Screening high risk patients

1. Screen High risk group

2. What is NAFLD
• HS involving > 5% of the
hepatocytes,associated with insulin
resistance without other causes of HS
EASL–EASD–
EASO (2016)
• HS defined by imaging or histology
without other causes of HS
AASLD
• Fat accumulation in the liver
exceeding 5% of its weight
WGO
J Hepatol 2016 vol. 64 j 1388–1402, Hepatology 2018;67:328-57, J Clin Gastroenterol 2014;48:467-73

3. What is NAfLD
• The diagnosis of NAFLD is based on the
following
1. Presence of hepatic steatosis, in addition to
2. lack of significant alcohol consumption
3. Exclusion of other liver diseases

5. Essential components of screening
typed

6. Purpose to screen NAFLD
• Identify persons who are at risk of disease
progression and liver fibrosis (predictor of disease
outcomes)
• Early intervention can halt or reverse disease
progression

7. • Who to screen
• How to screen

8. Who to screen
Does not recommend
screening of
General populations
EASL–
EASD–
EASO
(2016)
AASLD
WGO Italian
American
Association
of
Endocrine
Chinese

10. • Who to screen

11. Who to Screen
• High Risk Population
EASL–EASD–
EASO (2016)
• High Risk Population
WGO (2014)
AACE (2022)
• No screening
AASLD (2018)
J Hepatol 2016 vol. 64 j 1388–1402, Endocrine Practice 28 (2022) 528-62, Hepatology 2018;67:328-57, J Clin Gastroenterol 2014;48:467-73
• High Risk Population

12. High risk population
• Insulin resistance
• Metabolic risk factors (obesity, MetS)
• Age > 50 years
• Persistent elevated Liver enzymes
EASL–EASD–
EASO (2016)
• Central obesity, T2 DM, dyslipidemia,
MetS, altered LEs, and fatty liver on US
WGO (2014)
• May consider..
AASLD

13. High Risk Population
• Obesity
• ≥2 risk factors of MetS
• Prediabetes or T2DM,
• Hepatic steatosis on any imaging
• Persistently elevated plasma
aminotransferase levels (over 6
months)
• Undergoing bariatric surgery
AACE
Endocrine Practice 28 (2022) 528-62

14. General recommendation
• All guidelines require the exclusion of patients with
secondary causes of liver steatosis including
– steatogenic drugs,
– excessive alcohol consumption

15. Alcohol threshold
• Weekly
• > 196 g in women
• > 294 g in men
• for previous 2 years
USA
• Weekly
• > 140 g in women and > 210 g in men
• Daily
• > 20 g in women and > 30 g in men
Other
guidelines

16. Screening Methods
•Ultrasound (First Line)
•Liver enzymes and/or
•Steatosis biomarkers
•Assessment of dietry and physical
habits
EASL–EASD–
EASO (2016)
• Fib-4
AACE
Journal of Hepatology 64 (2016)1388–1402 Endocrine Practice 28 (2022) 528-62

17. Metabolic Risk factors present
Ultrasound /OR Steatosis
biomarkers/OR Liver enzymes

18. Ultrasound

19. US and scores (easl)
• US has limited sensitivity and does
• not reliably detect steatosis when <20% [27,28] or in individuals
• with high body mass index (BMI) (>40 kg/m2) [29]. Despite
• observer dependency, US (or computed tomography [CT] or
• MRI) robustly diagnoses moderate and severe steatosis and provides
• additional hepatobiliary information, hence it should be
• performed as a first-line diagnostic test.
• 3). The best-validated steatosis scores are the fatty
• liver index (FLI), the SteatoTest and the NAFLD liver fat score;
• they have all been externally validated in the general population
• or in grade 3 obese persons and variably predict metabolic, hepatic
• and cardiovascular outcomes/mortality. These scores are
• associated with IR and reliably predict the presence, not the
• severity, of steatosis [30].

20. Steatosis Biomarkers (EASL)
• Define
• Fatty Liver Index, SteatoTest, NAFLD Fat score
• Liver tests: ALT
• AST, cGT. 3Any increase in ALT, AST or cGT.

