What is the management approach for liver parenchymal disease?

Management of Liver Parenchymal Disease

Begin with abdominal ultrasound as the mandatory first-line imaging to detect hepatic hypoechogenicity, portal vein wall thickening, "starry sky" appearance, and liver contour abnormalities, then proceed to MRI with IV contrast when ultrasound is equivocal or detailed parenchymal assessment is needed. 1

Initial Diagnostic Approach

First-Line Imaging

• Perform grayscale ultrasound plus Duplex Doppler to assess diffuse hepatic hypoechogenicity indicating acute inflammation, increased portal vein wall thickness, contracted gallbladder with wall thickening, and liver size/contour abnormalities suggesting chronicity 1, 2
• Add Duplex Doppler specifically when ischemic injury is suspected to evaluate vascular patency 1

Advanced Imaging Indications

• Obtain MRI with IV contrast when ultrasound findings are equivocal, inhomogeneous patterns require characterization, or detailed assessment of parenchymal inflammation and perfusion is needed 1, 2
• Evaluate for increased T2 signal intensity and decreased T1 signal (inflamed parenchyma), periportal edema, heterogeneous arterial phase enhancement, perihepatic fluid, and non-enhancing wedge-shaped areas indicating hepatic infarction 1, 2

Etiologic Workup

Laboratory Testing Strategy

• Direct testing by enzyme pattern: For hepatocellular pattern (elevated AST/ALT), obtain viral hepatitis serologies (HBsAg, anti-HBc, HCV antibody), autoimmune markers (ANA, ASMA, anti-LKM), metabolic screening (iron studies, ceruloplasmin, alpha-1 antitrypsin), and toxicology screen 1, 2
• For cholestatic pattern (elevated alkaline phosphatase), confirm hepatic origin with GGT and obtain antimitochondrial antibody for primary biliary cholangitis 1, 2

Screening for Metabolic and Alcohol-Related Disease

• Screen all patients with unexplained liver test abnormalities for steatotic liver disease due to metabolic syndrome and/or alcohol, as these are the most common risk factors for chronic liver damage 3
• Document alcohol intake using AUDIT-C questionnaire to identify consumption over 2 standard drinks/day for women or 3 standard drinks/day for men (1 standard drink = 10 g alcohol) 3
• Assess for metabolic syndrome components including obesity, diabetes, and cardiovascular risk factors 3

Additional Causes to Exclude

• Refer to hepatologist when unexplained aminotransferase or cholestatic enzyme elevation persists for evaluation of immune-mediated liver disease (autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis), hereditary metabolic disorders (hemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency), celiac disease, and vascular liver diseases 3
• Review medication history for drugs causing steatosis: amiodarone, carbamazepine, sodium valproate, NSAIDs, glucocorticoids, methotrexate, tamoxifen, and antiretrovirals 3

Disease Staging and Fibrosis Assessment

When to Perform Liver Biopsy

• Liver biopsy remains the reference standard when treatment decisions depend on fibrosis stage, requiring minimum 2-3 cm length, 16-gauge caliber, and at least 11 complete portal tracts for accurate grading and staging 1, 2
• Perform biopsy when transient elastography and serum biomarkers are discordant, or when multiple potential etiologies coexist requiring histologic differentiation 1, 2
• Use liver biopsy in individual cases and clinical trials to monitor disease progression or treatment response, though it is not suited for routine monitoring due to invasiveness 3

Non-Invasive Alternatives

• Use transient elastography combined with serum biomarkers to reduce biopsy need, particularly for detecting advanced fibrosis (≥15 kPa typically confirms cirrhosis) or excluding minimal fibrosis 1
• Repeat non-invasive tests at 3-year intervals in low-risk patients to assess fibrosis progression, though they provide limited information about treatment response at the individual level 3
• Recognize that single biopsies have 33% sampling variability with discordant results by at least one stage 1

Treatment Based on Etiology

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Weight Loss Targets

• Target sustained weight reduction of ≥5% to reduce liver fat, 7-10% to improve liver inflammation, and ≥10% to improve fibrosis in adults with MASLD and overweight 3
• Achieve this through 30% caloric reduction or 750-1,000 kcal/day deficit 1
• For patients with class II or III obesity, consider incretin-based weight loss drugs or bariatric procedures 3

