Gluten’s silent strike: Unmasking its impact on liver health

Table 1 Hepatic manifestations of gluten-related disorders and expected response to a gluten-free diet

Hepatic manifestation	Typical pattern	Proposed mechanisms	Suggested workup	Expected response to strict GFD	Additional management	Evidence base
Isolated transaminase elevation (“celiac hepatitis”)	Mild-moderate hepatocellular ALT/AST rise; normal bilirubin/ALP	Increased intestinal permeability; immune activation; micronutrient deficiencies	Rule out viral hepatitis, MASLD, alcohol, DILI, AIH/PBC; celiac serology (tTGIgA with total IgA ± DGPIgG)	Frequent normalization within 6-12 months; reassess if persistent > 12 months	Dietitianled GFD education; monitor ALT/AST at 3 months, 6 months, 12 months	Moderate (cohort and caseseries data)
MASLD/NAFLD overlap	Steatosis on imaging; ± insulin resistance, dyslipidemia	PostGFD weight gain; highgluten induced GF products; microbiome shifts; insulin resistance	Metabolic profile (BMI/waist, lipids, glucose); elastography or MRPDFF for risk stratification	Mixed; improves with weight loss and Mediterraneanstyle GFD	Lifestyle therapy; Mediterraneanstyle GFD; manage cardiometabolic risk per guidelines	Low-moderate (observational; small trials in NAFLD)
AIH overlap	Marked transaminase elevation; autoantibodies; interface hepatitis on biopsy	Shared HLA/immunogenetic susceptibility; loss of tolerance	Autoantibodies (ANA/SMA/LKM); IgG; liver biopsy when indicated	GFD may aid control, but immunosuppression usually required	Standard AIH therapy (steroids ± azathioprine) with GFD adherence	Low (case series/case reports)
PBC association	Cholestatic ALP/GGT elevation; AMA positivity	Autoimmune clustering; shared susceptibility	AMA, PBCspecific antibodies; cholestatic evaluation	Unclear; liver biochemistry typically responds to ursodeoxycholic acid (UDCA) rather than GFD alone	Treat per PBC guidelines (UDCA ± secondline therapy)	Low (observational association)
PSC association	Cholestatic labs; cholangiographic beading/strictures	Immune dysregulation; gut–liver axis perturbation	MRCP/ERCP; IBD screening; cholestatic panel	No established effect of GFD on PSC course	Manage per PSC guidance; surveillance for cholangiocarcinoma and IBD	Very low (limited reports)
Hypoalbuminemia, coagulopathy; steatosis secondary to malnutrition	Low albumin; elevated INR (vitamin K deficiency); fatty liver on imaging	Protein–calorie and fatsoluble vitamin deficiencies; smallbowel injury	Nutritional panel (iron, folate, B12, vitamins A/D/E/K); celiac activity assessment	Improves with mucosal healing and targeted supplementation	Vitamin repletion; dietitian followup; repeat labs to document correction	Low (case series, pediatric prominence)

ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Akaline phosphatase; MASLD: Metabolic dysfunctionassociated steatotic liver disease; DILI: Druginduced liver injury; AIH: Autoimmune hepatitis; PBC: Primary biliary cholangitis; tTG: Tissue transglutaminase; DGP: Deamidated gliadin peptide; GFD: Glutenfree diet; GF: Gluten free; BMI: Body mass index; MR: Magnetic resonance; PDFF: Platelet discriminant fraction; NAFLD: Nonalcoholic fatty liver disease; HLA: Human leukocyte agent; ANA: Anti-nuclear antibody; SMA: Smooth muscle antibody; LKM: Liver kidney muscle; GGT: Gamma glutamyl transferases; UDCA: Ursodeoxycholic acid; MRCP: Magnetic resonance cholangiopancreatography; PSC: Primary sclerosing cholangitis; ERCP: Endoscopic retrograde cholangio-pancreaticography; IBD: Inflammatory bowel disease; INR: International normalised ratio.