Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population and is the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of ...NAFLD, with hepatic necroinflammation and faster fibrosis progression. With an increasing number of patients developing NASH-related end-stage liver disease and pharmacological treatments on the horizon, there is a pressing need to develop NAFLD and NASH biomarkers for prognostication, selection of patients for treatment and monitoring. This requirement is particularly true as liver biopsy utility is limited by its invasive nature, poor patient acceptability and sampling variability. This article reviews current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis. For each biomarker, we evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. We cover biochemical, imaging and genetic biomarkers and discuss biomarker discovery in the omics era.
Although nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity, around 10%‐20% of nonobese Americans and Asians still develop NAFLD. Data on this special group are limited. We ...therefore studied the severity and clinical outcomes of nonobese NAFLD patients. Consecutive NAFLD patients who underwent liver biopsy were prospectively recruited. We used the NASH Clinical Research Network system to score the histology. The Asian body mass index cutoff of 25 kg/m2 was used to define nonobese NAFLD. Among 307 recruited NAFLD patients, 72 (23.5%) were nonobese. Compared to obese patients, nonobese patients had lower NAFLD activity score (3.3 ± 1.3 vs. 3.8 ± 1.2; P = 0.019), mainly contributed by steatosis (1.7 ± 0.8 vs. 2.0 ± 0.8; P = 0.014) and presence of hepatocyte ballooning (60.9% vs. 73.4%; P = 0.045). Similarly, nonobese patients had lower fibrosis stage (1.3 ± 1.5 vs. 1.7 ± 1.4; P = 0.004), serum cytokeratin‐18 fragments (283 vs. 404 U/L; P < 0.001) and liver stiffness measurement by transient elastography (6.3 vs. 8.6 kilopascals; P < 0.001). By multivariate analysis in nonobese patients, only elevated serum triglyceride level was independently associated with higher NAFLD activity score (adjusted odds ratio OR, 1.644; P = 0.021), whereas elevated creatinine level was the only factor associated with advanced fibrosis (adjusted OR, 1.044; P = 0.025). After a median follow‐up of 49 months, 6 patients died, 2 developed hepatocellular carcinoma, and 1 had liver failure, all of whom were in the obese group. Conclusion: Nonobese NAFLD patients tend to have less‐severe disease and may have a better prognosis than obese patients. Hypertriglyceridemia and higher creatinine are the key factors associated with advanced liver disease in nonobese patients. (Hepatology 2017;65:54‐64)
Non‐invasive assessment of liver fibrosis has been one of the most rapidly advancing fields in hepatology in the last decade. Progressive liver fibrosis results in cirrhosis, hepatocellular carcinoma ...(HCC), and various liver‐related complications in essentially all chronic liver diseases. Assessment of liver fibrosis allows clinicians to determine the prognosis, need of treatment, disease progression, and response to treatment in patients with chronic liver disease. Liver biopsy has been the gold standard in last few decades and most adopted diagnostic tool in clinical trials. Nonetheless, it is impractical to apply the test in a large number of patients or to do it serially. Hence, various non‐invasive assessments have been developed and adopted in some international management guidelines. Liver stiffness measurement (LSM) with transient elastography is one of the most widely validated non‐invasive assessments for liver fibrosis. It is an accurate and reproducible method to predict advanced fibrosis in chronic hepatitis B. Using transient elastography, it is possible to perform repeated liver fibrosis assessments on a large number of asymptomatic patients. The key challenge of his tool is the confounding effect of alanine aminotransferase (ALT) level, such that decrease in LSM may only reflect ALT normalization, hence not accurate enough to indicate regression of liver fibrosis. This may be partially handled by combining LSM with a serum‐based formula, which is independent of ALT such as the Forns index and enhanced liver fibrosis test. An LSM‐based HCC risk score is useful to prioritize patients for HCC surveillance.
Can we use old NAFLD data under the new MASLD definition? Song, Sherlot Juan; Lai, Jimmy Che-To; Wong, Grace Lai-Hung ...
Journal of hepatology,
February 2024, 2024-Feb, 2024-02-00, 20240201, Letnik:
80, Številka:
2
Journal Article
Background and Aims
Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can inhibit liver fibrogenesis in animal models. We aimed to evaluate the impact of ...ACEI/ARB use on the risk of liver cancer and cirrhosis complications in patients with NAFLD.
Approach and Results
We conducted a retrospective, territory‐wide cohort study of adult patients with NAFLD diagnosed between January 2000 and December 2014 to allow for at least 5 years of follow‐up. ACEI or ARB users were defined as patients who had received ACEI or ARB treatment for at least 6 months. The primary endpoint was liver‐related events (LREs), defined as a composite endpoint of liver cancer and cirrhosis complications. We analyzed data from 12,327 NAFLD patients (mean age, 54.2 ± 14.7 years; 6163 men 50.0%); 6805 received ACEIs, and 2877 received ARBs. After propensity score weighting, ACEI treatment was associated with a lower risk of LREs (weighted subdistribution hazard ratio SHR, 0.48; 95% CI, 0.35–0.66; p < 0.001), liver cancer (weighted SHR, 0.46; 95% CI, 0.28–0.75; p = 0.002), and cirrhosis complications (weighted SHR, 0.42; 95% CI, 0.27–0.66; p < 0.001), but ARB was not. In subgroup analysis, ACEI treatment was associated with greater reduction in LREs in patients with chronic kidney diseases (CKDs) than those without (CKD‐weighted SHR, 0.74; 95% CI, 0.52–0.96; p = 0.036; non‐CKD‐weighted SHR, 0.15; 95% CI, 0.07–0.33; p < 0.001).
Conclusions
ACEI, rather than ARB, treatment is associated with a lower risk of LREs in NAFLD patients, especially among those with CKD.
ObjectiveAlthough COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is ...linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.MethodsIn this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.ResultsGut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.ConclusionAssociations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
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