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Nonalcoholic fatty liver disease (NAFLD) is an independent predictor of systemic insulin resistance and type 2 diabetes mellitus (T2DM). However, converse correlates between excess liver fat content and β-cell function remain equivocal. Specifically, how the accumulation of liver fat consequent to the enhanced de novo lipogenesis (DNL) leads to pancreatic β-cell failure and eventually to T2DM is elusive. Here we have identified low-molecular-weight calcium-binding protein S100A6 or calcyclin inhibits glucose-stimulated insulin secretion (GSIS) from β-cells through activation of the receptor for the advanced glycation end product (RAGE) and diminution of mitochondrial respiration. Serum S100A6 level is elevated both in human NAFLD patients and in a high-fat diet (HFD) induced mouse model of NAFLD. While serum S100A6 levels are negatively associated with β-cell insulin secretory capacity in human patients, depletion of hepatic S100A6 improves GSIS and glycemia in mice suggesting that S100A6 contributes to the pathophysiology of diabetes in NAFLD. Moreover, transcriptional induction of hepatic S100A6 is driven by the potent regulator of DNL, carbohydrate response element-binding protein (ChREBP), and ectopic expression of ChREBP in the liver suppresses GSIS in a S100A6 sensitive manner. Together, these data suggest elevated serum levels of S100A6 may serve as a biomarker in identifying NAFLD patients with a heightened risk of developing β-cell dysfunction. Overall, our data, implicate S100A6 as a hitherto unknown hepatokine to be activated by ChREBP and participates in the hepato-pancreatic communication to impair insulin secretion and drive the development of T2DM in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is an independent predictor of systemic insulin resistance and type 2 diabetes mellitus (T2DM). However, converse correlates between excess liver fat content and β-cell function remain equivocal. Specifically, how the accumulation of liver fat consequent to the enhanced de novo lipogenesis (DNL) leads to pancreatic β-cell failure and eventually to T2DM is elusive. Here, we have identified that low-molecular-weight calcium-binding protein S100A6, or calcyclin, inhibits glucose-stimulated insulin secretion (GSIS) from β cells through activation of the receptor for the advanced glycation end products and diminution of mitochondrial respiration. Serum S100A6 level is elevated both in human patients with NAFLD and in a high-fat diet–induced mouse model of NAFLD. Although serum S100A6 levels are negatively associated with β-cell insulin secretory capacity in human patients, depletion of hepatic S100A6 improves GSIS and glycemia in mice, suggesting that S100A6 contributes to the pathophysiology of diabetes in NAFLD. Moreover, transcriptional induction of hepatic S100A6 is driven by the potent regulator of DNL, carbohydrate response element-binding protein (ChREBP), and ectopic expression of ChREBP in the liver suppresses GSIS in a S100A6-sensitive manner. Together, these data suggest elevated serum levels of S100A6 may serve as a biomarker in identifying patients with NAFLD with a heightened risk of developing β-cell dysfunction. Overall, our data implicate S100A6 as, to our knowledge, a hitherto unknown hepatokine to be activated by ChREBP and that participates in the hepato-pancreatic communication to impair insulin secretion and drive the development of T2DM in NAFLD.

Background and study aims Anti-helminthic therapy and endoscopic worm extraction had variable success rates in biliary ascariasis . Recurrent biliary events after worm clearance are common. We aimed to evaluate the outcomes of management in biliary ascariasis and find out the incidence and risk factors for the development of recurrent biliary events. Patients and methods Consecutive patients with biliary ascariasis detected on abdominal ultrasound (AUS), were selected. Initial conservative treatment with oral Albendazole (400 mg) and analgesics was started in all. Successful therapy was defined as symptomatic resolution, and AUS confirmed biliary clearance after three weeks. ERCP (Endoscopic retrograde cholangiopancreatography) was performed in patients with failed conservative management. The patients were prospectively followed up for a minimum period of 1 year. Results Among 98 patients with biliary ascariasis, 23 (23.5%) responded to medical management alone. A presentation with obstructive jaundice (p = 0.04) and cholangitis (p = 0.007) was significantly associated with failure to medical management. Sixty-five (86.7%) among 75 patients had successful biliary clearance with ERCP. During a median follow up of 16 months, 24 (24.5%) patients had recurrent biliary events. Lower socioeconomic status (OR = 0.78, p = 0.023) and longer follow-up (OR = 1.16, p = 0.001) were independent risk factors for recurrent biliary events. Conclusion Early ERCP among high-risk patients and proper hygiene are the keys to successful management in biliary ascariasis.

Liver diseases are fast emerging as global health priorities. Fatty liver is described in the setting of non-alcoholic fatty liver disease (NAFLD) as well as alcoholic liver disease (ALD), the pathogenesis of excess fat being different in the two conditions while both are important components of the changing face of burden of liver diseases worldwide. They are intimately associated with a globalized economy and an increasingly homogenous socio- cultural order with a westernized lifestyle. The accompanying adoption of a progressively sedentary life, consumption of diet dense in calories facilitate development of NAFLD while a spiraling upward trend in alcohol use along with earlier age of drinking as well as increased amount of per capita alcohol consumption increases the prevalence of ALD globally. Adverse health outcomes in NAFLD as well as ALD are caused not only by progressive liver fibrosis that is the most significant factor for liver related and all-cause mortality in both but also by non-liver (cardiovascular, cancer, accidents, neurological) clinical outcomes that calls for a multidisciplinary and social approach to these conditions. We present here an outline of facets of epidemiology of both NAFLD as well as ALD along with its’ public health implications. A broad-based integrated approach that incorporates social, behavioral as well as biological targets need to be undertaken at a health system level in a planned manner for these evolving liver health priorities that disproportionately challenges the low- and middle-income countries of Asia, South America and Africa.

Hypothyroidism can involve any organ system in the body with the involvement of haematopoietic system seen in about 30% of the cases. Anaemia is the most common haematological involvement with the affection of other cell lines being exceedingly rare and limited to occasional case reports. Here we present a case of a 14-year-old boy who presented with fever and pancytopenia and was later diagnosed to be a case of autoimmune hypothyroidism.