Glycogenic Hepatopathy Research Articles

Abstract #1184181: A case report about glycogenic hepatopathy

Glycogenic hepatopathy (GH) is a rare complication of uncontrolled diabetes mellitus that presents with hepatomegaly with transient elevation in serum aminotransferase enzymes. The pathophysiology of this condition presents with excessive accumulation of intrahepatic glycogen. GH is usually underdiagnosed because it is difficult to differentiate from other entities, such as nonalcoholic fatty liver (NAFLD). The gold standard to make the diagnosis is to perform a liver biopsy. GH can be reversed by the achievement of adequate glycemic control. A 19-year-old with history of poorly controlled type 1 diabetes mellitus that resulted in multiple prior admissions due to diabetic ketoacidosis. The patient presented to the emergency room with generalized weakness and fatigue found to have diabetic ketoacidosis. Blood tests revealed abnormal liver function with AST of 1129 U/L (13-37 U/L), ALT 766 U/L (13-56 U/L), Alkaline Phosphatase 216 (45-117), Total Bilirubin 1.0 (0.2-1.3 mg/dL), Albumin 3.8 (3.4-5.0 g/dl), PTT < 20s (23-31s), PT 11.8 (9.5-11.5s) and INR 1.1. Acute hepatitis serologies were negative. EBV and CMV were ruled out. Extensive autoimmune hepatitis tests were negative. Primary biliary cirrhosis was also ruled out. Then a liver biopsy was obtained; which provided a positive diagnosis for glycogenic hepatopathy. GH is a disorder associated with uncontrolled diabetes mellitus. It is characterized by a pathologic accumulation of glycogen in the hepatocytes. It is predominantly seen in patients with type 1 diabetes mellitus and is associated with recurrent episodes of DKA and higher HbA1C levels. Clinical symptoms vary from asymptomatic to abdominal pain, nausea or vomiting, or can present with signs of acute hepatitis. Most patients present with a higher AST to ALT levels. Diagnosis can be confirmed by performing a liver biopsy, which is characterized by the accumulation of glycogen in the cytoplasm and the nuclei of the hepatocytes. This is demonstrated by periodic acid-Schiff staining. There is no role for noninvasive tests like fibroscan or fibrotest for the diagnosis of GH or for differentiation of this situation from nonalcoholic fatty liver disease. Strict glycemic control results in improvement of liver function in patients with GH. GH must be suspected in patients, with type 1 diabetes mellitus, which present with elevated liver enzymes and abdominal pain. Treating this rare condition requires a timely diagnosis that include the following criteria: 1) perform a liver biopsy and 2) ensure strict glycemic control.

Acute glycogenic hepatopathy in pregnancy: a case report and literature review

Abstract Objectives Acute glycogenic hepatopathy (AGH) is a rare complication of poorly controlled diabetes mellitus. This is the first report in the English literature describing accurate diagnosis and management of AGH during pregnancy. Case presentation A 46 year-old gravida 4 para 2 presented at 30 weeks gestation with uncontrolled diabetes, ketoacidosis, and severe hypertension. Euglycemia and normotension were achieved within 24 h of admission but serum transaminase levels which had been normal on admission increased to a very high level over several days, and then resolved spontaneously. Conclusions AGH may occur during pregnancy and should be considered in the context of chronic poorly controlled overt diabetes, rapid normalization of maternal blood glucose levels following high dose insulin therapy, and unexplained new-onset serum transaminase levels elevation. Accurate diagnosis is important because the correct treatment is conservative management, not delivery.

Acute Benign Hepatitis Due to Glycogen Hepatopathy

Glycogen hepatopathy is a very rare and forgotten complication of poorly controlled type 1 diabetes mellitus. Glycogen hepatopathy may also present in type II diabetes mellitus, especially when managed with high doses of insulin. Although it is a benign condition, it is rarely diagnosed in a timely manner. It is characterised by hepatomegaly causing abdominal pain due to stretch on the liver capsule causing capsulitis, and derangement of liver enzymes. In this article we report a patient who presented with severe abdominal pain, hepatomegaly and transaminitis, the symptoms persisted for one year before the diagnosis of glycogen hepatopathy was made.