21. FLI

22. STetostest

23. Easl fibrsosi (NFS)
• NFS predicts incident diabetes,
• and changes in NFS are associated with mortality. The tests
• perform best at distinguishing advanced (PF3) vs. non-advanced
• fibrosis but not significant (PF2) or any (PF1) fibrosis vs. no
• fibrosis [36]. Importantly, the negative predictive values (NPVs)
• for excluding advanced fibrosis are higher than the corresponding
• positive predictive values (PPVs) [36,37]; therefore, non-invasive
• tests may be confidently used for first-line risk stratification to
• exclude severe disease. However, predictive values depend on
• prevalence rates and most of these studies have been conducted
• in tertiary centres where the pre-test probability of advanced
• fibrosis is higher than in the community

24. Metabolic Risk factors present
Ultrasound /OR Steatosis
biomarkers/OR Liver enzymes
Steatosis
Present
Normal
liver enzymes
Abnormal
liver enzymes
Steatosis
Absent
Normal
liver enzymes

25. Steatosis
Absent
Steatosis
Present
Normal
liver enzymes
Serum
Fibrosis
Markers
Low Risk Medium /High
Risk
Abnormal
liver enzymes

26. Serum Fibrosis Marker
• 4Serum fibrosis markers: NAFLD
• Fibrosis Score, FIB-4, Commercial tests
(FibroTest, FibroMeter, ELF). 5Low risk:
• indicative of no/mild fibrosis; Medium/high
risk: indicative of significant fibrosis
• or cirrhosis

27. FIB -4

28. Steatosis
Absent
Steatosis
Present
Normal
liver
enzymes
Serum
Fibrosis
Markers
Low Risk
Follow up (2 yearly )
Liver Enzymes, Fibrosis
Markers
Medium
/High
Risk
Abnormal
liver
enzymes
Specialist
Referral
Identify other CLD
Assessment of disease Severity
Decision regrd. Liver Biopsy
Initiate therapy

29. Easl followup
• The optimal follow-up of patients with NAFLD is as yet
undetermined.
• Risk of progression of both the hepatic disease and the
• underlying metabolic conditions as well as the cost and workload
• for healthcare providers need to be considered. Monitoring
• should include routine biochemistry, assessment of comorbidities
• and non-invasive monitoring of fibrosis. NAFL patients without
• worsening of metabolic risk factors, should be monitored at
• 2–3-year intervals. Patients with NASH and/or fibrosis should
• be monitored annually, those with NASH cirrhosis at 6-month
• intervals. If indicated on a case-by-case basis, liver biopsy could
• be repeated after 5 years.

31. U/S or Fib 4
• Endo It is reasonable to perform a risk stratification (FIB-4) without
the need for a liver US for the diagnosis of hepatic steatosis (ie, in
the 3 at-risk groups, the chance of having hepatic steatosis is very
high
• and 70%).5,9-11,52,102-104 It is important to perform a complete
• medical history and routine clinical chemistries that allow clinicians
• to rule out secondary causes of liver steatosis (Table 4) and
• elevated plasma aminotransferase levels (Table 5). A thorough
• workup should be performed to rule out competing causes for
• steatosis, in addition to excluding significant alcohol consumption.

33. elastography
• Endo As mentioned earlier, VCTE (Table 1 and Algorithm Fig. 2) is
the
• most broadly used noninvasive method for LSM and, thus, for
• establishing the risk of liver fibrosis158-160 and for eventually
• excluding cirrhosis.158 At a fixed sensitivity, a cutoff LSM of 6.5 kPa
• excluded advanced fibrosis with an NPV of 0.91, and a cutoff LSM of
• 12.1 kPa excluded cirrhosis with an NPV of 0.99.158 Minor
limitations
• of VCTE include overestimation of LSMs at higher stages of
• fibrosis and unsuccessful LSMs with inappropriate use of probes in
individuals with overweight and obesity, which can be circumvented
• using the right probe in individuals with higher BMI.

34. elastography
• Endo A European study in 450 adults who underwent TE and a liver biopsy
• using an LSM Youden cutoff value for clinically significant fibrosis
• (F2) of 8.2 kPa demonstrated NPVs of 78% in persons from diabetes
• clinics and 97% in the general population.159 Another study in
• 1073 persons with NAFLD among 10 European tertiary liver centers
• confirmed these cutoffs, reporting that a cutoff of 8.0 kPa had a 93%
• sensitivity to exclude advanced fibrosis (F3-F4).163 Similarly, a
• recent systematic review further supported the cutoff of 8.0 kPa for
• screening for clinically significant liver fibrosis.164 For practical
• purposes then, people with an LSM of <8.0 kPa determined using
• TE are considered low risk for clinically significant fibrosis (F2)
• and are best managed in the nonspecialty clinics with repeat surveillance
• testing in 2 to 3 years.