Dietary Modifications

• Recommend Mediterranean dietary pattern, minimizing processed meat, ultra-processed foods, and sugar-sweetened beverages while increasing unprocessed/minimally processed foods 3
• Specifically limit commercially produced fructose consumption 4
• Improve diet quality to reduce histologically or non-invasively assessed liver injury 3

Physical Activity Requirements

• Prescribe ≥150 minutes/week of moderate-intensity or 75 minutes/week of vigorous-intensity physical activity (≥6 METs required for fibrosis improvement) tailored to individual preference and ability 3, 1
• Physical activity reduces steatosis even without weight loss 3

Pharmacological Treatment

• Limit pharmacological treatment to biopsy-proven NASH with fibrosis 1
• Prioritize treatment for patients with F3-F4 fibrosis due to higher complication risk 1, 2

Viral Hepatitis Management

Active HBV/HCV Infection

• Refer patients with HCV RNA-positive or HBsAg-positive ± HDV antibody to hepatologist or infectious disease specialist for antiviral management 3
• For HCV genotype 1 or 4, use ledipasvir/sofosbuvir for 12 weeks in treatment-naïve patients without cirrhosis or with compensated cirrhosis 5
• For HCV genotype 2, use sofosbuvir plus ribavirin for 12 weeks 6
• For HCV genotype 3, use sofosbuvir plus ribavirin for 24 weeks 6

Post-Viral Clearance Monitoring

• Screen all HCV antibody-positive/HCV RNA-negative and HBsAg-negative/HBcAb-positive patients for additional chronic liver damage factors (alcohol, metabolic syndrome) and evaluate for signs of advanced chronic liver disease even if asymptomatic with normal liver tests 3
• Continue hepatological follow-up in patients with previous advanced fibrosis/cirrhosis despite successful antiviral therapy and decreased non-invasive fibrosis markers 3

Autoimmune Hepatitis

• Initiate corticosteroid therapy only after histological confirmation 1, 2

Alcoholic Liver Disease

• Enforce complete alcohol abstinence as the cornerstone of treatment 3
• Address alcohol use disorder with appropriate addiction medicine referral 3

Management of Cirrhosis Complications

Portal Hypertension and Variceal Bleeding Prevention

• Prescribe nonselective β-blockers (carvedilol or propranolol) to reduce risk of decompensation or death (16% vs 27% with placebo over 3 years) 7

Ascites Management

• Use combination aldosterone antagonist and loop diuretics rather than sequential initiation, achieving higher ascites resolution rates (76% vs 56%) with lower hyperkalemia rates (4% vs 18%) 7

Hepatic Encephalopathy

• Administer lactulose to reduce mortality (8.5% vs 14% with placebo) and prevent recurrent overt hepatic encephalopathy (25.5% vs 46.8%) 7

Hepatorenal Syndrome

• Use terlipressin to improve reversal rate from 18% to 39% 7

Symptom Management

• Prescribe hydroxyzine for sleep dysfunction 7
• Use pickle brine or taurine for muscle cramps 7
• Consider tadalafil for sexual dysfunction in men 7

Critical Pitfalls to Avoid

• Never perform percutaneous liver biopsy in patients with suspected hereditary hemorrhagic telangiectasia with liver vascular malformations 1
• Avoid NSAIDs in any patient with suspected cirrhosis due to risks of renal failure, GI bleeding, and hepatic decompensation 1
• Do not use liver biopsy for routine monitoring of disease evolution or treatment response due to invasiveness and procedure-related limitations 3

Multidisciplinary Approach

• Implement multidisciplinary care involving hepatology, endocrinology, cardiology, and nutrition to address all cardiometabolic comorbidities and improve both liver-related and extrahepatic outcomes 3
• Evaluate lifestyle factors during all healthcare visits 3

Ongoing Surveillance Requirements

Hepatocellular Carcinoma Screening

• Perform ultrasound every 6 months for lifelong HCC surveillance in all cirrhosis patients, even after successful treatment of underlying disease 1, 2
• Recognize that 1-4% of cirrhosis patients develop HCC annually with 5-year survival of approximately 20% 7

Repeat Staging Indications

• Reassess fibrosis staging when clinical status changes significantly, treatment decisions require reassessment, or initial staging was borderline for treatment eligibility 1, 2
• Continue screening for additional chronic liver damage factors in patients with cleared viral hepatitis 2