Evidence map›Paper›PMID 37425212›Full record

ReviewJHEP reports : innovation in hepatology2023

Role of ammonia in NAFLD: An unusual suspect.

Karen Louise Thomsen, Peter Lykke Eriksen, Annarein Jc Kerbert, Francesco De Chiara, Rajiv Jalan, Hendrik Vilstrup

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in JHEP reports : innovation in hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
6.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 3 countries.

Karen Louise ThomsenDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark.
Peter Lykke EriksenDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark.
Annarein Jc KerbertUCL Institute of Liver and Digestive Health, University College London, United Kingdom.
Francesco De ChiaraUCL Institute of Liver and Digestive Health, University College London, United Kingdom.
Rajiv JalanUCL Institute of Liver and Digestive Health, University College London, United Kingdom.
Hendrik VilstrupDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark.
Aarhus University Hospital · DKUniversity College London · GBEuropean Foundation for the Study of Chronic Liver Failure · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mechanistically, the symptomatology and disease progression of non-alcoholic fatty liver disease (NAFLD) remain poorly understood, which makes therapeutic progress difficult. In this review, we focus on the potential importance of decreased urea cycle activity as a pathogenic mechanism. Urea synthesis is an exclusive hepatic function and is the body's only on-demand and definitive pathway to remove toxic ammonia. The compromised urea cycle activity in NAFLD is likely caused by epigenetic damage to urea cycle enzyme genes and increased hepatocyte senescence. When the urea cycle is dysfunctional, ammonia accumulates in liver tissue and blood, as has been demonstrated in both animal models and patients with NAFLD. The problem may be augmented by parallel changes in the glutamine/glutamate system. In the liver, the accumulation of ammonia leads to inflammation, stellate cell activation and fibrogenesis, which is partially reversible. This may be an important mechanism for the transition of bland steatosis to steatohepatitis and further to cirrhosis and hepatocellular carcinoma. Systemic hyperammonaemia has widespread negative effects on other organs. Best known are the cerebral consequences that manifest as cognitive disturbances, which are prevalent in patients with NAFLD. Furthermore, high ammonia levels induce a negative muscle protein balance leading to sarcopenia, compromised immune function and increased risk of liver cancer. There is currently no rational way to reverse reduced urea cycle activity but there are promising animal and human reports of ammonia-lowering strategies correcting several of the mentioned untoward aspects of NAFLD. In conclusion, the ability of ammonia-lowering strategies to control the symptoms and prevent the progression of NAFLD should be explored in clinical trials.

Indexed as

AmmoniaCellular senescenceEpigeneticsGlutamine metabolismNon-alcoholic fatty liver diseaseUrea synthesis

Identifiers

PMID37425212
PMCPMC10326708
OpenAlexW4366977470

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.