A novel liquid biopsy is accurate, sensitive, and specific in diagnosing the presence and severity of non-alcoholic steatohepatitis (NASH) and/or liver fibrosis, and is more reliable than currently used biomarkers, according to a study published in the journal Gut.
Geltrude Mingrone, Università Cattolica del Sacro Cuore, Rome, Italy, and King's College London, London, United Kingdom, and colleagues identified 2 protein biomarkers -- PLIN2 and RAB14 -- that were used as part of an algorithm to identify people with NASH and/or liver fibrosis.
The machine learning-based algorithms gave impressive results, including a sensitivity of 88% to 95%, a specificity of 90% to 100%, and an overall accuracy of 92% to 93% for NASH. For fibrosis, they were even better, with a sensitivity of 99% to 100%, specificity of 90% to 96%, and accuracy of 98% to 99%.
"This blood test will allow us to define the real prevalence of NASH in large and small populations, including children and adolescents, avoiding the need for invasive liver biopsy," said Dr. Mingrone. "Importantly, it will also allow us to monitor the efficacy of NASH treatments over time, reducing screen failures and helping generate better drugs."
The multicentre study included a discovery cohort of 100 patients and a validation cohort of 150 patients with histologically proven non-alcoholic fatty liver disease or NASH, with or without fibrosis.
The algorithm for NASH using PLIN2 mean fluorescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT), and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively. The area under the receiver operating characteristic (AUROC) for NASH level prediction ranged from 83.7% in the discovery cohort to 97.8% in the validation cohort.
The algorithm including RAB14 plus MFI, age, waist circumference, high-density lipoprotein cholesterol, plasma glucose, and ALT levels as covariates to predict the presence of liver fibrosis yielded an AUROC of 95.9% in the discovery cohort and 99.3% in the validation cohort, respectively. Accuracy was 99.25%, sensitivity 100%, and specificity 95.8% in the discovery cohort and 97.6%, 99%, and 89.6% in the validation cohort.
This novel biomarker was superior to currently used FIB4, non-alcoholic fatty liver disease fibrosis score, and aspartate aminotransferase -to-platelet ratio, and was comparable to ultrasound 2-dimensional shear wave elastography.
Reference:https://gut.bmj.com/content/early/2022/07/12/gutjnl-2022-327498
SOURCE: King's College London
I thank the authors for a nice summary of updates on acne pathophysiology and novel treatments. My personal favorite topic was the role of the microbiome in acne. We have known that acne patients and healthy controls have different compositions of skin and gut microbiota. Now, we even see that acne treatment can alter the microbiome. In particular, treatment with oral antibiotics can lead to perturbations in not only the skin but also the gut microbiome (in addition to causing antibiotic resistance, which is another issue). Although consequences of long-term oral antibiotic use in acne are yet to be elucidated, literature from other disciplines have suggested that gut dysbiosis can be linked to chronic inflammation, obesity, cancer, cardiovascular disease, and neuropsychiatric conditions, such as dementia, depression, and anxiety. I started out as a gut mucosal immunologist before entering dermatology, and I am a believer that gut dysbiosis plays an important role in inflammatory skin conditions, including acne. Knowing this, it's hard not to question whether I am staying faithful to my oath to "do no harm" whenever I prescribe oral antibiotics. Well, I still use antibiotics when necessary. However, I make every effort to minimize its use and the length of use.
Fortunately, there are other options. I agree with the authors on using topical and oral retinoids as the cornerstone therapy, as well as spironolactone for females for long-term treatment. Topical anti-androgen clascosterone cream has been a great option, although insurance coverage has limited its use for my patients. I would love to see a study to evaluate the impact of low-dose narrow-spectrum antibiotics such as sarecycline on the microbiome (to see if the perturbations are less).
In addition to these conventional therapies, supplements can be incorporated for those who desired a more holistic approach, including pantothenic acid, L-carnitine, zinc, probiotics, omega 3, and borage seed oil. For female hormonal acne, myoinositol and diindolmethane can be considered. This practice has allowed me to limit the use of long-term antibiotics in acne.
Lastly, I emphasize nutrition counseling and appreciate that the authors brought light to the importance of diet in acne. Why is nutrition worth talking about? Because among the factors that shape the microbiome, nutrition is one that is modifiable.
Here are some nutrition tips that I share with my acne patients:
These recommendations align with those of our colleagues who treat metabolic diseases, such as heart disease, diabetes, and obesity – which are increasing at alarming rates, even in the youth. These recommendations can also help improve mental health, as the emerging gut-brain axis literature suggests.
Patients are particularly motivated to treat visible conditions such as acne. Wouldn't it be incredible if our young acne patients can be inspired to adapt habits that reduce their risk of inflammatory ailments in the long run? I sincerely hope that a holistic way of treating "beyond the skin" can become a mainstream phenomenon in dermatology. We have the privilege and responsibility to do so much more than clear the skin.