Hepatic Glucose Metabolism and Its Disorders in Fish.

Carbohydrate, which is the most abundant nutrient in plant-sourced feedstuffs, is an economically indispensable component in commercial compound feeds for fish. This nutrient can enhance the physical quality of diets and allow for pellet expansion during extrusion. There is compelling evidence that an excess dietary intake of starch causes hepatic disorders, thereby further reducing the overall food consumption and growth performance of fish species. Among the severe metabolic disturbances are glycogenic hepatopathy (hepatomegaly caused by the excessive accumulation of glycogenin hepatocytes) and hepaticsteatosis (the accumulation of large vacuoles of triacylglycerols in hepatocytes). The development of those disorders is mainly due to the limited ability of fish to oxidize glucose and control blood glucose concentration. The prolonged elevations of blood glucose increase glucose intake by the liver, and excess glucose is stored either as glycogen through glycogenesis in hepatocytes or as triglycerides via lipogenesis in tissues, depending on the species. In some fish species(e.g., largemouth bass), the liver has a low ability to regulate glycolysis, gluconeogenesis, and glycogen breakdown in response to high starch intake. For most species of fish, the liver size increases with lipid or glycogen accumulation when they have a high starch intake. It is a challenge to develop the same set of diagnostic criteria for all fish species as their physiology or metabolic patterns differ. Although glycogenic hepatopathy appears to be a common disease in carnivorous fish, it has been under-recognized in many studies. As a result, understanding these diseases and their pathogeneses in different fish species is crucial for manufacturing cost-effective pellet diets to promote the health, growth,survival, and feed efficiency of fish in future.

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

Autoimmune destruction of pancreatic β-cells results in the permanent loss of insulin production in type 1 diabetes (T1D). The daily necessity to inject exogenous insulin to treat hyperglycemia leads to a relative portal vein insulin deficiency and potentiates hypoglycemia which can induce weight gain, while daily fluctuations of blood sugar levels affect the hepatic glycogen storage and overall metabolic control. These, among others, fundamental characteristics of T1D are associated with the development of two distinct, but in part clinically similar hepatopathies, namely non-alcoholic fatty liver disease (NAFLD) and glycogen hepatopathy (GlyH). Recent studies suggest that NAFLD may be increasingly common in T1D because more people with T1D present with overweight and/or obesity, linked to the metabolic syndrome. GlyH is a rare but underdiagnosed complication hallmarked by extremely brittle metabolic control in, often young, individuals with T1D. Both hepatopathies share clinical similarities, troubling both diagnosis and differentiation. Since NAFLD is increasingly associated with cardiovascular and chronic kidney disease, whereas GlyH is considered self-limiting, awareness and differentiation between both condition is important in clinical care. The exact pathogenesis of both hepatopathies remains obscure, hence licensed pharmaceutical therapy is lacking and general awareness amongst physicians is low. This article aims to review the factors potentially contributing to fatty liver disease or glycogen storage disruption in T1D. It ends with a proposal for clinicians to approach patients with T1D and potential hepatopathy.

