Copyright ©The Author(s) 2018.
World J Hepatol. Feb 27, 2018; 10(2): 172-185
Published online Feb 27, 2018. doi: 10.4254/wjh.v10.i2.172
Table 1 Summary of the major case reports in English (pub med indexed) on Glycogenic hepatopathy in type 1 diabetes mellitus
Ref.Study designAge/sexHbA1CKeto acidosisHepatomegalyAST/ALT/ALP/T biliNormalization of LFTs
Ruschhaupt et al[1], 1970Case report13/MNAYesYes9/14/115/128/NA5 d
Berman et al[2], 1973Case report21/FNAYesYesUKExpired (5 d)
Olsson et al[3], 1989Case report15/FNAYesYes535/417/570/NA10 d
20/FNANoYes1117/1235/941/NA18 mo
Munns et al[4], 2000Case reports13/M14.1NoYes132/135/170/NA4 wk
17/F13.3NoYes102/147/175/NA2 wk
16/F12.2NoYes567/316/196/NA2 wk
Fridell et al[5], 2007Case report18/FNAYesYesElevated/NAfter pancreatic transplant
21/MNANoYesElevated/NAfter pancreatic transplant
Cuthbertson et al[6], 2007Case report19/F12.2YesYesNA/800/132/NNA
Sayuk et al[7], 2007Case report19/F8.1YesYes98/49/147/0.5NA
Bassett et al[8], 2008Case report10/F10.1NoNo143/147/137/NNA
Abaci et al[9], 2008Case report16/M11.1NoYes66/58/431/0.83 mo
Hudacko et al[10], 2008Case report20/F13.3NoYes249/383/NA/NA5 mo
Sweetser et al[11], 2010Case report27/M15.0NoYes6720/2549/529/1.73 mo
Van Den Brand[12], 2009Case report29/F15.3NoNo2500/1000/316/NANA
Saxena et al[13], 2010Case report33/F13.7NoNo428/404/205/N12 mo
Bua et al[14], 2010Case report17/F12.0NoYes138/164/NA/NA12 mo
Aljabri et al[15], 2011Case report13/F13.0NoYesNA/500/137/N3 mo
Dantuluri et al[16], 2012Case report14/F11.0NoYesElevatedFew days
Lin et al[17], 2012Case report10/ F12.8YesYes121/194/185/NA6 mo
Messeri et al[18], 2012Case report31/F10.3NoYes225/258/375/0.542 mo
Murata et al[19], 2012Case report21/M6.2YesNo119/122/NA/NA25 d
Cha et al[20], 2012Case report22/F13.8NoYes1028/365/346/0.58 wk
26/F12.9YesYes914/307/189/0.54 wk
20/F13.6NoNo1310/346/132/0.216 wk
Saadi T[21], 2012Case report18/M11.0NoYes144/92/123/1.43 mo
Saikusa et al[22], 2012Case report13/M12.0NoYes100/191/NA/NANA
Imtiaz et al[23], 2013Case report19/F14.6YesYesNA/199/139/NA5 mo
Butts et al[24], 2014Case report13/F8.8YesYesNA/113/NA/NANA
Jeong et al[25], 2014Case report13/F10.7YesYes105/84/NA/NA3 mo
Martin et al[26], 2014Case report13/M10.4YesYes3969/1196/NA/NA16 d
Parmar et al[27], 2015Case report21/FNAYesYes4202/973/N/N1 wk
Xu et al[28], 2015Case report22/M14.6NoYes331/223/223/0.3NA
Garcia-Suarez et al[29], 2015Case report28/F10.5NoYes1600/534/N/NNA
Atmaca et al[30], 2015Case report19/MNAYesYes603/570/921/NA3 wk
Irani et al[31], 2015Case report19/M12.0YesYes505/345/145/NNA
Brouwers et al[32], 2015Case report19/F9.5NoYesElevatedNA
Charndrasekaran et al[33], 2015Case report5/F16.1YesYes53/20/NA/0.7NA
Silva et al[34], 2016Case report21/F9.0YesYes110/120/190/0.74Few days
20/F10.1YesYes270/423/179/1Few days
29/F10.9NoYes910/461/172/0.353 mo
22/M15.7YesYes226/109/79/0.642 wk
Deemer et al[35], 2016Case report18/F11.3YesYesNA/36/120/NNA
Saracho et al[36], 2016Case report14/M12.8YesYesElevatedNA
Chandel et al[37], 2017Case report12/F10.5YesYes690/356/158/0.23 mo
Ikarashi et al[38], 2017Case report21/M11.7NoYes2723/956/NA/NA1 mo
24/F11.0YesYes658/216/NA/NAFew days
19/F13.6YesYes737/266/NA/NAFew days
29/F16.5YesYes469/243/NA/NA6 mo
