Recommendation of “Saisei no Mori (Forest of Regeneration)Liver complete medical checkup” to avoid missing fatty liver, especially progression from NAFLD to NASH – Suggestion from prevention to treatment.

About 40 years ago, when I first became a doctor, fatty liver was hardly recognized as a disease that needed to be treated. It was not considered that important, and even if we gave dietary and exercise guidance, it was only “go on a diet a little. However, it is now known that fatty liver is a risk factor for various lifestyle-related diseases. Medically, fatty liver is defined as a condition in which triglycerides accumulate in the cells of the liver to a level of 30% or more.

At present, it is estimated that as many as 20 or 30 million people in Japan have fatty liver, and the number is on the rise. Causes include alcohol and lifestyle factors such as overeating and lack of exercise. About 40 years ago, when I first became a doctor, fatty liver was hardly recognized as a disease that needed to be treated. Even if they did give guidance on diet and exercise, it was limited to “go on a diet a little bit”. Recently, the existence of fatty liver, which can progress to cirrhosis and liver cancer if left untreated, has also become apparent. In particular, attention has been focused on non-alcoholic steatohepatitis (NASH), which is a non-alcoholic fatty liver (NAFLD) that progresses to cirrhosis in those who do not consume alcohol, as well as those who do. And those patients need to be treated appropriately because they are frequently complicated by other adult diseases such as diabetes and hypertension. Diet and exercise therapy are the basics, but there are also drugs that have been shown to inhibit the progression of liver fibrosis in NASH, and oral administration of these drugs may be effective.

How to detect fatty liver at an early stage

Fatty liver disease can occur without being noticed. Even if liver values do not exceed standards, echo or CT images may show a subtle accumulation of fat in the liver. In particular, if either GOT or GPT is in the normal range but either exceeds 31 units, fat deposition in the liver may have begun, even if γGTP is normal. Fatty liver or suspected fatty liver is becoming more common among young people in their 30s in health checkups. High-calorie eating habits and the fact that metabolism begins to decline in one’s thirties may be the cause.
However, in its very early stages, fatty liver is really a “symptomless liver disease”. The liver is often referred to as a “silent organ,” but in many cases, the disease is well advanced when subjective symptoms appear. Therefore, it is important to evaluate the progression of fatty liver disease in order to detect it early and intervene in early treatment by FIB-4index* (calculated by GOT, GPT and platelet count), echo and CT when the patient is not aware of the disease. Progression is evaluated by liver fat content and liver stiffness. Fibroscan is the only globally accepted method of assessing progression without the need for an invasive liver biopsy. For more information on Fibroscan, please refer to the column. Fatty liver is also often complicated by various lifestyle-related diseases, and if left untreated, it is actually a dreadful disease that can lead to death due to these complications.

*：FIB-4index = (age x AST(IU/L))/(platelet count (109/L) x √ALT(IU/L)) 1.3 or higher is fatty liver with possible liver fibrosis

Column: About Fibroscan

Fibroscan was developed in France in June 2001 and is the only testing instrument that measures liver hardness and liver fat volume. Fibroscan uses a patented technology called Vibration-Controlled Transient Elastography (VCTE™) to measure the hardness of specific organs (liver or spleen hardness). Fibroscan evaluates liver fat volume by measuring ultrasound attenuation using a patented technology called Controlled Attenuation Parameter (CAP™). Ultrasound signals tend to attenuate more strongly when there is more fat deposition in the liver and less weakly when there is less. Fibroscan applies its properties to noninvasively measure the attenuation of ultrasound signals passing through the liver, providing information for assessing the volume of fat in the liver. Thus, it is a powerful instrument when assessing the extent of cirrhosis and fatty liver disease. Particularly, the aforementioned stage of transition from NAFLD to NASH can now be diagnosed at a relatively early stage and therapeutic intervention can be made to prevent progression to cirrhosis. There are 195 of these devices in Japan, with 35 registered in Tokyo. There are only four Smart Exam-equipped machines in Tokyo, three of which are in clinics, and one very valuable one is in our clinic in Roppongi, Saisei no Mori Clinic (Forest of Regeneration Clinic Roppongi).

