Jos Jansen

4 89 NAFLD Phenotype in Patients With V-ATPase Proton Pump Assembly Defects Introduction Nonalcoholic fatty liver disease (NAFLD) is a very common chronic liver disease marked by hepatic fat accumulation. In many patients, fat accumulation triggers hepatic inflammation and liver cell injury, a condition termed non-alcoholic steatohepatitis (NASH). NASH can promote fibrogenesis and evolve towards cirrhosis and primary liver cancer and is therefore considered the progressive extension of NAFLD. Considerable heterogeneity has been recognized in patients with NAFLD. Most patients carry several features of the metabolic syndrome such as insulin resistance. However, well documented cases of NAFLD are not associated with the metabolic syndrome (Table 1).(1, 2) For these cases of secondary NAFLD, the mechanism of steatogenesis appears to be independent of insulin resistance and adipose tissue expansion. Known inborn errors of metabolism to cause NAFLD are hypo/a betalipoproteinemia, lysosomal acid lipase deficiency, or Wilson disease.(3-5) Additionally, infections, surgical interventions, and drug- induced steatohepatitis have been recognized.(6-10) Table 1. Secondary causes of NAFLD Drug-induced fatty liver disease - Tamoxifen - Amiodarone - Atypical antipsychotic drugs - Many others Inflammatory causes - Infectious causes: Hepatitis C virus-associated fatty liver - Non-infectious causes: auto-immune hepatitis, psoriasis, coeliac disease Endocrine causes - Hypopituitarism - Hypothyroidism - Hypogonadism Inborn errors of metabolism - Wolman disease - Genetic haemochromatosis - Wilson disease - A/hypo-betalipoproteinaemia - α 1-antitrypsin deficiency Others - Acquired haemochromatosis - Starvation, parenteral nutrition