In recent years , a lot of research has been devoted to the role of BAs and BAs receptor FXR , in NAFLD [ 45][46][47 ] . However , there is currently no explanation for the alterations in BAs composition in blood , the decreased ratio of secondary / primary BAs observed by us ( Extended Data 7f - j ) and others 45,47,48 , and whether it correlates with changes in tissue morphology 47 . Our data shed new light on this problem . The altered BC microanatomy and consequent pericentral micro - cholestasis may hamper BAs secretion into BC , as apical pumps ( BSEP , MRP2 ) have to operate against elevated luminal BAs concentrations . This would lead to back - flux of primary BAs into the blood , reducing their availability for conversion into secondary BAs by the intestinal microbiota ( Extended Data 7j and 8 g ) , thus contributing to the changes in BAs composition observed in NAFLD 45,47,48 . Bile flow is essential for normal liver function . Bile accumulation , due to its detergent - like properties , can cause liver damage 49,50 and bile pressure can affect metabolism 51 . Indeed , the accumulation of LD 52 and BAs 53 could induce oxidative stress and trigger apoptosis 29 , which is consistent with the reduction in pericentral hepatocytes observed in STEA and eNASH . The occurrence of pericentral micro - cholestasis is a new piece in the NAFLD pathophysiology puzzle that contributes to clarify some aspects of the disease so far without explanation , e.g. increase of GGT levels 54 , BAs in serum 55 , upregulation of MRP3 in NASH 56 and the beneficial effect of UDCA treatment in NAFLD 57 , all signs of ongoing cholestasis 41,58 .