Association between hypothyroidism and liver fibrosis risk: a systematic review and meta-analysis

Abstract

Aim of the study: Non-alcoholic fatty liver disease (NAFLD), which encompasses a wide variety of liver pathology, is now the most common chronic liver disease worldwide. The presence of hypothyroidism has been linked to the development of NAFLD. However, its correlation with liver fibrosis, an important clinical entity in NAFLD, is less clear. We aimed to summarize the association between hypothyroidism and liver fibrosis risk. Material and methods:We conducted a search of PubMed and ProQuest from inception to June 30, 2021, for studies assessing the association between hypothyroidism and liver fibrosis risk. The quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS). We analyzed the pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed and random-effects model. Heterogeneity was assessed using I 2 . Results: Eight studies with a total of 14,588 patients were included. The quality of studies ranged from 6 to 8 stars. Thyroid stimulating hormone (TSH) ≥ 2.5 was significantly associated with increased risk of significant liver fibrosis (OR = 1.61, 95% CI = 1.21-2.15). Subclinical hypothyroidism was also correlated with an increased risk of advanced fibrosis (OR = 2.77, 95% CI = 1.65-4.65). A significant association was found between overt hypothyroidism and non-alcoholic steatohepatitis (NASH) risk (OR = 2.38, 95% CI = 1.61-3.53). However, no significant association was found between subclinical hypothyroidism and significant liver fibrosis. Conclusions: Hypothyroidism is associated with an increased risk of fibrosis in NAFLD patients.

Thyroid function, adipokines and mitokines in metabolic dysfunction‐associated steatohepatitis: A multi‐centre biopsy‐based observational study

“…The thyroid axis has profound effects on hepatic energy metabolism, including hepatic lipogenesis and fatty acid oxidation; the liver receives signals from thyroid hormones through activation of thyroid hormone receptors while it has also receptors for TSH, both of which alter hepatic metabolism 45,46 . A consistent line of evidence supports the notion that, compared to euthyroid subjects, both individuals with subclinical and overt hypothyroidism are at higher risk for developing and progressing to steatohepatitis and significant fibrosis 4,7–9,47,48 . One study yielded negative findings.…”

“…45,46 A consistent line of evidence supports the notion that, compared to euthyroid subjects, both individuals with subclinical and overt hypothyroidism are at higher risk for developing and progressing to steatohepatitis and significant fibrosis. 4,[7][8][9]47,48 One study yielded negative findings. Possibly owing to several reasons including failure to handle statistical heterogeneity due to differences in the populations enrolled, definitions of hypothyroidism, methods used to check thyroid hormone profile and study designs.…”

“…4 Improved understanding of such secondary endocrine forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches. 5 Hypothyroidism is probably the best characterized endocrine disorder associated with NAFLD and steatohepatitis, possibly due to underlying associations with lipid metabolism 4,[6][7][8][9] ; lipotoxicity in hepatocytes is a key driver and one of the most important characterizing features in NAFLD. 10 The role of thyroid axis in liver health is universally acknowledged in the literature-albeit with occasional conflicting data.…”

Resmetirom: Finally, the Light at the End of the NASH Tunnel?

“…This notion has universally been accepted by subsequent studies [17,18]. In parallel, strong epidemiological evidence has indicated that hypothyroidism is also tightly associated with the development and fibrotic progression of NAFLD and NASH [19][20][21][22]. This association has recently been found to be sex-specific and mediated by adipokines/mitokines [23].…”

Vitamin D alleviates hypothyroidism associated liver dysfunction: Histological and biochemical evidence

“…HSCs are the predominant precursor cells of liver myofibroblasts and upon activation, by TGF-β, fibrogenic myofibroblasts up-regulate production and deposition of α-smooth muscle actin and extracellular matrix proteins, the most abundant one being type I collagen. Likewise, experimental studies have shown that hypothyroidism can induce up-regulation of collagen type 1 gene expression, causing subsequent fibrosis [ [13] , [14] , [15] , [16] ].…”