What is the recommended workup for a new diagnosis of cirrhosis?

Workup for New Diagnosis of Cirrhosis

When cirrhosis is newly diagnosed, immediately initiate a comprehensive evaluation that includes determining the underlying etiology through viral hepatitis serologies and metabolic screening, assessing hepatic function with liver panel and coagulation studies, staging portal hypertension severity through upper endoscopy, and establishing hepatocellular carcinoma surveillance with ultrasound every 6 months. 1, 2

Determine the Underlying Etiology

The first priority is identifying what caused the cirrhosis, as this directly impacts treatment and reversibility:

Viral Hepatitis Screening

• Test for hepatitis B surface antigen (HBsAg), hepatitis B DNA, anti-hepatitis C antibody, and HCV RNA to identify viral causes 1, 2
• If HBsAg is positive, add anti-HDV testing to rule out hepatitis D coinfection 2

Metabolic and Autoimmune Workup

• Obtain iron studies (ferritin and transferrin saturation) as all patients with newly diagnosed cirrhosis should be screened for hemochromatosis 3, 1
• Check autoimmune markers including antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), antimitochondrial antibody (AMA), and immunoglobulin levels to diagnose autoimmune hepatitis or primary biliary cholangitis 1, 2
• Assess for metabolic syndrome components (obesity, diabetes, hypertension, dyslipidemia) as risk factors for nonalcoholic fatty liver disease 2, 4

Additional Etiologic Testing

• Obtain detailed alcohol consumption history using standardized questionnaires to identify alcoholic liver disease 2
• Consider HIV testing in at-risk populations as coinfection worsens liver disease outcomes 2

Assess Hepatic Function and Severity

Laboratory Panel

• Order complete liver panel including ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and prothrombin time/INR 1, 2
• Obtain complete blood count with platelet count as thrombocytopenia indicates portal hypertension 1
• Calculate Child-Pugh and MELD scores to quantify disease severity and prognosis 5

Non-Invasive Fibrosis Confirmation

• Perform vibration-controlled transient elastography (VCTE/FibroScan) with a cutoff of >20-25 kPa indicating clinically significant portal hypertension 1, 2
• Combine two non-invasive methods (such as VCTE and FIB-4 score) to improve diagnostic accuracy 1, 2
• MR elastography is the most accurate non-invasive imaging modality for diagnosing and staging hepatic fibrosis, particularly when conventional imaging is discordant or in obese patients 1

Evaluate for Portal Hypertension and Varices

Upper Endoscopy

• Perform upper endoscopy to screen for esophageal/gastric varices and hypertensive gastropathy in all patients with confirmed cirrhosis 1, 2
• This is mandatory regardless of platelet count or liver stiffness values 3

Alternative Assessment

• VCTE-defined liver stiffness of 19.5 (±2) kPa can help triage patients at low risk of high-risk varices, though this should not replace endoscopy in most cases 3
• Hepatic venous pressure gradient (HVPG) measurement via transjugular approach is the gold standard, with ≥10 mmHg defining clinically significant portal hypertension 1

Imaging Studies

Initial Imaging

• Obtain abdominal ultrasound with Doppler as the first-line imaging modality to evaluate liver morphology, detect portal hypertension signs (splenomegaly, portosystemic collaterals), and assess for focal lesions 1, 2
• A nodular liver surface has 86% sensitivity for cirrhosis 1
• Portosystemic collaterals are 100% specific for clinically significant portal hypertension 1

Advanced Imaging When Indicated

• Order MRI with MRCP when primary sclerosing cholangitis or primary biliary cirrhosis is suspected, or when ultrasound is inadequate 1
• Multiphasic CT or MRI can assess for hepatocellular carcinoma and characterize suspicious lesions 1

Common pitfall: CT has only 67-72% diagnostic accuracy for cirrhosis and is insensitive for early-stage disease, so do not rely on CT alone for diagnosis 1

Establish Hepatocellular Carcinoma Surveillance

• Initiate ultrasound screening every 6 months for all cirrhotic patients, regardless of etiology 1, 2, 4
• AFP measurement may be considered as an adjunct, though its accuracy as a standalone test is suboptimal 2
• Ultrasound has only 47% sensitivity for early-stage HCC detection, and approximately 20% of ultrasound examinations in cirrhotic patients are inadequate quality, particularly in obese patients 1
• Lifelong surveillance is required even after sustained virologic response in hepatitis C, as HCC risk persists at 1.39% per year 1

Additional Assessments

Cardiopulmonary Evaluation

• Obtain comprehensive echocardiography to assess systolic and diastolic function, right ventricular systolic pressure, and tricuspid annular plane excursion in patients considered for TIPS or other interventions 1

When to Consider Liver Biopsy

• Reserve liver biopsy for cases with discordant non-invasive test results, unknown etiology despite comprehensive workup, or when results would alter management 2, 5
• Biopsy should only be considered after thorough non-invasive evaluation has failed to confirm diagnosis 6

Ongoing Monitoring Schedule

• Perform clinical assessment with laboratory tests and Child-Pugh/MELD score calculation every 6 months 5
• Continue ultrasound surveillance for HCC every 6 months indefinitely 1, 2
• Repeat upper endoscopy based on initial findings: every 1-2 years if no varices, every 1-2 years if small varices without high-risk features, or initiate prophylaxis if high-risk varices are present 7

Critical consideration: Screen for hepatic encephalopathy using an animal naming test in all patients with cirrhosis regardless of liver function status, as covert hepatic encephalopathy is frequently underdiagnosed 3