What is Glycogenic Hepatopathy?

Glycogenic hepatopathy (GH) is a condition that’s not very common or perhaps under-recognized. It typically shows up in children and young adults with type 1 diabetes that isn’t well-managed, and in a small number of patients with type 2 diabetes. What happens in GH is that the liver cells, called hepatocytes, store too much of a sugar called glycogen. This causes the liver to enlarge and temporary increases in liver enzymes, particularly those called transaminases. The only way to confirm the diagnosis of GH is through a liver biopsy, which involves taking a small piece of the liver to examine under a microscope. The doctors would use a stain called hematoxylin and eosin (HE) to highlight the glycogen in the liver cells.

What Causes Glycogenic Hepatopathy?

Glycogenic hepatopathy was first recognised in the 1930s by a man named Pierre Mauriac. He found it in a child with difficult-to-manage type 1 diabetes who had an enlarged liver, physical features similar to someone with a particular type of hormonal disorder, and poor growth – a condition now known as Mauriac syndrome. However, we now know that people can have this liver condition without showing all of these signs. Over the years, different names have been used to define this condition including “hepatic glycogenosis”, “glycogen storage hepatomegaly”, and “hepatic glycogen storage disease”. However, the term “glycogenic hepatopathy” that was coined in 2006 is now accepted worldwide.

Not just people with diabetes, but those with other conditions can also develop glycogenic hepatopathy. This includes dumping syndrome (seen after major stomach surgeries), anorexia nervosa (an eating disorder), high dose steroid use, azathioprine use, and excessive insulin use.

In dumping syndrome – a complication post-surgery of the stomach, the food swiftly passes into the small intestine from the stomach, not giving it enough time to absorb properly. This creates a seesaw of high levels of sugar and insulin in the blood, similar to what happens in diabetes.

People with anorexia nervosa might also be at risk. In a case reported, a patient with this eating disorder showed high liver enzyme levels and glycogen deposits. It’s thought that a build-up of glycogen in the liver (hepatic glycogenosis) is the body’s way of protecting itself from low blood sugar, common in malnutrition.

Another risk factor is the short-term use of high-dose steroid therapy. Steroids can boost sugar levels and glycogen deposits in the body. In a study with 141 recipients of steroid therapy, a few had an enlarged liver and some even developed glycogenic hepatopathy. But, the good news is, their liver size returned back to normal after they stopped taking steroids. It seems that steroids create high blood sugar levels which causes more glycogen production and build-up in the liver.

Lastly, high insulin doses can also potentially cause this. In an example, a person with type 2 diabetes tried to kill themselves by injecting a large dose of insulin. This person received a large amount of glucose to balance out the blood sugar and developed an enlarged liver due to excessive glycogen storage. It was observed that their liver enzymes, which were normal before the suicide attempt, later increased drastically.

Risk Factors and Frequency for Glycogenic Hepatopathy

Glycogenic hepatopathy (GH), a type of liver disease, is not well understood due to lack of data. Most of what we know comes from case studies and research over the years. Liver disease is thought to affect between 17% to 100% of people with diabetes, with non-alcoholic fatty liver disease and hepatic glycogenosis being the most common types. Glycogenic hepatopathy mostly affects people with type 1 diabetes, accounting for 98% of the cases, and only 2% occur in those with type 2 diabetes. There is a slightly higher occurrence in females as compared to males, and it’s most often seen during adolescence.

The exact rates of glycogenic hepatopathy (GH) are unknown, most information comes from case studies and research.
Between 17% to 100% of people with diabetes might have liver disease, with GH being one of the common types.
About 98% of GH cases occur in type 1 diabetics and 2% in type 2 diabetics.
More females (62%) have GH than males (38%), and it’s usually diagnosed during adolescence.

Signs and Symptoms of Glycogenic Hepatopathy

Glycogenic hepatopathy is a condition that can lead to swollen liver enzymes, often without showing any symptoms. However, some people might experience symptoms associated with high blood sugar levels such as frequent urination, excessive thirst, weight loss, and tiredness. Symptoms can also mimic those of diabetic ketoacidosis including stomach pain, nausea, and vomiting.