Maharaj et al[39], 2017Case report23/F12.3YesYes127/199/160/2.7Few days
Al Sarkhy et al[40], 2017Case report6/M11.6YesYes367/205/221/NFew days
Shah et al[41], 2017Case report31/FNAYesYes627/185/280/0.7NA
Omer[42], 2017Case report14/M11.0YesYesNormalNA
Table 2 Summary of the major studies in English (pub med indexed) on Glycogenic hepatopathy in type 1 diabetes mellitus
Ref.Study designAge/sexHbA1CKeto acidosisHepatomegalyLiver abnormalityNormalization of LFTs
Chatila et al[43], 1996Retrospective StudyMild Fibrosis (14%)11patients (8-A and 3-P)
41/FNANANo20/45/1.4 x ULN/0.35Few days to weeks
21/FNANANo282/404/0.4 x ULN/0.28Few days to weeks
58/FNANAYes35/56/3.2 x ULN/0.40Few days to weeks
70/FNANAYes76/NA/NA/1.28Few days to weeks
36/FNANANo40/86/2.1 x ULN/0.28Few days to weeks
46/FNANAYes22/20/1.7 x ULN/NFew days to weeks
23/FNANAYes265/410/9.5 x ULN/0.40Few days to weeks
19/FNANAYes344/532/2.6 x ULN/0.8Few days to weeks
13/MNANAYes940/910/2 x ULN/0.30Few days to weeks
13/MNANAYes85/NA/0.3 x ULN/0.48Few days to weeks
15/MNANAYesNA/NA/1.9 x ULN/0.08Few days to weeks
Torbenson et al[44], 2006Retrospective Study14 patients
Fitzpatrick et al[45], 2014Retrospective31 patients11(Mean)Yes-all76/76/NA/NA(M)NA14 (73%) Fibrosis
16M/15F12Mild and 2Bridging
Median age 15Fibrosis
Mukewar et al[46], 2017Case control study20 patients11.4(Mean) 55%88.90%301/308/170/0.5(M)8 mo10% Mild fibrosis but no bridging fibrosis
24-A, 12-P
Table 3 Summary of the major case reports in English (PubMed indexed) on Glycogenic hepatopathy in type 2 diabetes mellitus
Ref.Study designAge/sexType of DM/insulinA1CKeto acidosisHepatomegalyAST/ALT/ALP/T bilinormalization fibrosis of LFTs
Olson et al[3], 1989Case report39/MType 2/insulinNAYesNo429/764/1882/NA21 d
Tsujimoto et al[47], 2006Case report41/MType 2/insulin10NoYes1064/1024/202/2.317 d
Umpaichitra[48], 2016Case report15/MT2DM/metformin6.5NoYes245/330/N/N18 mo
Table 4 Summary of the published articles in English (PubMed indexed) on Glycogenic hepatopathy without DM
Ref.PathologyStudy designAge/sexHepatomegalyAST/ALT/ALP/ T biliNormalizationFibrosis of LFTs
Resnick et al[56], 2011Dumping syndromeCase report2/MNoNA/199/NA/NA16 moNo fibrosis
Kransdorf et al[57], 2015Anorexia nervosaCase report26/FNA75/101/108/NANo fibrosis
Iancu et al[58], 1986Steroids useRetrospective6 mo-14 yrYesNormal3-5 dNo fibrosis
Table 5 Summery of the main differential diagnosis for glycogenic hepatopathy
Main etiologyClinical presentationImaging characteristicsKey, liver biopsy pathological featuresDiagnosisManagementCirrhosis
GHAcquired excessive glycogen deposition in the liver mostly seen in patients with T1DMHyperglycemia with hyperglycemic symptoms; could be asymptomatic. Liver enzyme elevation is mild to extreme range in some caseUS and CT shows increased echogenicity. Dual-Echo MRI; iso-intense between the in-phase and out-of-phase images, and low intensity on subtractionGlycogen 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 biopsyOptimal control of DMMay have mild fibrosis, severe fibrosis is very rare and seen in only a few reported cases
