Dated 11/23/2025, the article published in Cureus titled “Defining ‘Normal’ Liver Function Tests” is worth a careful read–
“Chronic liver disease often remains undiagnosed until cirrhosis develops, with standard liver function tests (LFTs) sometimes appearing normal despite significant hepatic dysfunction.”
This paper shows that “normal” liver blood tests definitely do not mean “normal” liver—even in people who already have cirrhosis.
What they did
- Retrospective, single-center study at York & Scarborough NHS (UK).
- From a database of 563 adults with confirmed cirrhosis (imaging and/or biopsy), they randomly selected 251 who:
- Had LFTs done in primary care between 2020–2023
- Had no obvious liver disease at the time (no jaundice, ascites, encephalopathy, varices, or known prior liver disease).
- They collected:
- Standard LFTs: bilirubin, albumin, ALP, ALT (AST in a subset)
- FBC, INR, ALBI score
- Clinical correlates: varices, ascites, encephalopathy
- Severity scores: Child-Pugh, ALBI
- “Normal LFTs” (nLFT) meant all four: albumin, ALP, ALT, and bilirubin within the lab reference range at the same time.
Main results
1. Normal LFTs are common in cirrhosis
- 37% (89/251) of cirrhotic patients had completely normal LFTs.
- Among patients without any clinical signs of cirrhosis (Child-Pugh A, no varices/ascites/encephalopathy, n=171), 48% had normal LFTs.
- Platelets and INR were often normal too:
- 57% had a normal platelet count
- 22% had a normal INR
2. Biochemistry doesn’t neatly distinguish “normal” vs “abnormal” groups
Comparing patients with normal LFTs vs abnormal LFTs:
- Age, sex, albumin, ALP, bilirubin, ALBI score: no meaningful differences.
- Only ALT was (slightly) lower in the normal group (38.5 vs 42.7 IU/L; p=0.029) – not clinically dramatic.
- MASLD/MASH was slightly more common in the normal-LFT group (41% vs 34%) but not statistically significant.
3. AST:ALT ratio and ALBI aren’t perfect safety nets
- In 117 patients with AST data, mean AST:ALT ratio:
- 1.5 in the whole cohort (cirrhotic pattern)
- 1.29 in the normal-LFT subgroup
- ALBI score:
- Normal in 59% of the whole cohort
- Normal in 83% of those with normal LFTs
So even “better” function scores like ALBI can look normal in well-compensated cirrhosis.
Why are so many cirrhotic patients “biochemically normal”?
The authors discuss several mechanisms:
- The liver’s huge functional reserve and regenerative capacity can keep labs near-normal until late disease.
- Enzyme release fluctuates—a single blood draw may miss activity.
- Certain aetiologies (e.g., NAFLD/MASLD) often have mild or absent enzyme elevations.
- Standard LFTs mainly reflect injury (AST/ALT), synthetic function (albumin/INR), or cholestasis (ALP, GGT), but do not directly measure fibrosis or portal pressure.
They also note that guidelines and medical education often start liver work-ups from “abnormal LFTs,” reinforcing the mistaken idea that normal LFTs = healthy liver.
Clinical implications
Normal LFTs do not rule out cirrhosis or advanced chronic liver disease, especially in high-risk patients.
The authors argue for:
- Not relying on LFTs alone for screening or exclusion of liver disease.
- Using risk-based approaches (metabolic risk, alcohol, viral hepatitis, etc.) even when LFTs are normal.
- Incorporating non-invasive fibrosis tools in primary care:
- Transient elastography (FibroScan and similar)
- Serum scores: FIB-4, APRI, etc.
- Exploring AI-based decision support tools that combine labs, imaging, and risk factors to detect cirrhosis earlier.
The Net Net
- Over a third of patients with confirmed cirrhosis had completely normal LFTs; nearly half of clinically compensated cirrhotics did.
- Platelets, INR, ALBI, and AST:ALT ratio are often not abnormal enough to raise alarm.
- Therefore, “normal” LFTs should never be used as a stand-alone reassurance in people with liver risk factors; a multi-parameter, non-invasive, and risk-stratified strategy is necessary for early cirrhosis detection.