Who is actually more likely to have fatty liver disease?

Statistically, it is still more common in people with obesity. People with lifestyle-related diseases such as diabetes, dyslipidemia, or metabolic syndrome often have fatty liver.

However, in the beginning stages, fatty liver can be seen in people with normal blood pressure, slightly high cholesterol and triglycerides, and who do not yet meet the criteria for metabolic syndrome. In dietary trends, people tend to drink a lot of alcohol, eat a lot of grilled meat, and have a sweet tooth even if they don’t drink alcohol. Of course, there are people who do not have a fatty liver even if they have the same diet. This is thought to be due to differences in physical activity and basal metabolic rate, and in some cases, genetic factors are involved. However, it should be noted that there are people who develop fatty liver even if they are thin.

What are some concrete dietary points?

It is important to reduce the amount of sugar, or carbohydrates, in your diet. The first step is to cut in half the amount of rice, bread, noodles, and other carbohydrates that you habitually take. Some people often reduce their carbohydrate intake to 20% or even zero on a low-carbohydrate diet, but it is proven that too much reduction is not good for the body, and an excessive goal can be stressful. Some of you may also look forward to dessert. Even in that case, it is easier to achieve if you target half.

How much exercise therapy should be done?

In recent years, many people have told us that they no longer exercise due to their increased telework, but even doing sit-ups and squats indoors can make a difference. Doing about 30 minutes of exercise three times a week, just enough to get a little sweaty, makes quite a difference. If you do it outdoors, walking for 30 minutes is good, too. Some report that continuous exercise has improved their fatty liver, even if they do not lose weight.

If the fatty liver is advanced, will it be difficult to improve?

Once the disease has progressed from NAFLD to NASH or cirrhosis, there is no fundamental cure for the disease. This is because the hardened liver tissue will not return to its original state.
Development of drugs for the treatment of NASH is underway in the U.S. and Europe, but a safe and effective drug has not yet been developed. Some diabetic drugs have been reported to improve NAFLD conditions, but are not expected to be effective for NASH.

My Real Life Experience - From Fatty Liver to Myocardial Infarction

    In fact, when I was around 20 years old, I also found out that I had a fatty liver when I was diagnosed with another disease. But I was a member of the swimming club at the time and exercised a lot, so I was told I was fine. But when I became a doctor, I had a busy schedule and had to eat at irregular times. I often ate late at night and gradually gained weight. After that, I lived a research life for a while, but that was also stressful, and when I became a doctor again, I was back to hard work. I also knew that my triglycerides were high, and as a result, I had a myocardial infarction attack in 2021. It is embarrassing, but it is truly physician, heal thyself. I realize that test results should not be underestimated. In particular, when I see patients in their 30s and 40s who have had their test results confirmed but have neglected them, I tell them that it is better to take action as early as possible because the risk is higher.

"Saisei no Mori" liver complete medical checkup - from prevention to treatment of fatty liver

Pre-treatment evaluation (liver completer checkup)

Our clinic performs a comprehensive analysis of liver status, including liver fibrosis markers (M2BPGi, hyaluronic acid, type IV collagen, PIIIP), and also calculates FIB4 index to determine liver status. Abdominal ultrasonography (echo) is used to evaluate the presence and extent of fatty liver, and fibrosis and fat content of the liver are quantitatively measured using Fibroscan testing equipment to determine the stage of fatty liver.

Prevention and treatment

If the stage is early without abnormal blood tests (simple fatty liver), treatment with diet, exercise, and supplements (prophylactic treatment) is used to prevent the transition to NAFLD. As the stage progresses, drug intervention is used to treat the transition to NAFLD. The treatment is mainly a combination of drugs that act as antioxidants, regulate cholesterol metabolism and absorption, improve glucose metabolism, and treat obesity. These drugs are not covered by insurance for fatty liver and are therefore self-pay. If NASH occurs, conventional treatment should be continued, but one way to control fibrosis and prevent it from leading to cirrhosis is to use stem cell culture supernatant fluid containing anti-inflammatory cytokines or anti-inflammatory cytokines produced by cultured stem cells to control inflammation is important. Fatty hepatitis (NASH) is also a type of inflammation, so reducing inflammation, especially chronic inflammation, is essential to prevent disease progression. Even though diet is important, it may be difficult if you are a single man in the peak of your career.

