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Article
21.02.2026
Current algorithm for treating patients with MASHP and obesity: implementation of European guidelines and new data from 2025 into clinical practice
A patient with a body mass index (BMI) of 33 kg/m2 came in for a consultation. Discomfort in the right upper quadrant, plasma triglycerides – 1.9 mmol/L, signs of hepatic steatosis according to ultrasound. What should the further examination be? What could be the treatment strategy?
Steatotic liver disease associated with metabolic dysfunction (or metabolically associated steatotic liver disease, MASLD) has become the most common chronic liver disease with a tendency to increase. MAFL is pathogenetically closely related to type 2 diabetes mellitus (DM), obesity, and other cardiometabolic risk factors. The 2024 updated clinical practice guidelines for the treatment of MASHF, a joint project of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD), and the European Association for the Study of Obesity (EASO). The guidelines contain recommendations for lifestyle changes and basic drug therapy, taking into account concomitant diseases. In October 2025, the results of the SteatoChoke study were published, providing additional evidence of the effectiveness of ad hepatoprotection, confirming that artichoke leaf extract reduces steatosis and liver size in patients with obesity and NAFLD.
Terms and definitions: what is required for a diagnosis of NAFLD?
EASL defines NAFLD as excessive accumulation of triglycerides in the liver in the presence of at least one cardiometabolic risk factor (Table 1) and in the absence of alcohol abuse. Therefore, to establish a diagnosis of NAFLD, a patient with documented hepatic steatosis
(according to ultrasonography) and no history of chronic alcohol consumption in amounts exceeding 20 g of ethanol per day for women and 30 g/day for men.
| Table 1. Cardiometabolic risk factors included in the definition of NAFLD | |
|---|---|
| Risk factors | Criteria for adults |
| Overweight or obesity | BMI ≥25 kg/m² (≥23 kg/m² in people of Asian descent) Waist circumference ≥94 cm in men and ≥80 cm in women (Europeans) |
| Dysglycemia or type 2 diabetes mellitus | Prediabetes: HbA1c 5.7–6.4%, or fasting plasma glucose 5.6–6.9 mmol/L, or plasma glucose 2 hours after a glucose tolerance test 7.8–11 mmol/L. Type 2 diabetes: HbA1c ≥6.5%, or fasting plasma glucose ≥7.0 mmol/L, or plasma glucose 2 hours after an oral glucose tolerance test ≥11.1 mmol/L; or the patient is already receiving treatment for type 2 diabetes. |
| Dyslipidemia | Plasma triglycerides ≥1.7 mmol/L, or HDL cholesterol ≤1.0 mmol/L in men and ≤1.3 mmol/L in women; or the patient is already receiving lipid-lowering therapy. |
| Elevated blood pressure | ≥130/85 mmHg or the patient is already receiving treatment for hypertension. |
| Notes: HbA1c – glycated hemoglobin; HDL – high-density lipoproteins; OGTT – oral glucose tolerance test. | |
The term “metabolically associated steatotic liver disease” replaces the old term “non-alcoholic fatty liver disease” to more accurately reflect the nature of the disease and also covers a range of histological conditions of the liver:
- isolated hepatic steatosis (steatotic liver associated with metabolic dysfunction, MASD);
- steatohepatitis associated with metabolic dysfunction (MASG), characterized by histological features of hepatocyte ballooning and lobular inflammation;
- fibrosis and cirrhosis as terminal stages of the process.
Although there is no single definition of the term “metabolic dysfunction,” the main metabolic dysfunction underlying NAFLD is considered to be tissue resistance to insulin, which is closely related to the pathogenesis of type 2 diabetes. A diagnosis of NAFLD does not mean that other causes of liver damage should not be considered (e.g., hepatotoxic drugs, viral hepatitis).
A separate category has also been introduced for patients with NAFLD and excessive alcohol consumption (MetAFLD) to describe patients with liver steatosis who consume larger amounts of alcohol (20-50 g/day for women and 30-60 g/day for men, respectively) but do not meet the criteria for alcoholic liver disease (ALD). For the diagnosis of ALD, the criterion for excessive alcohol consumption is >50 g/day for women and >60 g/day for men. Alcohol use history is an important diagnostic factor, as current alcohol consumption patterns do not necessarily reflect previous behavior.
Obesity and overweight as comorbid conditions and criteria for NAFLD
The presence, duration, and degree of obesity are associated with an increased risk of NAFLD progression. According to the World Health Organization, a BMI threshold of 25-29.9 kg/m2 defines overweight, while a BMI threshold of ≥30 kg/m² indicates obesity in non-Asian populations. Excessive accumulation of visceral fat, i.e., abdominal obesity, mediates most of the cardiometabolic risk. Waist circumference is an approximate indicator of abdominal obesity, with thresholds depending on gender and population. Current thresholds are ≥94 cm for men and ≥80 cm for women of Caucasian descent. Table 2 presents additional criteria for overweight and obesity used in the EASL guidelines.
| Table 2. Criteria for overweight/obesity | ||
|---|---|---|
| Category | BMI, kg/m² (for non-Asians) | BMI, kg/m² (for Asians) |
| Normal weight | <25 | <23 |
| Overweight | 25-29.9 | 23-24.9 |
| Obese | ≥30 | ≥25 |
| Class II obesity | ≥35 | ≥30 |
General principles of NAFLD treatment: lifestyle modification
EASL recommendations
- In adults with NAFLD and excess weight, dietary recommendations and behavioral therapy should be aimed at achieving a sustained weight loss of ≥5% to reduce liver fat content, by 7-10% to reduce liver inflammation, and by ≥10% to reduce fibrosis (level of evidence 2, strong recommendation, strong expert consensus).