GSDInborn errors of glucose and glycogen metabolism results in abnormal deposition of glycogenPresentation 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, etcLike GHFindings vary in different type of GSDs; Nonspecific histologic findings to PAS positive glycogen deposition which could be diastase sensitive or resistantBiochemical tests and molecular testingSymptomatic treatment to dietary changes to maintain the blood glucose level and pharmacologic therapy in different types of GSDs. May need liver transplantation in selected casesSome GSD can progress to cirrhosis
NAFLDHepatic steatosisMost patients asymptomatic and some may have minor symptoms, Liver enzymes elevation usually < 5 times upper limit of normalUS 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 fibrosisRadiologic and liver biopsyLifestyle modification and pharmacologic therapies. May need liver transplant in advanced cirrhosisCan progress to cirrhosis
HepatosclerosisIs a hepatic manifestation of microangiopathic disease seen in long -standing DMOften clinically silent, Serum aminotransferases are normal or minimally elevated. ALP, Total bilirubin may be elevatedNo specific imaging characteristicsExtensive dense perisinusoidal fibrosisLiver biopsyUnknownUnknown
AIHChronic Hepatitis of unknown etiologySpectrum of clinical manifestations ranges from asymptomatic patients to those with considerable symptoms, and rarely presents with acute liver failureNo characteristic imaging features, may show cirrhotic liver in advance caseInterface hepatitis and portal lymphoplasmacytic infiltrate with varying degree of fibrosisCharacteristic biochemical tests and liver biopsyGlucocorticoid monotherapy or in combination with immunomodulators. Rarely may require liver transplantationCan progress to cirrhosis
HemochromatosisAutosomal recessive disorder. Mutations cause increased iron absorption and excessive deposition in the liver, heart, pancreas, and pituitaryAsymptomatic or chronic liver disease with elevated transaminases, skin pigmentation, DM, arthropathy, impotence and cardiac enlargement, etcMRI 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 determinedBiochemical tests including genetic testing, radiologic, and liver biopsyPhlebotomy or Chelation therapy if unable to tolerate phlebotomyCan progress to cirrhosis
Wilson diseaseAutosomal 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 subnormalUS, CT, may show signs of cirrhosis and normal caudate lobe which is contrary to other types cirrhosisVary largely from fatty changes to cirrhosis and occasionally fulminant hepatic necrosis. Can be stained for copperBiochemical tests and slit lamp examination with or without genetic testing and liver biopsyTreatment with a chelating agent. Some cases may require liver transplantationCan progress to cirrhosis
Acute viral hepatitis A, B, C, D and E. Rarely, HSV, VZ, EBV and CMVHepatitis 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 motherMany of the symptoms are nonspecific; May have marked elevation in transaminases often > 15 times the normalUS or CT findings are nonspecific; Could be used to rule out other causesLiver biopsy shows hepatocyte necrosis with a portal, periportal and lobular lymphocytic infiltration; Plasma cells present during resolving phaseDiagnosis by biochemical testsTreatment conservative or antiviral therapyAcute infection may progress to chronic, and that may progress to cirrhosis