Post-treatment evaluation

The same test as the pre-treatment evaluation is performed to evaluate the effectiveness of the treatment

How important it is to improve fatty liver

Since fatty liver is at the start of the metabolic domino, its improvement requires daily diet and exercise measures, which also coincide with measures against lifestyle-related diseases. Therefore, efforts to prevent fatty liver should also be helpful for diabetes, dyslipidemia, and hypertension. Prevention is the key to such measures, and we encourage you to make it a priority.

About Liraglutide, a drug for the treatment of obesity

Liraglutide suppresses (1) appetite through the action of GLP-1, a slimming hormone. (2) It makes it easier to decompose fat. (3) It raises basal metabolism, resulting in weight loss effects. The hormone GLP-1 is originally secreted from L cells in the small intestine when blood glucose levels rise after eating a meal, causing insulin to be secreted from within the beta cells of the pancreasGLP-1 not only suppresses appetite by causing insulin to be secreted only when blood glucose levels are high and slowing the rise in blood glucose levels, but also acts on the appetite center in the hypothalamus to suppress appetite and prevent overeating. The method of administration is to inject a set dose subcutaneously at regular intervals every day. The effect of weight loss is seen as early as one month for some people, and usually from three months to one year. A 2015 test on obese individuals reported an average weight loss of 8.4 kg over 54 weeks. However, because the test was designed for people with a BMI over 27, the effect may be reduced in those who are mildly obese or not obese.

Side effects of liraglutide include the followings.

  • Headache
  • Dizziness
  • Nausea/vomiting
  • Diarrhea
  • Gastrointestinal problems
  • Hypoglycemia
  • Old kidney failure
  • Dehydration
  • Anaphylactic shock
  • Intestinal obstruction
  • Depression

However, side effects often occur when the drug is first administered, and even if side effects do occur, they usually lighten and disappear with continued administration. Please refrain from the treatment if any of the following is applicable. ・Under 18 years of age or over 70 years of age (those under 20 years of age must have the consent of a parent or guardian).

  • BMI less than 18.5
  • Body fat percentage less than 15% for men and 25% for women
  • Pregnant or nursing mothers
  • Patients with diabetes, pancreatitis, cholelithiasis, cholecystitis, severe renal or hepatic dysfunction
  • Patients with a history of major abdominal surgery
  • Patients with a history of intestinal obstruction
  • Those with eating disorders
  • Obesity due to endocrine disorders or drugs such as steroids
  • Those with thyroid disease
  • Those with a family history of multiple endocrine neoplasia type 2
  • Those with depression or suicide attempts
  • Those who are allergic to the additives in liraglutide
    • (Disodium hydrogen phosphate dihydrate, propylene glycol, phenol)
  • Should not be used with other GLP-1 receptor agonists.

Cost "Saisei no Mori" liver complete medical checkup

 (including tax)

Initial examination fee 5,500 yen
Blood and imaging tests 33,000 yen

"Saisei no Mori" Fatty Liver Outpatient Clinic
Re-examination fee 3,300yen
Blood test fee 16,500yen once every 3 months回
Diagnostic Imaging Fee
(Abdominal Ultrasonography + Fibroscan)）		 16,500yen once every 3 months
Drugs for Fatty Liver Disease
①Glucose metabolism improving drug set (SGLT-2 inhibitor, Pioglitazone hydrochloride） 1 month 8,800 yen
②Lipid metabolism improving drugs (pemafibrate, ezetimibe, polyenphosphatidylcholine) 1 month 8,800 yen
③Antioxidants (tocopherol acetate) 1 month 1,100 yen
④ Liver function improving drug set (glycyrrhizin products, taurine, ursodeoxycholic acid) 1 month 7,700 yen
⑤Obesity drug (liraglutide) One time 0.6mg subcutaneous injection 30 doses 110,000 yen
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