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Acute and Relapsing Hepatitis Caused by Glycogenic Hepatopathy
Accepted Manuscript Acute and Relapsing Hepatitis Caused by Glycogenic Hepatopathy Neil D. Shah, Eizaburo Sasatomi, Todd H. Baron
PII: DOI: Reference:
S1542-3565(17)30148-9 10.1016/j.cgh.2017.02.004 YJCGH 55102
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 3 February 2017 Please cite this article as: Shah ND, Sasatomi E, Baron TH, Acute and Relapsing Hepatitis Caused by Glycogenic Hepatopathy, Clinical Gastroenterology and Hepatology (2017), doi: 10.1016/ j.cgh.2017.02.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Acute and Relapsing Hepatitis Caused by Glycogenic Hepatopathy
Neil D. Shah1, Eizaburo Sasatomi2 and Todd H. Baron1 Division of Gastroenterology and Hepatology1, Department of Pathology and Laboratory Medicine2
Neil D. Shah: Drafting of Manuscript Eizaburo Sasatomi: Acquisition of Pathology images Todd H. Baron: Critical revision of manuscript
Neil D. Shah: None to Report Eizaburo Sasatomi: None to Report
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Disclosures:
SC
Author Involvement:
RI PT
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Todd H. Baron: Speaker and Consultant with Medtronic, BSCI, Cook and Olympus
Todd H. Baron, MD
TE D
Address for correspondence:
130 Mason Farm Road, CB 7080 Chapel Hill, NC 27599
Fax: 984-974-0744
EP
Phone: 984-974-0132
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E-mail: [email protected]
Word Count: 542 (Including References)
ACCEPTED MANUSCRIPT
A 31 year-old woman with long-standing type 1 diabetes mellitus (DM) and prior cholecystectomy was referred for evaluation of persistent, abnormal liver function tests (LFTs) and recurrent acute pancreatitis. There was no prior history of heavy alcohol intake. She was hospitalized 6 weeks prior with nausea, vomiting and abdominal pain. Laboratory parameters revealed alanine
RI PT
transaminase (ALT) 756 U/L, aspartate transaminase (AST) 2334 U/L, alkaline phosphatase (ALP) 287 U/L, total bilirubin 2.4 mg/dL, lactic acid 6.4 mmol/L and INR 1.0. Abdominopelvic CT showed only
hepatomegaly. Additional labs included negative viral hepatitis serologies, negative transglutaminase IgA, negative anti-mitochondrial antibody, negative anti-smooth muscle antibody and positive
SC
antinuclear antibody with titer 1:160 in a homogeneous pattern. Her hospital course was complicated by development of diabetic ketoacidosis (DKA). After resolution of her acute illness, LFTs normalized. Four weeks later she was re-admitted for acute pancreatitis and DKA. ALT was 268 U/L, AST 344 U/L, ALP 289
M AN U
U/L, and total bilirubin 1.8 mg/dL. Repeat CT revealed diffuse pancreatic stranding and inflammation, consistent with acute pancreatitis. LFTs again normalized after treatment of DKA and pancreatitis. At presentation to our center, she complained of diffuse abdominal pain. Physical examination, vital signs and body mass index were within normal limits. ALT was 185 U/L, AST 627 U/L, ALP 280 U/L and total bilirubin 0.7 mg/dL. Upper endoscopic ultrasound (EUS) to assess for causes of recurrent
TE D
pancreatitis and abnormal LFTs showed hyperechoic strands and lobularity in the pancreatic parenchyma (Figure 1A). There was no evidence of pathology within the bile duct and no evidence of pancreatic or biliary ductal dilatation or evidence of pancreas divisum. A homogeneous, abnormal echotexture was seen in the left lobe of the liver. EUS-guided liver biopsy with a core needle (Olympus
EP
EZ Shot 3 Plus, Center Valley, PA) was performed as consent was obtained pre-procedurally. Histopathology revealed glycogenic hepatopathy with focal portal tract fibrosis (Figure 1B).
AC C
Glycogenic hepatopathy, a rare and unique condition, is seen in patients with poorly controlled DM where glycogen deposits heavily within hepatocytes.1 Patients may be asymptomatic or present with symptoms of acute DKA such as nausea, vomiting and abdominal pain. On physical exam, hepatomegaly is typically present. LFTs can be elevated up to 10X upper limits of normal. Lactic acid can also be elevated. It is difficult to clinically differentiate from non-alcoholic steatohepatitis (NASH) since both commonly cause hepatomegaly and elevated LFTs; therefore liver biopsy is useful to establish a diagnosis. This is the first case of glycogenic hepatopathy discovered using EUS-guided liver biopsy. The characteristic histologic changes seen include abundant cytoplasmic glycogen deposits within hepatocytes on PAS (Figure 1C). Hepatocytes become “ghost cells” upon diastase digestion of the
ACCEPTED MANUSCRIPT
glycogen (Figure 1D).1 Similar findings are seen in glycogen storage diseases, which should be excluded clinically. Tight glycemic control is the mainstay of therapy which results in complete resolution of symptoms and laboratory abnormalities.2 Our patient had associated recurrent pancreatitis, although its relationship to hepatopathy is unclear. With adjustment of her insulin regimen and improved
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EP
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M AN U
SC
RI PT
adherence, LFTs normalized and there were no further episodes of pancreatitis.
ACCEPTED MANUSCRIPT
References: 1. Torbenson M, et al. Glycogenic hepatopathy: an underrecognized complication of diabetes mellitus. Am J Surg Pathol 2006;30:508-513.
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EP
TE D
M AN U
SC
control. J Diabetes Complications 2008;22:329–330.