In children, this condition can lead to stunted growth, delayed puberty, and an enlarged liver, which could cause abdominal pain due to the stretching of the liver capsule. The main physical sign of glycogenic hepatopathy is an enlarged liver; typically, there are no other notable physical signs.

No signs or symptoms (in some patients)
Frequent urination
Excessive thirst
Weight loss
Tiredness
Stomach pain
Nausea
Vomiting
Stunted growth (in children)
Delayed puberty (in children)
Enlarged liver

Testing for Glycogenic Hepatopathy

A liver biopsy is really important when trying to diagnose glycogenic hepatopathy, or GH, a condition that affects the liver. There isn’t a single blood test that can diagnose GH, so your doctor might conduct a liver biopsy. Their goal is to rule out any other common causes of chronic hepatitis, an inflammation of the liver, based on your symptoms. There is also a possibility that they may recommend an autoimmune serology testing, which is a test to check if your immune system is functioning properly. In the case of glycogen storage diseases, these usually occur in newborns and infants due to the lack of certain enzymes from birth. This usually causes symptoms such as an enlarged liver and low blood sugar.

In most cases of GH, over 90% of patients have reported having an enlarged liver along with varying levels of liver enzymes. One thing to note is that, in GH, almost no elevation in alkaline phosphatase, another type of enzyme, is observed. Despite these changes, the liver still functions normally. It’s believed that the elevated enzymes could be a result of damage to the cell membrane, rather than cell death.

Imaging tests, such as ultrasound, can also provide helpful information. In ultrasound imaging, an enlarged liver is generally seen to have uniform brightness throughout, which can also be a symptom of non-alcoholic fatty liver disease (NAFLD). But it’s important to note that the ultrasound can’t differentiate between NAFLD and GH.

In contrast to ultrasound, computed tomography (CT) scans can help distinguish between a fatty liver and GH. In these scans, a fatty liver appears less dense, but a liver affected by GH appears more dense. So if your liver appears bright on a CT scan, it could be a hint towards GH. However, it’s worth considering other causes of this increased density, such as hemochromatosis, a condition where too much iron builds up in your body. Magnetic resonance imaging (MRI) can also aid in diagnosing GH.

Treatment Options for Glycogenic Hepatopathy

Glycogenic hepatopathy (GH) is a condition that affects the liver, but it’s good news – it’s both harmless and potentially reversible within 2 to 14 weeks. A major part of dealing with GH lies in managing blood sugar levels, which is known as glycemic control. If you can properly manage your blood sugar levels, the symptoms and biochemical signs of GH can disappear in as little as days to weeks. However, right now, the medical field does not have a concrete guideline of what the perfect blood sugar level should be to treat GH. What we do know is, you don’t need extremely aggressive insulin treatment in dealing with this. As an example, a report by Parmar et al. pointed out a case where just a slight rise of 0.6% in a patient’s HbA1c (a measure of average blood sugar levels over the past 2-3 months) was enough to alleviate abdominal pain and reduce liver enzymes, which are substances that signal how well your liver is working.

For people with diabetes, some other illnesses could make liver enzymes rise and cause the liver to enlarge. These include:

Non-alcoholic fatty liver disease (NAFLD)
Autoimmune hepatitis
Celiac disease
Viral hepatitis
Hemochromatosis
Wilson disease

What to expect with Glycogenic Hepatopathy

Glycogenic hepatopathy (GH), a harmless condition that could potentially reverse itself within a few days to weeks when blood sugar levels are well-managed, typically has a very good outlook. It’s crucial to distinguish GH from non-alcoholic fatty liver disease (NAFLD), as the latter could progress to fibrosis (a condition where the liver replaces normal, healthy tissue with scar tissue), while GH does not.

Possible Complications When Diagnosed with Glycogenic Hepatopathy

Glycogenic hepatopathy is a liver complication that can happen when diabetes is not well managed. However, it’s not a serious condition and tends to resolve itself when blood sugar levels are controlled effectively. This means it doesn’t cause any severe health complications.

Preventing Glycogenic Hepatopathy

Controlling your blood sugar when you have diabetes can treat the physical and biochemical symptoms of a condition called glycogenic hepatopathy, which affects your liver. As such, changes in your diet and daily exercise are advised for everyone with diabetes to ensure good control of blood sugar levels. This can lead to improved overall health and may reverse the symptoms of this liver disease.