TBL 6: non alcohol liver disease and alcoholic steatohepatitis Flashcards
- Non-alcoholic fatty liver disease (NAFLD) is present when liver contains more than _________ by weight
o The prevalence of NAFLD is directly related to the degree of obesity and NAFLD is present in over 80% of subjects with ____________________ - ________________, the central feature of the metabolic syndrome, is thought to play a critical role in development of NAFLD
o NAFLD usually is suspected because of ________________ on routine laboratory studies
o Resistance to the action of insulin results in important changes in lipid metabolism – include enhanced ______________, increased ________________, and increased hepatic uptake of fatty acids
o Each of these may contribute to the accumulation of hepatocellular triglyceride which in turn results in a preferential shift from carbohydrate to FFA beta-oxidation, an occurrence that has been demonstrated in patients with insulin resistance
o Significantly increased FFA levels have been observed in patients with NAFLD and type 2 diabetes mellitus (compared with type 2 diabetics without NAFLD)
o Insulin resistance also results in increased release of ___________ that disrupt regular fat metabolism leading to inflammation and fibrosis
5% fat;
body mass index >35 kg/m2;
Insulin resistance;
elevated transaminases
peripheral lipolysis; triglyceride synthesis;
cytokines
Pathogenesis of NASH
- Insulin resistance as the key mechanism leading to hepatic steatosis, and perhaps also to steatohepatitis
- Increased hepatic synthesis of free fatty acids and decreased _______________ of free fatty acids – lipid accumulation in liver
- Additional oxidative injury is required to manifest the necroinflammatory component of steatohepatitis
- Liver inflammation – induces _________________ and subsequent healing by liver fibrosis and finally scarring and cirrhosis
- NAFLD – follows a largely benign course of disease with minimal or no inflammation on liver biopsy (bland steatosis)
o NASH is a subset of NAFLD (10 to 30%) with a more sinister prognosis
§ Presence of inflammation on liver biopsy: ballooning degeneration, necroapoptosis, and fibrosis
§ More than 10-fold increased risk of liver related death (2.8 vs. 0.2%) and 2x CVS mortality
hepatic oxidation;
stellate cells activation ;
Nature and progression of NAFLD
- NAFLD is a multisystem disorder – hepatic manifestation of the metabolic syndrome and frequently associated with _______________________
- More recently, recognized associations include sleep
apnea and chronic kidney injury
- NAFLD is associated with an increased cardiovascular
risk and risk for malignancies (e.g. HCC or colorectal
cancer)
- Patient management needs to consider these multisystem implications for individual prognosis
- Simple steatosis appears to represent the hepatological and in most cases probably benign variant of NAFLD
o Individual disease progression is unpredictable
- Once NASH is present, the risk for progression to advanced liver fibrosis, cirrhosis and HCC is increased and the prognosis becomes more serious and predictable
diabetes, obesity, hyperlipidaemia and arterial hypertension
Management of NAFLD
- Initial approach to treatment of NAFLD focuses on improving insulin sensitivity via _________________
- All patients should be advised to avoid alcohol
- Weight loss is key for overweight and obese patients – weight loss amounts for >10% associated with fibrosis regression
o Weight reduction more than 7% to 10% sustained over 48 weeks is associated with significant reduction in histological severity of NASH
o ________________ may be considered in morbidly obese patients
- Aggressive risk factor identification and modification i.e. diabetes mellitus, hyperdyslipidaemia so as to reduce cardiovascular risk profile for the patient
- Limits of lifestyle approach – compliance of the patients and difficulty to present a unique and clear scientific vision
diet, exercise and lifestyle modification;
Bariatric surgery