35. eAsl elsto
• Among imaging techniques, transient elastography performs
• better for cirrhosis (F4) than for advanced fibrosis (F3). Elastography
• has a higher rate of false-positive than false-negative results
• and higher NPV than PPV [38], hence the ability to diagnose
• bridging fibrosis or cirrhosis is insufficient for clinical
decisionmaking.
• The main shortcoming of transient elastography is unreliable
• results in the presence of high BMI and/or thoracic fold
• thickness. In a large, unselected European series, up to 20% of
• examinations had unreliable results [39], mainly in obese NAFLD
• [38]. The XL probe should be used in these patients to reduce the
• failure rate, which remains high (35%) [40].

36. ELF

39. extra

40. US
• The accuracy of liver US for the detection of
• moderate and severe steatosis was >80% in a meta-analysis when
• compared with liver histology.129 However, this was based on data
• from hepatology clinics and does not represent the population with
• less severe disease observed in primary care or endocrinology
clinics,
• where liver US was shown to have suboptimal sensitivity for mildto-
• moderate steatosis (below a liver fat content of 12.5%)
• compared with 1H-MRS and liver biopsy in 146 individuals.24 Liver
• US is also highly operator dependent and does not inform about the
• severity of liver fibrosis (unless cirrhosis is present)

41. US endocrine guideline
• Hepatic steatosis may be assessed by
• means of simple noninvasive liver steatosis scores (fatty liver index,
• US fatty liver index, and hepatic steatosis index), although these
• diagnostic modalities have inherent limitations.11,115,152 A liver US is
• not recommended for routine clinical diagnosis.115 Instead, TE is
• preferred over liver US,
• The accuracy of liver US for the detection of
• moderate and severe steatosis was >80% in a meta-analysis when
• compared with liver histology.129 However, this was based on data
• from hepatology clinics and does not represent the population with
• less severe disease observed in primary care or endocrinology clinics,
• where liver US was shown to have suboptimal sensitivity for mildto-
• moderate steatosis (below a liver fat content of 12.5%)
• compared with 1H-MRS and liver biopsy in 146 individuals.24 Liver
• US is also highly operator dependent and does not inform about the
• severity of liver fibrosis (unless cirrhosis is present)

42. Fib 4 (endocrin)
• 2.2.1. Clinicians should use liver fibrosis
prediction
• calculations to assess the risk of NAFLD with
liver fibrosis. The
• preferred noninvasive initial test is the
fibrosis-4 index (FIB-4).

43. EaSl Diagnostic algorithm and follow-
up
• The incidental discovery of steatosis should lead to comprehensive
• evaluation of family and personal history of NAFLDassociated
• diseases and the exclusion of secondary causes of
• steatosis. Metabolic work-up has to include a careful assessment
• of all components of MetS [63]. Similarly, the presence of obesity/
• T2DM or the incidental finding of raised liver enzymes in patients
• with metabolic risk factors should prompt non-invasive screening
• to predict steatosis, NASH and fibrosis (Table 3).
• Surrogate markers of fibrosis (NFS, FIB-4, ELF or FibroTest)
• should be calculated for every NAFLD patient, in order to rule out
• significant fibrosis (PF2). If significant fibrosis cannot be ruled
• out, patients should be referred to a Liver Clinic for transient elastography;
• if significant fibrosis is confirmed, the final diagnosis
• should be made by liver biopsy (Fig. 1). All cases with diabetes or
• diabetes risk should be referred to a Diabetes Clinic for optimal
• management. Those at increased diabetes risk should be included
• in a structured lifestyle modification program. Obesity should
• prompt the inclusion of the patient in a structured weight loss programand/
• orreferral toanobesity specialist. Finally, all casesshould
• receive comprehensive cardiovascular disease (CVD) work-up.

44. EAsl
• Biomarkers and scores of fibrosis, as well as transient
• elastography, are acceptable non-invasive procedures
• for the identification of cases at low risk of advanced
• fibrosis/cirrhosis (A2). The combination of biomarkers/
• scores and transient elastography might confer
• additional diagnostic accuracy and might save a
• number of diagnostic liver biopsies (B2)
• • Monitoring of fibrosis progression in clinical practice
• may rely on a combination of biomarkers/scores and
• transient elastography, although this strategy requires
• validation (C2)
• • The identification of advanced fibrosis or cirrhosis by
• serum biomarkers/scores and/or elastography is less
• accurate and needs to be confirmed by liver biopsy,
• according to the clinical context (B2)
• • In selected patients at high risk of liver disease
• progression, monitoring should include a repeat liver
• biopsy after at least 5-year follow-up (C2)