S2596 Glycogenic Hepatopathy: A Rare Cause of Reversible Severe Hepatitis

Introduction: Glycogenic hepatopathy (GH) is a rare reversible complication of poorly controlled diabetes mellitus. Its presentation can range from mild to severe hepatitis and diagnosis can be challenging. Here we present a case of GH presenting as severe hepatitis. Case Description/Methods: A 51-year-old male with a history of hypertension and poorly uncontrolled T1DM presented with two days of intractable nausea and vomiting. Physical examination revealed cachectic male only oriented to name. Abdominal exam was normal without tenderness to palpation or organomegaly. Laboratory results were significant for bicarbonate < 5.0 mmol/L, glucose 1169 mg/dL, total bilirubin (T bili.) 0.4 mg/dL, alkaline phosphatase (ALKP) 141 U/L, alanine aminotransferase (ALT) 161 U/L, aspartate aminotransferase (AST) 107 U/L, albumin 3.6 g/dL, INR 1.0, hemoglobin A1c 13.7%. Head computed tomography showed no acute intracranial pathology. He was admitted to the intensive care unit, diagnosed with DKA and treated with insulin infusion therapy. On day 4, laboratory results showed T bili. 0.4 mg/dL, ALKP 295 U/L, ALT 1570 U/L, AST 5250 U/L, INR 1.0. An ultrasound showed mild hepatomegaly 14cm, hyperechoic liver parenchyma, no intra or extra hepatic biliary dilation, and patent hepatic and portal veins. Workup of viral hepatitis A, B and C, autoimmune hepatitis, Wilson’s disease, alpha 1 antitrypsin deficiency, and hemochromatosis was negative. An ultrasound guided liver biopsy showed diffuse swollen hepatocytes, minimal focal fibrosis and mild inflammation composed of scattered lymphocytes, plasma cells and few polymorphonuclear leukocytes. Periodic acid-Schiff (PAS) stain with and without diastase highlighted abundant cytoplasmic glycogen. Patient was diagnosed with GH and a rapid downtrend in liver enzymes was noted with DKA treatment. Discussion: GH was first described by Peter Mauriac in 1930 in children with uncontrolled T1DM. Its incidence is unknown as there have been less than 100 cases reported so far in English literature. Pathophysiology of GH remains unclear but rapid fluctuations in glucose and insulin leading to excessive glycogen deposition in hepatocytes has been suggested. Distinguishing GH from NASH, DILI and other chronic liver disease is challenging without a liver biopsy. With proper glycemic control, GH is quickly reversible and has a good prognosis. No long term hepatic complications are known. GH remains underdiagnosed due to a combination of diagnostic challenges and lack of awareness amongst specialists.Figure 1.: Histopathological section of the liver showing: A) Hepatocytes with clear and fine granular cytoplasm under hematoxylin and eosin stain, B) PAS stain showing large amount of dark red-colored glycogen in hepatocytes, C) Complete digestion of glycogen after adding diastase stain and reappearance of clear hepatocytes.

S2817 Glycopenic Hepatopathy in a Patient With Recurrent Diabetic Ketoacidosis: A Rare Complication of Poorly Controlled Type 1 Diabetes Mellitus

Introduction: Glycogenic hepatopathy (GH) is a rare condition predominately seen in patients with poorly controlled type 1 diabetes mellitus. This condition develops due to excessive accumulation of glycogen in the hepatocytes, leading to significant hepatomegaly and transient liver dysfunction with elevated liver enzymes. Case Description/Methods: A 24-year-old female with a history of poorly controlled type 1 diabetes mellitus complicated by multiple admissions for diabetic ketoacidosis (DKA) presented with acute onset abdominal pain, nausea and vomiting. Physical exam was significant for tender hepatomegaly. Admission laboratory results were significant for serum glucose 189 mg/dL, bicarbonate 5 mmol/L, anion gap 35 mmol/L, beta-hydroxybutyrate 6.5 mmol/L, and HbA1c 11.4%. Admission hepatic panel was significant for alanine aminotransferase 31 U/L, aspartate aminotransferase 56 U/L, alkaline phosphatase 138 U/L with normal bilirubin and prothrombin time. Patient was treated with insulin and intravenous fluids with resolution of her DKA. However, her clinical course was complicated by persistent abdominal pain with an acute rise in liver enzymes (alanine aminotransferase 216 U/L, aspartate aminotransferase 249 U/L, alkaline phosphatase 116 U/L with normal bilirubin and prothrombin time). Triglyceride level was elevated at 214mg/dL. Abdominal computed tomography was notable for hepatomegaly with liver size of 24 cm. Workup for hepatitis, HIV, COVID-19, autoimmune hepatitis, hemochromatosis, and Wilson's disease were negative. Patient underwent liver biopsy that demonstrated diffuse hepatocyte cytoplasmic clearing, consistent with GH. The patient was medically managed with strict glycemic control, diabetic diet and endocrinology input throughout admission. One week after hospital discharge, the patient remained asymptomatic and liver function tests returned to normal limits. Discussion: GH is a rare condition that should be considered in patients with poorly controlled diabetes mellitus who present with hepatomegaly and acute liver injury. While GH presents similarly to NAFLD, it can only be differentiated and definitely diagnosed by liver biopsy. This condition should not be overlooked as it is a favorable diagnosis with a good prognosis compared to other liver disease associated with diabetes mellitus. Further studies are needed to better understand the characteristics of this disease, and future development of non-invasive, rapid diagnostic testing could help avoid extensive and costly workups. (Figure Presented).

