Hepatic/Liver
for neonatal cholestasis, intrahepatic cholestasis, and genetic liver diseases with NGS panels and exome sequencing
System Profile
Yield Comparison
Clinical Dimensions
- Cholestasis
- Hepatomegaly
- Neonatal jaundice
- Recurrent transaminitis
- Coagulopathy
- Wilson disease
- Alpha-1 antitrypsin deficiency
- Juvenile hemochromatosis
- PFIC
- Glycogen storage disease with liver involvement
- Congenital hepatic fibrosis
- Jaundice
- Scleral icterus
- Hepatomegaly
- Ascites
- Spider angiomas
- Palmar erythema
- Muscle wasting in a child
- Bruising from coagulopathy
- Persistent jaundice
- RUQ pain
- Abdominal swelling
- Dark urine
- Pale stools
- Fatigue
- Easy bleeding
- Poor appetite
- Pruritus
- Elevated direct bilirubin
- AST/ALT
- Low albumin
- Prolonged PT/INR
- Very high GGT or bile acids
- Low ceruloplasmin
- Elevated AFP
- Abnormal copper excretion
- US or MRI liver with coarse echotexture
- Periportal fibrosis
- Nodularity
- Duct paucity (Alagille)
- Iron overload patterns
- Hepatic cysts
- FibroScan showing fibrosis in a child
- Liver biopsy with duct paucity, cholestasis, storage material
- HIDA scan with abnormal bile flow
- Vitamin K
- Ursodiol
- Ammonia scavengers
- Copper chelators (Wilson)
- Specialized hepatology medications
- High-dose fat-soluble vitamins
- Drug-induced liver injury at low doses or with multiple unrelated meds
- Cholestasis from mild agents
- Strongly abnormal LFTs with usual dosing
- Kasai procedure for biliary atresia
- Liver biopsy
- Liver transplant
- Porto-systemic shunt procedures
- Diet and lifestyle counseling for liver disease
- Monitoring of medications and supplements
- Education on avoiding hepatotoxins
- Feeding tubes
- Central lines
- Paracentesis drains
- Liver transplant hardware follow-up
- Hepatology and transplant services following chronic liver disease
- Metabolic liver clinics involved
- Hepatology requesting genetics/metabolic workup
- Wilson disease or other metabolic liver disease
- Unexplained childhood cirrhosis
- Liver failure in young adults
- Cholestatic syndromes in family
- No alcohol/drug/toxin exposure explaining liver disease
- No viral hepatitis risk factors
- Jaundice and liver issues present from early life
- Prolonged jaundice (>2-3 weeks)
- Direct hyperbilirubinemia
- Hepatomegaly
- Coagulopathy
- Pale stools
- Liver anomalies on prenatal imaging
Red Flag Combinations
Clinical patterns that should prompt consideration of genetic testing
Prolonged jaundice + hypotonia
Cholestasis + CHD (Alagille)
Liver failure + neurologic decline
Hepatosplenomegaly + cytopenias
Screening Decision Pathway
When to consider genetic testing for hepatic/liver presentations
graph TD
START["Patient Presents with\nHepatic/Liver Concerns"] --> SCREEN{"Screen for\nRed Flags"}
SCREEN --> RF1["Abnormal newborn screening for metabolic liver dis..."]
SCREEN --> RF2["Prolonged jaundice follow-up flags"]
SCREEN --> RF3["Elevated LFTs on routine screening"]
RF1 --> EVAL{"Multiple\nFlags Present?"}
RF2 --> EVAL{"Multiple\nFlags Present?"}
RF3 --> EVAL{"Multiple\nFlags Present?"}
EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
TEST --> DX["Molecular Diagnosis\n25-60% yield"]
style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e
Screening Red Flags
Findings on routine screening that may indicate genetic etiology
- Abnormal newborn screening for metabolic liver disease
- Prolonged jaundice follow-up flags
- Elevated LFTs on routine screening
Exome / Genome Sequencing Indications
Clinical scenarios supporting ES/GS as a diagnostic approach
- Unexplained cholestasis
- Early cirrhosis
- Metabolic liver disease suspicion with nondiagnostic initial workup
- Combined liver and extrahepatic features
Key Evidence
Published studies supporting genetic testing for hepatic/liver conditions
| Study | Year | Type | Sample | Yield | Key Finding |
|---|---|---|---|---|---|
| Next-Generation Sequencing Panel for Cholestatic Liver Disea... | 2018 | Cohort | None | 32.4% | NGS panel for cholestatic liver diseases achieved 32.4% diagnostic yield identif... |
| Clinical Utility of Genomic Analysis in Adults with Idiopath... | 2019 | Cohort | None | 25% | ~25% diagnostic yield with WES in 19 adults with unexplained chronic liver disea... |
| Diagnostic Yield of an Algorithm for Neonatal and Infantile ... | 2019 | Cohort | None | 60% | 60% detection rate for neonatal cholestasis with targeted NGS panel (SERPINA1, J... |
| Combined Gene Panel and Whole Exome Sequencing for Genetic L... | 2023 | Cohort | 374 | None | Tiered genetic testing approach with panel followed by WES achieves high diagnos... |
| Diagnostic Yield and Novel Candidate Genes by Next Generatio... | 2023 | Cohort | None | 31% | 31% diagnostic yield with WES in 166 children with unexplained liver disease; 42... |
Updated: 2026-02-25
Curated by: human
Status: human reviewed