- Adults with NAFLD should be advised to improve their diet (such as the Mediterranean diet model), limit their consumption of ultra-processed foods (rich in sugars and saturated fats), and avoiding sweetened beverages to improve histologically or non-invasively assessed liver condition (level of evidence 2, strong recommendation, strong expert consensus).
- Adults with NAFLD should be recommended physical activity and exercise to reduce steatosis, adapted to the individual’s preferences and capabilities (preferably > 150 min/week of moderate or 75 min/week of high-intensity physical activity) (level of evidence 1, strong recommendation, strong consensus) (Fig. 1).
Behavioral therapy includes self-monitoring, support and motivation from clinicians, setting realistic goals, and overcoming barriers.
Examples of unprocessed/minimally processed foods: vegetables, fruits (without juice), low-fat dairy products, nuts, olive oil, legumes, unprocessed fish, and poultry.
Basic pharmacotherapy for NAFLD
EASL recommendations
- If approved locally and depending on the indications in the instructions, resmetir should be considered as a targeted therapy for the treatment of adults with non-cirrhotic NAFLD with significant liver fibrosis (stage ≥2). In a large Phase III registration study, resmetir demonstrated histological efficacy in steatohepatitis and fibrosis with an acceptable safety and tolerability profile (level of evidence 2, strong recommendation, consensus) (Fig. 2).
Notes: GLP1RA – glucagon-like peptide 1 receptor agonist; HCC – hepatocellular carcinoma; SGLT2 – sodium-glucose cotransporter 2.
Commentary. Resmetir is an oral agonist of thyroid hormone receptors with high selectivity for the b1 receptor, expressed in the liver. It has been established that the frequency of clinical and subclinical hypothyroidism is higher in individuals with NAFLD and NASH compared to a control group of the same age, and low thyroid function is associated with more severe consequences. Thyroid hormones reduce liver steatosis by stimulating hepatic lipophagy and mitochondrial biogenesis, as well as by inhibiting hepatic lipogenesis. They may also influence fibrogenesis by inhibiting TGF-β signaling. As of December 2025, resmetir is not registered in Ukraine.
- In the absence of official demonstration of histological improvement in large, well-designed phase III studies, glucagon-like peptide 1 receptor agonists (GLP1RAs) cannot currently be recommended as a therapy for the treatment of NAFLD (level of evidence 5, strong recommendation, strong consensus).
- GLP1RAs are safe for use in NAFLD (including compensated cirrhosis) and should be used for the appropriate indications, namely type 2 diabetes and obesity, as their use improves cardiometabolic outcomes (level of evidence 2, strong recommendation, strong consensus).
- Pioglitazone is safe for use in adults with non-cirrhotic NAFLD, but given the lack of convincing demonstration of histological efficacy in steatohepatitis and liver fibrosis in large phase III studies, pioglitazone cannot be recommended as a targeted therapy for NAFLD (level of evidence 2, weak recommendation, consensus).
- There is insufficient evidence to recommend the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors or metformin as targeted therapy for NAFLD; however, they are safe for use in NAFLD and should be used for the appropriate indications, namely type 2 diabetes, heart failure, and chronic kidney disease (level of evidence 3, strong recommendation, strong consensus).
Additional comments
In the case of significant weight loss caused by GLP1RA, a positive effect on liver histology can be expected, although this has not yet been widely documented (level of evidence 2, strong consensus).
There is insufficient evidence to support the use of any other class of glucose-lowering drugs as therapy for MASG (level of evidence 5, strong consensus).
Adjuvant hepatoprotection. Artichoke extract as a proven treatment for steatosis and lipid profile
A standardized dry artichoke extract at a dose of 2600 mg/day in 2 doses for 6 weeks reduces steatosis and liver size in patients with obesity and NAFLD, and also has additional beneficial metabolic effects. These conclusions were made based on data from the SteatoChoke study, conducted between 2022 and 2023 at a German bariatric surgery center. A total of 40 patients undergoing preparation for bariatric surgery were enrolled. Participants were randomly divided into two groups: the control group (n=20) received a placebo for six weeks; in the experimental group (n=20), patients took a standardized dry extract of artichoke leaves (ELA) at a dose of two 650 mg capsules twice a day with main meals during the same period. The average age in the experimental group was 43 years, in the placebo group – 45 years; the average BMI was 48.76 and 50.36 kg/m2, respectively (class III obesity).
