), Hepatitis C Virus (HCV) infection, Hepatitis B Virus (HBV) infection, and Autoimmune Hepatitis (AIH)

 

Many cases of chronic liver disease can be managed in the outpatient primary care setting without the input of a Gastroenterologist or Hepatologist. 

 

   1. The FIB-4 index

Otherwise short for Fibrosis-4 index, it is a noninvasive tool available to assess for liver fibrosis in MASLD/MASH. There exist cutoffs which may signal an at-risk patient. FIB-4 score is calculated using AST, ALT, platelet count, and Age. 

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Patients who do not meet the cutoff(FIB-4 < 1.5), will require yearly monitoring and repeat FIB-4 calculation for risk stratification. This can safely be managed with lifestyle modifications in primary care setting. 

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A FIB-4 score ≥1.5 warrants further evaluation to rule out secondary causes and consideration for a FibroScan

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Management Approach for FIB-4 > 2.6

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  • Liver Ultrasound with Doppler: Consider performing to assess liver morphology for signs of cirrhosis (e.g., nodular contour, portal vein dilation, caudate lobe hypertrophy), infiltrative liver diseases, masses or tumors, and vascular abnormalities such as portal or hepatic vein thrombosis.

  • FibroScan: Generally, it is low-yield to pursue further testing if there are clear signs of cirrhosis without decompensation, indicated by biomarkers such as thrombocytopenia (platelet count <150,000), INR >1.5, and total bilirubin >32 µmol/L, along with radiographic evidence of cirrhosis on abdominal ultrasound (e.g., nodular liver, portal hypertension, caudate lobe hypertrophy). Please note that wait times at QEII are approximately 1 to 1.5 years.

  • CT Abdomen and Pelvis with IV Contrast: Consider if ultrasound findings are inconclusive. The presence of esophageal or gastric varices, in conjunction with suggestive serologies, confirms cirrhosis with portal hypertension.

  • Referral for Advanced Liver Disease: FibroScan is also low yield in cases of decompensated liver disease, such as ascites, history of portal hypertension-related bleeding, or hepatic encephalopathy. These patients should be referred to hepatology or gastroenterology based on local triage guidelines.

  • Management of Chronic Viral Hepatitis: Active chronic hepatitis B or C should be co-managed with infectious disease specialists when appropriate.

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If the FIB-4 score is > 1.5, consider a consultation through Virtual Hallway for expedited care or to address any questions or concerns

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   2. Investigations to Rule Out Secondary Causes of Liver Disease

Indication:

Secondary causes should be evaluated when the FIB-4 score is >1.5 for more than 6 months in patients with MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) or MASH (Metabolic Dysfunction-Associated Steatohepatitis).

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Summary: Order a liver ultrasound with Doppler, along with the following laboratory tests: HBsAg, HBsAb, HBcAb, HCV Ab, ceruloplasmin (if <60 years old), immunoglobulins (IgG, IgA, IgM), antinuclear antibody (ANA), anti-mitochondrial antibody (AMA), autoimmune hepatitis panel (including anti-smooth muscle antibody), iron studies(iron saturation, ferritin), thyroid-stimulating hormone (TSH), proBNP (if clinically indicated, e.g., in obesity-related liver disease), creatine kinase (CK), and alpha-1 antitrypsin levels.

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  • Vascular or Structural Liver Disease

    • Initial Test:

      • ​Liver Ultrasound with Doppler:

        • Purpose: Evaluate liver morphology for signs of cirrhosis (e.g., nodular contour, caudate lobe hypertrophy, portal vein dilation).

        • Detects: Infiltrative diseases, liver masses or tumors, and vascular abnormalities such as portal vein thrombosis or hepatic vein thrombosis (Budd-Chiari syndrome).

      • Further Imaging:

        • Indications: If the ultrasound is non-diagnostic or inconclusive, and there's high suspicion of cirrhosis or vascular abnormalities, especially when FibroScan is unavailable:

          • CT Abdomen with Contrast: To rule out portal vein, hepatic vein, or splenic vein thrombosis.

          • CT Abdomen and Pelvis: Helpful in assessing signs of portal hypertension, such as esophageal or gastric varices, which suggest advanced cirrhosis.

        • Case-by-Case Basis: Imaging decisions should be tailored to clinical suspicion and patient presentation.

  • Infectious Causes of Liver Disease

    • Viral Hepatitis Panel:

      • Hepatitis B: HBsAg, HBsAb, HBcAb

      • Hepatitis C: HCV Antibody (HCV Ab)

      • Hepatitis A: HAV Antibody (IgM, IgG)

    • Consider Additional Testing: If clinically indicated (e.g., HIV1+2 Ab, CMV viral load, EBNA for EBV, HBV viral load, HCV viral load). Recommended in acute on chronic hepatitis. 

  • Autoimmune Liver Diseases(AIH)

    • Markers:

      • Antinuclear Antibody (ANA)

      • Anti-Smooth Muscle Antibody (ASMA)

      • Immunoglobulin levels (IgG, IgM, IgA)

    • Primary Biliary Cholangitis (PBC):

      • Marker: Anti-Mitochondrial Antibody (AMA), Immunoglobulins (IgM)

    • Celiac Disease (associated with liver abnormalities):

      • Marker: Anti-Tissue Transglutaminase (Anti-tTG)

    • Note: Consider ordering an autoimmune hepatitis panel for efficiency when AIH or PBC is suspected.

  • Metabolic and Genetic Liver Diseases:  

    • ​Wilson’s Disease: Screening test: Ceruloplasmin.

