What is NAFLD?

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat is stored in your liver. This buildup of fat is not caused by heavy alcohol use. When heavy alcohol use causes fat to build up in the liver, this condition is called alcoholic liver disease.

Two types of NAFLD are simple fatty liver and nonalcoholic steatohepatitis (NASH). Simple fatty liver and NASH are two separate conditions. People typically develop one type of NAFLD or the other, although sometimes people with one form are later diagnosed with the other form of NAFLD.

Simple fatty liver

Simple fatty liver, also called nonalcoholic fatty liver (NAFL), is a form of NAFLD in which you have fat in your liver but little or no inflammation or liver cell damage. Simple fatty liver typically does not progress to cause liver damage or complications.

NASH

NASH is a form of NAFLD in which you have hepatitis—inflammation of the liver—and liver cell damage, in addition to fat in your liver. Inflammation and liver cell damage can cause fibrosis, or scarring, of the liver. NASH may lead to cirrhosis or liver cancer.

Experts are not sure why some people with NAFLD have NASH while others have simple fatty liver.

How common are NAFLD and NASH?

NAFLD is one of the most common causes of liver disease in the United States. Most people with NAFLD have simple fatty liver. Only a small number of people with NAFLD have NASH. Experts estimate that about 20 percent of people with NAFLD have NASH. Between 30 and 40 percent of adults in the United States have NAFLD. About 3 to 12 percent of adults in the United States have NASH.

Who is more likely to develop NAFLD?

NAFLD is more common in people who have certain conditions, including obesity, and conditions that may be related to obesity, such as type 2 diabetes. Researchers have found NAFLD in 40 to 80 percent of people who have type 2 diabetes and in 30 to 90 percent of people who are obese. In research that tested for NAFLD in people who were severely obese and undergoing bariatric surgery, more than 90 percent of the people studied had NAFLD.

NAFLD can affect people of any age, including children. Research suggests that close to 10 percent of U.S. children ages 2 to 19 have NAFLD. However, people are more likely to develop NAFLD as they age.

While NAFLD occurs in people of all races and ethnicities, it is most common in Hispanics, followed by non-Hispanic whites. NAFLD is less common in African Americans. Asian Americans are more likely than people of other racial or ethnic groups to develop NAFLD when their weight is within the normal range.

What are the complications of NAFLD and NASH?

The majority of people with NAFLD have simple fatty liver, and people with simple fatty liver typically don’t develop complications.

NASH can lead to complications, such as cirrhosis and liver cancer. People with NASH have an increased chance of dying from liver-related causes. If NASH leads to cirrhosis, and cirrhosis leads to liver failure, you may need a liver transplant to survive.

Studies also suggest that people with NAFLD have a greater chance of developing cardiovascular disease. Cardiovascular disease is the most common cause of death in people who have either form of NAFLD.

Symptoms & Causes of NAFLD & NASH

Usually, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are silent diseases with few or no symptoms. You may not have symptoms even if you develop cirrhosis due to NASH.

If you do have symptoms, you may feel tired or have discomfort in the upper right side of your abdomen.

What causes NAFLD and NASH?

Experts are still studying the causes of NAFLD and NASH. Research suggests that certain health conditions make you more likely to develop NAFLD or NASH.

Causes of NAFLD

You are more likely to develop NAFLD—either simple fatty liver or NASH—if you

• are overweight or obese
• have insulin resistance 
• have abnormal levels of fats in your blood, which may include
  • high levels of triglycerides
  • abnormal levels of cholesterol—high total cholesterol, high LDL cholesterol, or low HDL cholesterol
• have metabolic syndrome or one or more traits of metabolic syndrome. Metabolic syndrome is a group of traits and medical conditions linked to overweight and obesity. People with metabolic syndrome are more likely to develop type 2 diabetes and heart disease. Experts think NAFLD may be closely linked to metabolic syndrome. Doctors define metabolic syndrome as the presence of any three of the following:
  • large waist size
  • high levels of triglycerides in your blood
  • low levels of HDL cholesterol in your blood
  • high blood pressure
  • higher than normal blood glucose levels
• have type 2 diabetes

Research also suggests that certain genes may make you more likely to develop NAFLD. Experts are still studying the genes that may play a role in NAFLD.