S2581 LAL-D: A Rare Liver Disease

Introduction: Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disease associated with abnormal liver enzyme elevation. Mutations in the LIPA gene cause lysosomal acid lipase deficiency with the inability to break down cholesteryl esters in the body. Cholesteryl ester storage disease is associated with an abnormal accumulation of cholesteryl ester and triglycerides in various organs, including the liver, spleen, intestinal mucosa, and lymph nodes, to name a few. There are very few cases of LAL-D reported in the adult population. Case Description/Methods: An 18-year-old male with no significant medical history presented to the outpatient hepatology clinic for evaluation of elevated liver enzymes. The physical exam was unremarkable. Further work-up revealed leukopenia, lymphocytopenia, and elevated INR. The lipid profile was unremarkable. Ultrasound of the liver revealed mild hepatomegaly, splenomegaly, and porta hepatis lymphadenopathy. CT of the abdomen with contrast revealed diffuse hypodense liver suggesting fatty liver disease, massive splenomegaly. Liver biopsy performed and revealed glycogenic hepatopathy with periportal and focal bridging fibrosis. The patient also underwent an esophagogastroduodenoscopy with biopsy, which showed clear foamy appearing cytoplasm that contains PAS-positive and diastase-resistant material. Chronic liver disease work-up was unrevealing except for positivity for alpha-1-antitrypsin deficiency carrier (MZ phenotype). Measurement of liposomal acid lipase in the leukocytes from the blood sample was zero (0) with genetic testing confirmation of LAL-D. The patient was referred to the transplant center to initiate the lysosomal acid lipase infusion treatment with close follow-up. Discussion: Liver damage in cholesteryl ester storage disease may progress to hepatocellular failure along with fibrosis and micronodular cirrhosis. Commonly, patients are misdiagnosed with non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cryptogenic cirrhosis, heterozygous familial hypercholesterolemia. It is imperative that gastroenterologists are familiar with the diagnostic and therapeutic approaches for this rare illness termed lysosomal acid lipase deficiency.

Elevated lactate in Mauriac syndrome: still a mystery

BackgroundThe Mauriac syndrome was described in 1930 as a peculiar combination of poorly controlled diabetes mellitus type 1, stunted growth and glycogenic hepatopathy. More recently, lactic acidosis was recognized as an additional feature, often induced by insulin treatment.Case presentationA 17-year old girl known for diabetes type 1A and Mauriac syndrome was admitted to the emergency room with hyperglycemia of > 41 mmol/l without ketoacidosis. Under a standard insulin regimen, hyperglycemia was rapidly corrected but marked hyperlactatemia occurred.ConclusionsThe mechanism of impaired glucose utilization and lactate elevation independent of ketoacidosis in Mauriac syndrome is intriguing. The rarity of Mauriac syndrome and its resemblance to glycogen storage diseases suggest the presence of a specific metabolic or genetic predisposition that remains to be identified.

Liver Damage in Type 1 Diabetes Mellitus

Aim. An up-to-date review of the prevalence, pathogenesis, diagnosis and management of hepatological complications of type 1 diabetes mellitus (T1D).Key points. Diabetes type 1 causes a markedly more common liver injury than traditionally assumed. Three types of hepatic damage have been described to date in T1D patients, steatosis, glycogen hepatopathy and diabetic hepatosclerosis, with the latter two apparently pathognomonic of this diabetes type. Their pathogenesis is complex and not fully understood. Its important link is a likely inherited non-physiological insulin supply to the tissue, especially at marked glycaemic fluctuations. An adequate glycaemic control is the main prevention and treatment measure in these conditions. The practitioner’s understanding of liver damage in T1D is an earnest to avoid unnecessary tests and ineffective medications.Conclusion. Both endocrinologists and internists ought to contemplate the possibility of liver involvement in T1D for improving the patient outcomes.

