Presentation long Flashcards
(39 cards)
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- MASLD definiton
- MASLD exists in a spectrum
- MASLD vs NAFLD:
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- Incidence
- Age
- Gender
- Diseases linked to MASLD
- MASH morbidity significance
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- Environmental + genetic factors
- Two hit theory
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- Liver biopsy remains the gold standard for the diagnosis and evaluation of histopathological changes in patients with MASLD 56. Indeed, it is the only method that gives definite answers when it comes to the ability to differentiate between MASLD and MASH, as well as the severity of the disease
- In a meta-analysis, involving 64,356 percutaneous liver biopsy procedures, major complications occurred in 2.44% of patients, 0.48% of patients experiencing major bleeding, 0.65% of patients required hospitalization, incidence of moderate/severe pain at 0.34%, and death in 0.01% of patients. Pain was also a common outcome of the procedure that was observed in up to 12.9% of patients
sampling errors, limited accessibility, inter and intra-observer variability, poor patient compliance, and high costs
Sampling errors, limited accessibility, inter and intra-observer variability, poor patient compliance, and high costs
Sampling error is a concern since percutaneous liver biopsies assess only 1/50000 of liver mass and it is known that fibrosis is not spread equally throughout the liver
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- These scoring systems depend on either indirect biomarkers, reflecting liver function but not extracellular matrix metabolism (e.g. platelet count, liver aminotransferases, coagulation panels) or direct biomarkers of extracellular matrix metabolism (e.g. hyaluronic acid, Mac 2-binding protein glycan isomer, autotaxin, thrombospondin 2, procollagen types 1 and 3)
- of the most commonly employed scores to predict fibrosis in MASLD patients, relying on indirect biomarkers, include fibrosis 4 (FIB-4), NAFLD fibrosis score (NFS), and AST to Platelet Ratio Index (APRI)
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Talk about pros and cons of different techniques
- Mention other elastography methods
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- ## Read slides
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Talk about other significant factors
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ROC: Reciever operating characteristic curve
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- Survival curves were statistically different between patients in different risk groups according to baseline LSM
- Survival curves were not statistically different between patients who showed improvened, worsening, or stablness
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Survival curves were not statistically different between patients with stable, improved or worsened LSM
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- In the intermediate risk group, Survival curves were statistically different between patients with stable, improved, or worsened LSM (Log rank test p<0.05)
- As we can see those that improved had a 100% survival, while LSM stabless or worsening led to a very significant reduction in survival
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Survival curves were statistically different between patients with improved LSM compared with patients with stable or worsened LSM
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Incidence rate of composite outcome per 1000 person-year was 15.5, 19.7, 81.4 for LSM improved, stable, or worsened groups respectively
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- Having baseline LSM that falls within 10-20 kPa led to an 9.7x increased odds of LRE compared to those in low risk group, while those above 20 kpa had a 55.63x increased odds of developing LRE compared to those in low risk group
- LSM worsening in intermediate risk group was associated with a significantly higher risk of developing LRE, confirmed at at univariate and multivariate COX regression analysis (HR 6.66)
- LSM improvement in high risk group lead to significantly lower risk of LRE compared with those who remained stable (HR 0.16), confirmed at univariate and multivariate cox regression analysis
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Read slides
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- Read slides
- The European Association for the Study of Liver (EASL) offers a strong recommendation of using an LSM by VCTE <8 kPa to rule out advanced fibrosis and >12kPa to rule in advanced fibrosis
- XL probe reduces failure rate but still considered high
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MASLD definiton
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- Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously known as non-alcoholic fatty liver disease or NAFLD) is defined as the presence of steatotic liver disease (SLD) alongside at least one cardiometabolic risk factor
- This must exist without any secondary causes of steatosis, consisting of significant alcohol consumption (>20 g/d in females or >30 g in males), use of steatogenic drugs (e.g. amiodarone, methotrexate, and corticosteroids), co-existing liver disease (e.g. viral hepatitis), or genetic hepatic disorders
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Cardiometabolic risk factors
presence of hypertension, dyslipidaemia, type 2 diabetes, overweight or obesity, or impaired glucose regulation
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Steatotic liver disease definition
Steatotic liver disease is defined as the presence of increased lipid accumulation (>5% of liver mass) within the liver parenchyma
