Liver transplantation and non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.

Implication of the intestinal microbiome in complications of cirrhosis

The intestinal microbiome(IM) is altered in patients with cirrhosis,and emerging literature suggests that this impacts on the development of complications.The Pub Med database was searched from January 2000 to May 2015 for studies and review articles on the composition,pathophysiologic effects and therapeutic modulation of the IM in cirrhosis.The following combination of relevant text words and MeS H terms were used,namely intestinal microbiome,microbiota,or dysbiosis,and cirrhosis,encephalopathy,spontaneous bacterial peritonitis,hepatorenal syndrome,variceal bleeding,hepatopulmonary syndrome,portopulmonary hypertension and hepatocellular carcinoma.The search results were evaluated for pertinence to the subject of IM and cirrhosis,as well as for quality of study design.The IM in cirrhosis is characterized by a decreased proportion of Bacteroides and Lactobacilli,and an increased proportion of Enterobacteriaceae compared to healthy controls.Except for alcoholic cirrhosis,the composition of the IM in cirrhosis is not affected by the etiology of the liver disease.The percentage of Enterobacteriaceae increases with worsening liver disease severity and decompensation and is associated with bacteremia,spontaneous bacterial peritonitis and hepatic encephalopathy.Lactulose,rifaximin and Lactobacillus-containing probiotics have been shown to partial y reverse the cirrhosis associated enteric dysbiosis,in conjunction with improvement in encephalopathy.The IM is altered in cirrhosis,and this may contribute to the development of complications associated with end-stage liver disease.Therapies such as lactulose,rifaximin and probiotics may,at least partially,reverse the cirrhosisassociated changes in the IM.This,in turn,may prevent or alleviate the severity of complications.

Recurrence of autoimmune liver diseases after liver transplantation

Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.