Glycogenic Hepatopathy in a Patient with Pancreatogenic Diabetes

Glycogenic hepatopathy is characterized by acute liver injury secondary to reversible accumulation of excess glycogen in hepatocytes. This phenomenon has been described in type 1 diabetes, with few cases reported in patients with type 2 diabetes. Glycogenic hepatopathy in the setting of pancreatogenic (type 3c) diabetes has yet to be reported.A 57-year-old female with a history of insulin-requiring pancreatogenic diabetes mellitus secondary to alcohol-induced chronic pancreatitis status post distal pancreatectomy presented with recurrent admissions for abdominal pain, hyperglycemia, hyperosmolar hyperglycemic state (HHS), and unexplained elevation of liver transaminase levels. Glycemic control remained poor over many years with consistently elevated HbA1c in the setting of labile blood sugars, medication noncompliance, and lifestyle non-adherence.The patient was admitted to the hospital with altered mental status and markedly elevated blood glucose (1,182 mg/dL) concerning for HHS. On admission, her liver function tests (LFTs) revealed elevated alkaline phosphatase (1,011 U/L, n <150 U/L), AST (583 U/L, n <34 U/L), and ALT (517 U/L, n <55 U/L). Direct and total bilirubin were within normal limits. The patient underwent extensive workup including drug and toxin levels, autoimmune evaluation, serology for infectious causes, abdominal computed tomography scanning, right upper quadrant ultrasound, and magnetic resonance cholangiopancreatography (MRCP). All laboratory workup was negative, ultrasound was unremarkable, and MRCP showed no evidence of biliary or common bile duct dilatation. Throughout her hospitalization, LFTs gradually improved with optimization of blood glucose.Less than one week later, the patient returned with blood glucose of 673 mg/dL and LFTs notable for alkaline phosphatase 789 U/L, AST 1,068 U/L, and ALT 299 U/L. Again, all testing was negative for causes of rapid increase in liver enzymes. Similar to previous admissions, her LFTs improved with resolution of hyperglycemia. Review of electronic medical record revealed a similar trend during previous admissions. The patient did not undergo liver biopsy; however, the parallel relationship of LFTs and hyperglycemia, in the absence of radiologic or laboratory evidence of alternate liver pathology, supports the diagnosis of glycogenic hepatopathy.This is the first case of glycogenic hepatopathy reported in a patient with pancreatogenic diabetes. Due to the rarity of this condition and minimal literature of its occurrence in adult non-type-1 diabetics, glycogenic hepatopathy is likely infrequently considered when evaluating patients with recurrent hyperglycemia and elevated LFTs. This case accentuates the need for further research of this condition in non-type 1 diabetics as the prognosis and management differ from other forms of acute liver injury.

Endocrinopathies Associated With High Dose Methadone

Abstract Introduction: The opioid epidemic is a public health crisis and clinicians should be aware of the many under-recognized endocrinopathies associated with opioids. Herein, we present a case that exemplifies the endocrine-related adverse effects of methadone therapy. Clinical Case: A 43-year-old Caucasian female with chronic back pain with opioid dependence, high dose methadone use (195 mg daily), and diabetes presented with refractory hypoglycemia. She was diagnosed with ketone prone diabetes eight months prior. She had since been weaned off insulin and her most recent HbA1c was 4.2%. During this time, she had an intentional weight loss of 60 pounds. On examination, she had bilateral lower extremity pitting edema with scaly plaques on the extremities. Laboratory tests showed C-peptide of 0.8 (0.9–7.1 ng/mL), insulin level of &amp;lt; 2 (3–25 mcIntUnits/mL), proinsulin of 4.6 (&amp;lt;18.8 pMol/L) with concurrent glucose of 48 mg/dl. She failed the ACTH stimulation test with 60 minute cortisol of 16.8 mcg/dL and was started on prednisone for adrenal insufficiency (AI). The pituitary and adrenal were normal on imaging. Her albumin was 1.5 (3.7–5.5 gm/dL) and she had vitamin and micronutrient deficiencies including copper, zinc, thiamine, selenium, and vitamin A. The insulin antibody test, paraneoplastic panel, celiac panel, A1 antitrypsin test, EGD, and colonoscopy were all non-revealing. A liver biopsy showed glycogenic hepatopathy. She improved clinically after prednisone initiation and treatment of malnutrition. The hypoglycemia improved but did not resolve as she refused to reduce methadone dose. Discussion: The proposed mechanism of opioid-induced AI is the inhibitory effect on the hypothalamic-pituitary-adrenal axis, similar to the effect on the gonadal axis which causes hypogonadism. The risk for hypoglycemia is increased in patients taking more than 40 mg of oral methadone per day, and although the mechanism remains unclear, it is independent of adrenal function. Our patient had adrenal insufficiency and hypoglycemia related to methadone, which was further complicated by malnutrition. The glycogenic hepatopathy is a benign reversible condition that is believed to be a consequence of fluctuation in glucose levels. Conclusion: Given the life-threatening nature of adrenal crisis and the overlap in symptomatology with opiate overdose, clinicians should be prompt in evaluating for endocrinopathies in patients on chronic high dose opiates, and patients should be appropriately counseled on the potential consequences of methadone use.

