Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05194553 |
| Other study ID # |
UMPAX-21-1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 15, 2022 |
| Est. completion date |
June 15, 2023 |
Study information
| Verified date |
January 2024 |
| Source |
Maastricht University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Non-alcoholic fatty liver disease (NAFLD) is with 25% the most prevalent liver disorder in
Western society and is associated with overweight, obesity, metabolic syndrome (MetS), type 2
diabetes mellitus (T2DM) and cardiovascular diseases (CVD). NAFLD is defined by a hepatic fat
accumulation of more than 5% in the absence of classical causes of steatogenesis (e.g.
alcohol and steatogenic drugs). It represents a broad spectrum of clinical entities from
steatosis to advanced liver disease with hepatic failure. Most of the patients have simple
steatosis, however in about 15-30% non-alcoholic steatohepatitis (NASH) develops, which leads
to an overall increase in morbidity and mortality due to the progression to fibrosis,
cirrhosis and hepatocellular carcinoma (HCC). Patients with NAFLD have no or few, mainly
specific symptoms; and generally there is a silent progression of simple steatosis to NASH
and in the end liver-related morbidity and mortality. Despite the clinical importance and the
potential impact on healthcare resources, the majority of NAFLD patients are currently not
detected due to the lack of non-invasive methods to diagnose NAFLD. To date, the prevalance
of NAFLD in Turkey among subjects at risk, and its relation to common comorbidities such as
obesity, T2DM and CVD is not clear. Therefore, identification of NAFLD patients in this
cohort will give information on the prevalence in the group of uncomplicated overweight and
obesity and those with concomitant cardiometabolic diseases. By early detecting these
patients at risk to develop progressive liver diseases and extrahepatic manifestations, it
will be possible to intervene and improve health. Within this context, this study aims to
detect prevalence of NAFLD among risk groups. Also, the risk factors related to NAFLD
etiology and progression, such as overweight, obesity, T2DM, CVD, diet and physical activity
will be studied to have a better understanding of their presumed causal relationship with
NAFLD.
Description:
Non-alcoholic fatty liver disease (NAFLD), characterized with more than 5% intrahepatic fat
accumulation in the absence of classical causes of steatogenesis, is considered as a growing
epidemic with a global prevalence estimated around 25%. NAFLD usually manifests as simple
steatosis, however in about 15-30% cases it can progress to its inflammatory type of NASH,
which may in turn lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Given that
patients typically have no or few symptoms, it is fundamental to detect and treat NAFLD at
the earliest stage to decrease liver-related morbidity and mortality.
NAFLD is known to be the hepatic manifestation of the metabolic syndrome (MetS), a cluster of
metabolic disorders including abdominal obesity, type 2 diabetes mellitus (T2DM), and
cardiovascular diseases (CVD). It has been reported that NAFLD risk increases with obesity,
diabetes mellitus, and dyslipidemia. In line with this, the highest prevalence of NAFLD is
reported from South America and the Middle East, where MetS is also widespread, making it a
major public health issue in these regions. Similarly, the clinical significance of NAFLD has
progressively increased in Turkey lately. With an obesity rate of 32% according to latest WHO
reports, and T2DM rate of 15%, Turkey can be considered a risky region in terms of NAFLD
burden. Despite the increasing burden of NAFLD in Turkey, few studies have been undertaken to
identify its prevalence showing conflicting results due to excessive heterogeneity in design.
8 studies that were undertaken in the past 15 years reported a prevalence between 10,6% and
60%. One study that included subjects with MetS reported as high as 94.3%. It is critically
important to develop new evidence regarding NAFLD prevalence among this patient group in
Turkey and the association between MetS comorbidities and NAFLD severity so as to establish
NAFLD risk groups and develop effective population screening and public health policies
targeting this patient group.
The optimal screening method to detect hepatic steatosis in the general population remains to
be established. The reference standard is liver biopsy; however, it is problematic to conduct
studies that involve liver biopsy due to its invasiveness, high cost and patient discomfort.