In NAFLD, people have a buildup of fat in the liver that is not caused by alcohol use. If you have a history of heavy alcohol use and fat in your liver, your doctor may determine that you have alcoholic liver disease instead of NAFLD.

Causes of NASH

Experts are not sure why some people with NAFLD have NASH and others have simple fatty liver. Research suggests that certain genes may play a role.

People with NAFLD are more likely to have NASH if they have one or more of the following conditions:

• obesity, especially with a large waist size
• high blood pressure
• high levels of triglycerides or abnormal levels of cholesterol in their blood
• type 2 diabetes
• metabolic syndrome

Less common causes of NAFLD and NASH

Less common causes of NAFLD and NASH include

• disorders that cause your body to use or store fat improperly
• rapid weight loss
• certain infections, such as hepatitis C
• certain medicines, such as
  • amiodarone  (Cordarone, Pacerone)
  • diltiazem 
  • glucocorticoids
  • highly active antiretroviral therapy
  • methotrexate  (Rheumatrex, Trexall)
  • synthetic estrogens 
  • tamoxifen  (Nolvadex, Soltamox)
  • valproic acid 
• exposure to some toxins

A study funded by the National Institute of Diabetes and Digestive and Kidney Diseases found that people who had surgery to remove their gallbladder were more likely to develop NAFLD. More research is needed on the link between gallbladder removal and NAFLD.

Diagnosis of NAFLD & NASH

Doctors use your medical history, a physical exam, and tests to diagnose nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

Medical history

Your doctor will ask if you have a history of health conditions that make you more likely to develop NAFLD and NASH, such as

• overweight or obesity
• insulin resistance
• high levels of triglycerides or abnormal levels of cholesterol in your blood
• metabolic syndrome
• type 2 diabetes

Your doctor will ask about diet and lifestyle factors that may make you more likely to develop NAFLD and NASH, such as a lack of physical activity, eating a diet high in sugar and starch, or drinking sugary beverages.

Medical tests can’t show whether alcohol is the cause of fat in your liver. Your doctor will ask about your alcohol intake to find out whether fat in your liver is a sign of alcoholic liver disease or NAFLD.

Physical exam

During a physical exam, a doctor usually examines your body and checks your weight and height to calculate your body mass index. Your doctor will look for signs of NAFLD or NASH, such as

• an enlarged liver
• signs of insulin resistance such as darkened skin patches over your knuckles, elbows, and knees
• signs of cirrhosis, such as jaundice, a condition that causes your skin and whites of your eyes to turn yellow

What tests do doctors use to diagnose NAFLD and NASH?

Doctors use blood tests, imaging tests, and sometimes liver biopsy to diagnose NAFLD and NASH.

Blood tests

A health care professional may take a blood sample from you and send the sample to a lab. Your doctor may suspect you have NAFLD or NASH if your blood test shows increased levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Your doctor may perform additional blood tests to find out if you have other health conditions that may increase your liver enzyme levels.

Imaging tests

Your doctor may use the following imaging tests to help diagnose NAFLD:

• Ultrasound. Ultrasound uses a device called a transducer, which bounces safe, painless sound waves off your organs to create an image of their structure.
• Computerized tomography (CT) scans. CT scans use a combination of x-rays and computer technology to create images of your liver. For a CT scan, a health care professional may give you a solution to drink and an injection of a special dye, called contrast medium. Contrast medium makes the structures inside your body easier to see during the procedure. You’ll lie on a table that slides into a tunnel-shaped device that takes the x-rays.
• Magnetic resonance imaging (MRI). MRI  machines use radio waves and magnets to produce detailed images of your organs and soft tissues without using x-rays. A health care professional may give you an injection of contrast medium. With most MRI machines, you’ll lie on a table that slides into a tunnel-shaped device. Some machines allow you to lie in a more open space; examining the liver can be more difficult with these machines.