Mauriac syndrome: a rare cause of massive hepatomegaly

Mauriac syndrome or glycogen hepatopathy (GH) is an uncommon complication of poorly controlled type 1 diabetes mellitus commonly occurring in adolescents. It has become even less common after the emergence of advances on diabetes treatment, but still exists. It manifests as growth failure, hepatomegaly, elevated liver enzymes, and accumulation of glycogen in hepatocytes related to poorly controlled diabetes and a glucose trap in the liver. GH has got good prognosis and fast resolution after adequate glycemic control, with no progression to end-stage liver disease. We report a 10-year-old boy with poorly controlled type I diabetes mellitus (on pre-mix insulin), hepatomegaly, and extremely high levels of liver transaminases. He underwent a liver biopsy elsewhere which showed glycogen deposits. He was referred to our institution for confirmation of diagnosis of glycogen storage disorder. Clinical examination revealed short stature, moon facies, and protuberant abdomen with hepatomegaly of 8 cm below the right costal margin. After exclusion of other causes of hepatitis, we controlled his sugars using basal bolus insulin regimen. Clinical exome sequencing revealed no abnormal mutations in the enzymes linked to glycogen metabolism. In an about 8 weeks, his transaminases normalized and hepatomegaly regressed.

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

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. 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. A total of 192 patients were included, with median age of 20years, 73% adults, 66% females, median duration of T1DM before diagnosis 10years, median adult body mass index 21kg/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. 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.

Glycogenosis is common in nonalcoholic fatty liver disease and is independently associated with ballooning, but lower steatosis and lower fibrosis.

Background/AimsGlycogen synthesis and storage are normal hepatocyte functions. However, glycogenosis, defined as excess hepatocyte glycogen visible by routine H&E light microscopy, has not been well characterized in nonalcoholic fatty liver disease (NAFLD).MethodsGlycogenosis in NAFLD liver biopsies was graded as “none”, “focal” (in <50% of hepatocytes), or “diffuse” (in ≥50% of hepatocytes). Clinical and pathological variables associated with glycogenosis were assessed. 2047 liver biopsies were prospectively analysed.ResultsIn adults and children, any glycogenosis was present in 54% of cases; diffuse glycogenosis was noted in approximately 1/3 of cases. On multiple logistic regression analysis, adults with glycogenosis tended to be older (P = .003), female (P = .04), have higher serum glucose (P = .01), and use insulin (P = .02). Adults tended to have lower steatosis scores (P = .006) and lower fibrosis stages (P = .005); however, unexpectedly, they also tended to have more hepatocyte injury including ballooning (P = .003). On multiple logistic regression analysis, paediatric patients with glycogenosis were more likely to be Hispanic (P = .03), have lower body weight (P = .002), elevated triglycerides (P = .001), and a higher fasting glucose (P = .007). Paediatric patients with glycogenosis also had less steatosis (P < .001) than those without.ConclusionsGlycogenosis is common in adult and paediatric NAFLD, and is associated with clinical features of insulin resistance. Glycogenosis is important to recognize histologically because it may be misinterpreted as ballooning, and when diffuse, confusion with glycogen storage disorders or glycogenic hepatopathy must be avoided. The newly observed dichotomous relationship between glycogenosis and increased liver cell injury but decreased steatosis and fibrosis requires further study.