Therefore, ultrasonographic imaging (USG) is usually favored as the first-line modality in
most clinical practices. However, USG has limited sensitivity and does not reliably detect
steatosis when <20% or in individuals with BMI>40 kg/m2. Controlled attenuation parameter
(CAP) measured with transient elastography (TE), on the other hands, has recently emerged as
a reliable imaging tool for the screening and diagnosis of NAFLD on a population scale. It is
suggested to have high sensitivity in identifying mild steatosis and yields a good
correlation with steatosis grades. Therefore, CAP can enable early and noninvasive detection
of NAFLD at the subclinical level. It is important to detect NAFLD at the earliest possible
stage because once it is established hepatic insulin resistance increases, which, in turn,
may trigger, in 30-40% of cases, NAFLD progression to its inflammatory phenotype
Non-alcoholic Steatohepatitis (NASH) and eventually, hepatocarcinoma, cirrhosis, and liver
failure.
As of today, treatment of NAFLD is only possible through lifestyle modifications such as
following a healthy balanced diet and doing regular physical activity, given that no
pharmacological treatment has been approved yet for NAFLD. Weight loss of 7-10% BW seems to
have proven efficacy especially in overweight subjects. Different dietetic approaches have
been proposed to reach the weight loss goal; however, no consensus has been reached yet on
the type of medical nutrition therapy to be offered to NAFLD patients. Having said that, in
the recent EASL-EASD-EASO Clinical Practice Guidelines, Mediterranean diet (MED DIET) was
recommended as the diet of choice for the treatment of NAFLD together with weight loss
initiatives. Indeed, a growing body of evidence suggest that MED DIET exerts health benefits
even without accompanying weight reduction, which is the main obstacle in lifestyle
interventions.
Higher adherence to the MED DIET has shown to have beneficial effects on the progression of
hepatic steatosis in observational studies and clinical trials (n<90 followed up for<6
months) in patients with existing hepatic steatosis. These findings are confirmed in The
Swiss CoLaus and UK Fenland cohorts which reported lower risk of hepatic steatosis with
higher adherence to MED DIET.
Not only the dietary pattern, but also certain micronutrient deficiencies might be related to
NAFLD. New evidence suggests that also Vitamin D deficiency, which is known to associate with
obesity and sedentary lifestyle, may cause NAFLD. Hypovitaminosis D is proposed to have a
causative relationship with the severity and incidence of NAFLD. The association between
Hypovitaminosis D and NAFLD has been examined previously. A lower serum 25(OH)D level was
shown to be an independent risk factor for NAFLD. Various studies has shown a correlation
between Vitamin D level and disease severity. A cross-sectional study of 6567 men concluded
that participants in the lowest tertile of serum 25(OH)D levels had a significantly increased
risk for NAFLD compared to those in the highest tertile. Another study found similar results.
CAP was used as a tool to define hepatic steatosis in a study that showed a significant
association between serum 25(OH)D levels and NAFLD.9 However, some other studies reported
quite contradictory results. Collectively, the data from the published studies indicate that
NAFLD subjects are more likely to be vitamin D deficient compared to controls. However,
definite directionality of the results cannot be ascertained due to the limitations which
include the variability in the method of diagnosis of NAFLD, clinical heterogeneity among the
study groups and variability in defining vitamin D deficiency. Demonstration of a causal role
of hypovitaminosis D in NAFLD progress could have important therapeutic implications. Vitamin
D supplementation is easy to accomplish on a population level, hence, it can be an efficient
tool to prevent NAFLD. Cochrane performed a systematic review of randomized clinical trials
of Vitamin D supplementation in chronic liver diseases, 11 of which included NAFLD patients.
Given the high heterogeneity of studies included, they failed to assess the beneficial and
harmful effects of vitamin D supplementation in adults with chronic liver diseases.
Well-designed future studies are needed to investigate this potential relation.
