This guidance describes a wide spectrum of approaches to
identify the adults, young people and children with non-alcoholic fatty liver
disease (NAFLD) who have advanced liver fibrosis and are most at risk of
further complications. It outlines the lifestyle changes and pharmacological
treatments that can manage NAFLD and advanced liver fibrosis. This guidance is
developed by a panel of expert hepatologist with data supported system.
Guidance document is little different from guideline as guidelines are developed
by a multidisciplinary panel of experts and rate the quality of the evidence
and the strength of each recommendation using the grading of recommendations,
assessment development, and evaluation system. Guidance
statements are not recommendations, but help clinicians to understand and
implement the most recent evidence.
This practice guidance is developed for use by physicians and
other health professionals. The data have been retrieved by an extensive PubMed
search up to December 2017. Specific guidance statements are evidence based
whenever possible, and, when such evidence is not available or is inconsistent,
guidance statements are made based on the consensus opinion of the authors.
fatty liver disease has been defined as the accumulation of fat in the liver in
the absence of recent or ongoing intake of significant amount of alcohol. Two criteria must be fulfilled for defining NAFLD
NAFLD can be categorized histologically into nonalcoholic fatty
liver (NAFL) or nonalcoholic
Steatohepatitis. NAFL is defined as the presence of ?5% HS
without evidence of hepatocellular injury in the form of hepatocyte ballooning.
NASH is defined as the presence of ?5%
and inflammation with hepatocyte injury (e.g., ballooning), with
or without any fibrosis.
Till date, liver biopsy remains the gold standard for diagnosing
NASH. Though, liver biopsy is not feasible in studies of the general
population, there is no direct assessment of the incidence or prevalence of
NASH. But, there have been some attempts to estimate the prevalence of NASH by
Worldwide, obesity remains the most
important and well-described risk factor for NAFLD. The results of several
cross-sectional studies and case-control studies have shown that people with
NAFLD have higher waist circumference (WC) or BMI than those without NAFLD, and
have reported significant associations between abdominal obesity (OR =
1.10-1.13; 95% CI, 1.02-1.22 per 1-cm increase in WC) and NAFLD.(108) In the
Dionysos study, NAFLD was present in 94%, 67%, and 24.5% of the obese,
overweight, and normal weight populations, respectively. Although the
mechanisms responsible for the increased risk of NAFLD with abdominal obesity
have not been fully elucidated, current findings suggest that obesity leads to
insulin resistance, which, in turns, leads to NAFLD. At the other end of the
distribution, data on the prevalence of NAFLD among high-risk individuals with
severe obesity have become widely published. On average, these studies reported
that 76% (range 33 to 99%) of the patients undergoing bariatric surgery have
steatosis, 37% (range 9.8 to 72.5%) have NASH, 23% (range 7.3 to 49%) fibrosis,
and 5.8% (range 1.6 to 10%) cirrhosis.
Several studies have described a
higher prevalence of NAFLD among people with type 2 diabetes compared with
nondiabetics, with prevalence estimates ranging from 40% to 69.5%. Moreover, a
recent case-control study using proton-MRS demonstrated that people with type 2
diabetes have on average 80% more liver fat than age-, weight-, and sex-matched
controls. This difference was not explained by the type of medications used.
Furthermore, aspartate aminotransferase (AST) and alanine aminotransferase(ALT)
underestimated liver fat content among people with diabetes; for any given ALT
or AST level, adults with type 2 diabetes had 40 to 200% more liver fat than
nondiabetic adults.Patients with type 2 diabetes not only have a higher
prevalence of NAFLD, but also appear to have more severe forms of the disease,
including NASH and fibrosis.
Dyslipidemia: Dyslipidemia that is characterized by high
triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels predisposes
patients to arthrosclerosis. Approximately 20–80% of NAFLD patients also have
dyslipidemia. The prevalence of NAFLD in
individuals with dyslipidemia attending lipid clinics has been estimated to be
50%.(29,30) A very common change in the metabolic profile among patients with
T2DM, MS, and obesity is an alteration of serum lipid levels (dyslipidemia),
suggesting a close relationship between T2DM, MS, and obesity and NAFLD. It has
been shown that NASH significantly boosts the level of oxidized low-density
lipoprotein cholesterol (LDL-C). High LDL-C is a well-established risk factor
for arthrosclerosis. The most common form of dyslipidemia in NAFLD patients is
atherogenic dyslipidemia, which is characterized by hypertriglyceridemia, low
HDL-C levels, and high LDL-C levels.
Age, sex, and ethnicity: NAFLD is seen in all
age groups, prevalence peaks in the fourth decade in men and sixth decade in
women. The prevalence of NAFLD in India above 20 years age was 18.9%.The
prevalence of NAFLD increased with increasing age. More recent studies are
showing that the prevalence of NAFLD in men is equal to or greater than the
prevalence in women. But these findings are not consistent with our population.
Recently in a large cohort, it revealed that NAFLD is more prevalent in female
among Bangladeshi population and prevalence of NASH was 42.4% in NAFLD which is
much higher. In fact, both the prevalence of NAFLD
and stage of liver disease appear to increase with age.
using different diagnostic tools, US population-based studies all found that
Hispanics have the highest and non-Hispanic blacks have the lowest prevalence
of NAFLD. Echoing the racial/ethnic differences in the NAFLD prevalence,
Younossi et al recently reported that NASH was independently associated with
being Hispanic odds ratio (OR), 1.72; 95%CI: 1.28-2.33 and inversely
associated with being African-American (OR, 0.52; 95%CI: 0.34-0.78).
Furthermore, in a study using proton-MRS Peterson et al found that even after
adjusting for BMI and age, Asian Indian men have significantly higher HT
compared with their Caucasian counterparts (1.54 vs. 0.77%). It is intriguing that most of the recent data suggest
that the ethnic differences reported for NAFLD may be explained by the genetic
variation related to the patatin-like phospholipase domain-containing protein 3
(PNPLA-3) gene.(40) In summary, the incidence of NAFLD varies across the world,
ranging from 28.01 per 1,000 person-years (95% CI, 19.34-40.57) to 52.34 per
1,000 person years (95% CI, 28.31-96.77).