A technician performs these tests in an outpatient center or a hospital. A technician can perform an ultrasound in a doctor’s office as well. A radiologist reads and reports on the images. You don’t need anesthesia, although you may receive light sedation during an MRI if you have a fear of confined spaces.

Imaging tests can show fat in your liver. These tests can’t show inflammation or fibrosis, so your doctor can’t use these tests to find out whether you have simple fatty liver or NASH. If you have cirrhosis, imaging tests may show nodules, or lumps, on your liver.

Liver biopsy

During a liver biopsy, a doctor will take a piece of tissue from your liver. A pathologist will examine the tissue under a microscope to look for signs of damage or disease.

A doctor performs a liver biopsy at a hospital or an outpatient center. A health care professional will tell you how to prepare for a liver biopsy. You may need to stop taking certain medicines to prepare. You may be asked not to eat or drink anything for 8 hours before the procedure. During the procedure, you may receive a local anesthetic, sedatives, and pain medicine.

During the biopsy, you’ll lie on a table with your right hand resting above your head. The doctor will numb the area where he or she will insert the biopsy needle with a local anesthetic and then use the needle to take a small piece of liver tissue.

A liver biopsy is the only way to detect liver inflammation and damage to diagnose NASH. Doctors don’t recommend this test for everyone with NAFLD. Your doctor may recommend a liver biopsy if you are more likely to have NASH or if your other tests show signs of advanced liver disease or cirrhosis.

Treatment for NAFLD & NASH

Doctors recommend weight loss to treat nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Weight loss can reduce fat in the liver; inflammation; and fibrosis, or scarring.

If you are overweight or obese, losing weight by making healthy food choices, limiting portion sizes, and being physically active can improve NAFLD and NASH. Losing at least 3 to 5 percent of your body weight can reduce fat in the liver. You may need to lose up to 10 percent of your body weight to reduce liver inflammation.

Doctors recommend gradually losing 7 percent of your body weight or more over the course of 1 year. Rapid weight loss through fasting—eating and drinking nothing except water—can make NAFLD worse.

Medicines

No medicines have been approved to treat NAFLD and NASH. However, researchers are studying medicines that may improve these conditions.

Some studies suggest that pioglitazone (Actos), a medicine for type 2 diabetes, improves NASH in people who don’t have diabetes. Researchers need more information to find out whether this medicine is safe and effective for long-term use in people with NASH.

A study by the National Institute of Diabetes and Digestive and Kidney Diseases’ NASH Clinical Research Network found that treatment with vitamin E or pioglitazone improved NASH in about half of the people treated. Doctors may recommend vitamin E for people who have NASH and don’t have diabetes or cirrhosis. Talk with your doctor before taking vitamin E or pioglitazone.

For safety reasons, talk with your doctor before using dietary supplements, such as vitamins, or any complementary or alternative medicines or medical practices. Some herbal remedies can actually damage your liver.

How do doctors treat the complications of NASH?

If NASH leads to cirrhosis, doctors can treat the health problems caused by cirrhosis with medicines, operations, and other medical procedures. If cirrhosis leads to liver failure, you may need a liver transplant.

How can I prevent NAFLD and NASH?

You may be able to prevent NAFLD and NASH by eating a healthy diet, limiting your portion sizes, and maintaining a healthy weight.

The post NASH and Nonalcoholic Fatty Liver Disease (NAFLD) appeared first on Medika Life.

Hepion Introduces ‘AI-POWR^TM‘ Proprietary Big Data Analytics Platform in AMBITION Trial

• AI – Artificial Intelligence, using supervised and unsupervised machine learning
• P – Precision Medicine, individualizing treatments based on genetics, environment, and lifestyle
• O – Omics, including genomics, proteomics, lipidomics, and metabolomics
• W – World, accessing world genomic databases
• R – Response and clinical outcomes

DATE OF RELEASE: AUGUST 5, 2020

EDISON, NJ / ACCESSWIRE /  Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a biopharmaceutical company focusing on the development of therapeutic drugs for the treatment of liver disease arising from non-alcoholic steatohepatitis (“NASH”), today announced that CRV431 was administered to the first NASH patient. Hepion previously announced that CRV431 successfully progressed through a phase 1 program, where the safety, tolerability and pharmacokinetics of CRV431 were evaluated in healthy subjects.

