Normal Viral and Autoimmune Tests

Case Report: Normal Viral and Autoimmune Tests in a 61-Year-Old Patient – Clinical Insights

Introduction

In assessing patients with edema, ascites, and elevated liver enzymes, exclusion of viral hepatitis and autoimmune liver diseases is crucial. The following laboratory tests are used to distinguish between primary liver disorders and multisystem diseases involving various organs:
viral hepatitis panel, anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti-mitochondrial antibody (AMA), ferritin, serum protein electrophoresis (SPEP), and ceruloplasmin.

In this scenario, a 61-year-old African-American man presented with systemic complaints of edema, ascites, and hypoalbuminemia. Surprisingly, all viral and autoimmune studies were normal, leading the clinician towards a diagnosis of systemic amyloidosis instead of primary liver pathology.

Patient Profile

• Age: 61 years
• Ethnicity: African-American
• Gender: Male
• Relevant Medical History: Hypertension, mild diabetes
• Presenting Symptoms: Progressive lower extremity swelling, abdominal distension, fatigue

Clinical Presentation

The patient had:

• Bilateral leg edema (swelling) for 2–3 months
• Abdominal distension (ascites)
• Fatigue and generalized weakness
• Mild shortness of breath
  Physical Examination Findings:
• Pitting edema of the lower extremities
• Ascites, moderate, with positive fluid wave
• Jugular venous distention (JVD)
• Mild hepatomegaly
• No jaundice, no scleral icterus

Laboratory Findings

• Viral Hepatitis Panel: Negative for hepatitis A, B, C
• Anti-Nuclear Antibody (ANA): Normal
• Anti-Smooth Muscle Antibody (SMA): Negative
• Anti-Mitochondrial Antibody (AMA): Negative
• Ferritin: Normal
• Ceruloplasmin: Normal
• Serum Protein Electrophoresis (SPEP): Normal
• Other Labs:
• Albumin: 2.1 g/dL (low)
• Total Bilirubin: 0.5 mg/dL
• Alkaline Phosphatase: 718 IU/L
• AST: 158 IU/L
• ALT: 119 IU/L
• Creatinine: 0.9 mg/dL
• INR: 1.07

Significance of Normal Viral and Autoimmune Tests

1. Viral Hepatitis Panel

• Does not rule out acute or chronic hepatitis A, B, and C as the etiology of liver enzyme elevation.
• Normal findings indicate viral infection is not the cause of hepatic injury.

2. Autoimmune Liver Antibodies (ANA, SMA, AMA)

• ANA and SMA evaluate autoimmune hepatitis.
• AMA assesses primary biliary cholangitis (PBC).
• Negative tests exclude autoimmune hepatopathies, which may have elevated liver enzymes and fatigue.

3. Ferritin and Ceruloplasmin

• Ferritin is an acute phase reactant; normal levels reflect no active iron overload or systemic inflammation.
• Ceruloplasmin assesses Wilson disease, which is uncommon in this age group.

4. Serum Protein Electrophoresis (SPEP)

• Identifies monoclonal gammopathy, commonly seen with amyloidosis.
• SPEP normal in this patient implies that light-chain amyloidosis can exist without an identifiable M-spike, pointing to the necessity of immunofixation or free light chain assays.

Diagnostic Interpretation

• The routine viral and autoimmune studies rule out primary liver disease as the etiology for abnormal AP, AST, and ALT.
• This led to further investigation for systemic infiltrative or multi-organ disease.
• In addition to edema, hypoalbuminemia, and nephrotic-range proteinuria, the results favored the diagnosis of systemic AL amyloidosis.

Systemic Amyloidosis Diagnostic Workup

• Fat Pad Biopsy: Congo red positive with apple-green birefringence under polarized light.
• Renal Biopsy: Documented amyloid deposition in glomeruli.
• Cardiac Evaluation: Echocardiogram showed restrictive cardiomyopathy.
• Other Labs: Free light chain assay, immunofixation to identify monoclonal proteins.

Clinical Significance

1. Exclusion of Liver Disease:

• Normal viral and autoimmune labs avoid unnecessary therapy such as antivirals or immunosuppressants.

1. Emphasis on Systemic Disease:

• Shifts the focus to amyloidosis or other infiltrative diseases involving multiple organs.

1. Treatment Planning:

• Preservation of liver synthetic function enables safe chemotherapy and disease-specific therapy.

1. Prognostic Value:

• Normal viral and autoimmune markers indicate relatively preserved hepatic function, which is good for prognosis.

Management

Supportive Therapy

• Diuretics for ascites and edema
• Salt restriction and fluid management
• Nutritional support to correct hypoalbuminemia

Disease-Specific Therapy

• CyBorD regimen (Bortezomib + Cyclophosphamide + Dexamethasone)
• Stem Cell Transplant in eligible patients
• Novel agents like Daratumumab in refractory disease

Monitoring

• Serial liver function tests (AP, AST, ALT, bilirubin)
• Renal function (creatinine, eGFR, urine protein)
• Cardiac function (echocardiography)
• Albumin levels for nutritional and fluid balance

Patient Outcome

• After 6 months of therapy:
• Liver enzymes trended down; TB remained normal
• Edema and ascites improved with diuretics
• Albumin increased modestly
• Cardiac symptoms stabilized
• No autoimmune or viral complications arose

Clinical Insights

For Clinicians

• Normal autoimmune and viral tests should trigger consideration for systemic etiology of elevated liver enzymes.
• Amyloidosis may have multi-organ involvement with normal viral and autoimmune labs.
• Early diagnosis yields better results and avoids permanent organ damage.

For Patients & Families

• Normal results are reassuring but not diagnostic against systemic disease.
• Persistent edema, fatigue, or proteinuria should initiate specialist evaluation.
• Supportive care and strict therapy enhance prognosis.

Broader Implications

• Normal viral and autoimmune labs with accompanying multi-organ symptoms emphasize the value of holistic evaluation.
• Clinicians need to think of amyloidosis, infiltrative diseases, or unusual metabolic disorders if conventional labs are normal.
• Early, thorough assessment avoids misdiagnosis and delays in treatment.

Conclusion

Here, the 61-year-old African-American man had normal viral and autoimmune studies in the presence of systemic features such as edema, hypoalbuminemia, nephrotic-range proteinuria, and mild elevation of liver enzymes.

• They aided exclusion of primary liver disease.
• Systemic amyloidosis became a focus, which was proved by biopsy and expert laboratories.
• Maintenance of liver function enabled safe introduction of disease-specific treatment, resulting in better outcomes.
  Key Takeaway: There is no exclusion of severe systemic disease by normal viral and autoimmune markers; clinicians need to consider labs in the context of the overall clinical picture.