NAFLD in 2017: Novel insights into mechanisms of disease progression

  title={NAFLD in 2017: Novel insights into mechanisms of disease progression},
  author={Reenam S. Khan and Philip Noel Newsome},
  journal={Nature Reviews Gastroenterology \& Hepatology},
  • R. KhanP. Newsome
  • Published 4 January 2018
  • Biology
  • Nature Reviews Gastroenterology & Hepatology
In 2017, there have been substantial advances in our understanding of the immunological and endocrine mechanisms of disease progression in NAFLD, paving the way for novel therapeutic strategies. 

Progress and challenges in the prevention and control of nonalcoholic fatty liver disease

The characteristics and prevalence of nonalcoholic fatty liver disease are summarized and the status of the understanding of its mechanisms and potential therapeutic targets are summarized.


Previously published datasets of nonalcoholic fatty liver disease from GEO database have been reanalyzed by applying a series of R programs based novel bioinformatics approaches, which led to the identification of certain potential NAFLD therapeutic targets.

Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer. Akkermansia muciniphila (A. muciniphila) is a

Role of Innate lymphoid Cells in Obesity and Insulin Resistance

How ILCs in distinct metabolic organs may function to maintain metabolic homeostasis and contribute to obesity and its associated metabolic diseases is discussed.

Retained NK Cell Phenotype and Functionality in Non-alcoholic Fatty Liver Disease

The presence of disease-specific changes within circulating and tissue-resident NK cell populations, as well as within other major immune cell subsets, in patients with liver biopsy-confirmed NAFLD is explored and the importance of the local microenvironment in shaping the NK cell compartment is increased.

Emerging connections between oxidative stress, defective proteolysis, and metabolic diseases

The correlation between oxidative stress, defective proteolysis, and metabolic diseases is discussed and an understanding of how ROS affects intracellular proteolytic systems may provide new perspectives on the development of and control of diseases.

A Low Iron Diet Protects from Steatohepatitis in a Mouse Model

A lower tissue iron level prevents accelerated progression of NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the disease.

Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease

MAM-targeting drugs and compounds, most of which achieve their therapeutic or ameliorative effects on NAFLD by improving MAM integrity, are summarized and targeting MAMs may be a viable strategy forNAFLD treatment.



Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-β

Although type 2 immunity maintains healthy metabolic signaling in adipose tissues, it exacerbates the progression of NAFLD collaboratively with TGF-β in the liver, revealing that cytokine activity that is beneficial for the homeostasis of one tissue can be detrimental to another.

Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression

Hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury.

Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes

As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous, and random‐effects models were used to provide point estimates of prevalence, incidence, mortality and incidence rate ratios.

Hepatic stem cells and transforming growth factor β in hepatocellular carcinoma

These studies demonstrate that loss of TGF-β signalling yields a phenotype similar to a human CSC disorder, Beckwith–Wiedemann syndrome, and delineating key functional pathways in HCC and CSC formation could be important in preventing this disease.

Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults

It is suggested that circulating Nrg4 concentrations are inversely associated with subclinical atherosclerosis in obese adults, and indicating that circulatingNrg4 might play a role in identifying patients at high risk for CVD.

Sorafenib in Advanced Hepatocellular Carcinoma-Clinical Experience

Sorafenib as monotherapy has mild activity in HCC patients with unresectable and advanced disease and future prospective and or randomized studies should assess the benefits of sorafenIB combination with other targeted therapy or chemotherapy.

Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States.

Patients with NASH are less likely to undergo liver transplantation (LT) andLess likely to survive for 90 days on the waitlist than patients with HCV, ALD, or HCV and ALD.

Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity

It is shown that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells, which directly suppress liver cytotoxic CD8+ T lymphocytes, which prevent emergence of hepatocellular carcinoma.

Cell death and cell death responses in liver disease: mechanisms and clinical relevance.

The clinical relevance of celldeath, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets are reviewed.