Liver chemistries in glycogenic hepatopathy associated with type 1 diabetes mellitus: A systematic review and pooled analysis

Abstract

Background & Aims Glycogenic hepatopathy (GH) in type 1 diabetes‐mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy‐proven GH reports in T1DM patients to identify LC patterns. Methods A systematic review identified reports of biopsy‐proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST‐to‐ALT ratio, R‐ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed. Results A total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2, median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate‐to‐severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis. Conclusion GH tends to have AST‐predominant elevation with a median of 13 times the upper normal limit and R‐ratio >2, which may distinguish it from other etiologies of AST‐predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.

Hepatopathy Associated With Type 1 Diabetes: Distinguishing Non-alcoholic Fatty Liver Disease From Glycogenic Hepatopathy

“…Signs of liver cirrhosis might be present in advanced NAFLD. proven GlyH showed that both ALT and AST are moderate-toseverely elevated in 78 and 76% of cases, with an ASTpredominant pattern and improvement when glycemic control was obtained (Haffar et al, 2021). In this pooled analysis, the median HbA1c was 12% and median BMI 21 kg/m 2 , stressing the correlation with extremely poor glycemic control, which is hardly seen any longer in current practice, but not necessarily with abdominal adiposity.…”

“…One study compared T1D patients with and without hepatopathy (based on imaging, not on histology) and did not find significant correlations between ALT and AST levels and aberrant ultrasonographic imaging, but hyperechogenicity was indeed correlated to poor glycemic control ( Aydın et al, 2019 ). One pooled analysis of 192 documented cases of histologically proven GlyH showed that both ALT and AST are moderate-to-severely elevated in 78 and 76% of cases, with an AST-predominant pattern and improvement when glycemic control was obtained ( Haffar et al, 2021 ). In this pooled analysis, the median HbA1c was 12% and median BMI 21 kg/m 2 , stressing the correlation with extremely poor glycemic control, which is hardly seen any longer in current practice, but not necessarily with abdominal adiposity.…”

Hepatic Glycogenosis: An Underdiagnosed Entity?

“…Laboratory workup often presents mild to moderate elevation in liver aminotransferases, with a predominant elevation of glutamate oxaloacetate transaminase (GOT) over glutamic pyruvic transaminase (GPT) (ratio GOT/GPT >1). Most reported cases showed a hepatocellular pattern, although a mixed pattern or even a cholestatic pattern can rarely occur [13]. Marked elevations of aminotransferases (up to 100× the upper limit of normal) have been reported, generally in patients presenting with DKA.…”

A Case of Glycogenic Hepatopathy as a Complication of Poorly Controlled Type 1 Diabetes Mellitus

“…GH is associated with the following patterns of abnormal liver enzymes: Elevations in ALT and AST in out of proportion to ALP and bilirubin indicating predominant hepatocellular injury [ 13 , 16 , 18 ]. AST is higher than ALT [ 19 ]. Synthetic function of the liver is preserved, that is, normal albumin and INR levels [ 13 , 20 , 21 ].…”

“…GH is usually noted to have aminotransferases elevated about 13 times the upper normal limit [ 19 ]. Our patient had a pattern of liver enzymes similar to that described above.…”