Glycogenic hepatopathy in children with poorly controlled type 1 diabetes mellitus

.Mauriac syndrome is a rare and underdiagnosed complication of type 1 diabetes mellitus (T1DM). It is characterized by growth retardation, delayed puberty, Cushingoid features, hepatomegaly, and increased transaminase levels. The term glycogenic hepatopathy has been used to describe patients with poorly controlled T1DM and glycogen overload in the hepatocytes but without all the features of Mauriac syndrome. Although rare, glycogenic hepatopathy is reported to be the main cause of hepatomegaly in young patients with T1DM. We report two cases of glycogenic hepatopathy in children with poorly controlled T1DM. Both children had hepatomegaly, elevated liver enzyme levels, and elevated lactate levels. A liver biopsy confirmed the diagnosis of glycogenic hepatopathy in both patients. In conclusion, hepatomegaly with elevated liver enzymes, negative infective and metabolic screenings and persistently elevated plasma lactate levels should raise the suspicion of glycogenic hepatopathy in poorly controlled T1DM. Early diagnosis and improvement in glycemic control are the mainstays of treatment, which can prevent long-term complications.

A case of type 2 diabetes with glycogenic hepatopathy

A case of type 2 diabetes with glycogenic hepatopathy

Features of Dynamic Computed Tomography Imaging of Glycogenic Hepatopathy.

Features of Dynamic Computed Tomography Imaging of Glycogenic Hepatopathy.

S2490 Glycogenic Hepatopathy Masquerading as Acute Pancreatitis

INTRODUCTION: Glycogenic hepatopathy (GH) is underrecognized amongst clinicians.1,2 We present a case of GH clinically appearing at first as acute pancreatitis. CASE DESCRIPTION/METHODS: A 20-year-old female with a medical history of poorly controlled T1DM and prior episode of pancreatitis, presented with sharp epigastric pain worsened by eating. The patient was tachycardic to 115 bpm and physical exam revealed tenderness in the RUQ-epigastric region with negative Murphy's. Lab work was significant for WBC count 12,900/ μL, lipase 353 U/L, amylase 264 U/L, BHBA 3.02 mmol/L, HbA1C 13.5, ALT and AST 34 U/L and later AST 51 U/L, ALK 191, TG 162 mg/dL, and lactate 5.4 mmol/L which increased to 8.2 mmol/L. CT abdomen revealed hepatomegaly of approximately 24–25 cm craniocaudally, hepatic steatosis, trace pelvic ascites, and normal pancreas. Abdominal U/S showed an enlarged liver with diffuse increase in parenchymal echogenicity, consistent with steatosis, without any focal lesions. Mesenteric vascular doppler showed normal vasculature and flow. Hepatitis panel, iron panel, ANA, anti-smooth muscle antibody, and ceruloplasmin were negative. Liver biopsy showed preserved parenchyma without fibrosis, focal mild macrovesicular steatosis, and occasional glycogenated nuclei. The hepatocytes had increased swelling and cytoplasmic clearing, suggestive of glycogen deposition. PAS stain revealed abundant hepatocyte glycogen deposits which were not visible after diastase digestion. The histological findings are consistent with a GH diagnosis. DISCUSSION: GH, characterized by tender hepatomegaly with elevated liver enzymes in the setting of DM, exists within the Mauriac Syndrome spectrum, but lacks the syndrome's additional cushingoid features and poor growth. GH almost always occurs with T1DM and has slight female predominance. The pathobiology of GH may involve oscillation of glucose levels with poor insulin management leading to hepatocyte glucose trapping and glycogenosis.1 Biochemical findings include elevated HbA1c, AST greater than ALT, and elevated ALK.1,2 Increased amylase and lipase levels are reported as in our patient.3 DKA and lactic acidosis is common.4 Ascites has been reported.1 On CT the liver is hyperdense, unlike a hypodense liver of NAFLD.5 Definitive diagnosis is by findings of swollen hepatocytes with glycogen accumulation on biopsy, with limited or absent fatty change, inflammation, necrosis or fibrosis.1 Unlike NAFLD which may progress to fibrosis or cirrhosis, GH resolves with dysglycemia control.6,7Figure 1.: Benign liver parenchyma with focal mild macrovascular steatosis. Many hepatocytes have increased swelling and cytoplasmic clearing.Figure 2.: Occasional glycogenated nuclei are seen, as indicated by the black arrow.Figure 3.: A PAS stain highlights abundant glycogen in the hepatocytes, as evidenced by the magenta staining, but is not seen in the PASD stain (PAS stain after diastase pretreatment).

