Rates of nonalcoholic steatohepatitis are rising worldwide. The condition is a complication of nonalcoholic fatty liver disease, where - as well as there being fat in the liver - there is also inflammation and damage. There are no effective treatments, especially once fibrosis or scar tissue develops. Now, a Japanese study has uncovered a mechanism through which a hormone called IGF-I may limit such damage.
The researchers, from Kobe University in Japan, report their findings in the journal Scientific Reports.
Nonalcoholic fatty liver disease (NAFLD) is a condition where, like alcoholic liver disease, fat builds up in the liver - except it is also found in people who drink little or no alcohol.
Scientists are not sure what causes NAFLD, although obesity is a clear risk factor. Other risk factors include diabetes, high cholesterol, high blood pressure, high blood fats, advancing age, and smoking.
The disease has a range of conditions and can develop through four stages. The stages are: steatosis (or simple fatty liver), nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis.
The major feature of NASH is fat in the liver, along with inflammation and damage. Most people with NASH feel well and may not realize they have it.
However, NASH can progress to a stage where the liver develops fibrosis or scarring and then the more severe cirrhosis, where the organ's fundamental biology is affected. Not everyone with NASH develops cirrhosis, but once it is present, few treatments can halt the progression.
IGF-I reduces key features of NASH in animal models
Around 10-20 percent of Americans have fat in their liver, and another 2-5 percent have NASH. In Japan, where the study took place, estimates suggest NASH affects around 3-4 million people. The disease is becoming a serious public health issue.
- Nonalcoholic steatohepatitis (NASH) may be suspected if tests show high levels of liver enzymes in the blood or if scans reveal fatty liver
- Diagnosis is confirmed by needle biopsy of the liver
- People with NASH are generally advised to reduce weight, eat a balanced diet, exercise, and avoid alcohol and unnecessary medications.
A study published last year found that over a 14-year period, the chances of dying were about 50 percent higher in people with NASH than people with NAFLD.
A big factor in the prognosis of patients with NASH is the presence and extent of fibrosis and cirrhosis.
The Japanese researchers note that rates of NAFLD and NASH are much higher in patients deficient in growth hormone.
In the study, they showed this was due to lack of insulin-like growth factor-I (IGF-I), which is mainly induced by growth hormone.
On further investigation using animal models, the team found IGF-I was dramatically effective in reducing some key features of NASH.
For example, after receiving IGF-I for 1 month, mice with obesity-related NASH showed dramatic improvements in steatosis (abnormal retention of fat in cells), inflammation, and fibrosis.
Also, after receiving similar treatment, mice with liver cirrhosis showed reduction in fibrosis.
The team also explored the underlying mechanisms and discovered IGF-I acts on hepatic stellate cells, which play a key role in promoting fibrosis.
The researchers found IGF-I triggers a process called cellular senescence - where cells lose their ability to divide and grow - in the hepatic stellate cells.
They also found the hormone improved mitochondrial function and oxidative stress in the liver, leading to fewer fatty deposits and less inflammation.
There are currently few approved drugs that suppress NASH-related liver fibrosis and other complications.
The researchers suggest their findings could lead to new ways to prevent fibrosis and thus improve the prognosis for people with NASH and cirrhosis. They may also help with other liver conditions involving fibrosis, such as viral hepatitis.
"We demonstrated that IGF-I has a potential therapeutic application for NASH and liver cirrhosis."
Hitoshi Nishizawa et al.