Corina Cerlat

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with type II diabetes (T2D) and has become the main cause of cirrhosis. Both NAFLD and T2D are associated with cognitive and neurological impairments. T2D has been established as a risk factor for first-time development of overt hepatic encephalopathy (HE) in cirrhotic patients. The onset of HE in diabetic patients with cirrhosis develops earlier compared to cirrhosis patients without T2D. However it remains unclear whether NAFLD-induced cirrhosis increases the risk for HE. The present study aims to address the association between NAFLD, T2D and HE. Methods: Our retrospective study includes 102 cirrhotic patients on the liver transplant list at the Liver Unit of the Montreal University Hospital Center. Patients were classified by etiology of cirrhosis; 1) NAFLD and 2) non-NAFLD. Demographic data, blood biochemistry, clinical information on T2D-related comorbidities and cirrhosis complications (including number and severity of HE episodes) were collected. These factors were statistically associated with HE episodes. Results: Our cohort comprised 20 (19%) NAFLD and 82 (79%) non-NAFLD patients presenting similar MELD and Child-Pugh scores. The prevalence of T2D was higher in NAFLD vs non-NAFLD cirrhotics (15 (75%) vs 24 (29%) respectively) and was associated to co-morbidities such as cardiac disease, dyslipidemia, hypertension and obesity. Among non-NAFLD cirrhotics, 47 (57%) patients had a history of HE whereas 8 (40%) were found in the NAFLD cirrhotics (p>0.05). Since T2D is already known as a risk factor for HE, we subdivided both NAFLD and non-NAFLD groups into non-T2D and T2D subgroups. HE was significantly more prevalent in patients with T2D: in the NAFLD group, 5 (25%) T2D patients had developed an episode of HE compared to 3 (15%) patients without T2D (p<0.05); in the non-NAFLD group, 16 (67%) patients had T2D and HE compared to 31 (53%) HE patients without T2D (p<0.001). Fasting glycemia levels analysis in the 4 sub-groups of patients revealed increased levels in patients with history of HE and T2D, regardless of NAFLD etiology; in the NAFLD group 8.60 ± 0.84 mmol/l in patients with HE and T2D vs 6.00 ± 1.35 mmol/l in patients with HE without T2D (p<0.01); in the non-NAFLD group: 9.23 ± 0.93 mmol/l in patients with HE and T2D vs 5.82 ± 0.27 mmol/l in patients with HE without T2D (p<0.001). Conclusion: Our results sustain the association between T2D and HE and suggest high glucose might play a pathological role in the development of cognitive decline. NAFLD is not a risk factor for the development of HE. These interesting results provide new insights in the role of T2D in the development of HE and further studies are required to understand the underlying mechanisms. Furthermore, identifying patients who are at higher risk of developing HE is imperative to initiate early treatment strategies to protect neurological decline in patients with cirrhosis.

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with type II diabetes (T2D) and has become the main cause of cirrhosis. Both NAFLD and T2D are associated with cognitive and neurological impairments. T2D has been established as a risk factor for first-time development of overt hepatic encephalopathy (HE) in cirrhotic patients. The onset of HE in diabetic patients with cirrhosis develops earlier compared to cirrhosis patients without T2D. However it remains unclear whether NAFLD-induced cirrhosis increases the risk for HE. The present study aims to address the association between NAFLD, T2D and HE. Methods: Our retrospective study includes 102 cirrhotic patients on the liver transplant list at the Liver Unit of the Montreal University Hospital Center. Patients were classified by etiology of cirrhosis; 1) NAFLD and 2) non-NAFLD. Demographic data, blood biochemistry, clinical information on T2D-related comorbidities and cirrhosis complications (including number and severity of HE episodes) were collected. These factors were statistically associated with HE episodes. Results: Our cohort comprised 20 (19%) NAFLD and 82 (79%) non-NAFLD patients presenting similar MELD and Child-Pugh scores. The prevalence of T2D was higher in NAFLD vs non-NAFLD cirrhotics (15 (75%) vs 24 (29%) respectively) and was associated to co-morbidities such as cardiac disease, dyslipidemia, hypertension and obesity. Among non-NAFLD cirrhotics, 47 (57%) patients had a history of HE whereas 8 (40%) were found in the NAFLD cirrhotics (p>0.05). Since T2D is already known as a risk factor for HE, we subdivided both NAFLD and non-NAFLD groups into non-T2D and T2D subgroups. HE was significantly more prevalent in patients with T2D: in the NAFLD group, 5 (25%) T2D patients had developed an episode of HE compared to 3 (15%) patients without T2D (p<0.05); in the non-NAFLD group, 16 (67%) patients had T2D and HE compared to 31 (53%) HE patients without T2D (p<0.001). Fasting glycemia levels analysis in the 4 sub-groups of patients revealed increased levels in patients with history of HE and T2D, regardless of NAFLD etiology; in the NAFLD group 8.60 ± 0.84 mmol/l in patients with HE and T2D vs 6.00 ± 1.35 mmol/l in patients with HE without T2D (p<0.01); in the non-NAFLD group: 9.23 ± 0.93 mmol/l in patients with HE and T2D vs 5.82 ± 0.27 mmol/l in patients with HE without T2D (p<0.001). Conclusion: Our results sustain the association between T2D and HE and suggest high glucose might play a pathological role in the development of cognitive decline. NAFLD is not a risk factor for the development of HE. These interesting results provide new insights in the role of T2D in the development of HE and further studies are required to understand the underlying mechanisms. Furthermore, identifying patients who are at higher risk of developing HE is imperative to initiate early treatment strategies to protect neurological decline in patients with cirrhosis.