AN UNUSUAL CAUSE OF TRANSAMINITIS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Elevation of liver enzymes often results from damage to the liver or biliary tract. Transaminitis may be seen in patients with sign and symptoms suggestive of liver disease or it may be an incidental finding on laboratory investigations. The initial evaluation of a patient with transaminitis includes obtaining thorough history to identify potential risk factors and performing a physical examination to look for the signs of liver disease and clues to the etiology. CASE PRESENTATION: 36 year old Caucasian male with history of type-1 diabetes mellitus presented with generalized weakness, fatigue and body aches. Hemodynamics were stable. He was noted to have sodium 123 meq/L( 135-145), potassium 6.9 meq/L( 3.7-5.2 meq/L), bicarbonate 21 meq/L( 23-30 meq/L) creatinine 2.31 mg/dL( 0.8-1.1 mg/dL), AST 2792 U/L( 5-40 U/L), ALT 1671U/L( 7-56 U/L), total bilirubin 0.7 mg/dL , blood glucose 966 mg/dL , beta-hydroxybutyrate 0.3 mmol/L( 0.4-0.5 mmol/L), CK total 109 U/L( 22-98 U/L). Patient was diagnosed with hyperglycemic-hyperosmolar state. Appropriate therapy was started including intravenous fluids and insulin. Prior blood workup did not reveal any liver function abnormality. There was no history of intravenous drug use, blood transfusions, skin tattooing or any recent travel. Salicylate and acetaminophen levels were unremarkable. Differential diagnosis including acute viral hepatitis, drug induced liver injury, infiltrative disease, autoimmune and alcoholic hepatitis were considered. Blood workup including hepatitis A, B & C serology, ANA, anti-mitochondrial and anti-smooth muscle antibody were unremarkable. Alpha-1 antitrypsin, serum ceruloplasmin and iron studies were unremarkable as well. During the course of hospitalization, transaminitis significantly improved (AST 50 U/L and ALT 317 U/L) with the treatment of hyperglycemia, hence, was attributed to severe hyperglycemia associated with poorly controlled diabetes mellitus. Later, patient had normalization of liver enzymes upon outpatient follow up. DISCUSSION: Glycogen Hepatopathy (GH) is a rare cause of transaminitis in patients with uncontrolled type 1 diabetes mellitus. It is characterized by hepatomegaly related to glycogen accumulation and elevated liver enzymes. Glycogen accumulation takes place in the liver when hyperglycemia activates glycogen synthase enzyme.The hallmark of GH is its reversibility with improved glycemic control.The correct diagnosis is important given its potential resolution after improved glycemic control. CONCLUSIONS: Hyperglycemia is a rare cause of transaminitis but should be kept in differentials particularly in patients with diabetes mellitus. Reference #1: Kumar K, Mehershahi S, Chime C, Tariq H, Nayudu SK, Chilimuri S. Glycogen Hepatopathy: A Rare and Underrecognized Cause of Recurrent Transaminitis in Patients with Uncontrolled Type 2 Diabetes Mellitus. Case Rep Gastroenterol. 2018;12(2):466-472. Published 2018 Aug 23. doi:10.1159/000492205 Reference #2: J. West, J. Brousil, A. Gazis et al., “Elevated serum alanine transaminase in patients with type 1 or type 2 diabetes mellitus,” QJM, vol. 99, no. 12, pp. 871–876, 2006. Reference #3: Kumar, Kishore MD; Mehershahi, Shehriyar MD; Nayudu, Suresh Kumar MD; Singh, Amandeep MD; Bajantri, Bharat MD; Chilimuri, Sridhar MDAuthor Information American Journal of Gastroenterology: October 2016 - Volume 111 - Issue - p S851-S852 DISCLOSURES: No relevant relationships by Muhammad Aamir, source=Web Response No relevant relationships by Muhammad Afzal, source=Web Response No relevant relationships by Saleha Dar, source=Web Response