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Change from NAFLD to MASLD
Although the change in nomenclature from NAFLD to MASLD might lead to speculation that such change would lead to a significant effect on the validity and use of the current pool of studies to extrapolate treatment and prognosis of current and future patients under the new definition, multiple studies have demonstrated that MASLD and NAFLD share nearly all epidemiological, diagnostic, prognostic, and therapeutic features
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MASLD spectrum
MASLD exists in a spectrum, with simple steatosis at the mildest end [known as metabolic dysfunction associated steatosis (MASL)], MASLD induced cirrhosis at the severe end of the spectrum, and metabolic dysfunction-associated steatohepatitis (MASH) in between (MASH) 6. MASH is defined as the presence of MASL alongside a necroinflammatory component (i.e. hepatocyte ballooning, lobular inflammation, and/or fibrosis) of variable severity
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Incidence of MASLD
MASLD is one of the most common and growing causes of chronic liver diseases in the world, affecting around 30% of the population, with an incidence rate that has tripled between 2000 and 2015 7. It is currently the most prevalent liver disorder in Western industrialized countries, where we commonly see the principal risk factors for MASLD, including type 2 diabetes mellitus (T2D), dyslipidaemia, central obesity, and metabolic syndrome
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Age MASLD
It can affect individuals at any age, including children (Younossi et al., 2011), although it’s incidence progressively increases as one ages, with most patients being diagnosed with MASLD hovering around the ages of 40-60
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Gender MASLD
Males are more likely to develop MASLD compared to females
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MASLD link to other diseases
- MASLD has been linked to several diseases.
- It is estimated that in up to 90% of obese individuals, MASLD is present (depending on the severity of obesity), and that in up to 70% of people living with T2D (particularly in those who are overweight and with poor metabolic control or dyslipidaemia)
- A range of other conditions have been linked to MASLD, independent to their relationship to obesity, and include hypopituitarism, hypothyroidism, hypogonadism, polycystic ovary syndrome, and obstructive sleep apnea
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MASH morbidity intro
MASH is now considered one of the leading drivers of cryptogenic cirrhosis, cirrhosis, and hepatocellular cancer (HCC) around the world. 13,14. It has also become the most quickly expanding indication for liver transplantation in the United States, and the most common indication for liver transplantation in the United States senior population
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Pathogenesis intro
The exact pathogenic mechanisms that lead to the development of MASLD and its progression has not been fully deciphered. What is currently known is that multiple components, including both environmental and genetic factors, play a role in its development16 . One theory that currently holds the most weight in this field, points towards insulin resistance being the main driver of hepatic steatosis, and likely its progression to steatohepatitis17. Other experts in the field have hypothesized that in order for necroinflammation in steatohepatitis to develop, a “second hit” (i.e. an additional oxidative insult), is needed.
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Second hit factors
antioxidant deficiencies, hepatic iron, genetic and epigenetic factors, mitochondrial dysfunction, intestinal bacteria, and gut hormones
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Non invasise testing intro
Due to the invasiveness and limitations of liver biopsies, the use of non-invasive testing has gained considerable ground in the context of MASLD and are considered first-line tests in assessing the disease
Non-invasive tests can be divided into two general categories: Imaging examinations and serological biomarkers
- These attempt to offer predictions on the steatotic and fibrotic state of hepatic tissue, and hence the severity of MASLD in patients, bypassing the need of further assessment with a biopsy
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Direct biomarker advantages and downfalls
Several studies have shown promising results when it comes to the sensitivity and specificity of blood-based tests that utilise direct biomarkers to detect liver fibrosis and its complications 106–110. There are however limitations of using direct biomarkers. The majority of direct biomarkers do not explore whole tissue or body function, providing information of limited clinical value, making them rarely seen in routine clinical practice 111. Availability of such tests are mainly seen in specialist and research settings, leading to increased turnaround times and costs compared to indirect biomarkers 111. Another downfall is that not all direct biomarkers are liver derived or liver specific, leading to other factors (e.g. infection and acute system inflammation) that may influence their serum levels
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Concurrent liver diseases
chronic viral hepatitis B or C, autoimmune or cholestatic liver diseases, Wilson’s disease, Hemocromatosis
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LRE definition
LRE was defined as either ascites development, variceal bleeding or new evidence of high-risk varices needing treatment, Spontaneous Bacterial Peritonitis (SBP), MELD score >=15, over hepatic encephalopathy, hepatocellular carcinoma diagnosis, liver related death