The open-label phase 2a study, called the ‘AMBITION’ trial, is designed to assess safety, tolerability, and pharmacokinetics of 75 mg CRV431, administered orally to F2 and F3 NASH patients (n=18), once daily for 28 days. Additionally, our Clinical Pharmacology group will be examining certain biomarkers including, for example, collagen, matrix metalloproteinases, lipidomics, genomics, liver transaminases, Pro-C3, ELF score, gene-gene, gene-protein network analysis, and Fibroscan in a multivariate multi-omics analysis to elucidate CRV431 activity in NASH. AI-POWR, Hepion’s in-house proprietary big data analytics platform that allows for precision medicine will be used to optimize the understanding of CRV431 in NASH.

“Our phase 2a trial is a relatively small study of 28-days duration with CRV431 dosing in NASH patients,” said Dr. Patrick Mayo, Hepion’s Senior Vice-President, Clinical Pharmacology. “The primary endpoint of this trial assesses safety, tolerability, and pharmacokinetics. From a secondary endpoint perspective, we are not looking to see histological changes in fibrosis in such a short period of time. However, we believe our proprietary big data analytical platform which integrates clinical pharmacology with bioinformatics, systems pharmacology, and machine learning will allow us to rapidly identify meaningful outcomes that can be used in future clinical trials. This proprietary platform has already been applied to previous studies, for example, where we conducted a genetic analysis of over 28,000 genes and variants in a prior study of CRV431 in human Precision Cut Liver Slices obtained from Fibrofind in the UK. This method of data analytics has allowed us to enrich our current phase 2a study design.”

Dr. Robert Foster, Hepion’s Chief Executive Officer added, “By its very nature, drug development is a risky venture but is absolutely necessary. In particular, we believe NASH is a very heterogenous disease with complex biochemical and pathological processes complicated, for example, by time and genetics. As such, treating NASH may be tantamount to hitting a moving target. We believe we can mitigate much of the usual risks associated with clinical trials, and NASH in particular, by utilizing cutting edge data tools allowing for precision medicine. We will be drawing upon our vast expertise in cyclophilin drug development, honed over decades of experience, to further the advancement of CRV431 in the clinic. Dr. Mayo and our research group have developed a highly sophisticated and proprietary analytics program, called AI-POWR, to make the most of our non-clinical and clinical data in a way that is a novel step forward.”

Dr. Stephen Harrison, Principal Investigator and Hepion’s consultant Medical Director, further commented, “I find Hepion’s unique approach, utilizing big data analytics in a phase 2a NASH trial with AI, personally very exciting and should allow us to further drill down into this complex disease. There are no other cyclophilin inhibitors, such as CRV431, that are currently being used in this patient population. As such, Hepion’s CRV431 represents an entirely novel approach to treating this serious disease.”

About Hepion Pharmaceuticals

Hepion Pharmaceuticals is a clinical stage biopharmaceutical company focused on the development of targeted therapies for liver disease arising from non-alcoholic steatohepatitis (NASH) and other types of hepatitis. The Company’s lead drug candidate, CRV431, reduces liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH. Preclinical studies also have demonstrated antiviral activities towards HBV, HCV, and HDV through several mechanisms. These diverse therapeutic activities result from CRV431’s potent inhibition of cyclophilins, which are involved in many disease processes. Currently in clinical phase development, CRV431 shows potential to play an important role in the overall treatment of liver disease – from triggering events through to end-stage disease

Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2019 and other periodic reports filed with the Securities and Exchange Commission.

For further information, please contact:
Stephen Kilmer
Hepion Pharmaceuticals Investor Relations
Direct: (646) 274-3580
skilmer@hepionpharma.com

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