      • When there's high index of Wilson's disease in, in addition to serum ceruloplasmin, 24-hour urinary copper (if high suspicion), and slit-lamp examination for Kayser-Fleischer rings are recommended.

        • Clinical Pearl: Wilson's disease is an autosomal recessive disorder caused by mutations in the ATP7B gene, leading to impaired copper transport and excretion, resulting in copper accumulation in the liver, brain, and cornea. It can present with a range of symptoms, including CLD, cirrhosis, and acute liver failure, especially in young patients, as well as neurological and psychiatric manifestations such as dystonia, tremors, Parkinsonism, depression, behavioural changes, and psychosis. Wilson’s disease testing is low-yield in patients over 60 years old, as it typically presents earlier in life. Treatment involves oral chelation therapy with agents like D-penicillamine or trientine, along with zinc supplementation to reduce copper absorption.  

  • ​Hereditary Hemochromatosis (HH):

    • ​Initial Screening: Ferritin, iron panel (serum iron, transferrin saturation, TIBC, reticulocyte count).

    • Key Indicator: If transferrin saturation >45%, consider HFE gene testing.

      • Common Mutation: C282Y homozygosity

      • Advanced HH: Often presents with ferritin >1,000 ng/mL due to significant iron overload.

    • Important Consideration: Ferritin is an acute-phase reactant and may be elevated in conditions like inflammation, MASLD/MASH, infection, or malignancy—interpret results cautiously.

    • Clinical Pearl: HFE gene testing is cost-effective when evaluating cirrhosis, especially if HH is suspected. Early detection and treatment with phlebotomy can significantly improve outcomes.

  • Alpha-1 Antitrypsin Deficiency:

    • Test: Serum Alpha-1 Antitrypsin (A1AT) levels. 

  • Endocrine Disorders:

    • ​Thyroid stimulating hormone (TSH)

  • ​ Ischemic Liver injury: 

    • Considerations: Evaluate on a case-by-case basis, particularly in patients with risk factors for cardiac or vascular disease.

      • ​ProBNP: To assess for right heart failure

      • CK: For muscle breakdown

      • Transthoracic Echocardiogram (TTE): To evaluate cardiac function

      • CT Angiogram of the Chest: Consider if chronic pulmonary emboli are suspected

  • Medication and Toxin Review:

    • Evaluate the patient’s current medication list for hepatotoxic drugs.

    • Screen for the use of herbal supplements, weight-loss products, and bulking agents, which are common but often overlooked causes of liver injury.

    • Consider unintentional toxin exposures, including over-the-counter medications like acetaminophen.

 

   3. Workup for Cirrhosis 

  • For portal hypertension (PHTN) screening, refer patients with confirmed cirrhosis based on clinical picture and/or FibroScan for an esophagogastroduodenoscopy (EGD) to screen for varices. If cirrhosis is suspected but FibroScan is unavailable, order a CT abdomen with contrast to assess for varices and signs of PHTN. The presence of varices on endoscopy or imaging confirms cirrhosis. If PHTN is confirmed, start Carvedilol 3.125 mg BID if the heart rate > 60 bpm and sodium > 130 mmol/L, as non-selective beta-blockers can reduce variceal bleeding risk by up to 50%.

  • For hepatocellular carcinoma (HCC) screening, perform a liver ultrasound and measure alpha-fetoprotein (AFP)every 6 months. Triple phase CT abdomen or liver MRI is helpful to further delineate liver lesions > 1cm.  

  • To assess for hepatic encephalopathy (HE), screen for cognitive changes (e.g., confusion, impaired concentration), behavioral symptoms (e.g., distractibility), and sleep-wake disturbances (e.g., reversed sleep patterns). Use tools like the West Haven Criteria to grade severity when needed.

 

   4. General advice to give patients

  • Patients with liver cirrhosis should avoid NSAIDs due to the risk of kidney injury and gastrointestinal bleeding. Acetaminophen (Tylenol) can be used safely but should be limited to 2 g/day in cirrhosis. In cases of chronic liver disease without cirrhosis, acetaminophen can be used up to 3 g/day, provided there is no ongoing alcohol use or other hepatotoxic risk factors.

  • Alcohol consumption should be minimized in all forms of chronic liver disease and completely avoided in patients with cirrhosis, as it significantly increases the risk of disease progression and complications. For patients struggling with alcohol dependence, a referral to addiction services should be considered to support abstinence.

  • Patients with cirrhosis should avoid eating uncooked shellfish, such as raw oysters, due to the risk of serious infections like Vibrio vulnificus, which can cause life-threatening sepsis in immunocompromised individuals, including those with liver disease.

  • Vaccination is important for preventing infections in cirrhotic patients. Vaccines for pneumococcus and shingles are recommended, while live vaccines should be avoided in patients with decompensated cirrhosis (Child-Pugh Class B or C) due to the risk of vaccine-related complications.

  • Maintaining good nutrition is crucial in liver disease management. Patients should aim for adequate protein intake to prevent muscle wasting (sarcopenia), especially in cirrhosis. If there are concerns about malnutrition, referral to a dietitian can help optimize dietary intake and support liver health.

     

  • References:
    Rinella, Mary E.(1); Neuschwander-Tetri, Brent A.(2); Siddiqui, Mohammad Shadab(3); Abdelmalek, Manal F.(4); Caldwell, Stephen(5); Barb, Diana(6); Kleiner, David E.(7); Loomba, Rohit(8). AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 77(5):p 1797-1835, May 2023. | DOI: 10.1097/HEP.0000000000000323

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