After the initial 3-week treatment phase, both groups additionally followed a special diet to reduce liver size. The daily regimen consisted of 2 protein shakes (≥80% protein content), which were consumed for breakfast and dinner. The main meal at lunchtime consisted of raw vegetables or salad, 180 g of lean meat or fish, and 200 g of cooked vegetables. Simple and complex carbohydrates were strictly excluded throughout the dietary phase. The target macronutrient composition was ≈35 to 45% protein, 30 to 40% fat, and 20 to 30% carbohydrates. Total daily energy intake was limited to a maximum of 1,100 kcal, which is a significant calorie deficit compared to the calculated requirements for this group of patients.
At control points, blood tests with a lipid profile, ultrasound measurement of liver size, and assessment of liver steatosis using the FibroScan method with determination of the controlled attenuation parameter (CAP) were performed. In addition, changes in body composition were assessed using bioelectrical impedance analysis (BIA).
The design and main results of the study are presented in Figure 3.
Note: data are presented as mean ± SEM (standard error of the mean).
For CAP: *p<0.05: between-group difference at the corresponding time point; #p<0.001: between-group difference at the corresponding time point; § p=0.001: change within the group from TP0 to TP1 in the ELA group; &p<0.0001: change within the group from TP0 to TP2 in the ELA group.
For liver size: <p<0.05: between-group difference at the corresponding time point; #p<0.001: change within the group from TP0 to TP1 in the ELA group; § p<0.001: change within the group from TP0 to TP2 in the ELA group; &p<0.05: change within the group from TP0 to TP2 in the ELA group.
Throughout the study, no side effects of treatment were observed, i.e., the addition of artichoke extract to the treatment regimen did not affect its tolerability. This may be a key argument for comorbid patients who are forced to take multiple medications.
Practical conclusions. What can be expected after 3-6 weeks of artichoke extract therapy?
The SteatoChoke study showed for the first time that in patients with morbid obesity and NAFLD, artichoke extract can reduce steatosis and liver volume in 6 weeks, as measured quantitatively by FibroScan and standardized sonography.
Despite the statistically significant effect of steatosis reduction in the ELA group, the mean CAP value remained >280 dB/m throughout the study period, corresponding to grade 3 steatosis. However, the authors believe that longer use of ELA may further reduce steatosis levels. After 6 weeks of observation, a further decrease in mean CAP values was observed in the study group. This assumption is supported by a previous study that showed a time-dependent improvement in liver steatosis when taking ELA for up to 8 weeks (Panahi et al., 2018).
An additional finding of the SteatoChoke study was a trend toward a decrease in low-density lipoprotein (LDL) and total cholesterol levels in the female population. Between time points TP0 and TP1, female participants showed an increase in LDL cholesterol levels when taking the placebo (+6.82 mg/dL in the placebo group during the first 3 weeks; p=0.181) and a decrease when taking artichoke extract (-8.29 mg/dL; p=0.115). For total cholesterol, the results showed a numerical but statistically insignificant increase in the placebo group (+7.64 mg/dL; p=0.242) and a decrease in the artichoke group (–9.98 mg/dL; p=0.120). These changes, together with a tendency toward a decrease in the percentage of body fat according to bioimpedance analysis, indicate that the effects of artichoke extract are not limited to the liver but reflect a systemic improvement in fat and carbohydrate metabolism.
Therefore, artichoke extract is an attractive adjunctive treatment for MASLD: it is available without a prescription, inexpensive, well tolerated, and easily integrated into outpatient and inpatient care.
References
1. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol., 2024 Sep; 81 (3): 492-542. doi: 10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7. PMID: 38851997.
2. Holländer et al. Artichoke leaf extract reduces steatosis and decreases liver size in prebariatric patients: A randomized placebo-controlled pilot trial – The SteatoChoke-Study, Journal of Clinical Lipidology, https:// doi.org/10.1016/j.jacl.2025.10.063.
3. Stefan N., Yki-Jär vinen H., Neuschwander-Tetri B. A . Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment. Lancet Diabetes Endocrinol., 2025 Feb; 13 (2): 134-148. doi: 10.1016/S2213-8587(24)00318-8.
Prepared by Igor Petrenko
Reference “ZU”
In Ukraine, Artichol from JSC “Kyiv Vitamin Plant” is an affordable high-dose artichoke extract preparation. One tablet of the drug contains 200 or 400 mg of dry artichoke extract, which simplifies dosing and improves patient compliance. The pharmacological properties are due to the action of a complex of biologically active substances contained in the leaves of the field artichoke, namely cynarin, phenolic acids, bioflavonoids, ascorbic acid, carotene, vitamins B1 and B2, and inulin. These components have a choleretic, hepatoprotective, and diuretic effect, and also reduce the content of urea, atherogenic cholesterol, and sugar in the blood. Artichol is produced from a French substance (Evear Extraction Vegetale et Aromas) – artichoke extract, standardized for its content of key active substances. Thus, Artichol is a reliable tool for implementing a high-dose artichoke hepatoprotection strategy, which has proven its effectiveness in clinical studies.
