The Lasting Effects of COVID-19 on the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Abstract

It is estimated that around 30% of the population living in Western countries has metabolic dysfunctionassociated steatotic liver disease (MASLD), a spectrum of pathology (not attributed to alcohol/substance intake) initiated by steatosis and progression toward inflammation and irreversible fibrosis metabolic dysfunction-associated steatohepatitis (MASH). With inflammation being a key component of the transition to MASH, it raises the question of whether the ongoing COVID-19 pandemic, which has notoriously induced hyperinflammatory states, may influence the progression of MASLD. Specifically, it remains unclear if the potential chronic sequelae of COVID-19 in patients who recovered from it may increase the predisposition for MASH. Since MASH maintains a high risk for hepatocellular carcinoma, liver failure, and the need for a liver transplant, the potential additive effects of COVID-19 could prove critical to study. Thus, the objective of this study was to conduct a literature review to examine if COVID-19 could have chronic sequelae that affect the progression of MASLD pathogenesis. It was hypothesized that severe cases of COVID-19 could induce systemic inflammation, metabolic changes, and lasting gut microbiome alterations that lead to inflammatory and fibrotic changes in the liver, similar to those seen in MASH. A scoping review of the literature was conducted utilizing the PubMed database. Studies that examined hepatobiliary pathology, gut microbiome, systemic inflammation, metabolic changes, drug-induced liver injury (DILI), and hypoxia seen in COVID-19 were included. Human studies of adult cohorts, animal models, and in vitro experiments were included. Genetic components of MASLD were not examined. Exclusion criteria also encompassed any studies not referencing the hepatobiliary, gastrointestinal tract, portal system, or systemic circulation. Findings indicated a frequent trend of elevated liver enzymes, mild steatosis, Kupffer cell hyperplasia, and hepatobiliary congestion. It was found that direct cytopathic effects on hepatocytes were unlikely, but the direct viral insult of cholangiocytes was a potential complication. High serum levels of IL-1, TNF-a, and MCP-1, in COVID-19 were found as potential risk factors for MASH development. Hypoxia, altered lipid metabolism, and iatrogenic DILI were also proposed as potential precipitators of MASH development. Notably, lasting changes in gut microbiome were also frequently observed and correlated closely with those seen in MASH.

The clinician's view on the advantages and contradictions of the new nomenclature of steatotic liver disease: A review

“…В ходе очередного исследования проведен анализ в когорте индийских пациентов с NAFLD (n=1643), из которых 170 больных имели ИМТ<23 кг/м 2 [38]. В ходе другого исследования также подтвердили, что потребление алкоголя взаимодействует с кардиометаболическими факторами риска и увеличивает риск декомпенсации SLD [36].…”

“…Актуальность изучения неалкогольной жировой болезни печени (non-alcoholic fatty liver disease -NAFLD)/ метаболически-ассоциированной жировой болезни печени (metabolic associated fatty liver disease -MAFLD) или, согласно последнему пересмотру номенклатуры, «ассоциированной с метаболической дисфункцией стеатозной болезни печени (metabolic dysfunction-associated steatotic liver disease -MASLD)» определяется высоким уровнем распространенности и значимостью исходов. Распространенность данной нозологии в общей популяции в мире достигает 33,0% [1][2][3][4][5][6], заболевание выявляется во всех возрастных группах, у лиц с ожирением частота встречаемости составляет 62-93%. В Российской Федерации это заболевание занимает лидирующую позицию в структуре заболеваний внутренних органов, в 2007 г. его распространенность у пациентов амбулаторных лечебно-профи-лактических учреждений составляла 27%, а в 2015 г.…”

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

“…Liver biopsies from COVID-19 patients often reveal non-specific morphological changes in the liver parenchyma, which are likely results of indirect damage from the viral infection or therapeutic interventions [ 281 ]. In the review article by Backer et al, it was noted that post-COVID-19 changes such as Kupffer cell hypertrophy in sinusoidal capillaries, moderate steatosis, elevated levels of atherogenic lipoproteins, and alterations in the intestinal microbiome might be risk factors for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) [ 282 ]. Additionally, several severe cases of post-COVID-19 cholangiopathy have been documented, suggesting potential for long-term liver disease [ 283 ].…”

COVID-19 and Its Ophthalmic Manifestations: A Literature Review

“…Seriously ill patients can also suffer from cytokine storm as a response by the body in an attempt to eliminate the virus. However, an increasing number of patients have begun to present with various other systemic symptoms and signs such as neurological, hepatic, and ophthalmic [7][8][9].…”