Glycogenic hepatopathy: A narrative review

Table 5 Summery of the main differential diagnosis for glycogenic hepatopathy

	Main etiology	Clinical presentation	Imaging characteristics	Key, liver biopsy pathological features	Diagnosis	Management	Cirrhosis
GH	Acquired excessive glycogen deposition in the liver mostly seen in patients with T1DM	Hyperglycemia with hyperglycemic symptoms; could be asymptomatic. Liver enzyme elevation is mild to extreme range in some case	US and CT shows increased echogenicity. Dual-Echo MRI; iso-intense between the in-phase and out-of-phase images, and low intensity on subtraction	Glycogen deposition in the cytoplasm with swollen hepatocytes, with or without mild steatosis and fibrosis. Diastase digestion of glycogen cause hepatocytes to turn into “ghost cells”	Radiologic and liver biopsy	Optimal control of DM	May have mild fibrosis, severe fibrosis is very rare and seen in only a few reported cases
GSD	Inborn errors of glucose and glycogen metabolism results in abnormal deposition of glycogen	Presentation varies depend on types of GSDs They will have manifestations of a liver, kidney, and skeletal muscle involvement with hypoglycemia, hepatomegaly, muscle cramps, and weakness, etc	Like GH	Findings vary in different type of GSDs; Nonspecific histologic findings to PAS positive glycogen deposition which could be diastase sensitive or resistant	Biochemical tests and molecular testing	Symptomatic treatment to dietary changes to maintain the blood glucose level and pharmacologic therapy in different types of GSDs. May need liver transplantation in selected cases	Some GSD can progress to cirrhosis
NAFLD	Hepatic steatosis	Most patients asymptomatic and some may have minor symptoms, Liver enzymes elevation usually < 5 times upper limit of normal	US and CT shows increased echogenicity. Dual-Echo MRI; low intensity on the in-phase image, and high intensity on the out-of-phase image and high intensity on subtraction.	Steatosis with or without lobular inflammation and hepatocyte ballooning. May have varying degrees of fibrosis	Radiologic and liver biopsy	Lifestyle modification and pharmacologic therapies. May need liver transplant in advanced cirrhosis	Can progress to cirrhosis
Hepatosclerosis	Is a hepatic manifestation of microangiopathic disease seen in long -standing DM	Often clinically silent, Serum aminotransferases are normal or minimally elevated. ALP, Total bilirubin may be elevated	No specific imaging characteristics	Extensive dense perisinusoidal fibrosis	Liver biopsy	Unknown	Unknown
AIH	Chronic Hepatitis of unknown etiology	Spectrum of clinical manifestations ranges from asymptomatic patients to those with considerable symptoms, and rarely presents with acute liver failure	No characteristic imaging features, may show cirrhotic liver in advance case	Interface hepatitis and portal lymphoplasmacytic infiltrate with varying degree of fibrosis	Characteristic biochemical tests and liver biopsy	Glucocorticoid monotherapy or in combination with immunomodulators. Rarely may require liver transplantation	Can progress to cirrhosis
Hemochromatosis	Autosomal recessive disorder. Mutations cause increased iron absorption and excessive deposition in the liver, heart, pancreas, and pituitary	Asymptomatic or chronic liver disease with elevated transaminases, skin pigmentation, DM, arthropathy, impotence and cardiac enlargement, etc	MRI is most sensitive and can estimate iron concentration in the liver. Dual-Echo MRI; demonstrates decreased signal intensity in the affected tissues on the in-phase images compared with the out of- phase images (opposite of steatosis)	A liver biopsy will reveal iron overload. Presence of cirrhosis can be determined	Biochemical tests including genetic testing, radiologic, and liver biopsy	Phlebotomy or Chelation therapy if unable to tolerate phlebotomy	Can progress to cirrhosis
Wilson disease	Autosomal recessive disorder with impaired cellular copper transport and impaired biliary copper excretion results in accumulation of copper most notably the liver, brain, and cornea.	Predominantly hepatic, neurologic, and psychiatric manifestations. Elevated transaminases mild to moderate and ALP may be markedly subnormal	US, CT, may show signs of cirrhosis and normal caudate lobe which is contrary to other types cirrhosis	Vary largely from fatty changes to cirrhosis and occasionally fulminant hepatic necrosis. Can be stained for copper	Biochemical tests and slit lamp examination with or without genetic testing and liver biopsy	Treatment with a chelating agent. Some cases may require liver transplantation	Can progress to cirrhosis
Acute viral hepatitis A, B, C, D and E. Rarely, HSV, VZ, EBV and CMV	Hepatitis A and E are transmitted by feco- oral route; Rest of the viruses spread either by sexual contact, contact with body fluids or blood or from birth from an infected mother	Many of the symptoms are nonspecific; May have marked elevation in transaminases often > 15 times the normal	US or CT findings are nonspecific; Could be used to rule out other causes	Liver biopsy shows hepatocyte necrosis with a portal, periportal and lobular lymphocytic infiltration; Plasma cells present during resolving phase	Diagnosis by biochemical tests	Treatment conservative or antiviral therapy	Acute infection may progress to chronic, and that may progress to cirrhosis

PAS: Periodic-acid Schiff; T1DM: Type 1 diabetes mellitus; US: Ultrasound; CT: Computed tomography; GH: Glycogenic hepatopathy; GSD: Glycogen storage disease; NAFLD: Non-alcoholic fatty liver disease; AIH: Auto immune hepatitis; DM: Diabetes mellitus; ALP: Alkaline phosphatase; HSV: Herpes simplex virus; VZ: Varicella zoster virus; CMV; Cytomegalovirus.