RI PT
2. Hudacko RM, et al. Clinical resolution of glycogenic hepatopathy following improved glycemic
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
PII: DOI: Reference:
S1542-3565(17)30148-9 10.1016/j.cgh.2017.02.004 YJCGH 55102
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 3 February 2017 Please cite this article as: Shah ND, Sasatomi E, Baron TH, Acute and Relapsing Hepatitis Caused by Glycogenic Hepatopathy, Clinical Gastroenterology and Hepatology (2017), doi: 10.1016/ j.cgh.2017.02.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Acute and Relapsing Hepatitis Caused by Glycogenic Hepatopathy
Neil D. Shah1, Eizaburo Sasatomi2 and Todd H. Baron1 Division of Gastroenterology and Hepatology1, Department of Pathology and Laboratory Medicine2
Neil D. Shah: Drafting of Manuscript Eizaburo Sasatomi: Acquisition of Pathology images Todd H. Baron: Critical revision of manuscript
Neil D. Shah: None to Report Eizaburo Sasatomi: None to Report
M AN U
Disclosures:
SC
Author Involvement:
RI PT
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Todd H. Baron: Speaker and Consultant with Medtronic, BSCI, Cook and Olympus
Todd H. Baron, MD
TE D
Address for correspondence:
130 Mason Farm Road, CB 7080 Chapel Hill, NC 27599
Fax: 984-974-0744
EP
Phone: 984-974-0132
AC C
E-mail: [email protected]
Word Count: 542 (Including References)
ACCEPTED MANUSCRIPT
A 31 year-old woman with long-standing type 1 diabetes mellitus (DM) and prior cholecystectomy was referred for evaluation of persistent, abnormal liver function tests (LFTs) and recurrent acute pancreatitis. There was no prior history of heavy alcohol intake. She was hospitalized 6 weeks prior with nausea, vomiting and abdominal pain. Laboratory parameters revealed alanine
RI PT
transaminase (ALT) 756 U/L, aspartate transaminase (AST) 2334 U/L, alkaline phosphatase (ALP) 287 U/L, total bilirubin 2.4 mg/dL, lactic acid 6.4 mmol/L and INR 1.0. Abdominopelvic CT showed only
hepatomegaly. Additional labs included negative viral hepatitis serologies, negative transglutaminase IgA, negative anti-mitochondrial antibody, negative anti-smooth muscle antibody and positive
SC
antinuclear antibody with titer 1:160 in a homogeneous pattern. Her hospital course was complicated by development of diabetic ketoacidosis (DKA). After resolution of her acute illness, LFTs normalized. Four weeks later she was re-admitted for acute pancreatitis and DKA. ALT was 268 U/L, AST 344 U/L, ALP 289
M AN U
U/L, and total bilirubin 1.8 mg/dL. Repeat CT revealed diffuse pancreatic stranding and inflammation, consistent with acute pancreatitis. LFTs again normalized after treatment of DKA and pancreatitis. At presentation to our center, she complained of diffuse abdominal pain. Physical examination, vital signs and body mass index were within normal limits. ALT was 185 U/L, AST 627 U/L, ALP 280 U/L and total bilirubin 0.7 mg/dL. Upper endoscopic ultrasound (EUS) to assess for causes of recurrent
TE D
pancreatitis and abnormal LFTs showed hyperechoic strands and lobularity in the pancreatic parenchyma (Figure 1A). There was no evidence of pathology within the bile duct and no evidence of pancreatic or biliary ductal dilatation or evidence of pancreas divisum. A homogeneous, abnormal echotexture was seen in the left lobe of the liver. EUS-guided liver biopsy with a core needle (Olympus
EP
EZ Shot 3 Plus, Center Valley, PA) was performed as consent was obtained pre-procedurally. Histopathology revealed glycogenic hepatopathy with focal portal tract fibrosis (Figure 1B).
AC C
Glycogenic hepatopathy, a rare and unique condition, is seen in patients with poorly controlled DM where glycogen deposits heavily within hepatocytes.1 Patients may be asymptomatic or present with symptoms of acute DKA such as nausea, vomiting and abdominal pain. On physical exam, hepatomegaly is typically present. LFTs can be elevated up to 10X upper limits of normal. Lactic acid can also be elevated. It is difficult to clinically differentiate from non-alcoholic steatohepatitis (NASH) since both commonly cause hepatomegaly and elevated LFTs; therefore liver biopsy is useful to establish a diagnosis. This is the first case of glycogenic hepatopathy discovered using EUS-guided liver biopsy. The characteristic histologic changes seen include abundant cytoplasmic glycogen deposits within hepatocytes on PAS (Figure 1C). Hepatocytes become “ghost cells” upon diastase digestion of the
ACCEPTED MANUSCRIPT
glycogen (Figure 1D).1 Similar findings are seen in glycogen storage diseases, which should be excluded clinically. Tight glycemic control is the mainstay of therapy which results in complete resolution of symptoms and laboratory abnormalities.2 Our patient had associated recurrent pancreatitis, although its relationship to hepatopathy is unclear. With adjustment of her insulin regimen and improved
AC C
EP
TE D
M AN U
SC
RI PT
adherence, LFTs normalized and there were no further episodes of pancreatitis.
ACCEPTED MANUSCRIPT
References: 1. Torbenson M, et al. Glycogenic hepatopathy: an underrecognized complication of diabetes mellitus. Am J Surg Pathol 2006;30:508-513.
AC C
EP
TE D
M AN U
SC
control. J Diabetes Complications 2008;22:329–330.
RI PT
2. Hudacko RM, et al. Clinical resolution of glycogenic hepatopathy following improved glycemic
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT