Can weight loss reverse non-alcoholic fatty liver disease? Different from foreign guidelines, new evidence from the Chinese population

As we all know, excessive drinking and viral hepatitis are the culprits of liver disease. In fact, for those who do not drink and have never suffered from hepatitis, there is another culprit behind the scenes - fat.

Excessive accumulation of fat (mainly triglycerides) in the liver leads to liver damage, which is called " non-alcoholic fatty liver disease ."

Non-alcoholic fatty liver disease includes simple fatty liver, non-alcoholic steatohepatitis and non-alcoholic cirrhosis. At present, it has become the number one chronic liver disease in my country and even in the world. The global adult prevalence rate is 25.24%, while in my country it has reached 29.2%, and it is on the rise.

Nonalcoholic fatty liver disease can lead to a series of adverse outcomes both inside and outside the liver and has become the leading cause of liver-related death worldwide.

Guidelines developed by the American Association of Clinical Endocrinology and the American Association of Liver Diseases believe that weight loss through improving lifestyle is an effective way to reduce the disease burden of non-alcoholic fatty liver disease. However, because the degree of liver steatosis, fibrosis and accompanying metabolic phenotype vary among patients, the benefits of weight loss for patients with different characteristics may be heterogeneous.

In addition, current evidence on the association between weight loss and non-alcoholic fatty liver disease is mostly based on foreign populations. The metabolic status of the Chinese population and the Western population at the same BMI is significantly different, which suggests that the weight control strategy for such patients in the Chinese population may be different from that in Western countries.

To this end, Professor Wang Li 's team from the Department of Epidemiology and Health Statistics, School of Basic Medicine, Institute of Basic Medicine, Chinese Academy of Medical Sciences, and Peking Union Medical College analyzed the effects of body mass control on the prevention of non-alcoholic fatty liver disease and its long-term outcomes based on the research results of this research group and combined with local Chinese evidence. They also published "Body Mass Control and Non-alcoholic Fatty Liver Disease: Evidence from the Chinese Population" in the Peking Union Medical College Journal, providing high-quality evidence-based medicine for the prevention and control of the disease.

Author: Yang Chenlu, Zhao Xinyu, Hu Shiqi, Lan Yanqi, Feng Baoyu, Wang Li

Contents

Body weight and risk of nonalcoholic fatty liver disease

The risk of non-alcoholic fatty liver disease is significantly associated with being overweight or obese. The latest systematic review published in the Lancet in 2023 showed that the prevalence of non-alcoholic fatty liver disease in overweight and obese people worldwide is as high as 70.0%, while in China it is relatively low, at 45.4%.

A meta-analysis based on 21 Asian cohorts, including the Chinese population, showed that the risk of the disease in obese people defined by BMI was 3.53 times that of people with normal BMI, and there was a significant dose-response relationship between BMI and the risk of non-alcoholic fatty liver disease. Consistent results were also observed in the Kailuan, Hebei Province and Jinchang, Gansu, Northwest China cohort studies.

Body weight and reversal and adverse outcomes of nonalcoholic fatty liver disease

①Disease reversal

Nonalcoholic fatty liver disease is reversible. Two cohort studies based on populations in southern and northern my country showed that the BMI level of patients with nonalcoholic fatty liver disease was linearly negatively correlated with their remission rate.

②Adverse outcomes such as tumors or death

However, studies based on the Kailuan cohort have shown that the BMI level of patients with non-alcoholic fatty liver disease presents different nonlinear dose-response relationships with different clinical hard endpoints. Lean patients with non-alcoholic fatty liver disease have the highest risk of all-cause mortality, liver-related mortality, digestive system tumors, and obesity-related tumors; while overweight or obese patients with non-alcoholic fatty liver disease have the highest risk of cardiovascular disease. [Note: BMI ≥ 23.0 kg/m2 is used as the standard for overweight or obesity]

③Metabolic effects

The long-term follow-up data of the Kailuan cohort further revealed that the association between baseline BMI level and its adverse outcomes may be affected by other metabolic indicators. The study found that the risk of adverse outcomes in new male patients of different subtypes was also significantly different, that is, lean patients with severe hypertension had the highest risk of all-cause mortality and tumors, but their risk of cardiovascular disease and chronic kidney disease was slightly lower than that of age-related obese patients; and patients with metabolic syndrome-related obese non-alcoholic fatty liver disease had the highest risk of cardiovascular disease (Figure 1).

Figure 1 Cumulative incidence of adverse outcomes in male new-onset NAFLD patients with different subtypes

A. All-cause mortality; B. Cancer; C. Cardiovascular disease; D. Chronic kidney disease NAFLD: Non-vital fatty liver disease

[Comprehensive metabolic-related indicators: BMI, waist circumference, fasting blood sugar, blood pressure, high-density lipoprotein cholesterol, triglycerides and C-reactive protein; classification method: overweight or obese (BMI ≥ 23.0 kg/m2) NAFLD patients are divided into three subtypes: age-related obese NAFLD, metabolic syndrome-related obese NAFLD and early-onset severe obese NAFLD; lean NAFLD is divided into two subtypes: lean NAFLD with severe hypertension and lean NAFLD with moderate metabolic disorders ]

Body mass control for the prevention of nonalcoholic fatty liver disease

Although most studies have suggested that controlling body weight can reduce the risk of non-alcoholic fatty liver disease in the general population, due to different assessment methods and time windows for BMI changes in different studies, there is currently no consensus on how to control body weight to prevent the disease.

For example, a prospective cohort study based on the Kailuan cohort observed that weight loss could reduce the risk of non-alcoholic fatty liver disease only in men with a baseline BMI of <24 kg/m2, while no preventive effect was found in men and women with a baseline BMI of ≥ 24kg/m2.

Body mass control and metabolic status in patients with nonalcoholic fatty liver disease

Cohort studies and clinical trials from the Chinese population have shown that controlling body weight can improve metabolic status. For example, a study based on elderly Chinese male veterans showed that the risk of type 2 diabetes in patients with non-alcoholic fatty liver disease increased with the increase in BMI.

When the BMI change was less than -1.00 kg/m2, the risk of developing type 2 diabetes in patients with non-alcoholic fatty liver disease between -1.00 and 1.00 kg/m2 and greater than 1.00 kg/m2 increased by 59.9%, 64.0% and 91.8%, respectively.

Body weight control and prevention of adverse outcomes of nonalcoholic fatty liver disease

For people who already have nonalcoholic fatty liver disease, there is limited evidence that weight loss has different effects on the risk of different adverse outcomes.

①It has a preventive effect on the occurrence of chronic kidney disease

The results of the Kailuan cohort study showed that with the increase in weight loss, the risk of chronic kidney disease in patients with non-alcoholic fatty liver disease gradually decreased, and weight loss of 7% or more can significantly reduce the risk of chronic kidney disease.

②No preventive effect on cardiovascular disease has been found

The impact between the two was also analyzed based on the long-term follow-up data of 8591 adult men (18-59 years old) with no history of cardiovascular disease at baseline in the Kailuan cohort, and no protective effect of body weight loss on cardiovascular disease was observed.

Summary and Outlook

Nonalcoholic fatty liver disease has become the most important chronic liver disease in the world. It is not only an important cause of liver diseases such as cirrhosis and liver cancer, but also may increase the risk of extrahepatic adverse events such as chronic kidney disease, cardiovascular disease, and tumors, leading to an increased risk of all-cause mortality. However, the results of different studies are heterogeneous.

Body mass control is considered to be a promising method for the prevention and control of non-alcoholic fatty liver disease and has been recognized by guidelines, but weight loss strategies based on populations with different characteristics still need to be verified by high-quality clinical research.

Based on follow-up data of the Chinese population, this article analyzes the impact of body mass control on the prevention of non-alcoholic fatty liver disease and its long-term outcomes, providing high-quality evidence-based medicine for the prevention and control of the disease.

Study limitations

This article only summarizes the relevant evidence from existing domestic clinical trials and cohort studies, and lacks multi-dimensional stratification of the heterogeneity of patients with non-alcoholic fatty liver disease. In the future, multicenter prospective cohort studies are needed to fully consider the heterogeneity of non-alcoholic fatty liver disease and integrate demographic characteristics, lifestyle, genetics and other factors to accurately identify high-risk groups for non-alcoholic fatty liver disease and develop targeted and individualized body mass control strategies in order to achieve accurate prevention and control of non-alcoholic fatty liver disease.

Source of this article: Expert Forum of Peking Union Medical College Journal: Body Mass Control and Non-alcoholic Fatty Liver Disease: Evidence from the Chinese Population

Editor: Liu Yang and Zhao Na

Proofread by Li Na, Li Yule, and Dong Zhe

Producer: Wu Wenming

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