Hepatomegaly differential diagnosis

Hepatomegaly diagnosis in heart failure, viral hepatitis, and metabolic-associated fatty liver disease

1. ” Differential diagnosis of hepatomegaly in heart failure, viral hepatitis and metabolic-associated fatty liver disease

2. Hepatomegaly Refers to enlargement of liver Liver span larger than 12 cm at right midclavicular line is considered hepatomegaly Differential diagnosis: In suspected hepatomegaly -> liver ultrasound or CT to confirm diagnosis Ultrasound may detect fatty liver provided that it fits the diagnostic criteria In the setting of dyspnea -> evaluate for heart failure In the context of hepatomegaly with unknown cause -> hepatic panel Elevated ALT, AST, bilirubin, ALP -> further investigation with viral serologies is required Various other etiologies can cause elevated LFTs

3. METABOLIC-ASSOCIATED FATTY LIVER DISEASE Is defined on the presence of steatosis involving >5% of hepatocytes and the absence of significant alcohol consumption or other causes of chronic liver disease FL is the mildest form Steatohepatitis is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning), Mallory hyaline , and mixed lymphocytic and neutrophilic inflammatory infiltrate in perivenular areas with or without fibrosis FL and steatohepatitis could only be distinguished by liver biopsy and histology Diagnostic criteria: Hepatic steatosis detected by either imaging techniques (MRI, or ultrasonography), biomarkers, or liver histology In combination with either overweightness/obesity (BMI >25 kg/m2) Or diabetes mellitus Or metabolic dysregulation (High waist circumference, hypertension, impaired glucose tolerance, plasma triglycerides >150mg/dl, high c-reactive protein >2mg/L

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5. Etiology Insulin resistance is the primary metabolic defect leading to NAFLD Insulin resistance increases influx of FFA into the liver Fat accumulates in the liver due to increased delivery of FFA Increased synthesis of fatty acids Decreased oxidation of FFA Or decreased synthesis of VLDL Other factors: Medications (tamoxifen, amiodarone, methotrexate) Metabolic abnormalities Alcohol Wilsons disease or celiac sprue

6. History and evaluation Usually asymptomatic Nonspecific symptoms (fatigue, weightloss , etc ), or right upper quadrant discomfort. History must include alcohol use, family history, medications or supplements, diet, physical activity, changes in weight Evaluation for hypertension, obesity, diabetes, hyperlipidemia LFT’s: may be elevated ALT, AST, GGT, and occasionally, ALP GGT when elevated is a marker of increased mortality Serological tests to rule out viral hepatitis should be ordered Ultrasonography is the preferred method of diagnosis Ultrasonography features : increased echogenicity, hepatomegaly, coarsened echotexture

7. Viral hepatitis Virally mediated liver inflammation There are numerous viruses may affect the liver Including Epstein- barr virus, herpes simplex, cytomegalovirus More common h epatotropic viruses (A, B, C, D, E), with A, B, and C being the most common Complications (cirrhosis, and hepatocellular carcinoma) result in 1-4 million deaths / year / worldwide

8. Etiology Hepatitis A and E are transmitted via oral-fecal route Hepatitis B and C are primarily blood-borne Hepatitis B is a DNA virus, all others are RNA viruses HDV requires HBsAg to replicate History should include: Recent travel to endemic areas Parenteral exposure (intravenous drug use, or blood transfusion Sexual contact with infected individuals, or are suffering from jaundice Clinical picture: fever, anorexia, fatigue, vomiting, right upper quadrant pain, jaundice, dark urine, pale stools Hepatomegaly, scleral icterus or jaundice, right upper quadrant tenderness

9. Evaluations Elevated aminotransferases and bilirubin Acute hepatitis presents with aminotransferases levels in 1000s ELISA serology and PCR are used for diagnosis Positive anti-HAV IgM indicates acute HAV infection HBV : acute infection is indicated by presence of HBsAg , HBeAg , anti- HBc IgM, and elevated viral load Chronic HBV is denoted by presence of HBsAg >6 months, anti- HBc IgG, and absence of anti-HBs antibodies HCV : indicated by HCV RNA, with or without anti-HCV IgM HDV: Viral load indicates current infection HEV: anti-HEV IgM, HEV antigens, and RNA viral load are indicative of acute infection

10. Heart failure Hepatomegaly secondary to right-sided heart failure due to hepatic congestion Usually left-sided heart failure causes the right heart failure (i.e. congestive heart failure) Right heart failure causes an increase in venous congestion and increase of pressure in the hepatic sinusoids Heart failure is unlikely in the absence of dyspnea Common causes : Valvular disease (tricuspid regurgitation, mitral stenosis) Advanced left-sided heart failure Severe pulmonary hypertension Cor pulmonale Cardiomyopathy Pericardial disease Cardiac tamponade Constrictive pericarditis

11. Etiopathogenesis   Heart failure can result from increased demand, systolic dysfunction, or diastolic dysfunction . RVF is most often a result of LVF An increase in cardiac diastolic pressure or low cardiac output and impaired perfusion Increase in preload or central venous pressure due to right ventricular failure may cause direct liver damage which generates an elevation in liver enzymes The elevated pressure in right heart chambers leads to intrahepatic congestion, decreased perfusion and changes in liver tissue like fibrosis, and atrophy of hepatocytes and hemorrhage.

12. Clinical Presentation Hypoxemia and systemic venous congestion Dyspnea, orthopnea, peripheral edema Jugular venous distension Hepatojugular reflux Ascites Right-sided abdominal pain due to hepatic congestion Nausea, vomiting Constipation Jaundice in advanced disease Weight gain

13. EVALuations Initial assessment: thorough history and physical examination Medical history: anemia, CAD, valvular disease, diabetes mellitus, hypertension, AI disease, hemochromatosis, hypercholesterolemia, rheumatic fever, STD, hyperthyroidism, rheumatic fever, Social history: Travel, alcohol or drug abuse Family history: CAD, cardiomyopathies, arrhythmias Physical exam: bradycardia or tachycardia, bronze skin, arrhythmia, pedal edema, diminished peripheral pulses, heart murmurs, rales, weight loss or gain, jugular venous distension, hepatomegaly, splenomegaly ECG Chest radiograph Echocardiogram Coronary angiography in CAD, and angina.

14. Common echocardiogram features Reduced ejection fraction <50 % Wall motion abnormalities: akinesis , hypokinesis Increased left-ventricular diastolic and systolic diameter LV systolic dysfunction: LV fractional shortening (<25%) Left ventricular hypertrophy (>12mm) Right ventricular dilation and hypertrophy Right ventricular dysfunction (TAPSE <16 mm ) Dilated inferior vena cava Valvular abnormalities Aortic stenosis Mitral regurgitation Tricuspid regurgitation Pericardial effusion

15. Laboratory tests CBC BNP >100pg/mL and cardiac troponins are sensitive for early detection of RVF myocardial injury Blood lactate Liver panel Renal panel HIV-screening if indicated Metanephrines (suspected pheochromocytoma ) Serum TSH Serum electrolytes Lipid profile Serum ferritin (suspected hemochromatosis) Urinalysis ANA and RF screening (suspected AI disease)

16. Sources Ncbi.nlm.nih.gov Medscape Gastroenterologyadvisor.com Aafp.org Textbookofcardiology