Nodular lymphocyte predominant Hodgkin lymphoma was termed “nodular lymphocyte predominant B-cell lymphoma” in the International Consensus Classification (ICC), to emphasize clinical and biological differences from classic Hodgkin lymphoma (CHL). The abbreviation “NLP” represents both terms in the ICC and World Health Organization classifications. Variations in the growth pattern, originally reported as Fan patterns A-F, are designated as either grade 1 or grade 2 in the ICC. NLP is uncommon, and in some cases an accurate diagnosis is challenging. The objectives of this article were to review the histopathologic features of NLP and the differential diagnosis from other key entities including de novo T-cell/histiocyte-rich large B-cell lymphoma (THRLBL) and lymphocyte-rich classic Hodgkin lymphoma (LRCHL). Histologically, NLP Fan pattern E (THRLBL-like) can be indistinguishable from de novo THRLBL. However, focal nodular areas, clustering of tumor cells, presence of few admixed small B-cells or FDC meshworks, and T-cell rosettes favor NLP Fan pattern E and argue against de novo THRLBL. NLP may also be confused with LRCHL. Patients with NLP are younger than those with LRCHL, and LRCHL may show mediastinal involvement. In LRCHL, the nodular pattern often contains eccentrically located small regressed germinal centers and intact small dense FDC meshworks, in contrast to the expanded, and fragmented FDC meshworks in NLP. Neoplastic cells that are positive for CD30 and CD15 but negative for CD20 and CD79a are characteristic of LRCHL. Additionally, Fascin and Gata3 are commonly positive in LRCHL but usually negative in NLP.

As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6.

We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014–07/01/2021.

The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12.

In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy.

Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days.

Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count.

Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

The genome editing technology based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 (CRISPR/Cas9), is revolutionizing research, particularly in the context of human neurodegenerative disorders. This review examines recent advancements in CRISPR/Cas9 and its potential to address the protein misfolding mechanisms underlying these diseases. Proteins, the fundamental units of life, can misfold due to various changes, resulting in aggregation and contributing to devastating illnesses such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease. Understanding the pathology of these disorders and the methods used for their detection is vital for developing effective treatments. CRISPR/Cas9 offers a powerful tool for combating neurodegenerative disorders at the molecular level. Its groundbreaking gene-editing capabilities are advancing preclinical and animal studies, paving the way for potential human trials and innovative therapeutic strategies. This review explores the complex challenge of protein misfolding and highlights how CRISPR technology could provide a crucial breakthrough in the fight against neurodegenerative disorders. It offers a synthesis of CRISPR advancements for neurodegenerative disorders. However, it is essential to be aware of the review’s limitations, including potential selection bias, the risk of oversimplification, and possible obsolescence in rapidly changing research fields. Despite these considerations, the transformative promise of CRISPR in understanding and potentially treating neurodegenerative diseases warrants continued research and thorough analysis.

Chronic cholestasis due to heritable causes is usually diagnosed in childhood. However, many cases can present and survive into adulthood. The time course varies considerably depending on the underlying etiology. Laboratory data usually reveal elevated conjugated hyperbilirubinemia, alkaline phosphatase, and gamma-glutamyl transpeptidase. Patients may be asymptomatic; however, when present, the typical symptoms are pruritus, jaundice, fatigue, and alcoholic stools. The diagnostic methods and management required depend on the underlying etiology. The development of genome-wide associated studies has allowed the identification of specific genetic mutations related to the pathophysiology of cholestatic liver diseases. The aim of this review was to highlight the genetics, clinical pathophysiology, presentation, diagnosis, and treatment of heritable etiologies of chronic cholestatic liver disease.

HLA-G gene harbors certain polymorphic variations that can potentially impact its biological activity, and therefore, may confer a risk for recurrent pregnancy loss (RPL). This study aimed to analyze whether HLA-G polymorphic variations (G*0103, G*0104, and G0105N) are related to the risk of RPL in women from Kashmir, North India.

A total of 200 women who suffered ≥2 RPLs and 240 healthy controls were recruited from the same geographical region. Additionally, 100 spouses of RPL affected women and 60 products of conception were evaluated. HLA-G genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method.

The variant genotype 0103:0103 in exon 2 of HLA-G was not detected. The genotype 0104/0105 was detected in 100% of RPL patients, spouses, and controls. Exon 2 and variant genotypes G*0103 in exon 2 and G*0105 in exon 3 of HLA-G were absent in our population and thus did not contribute to the etiopathogenesis of RPL. In contrast, the exon 3 HLA-G variant G*0104N was significantly more frequent in RPL patients and their spouses compared to the control group (p<0.05). The presence of the HLA-G variant genotype G*0104N (exon 3) was detected in 13% of RPL patients and 7% of their male partners, indicating a significantly higher frequency than in controls and suggesting a substantial risk for RPL (p<0.05).

This study revealed that the higher frequency of the HLA-G*0104 allele in both partners strongly predicted a substantial risk for RPL in our population.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a role in the excessive generation of extracellular matrix in liver fibrosis. This study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1 (MCP-1) expression and promotes hepatic macrophage recruitment.

Liver fibrosis was triggered through carbon tetrachloride, and an adeno-associated virus containing small interfering RNA targeting TIMP-1 (siRNA-TIMP-1) was administered to both rats and mice. We assessed the extent of fibrosis and macrophage recruitment. The molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays, luciferase reporter assays, the use of pharmacological modulators, and an analysis of extracellular vesicles (EVs).

siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis, reducing macrophage migration and MCP-1 expression. Co-culturing macrophages with hepatic stellate cells (HSCs) post-TIMP-1 downregulation inhibited macrophage migration. In siRNA-TIMP-1-treated HSCs, microRNA-145 (miRNA-145) expression increased, while the expression of Friend leukemia virus integration-1 (Fli-1) and MCP-1 was inhibited. Downregulation of Fli-1 led to decreased MCP-1 expression, whereas Fli-1 overexpression increased MCP-1 expression within HSCs. Transfection with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1, while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in HSCs. miRNA-145 bound directly to the 3′-UTR of Fli-1, and miRNA-145-enriched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage recruitment.

TIMP-1 induces Fli-1 expression through miRNA-145, subsequently increasing MCP-1 expression and macrophage recruitment. MiRNA-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.

Feedback loops or compensatory mechanisms are present in a wide range of biological systems and processes. Here, we hypothesize that endogenous opioid peptides, such as endorphins and enkephalins, can be broken down and enzymatically converted to catecholamines (dopamine, norepinephrine, epinephrine) locally. Particularly, this proposed local production of norepinephrine may modulate analgesia through feedback mechanisms. A similar arrangement may occur for corticotropin-releasing factor and adrenocorticotropic hormone (hypothalamic-pituitary-adrenal axis mediation), insulin (blood glucose regulation), and angiotensin II (cardiovascular regulation). Endorphins, enkephalins, and dynorphins have an initial amino acid sequence of Tyr-Gly-Gly-Phe, where tyrosine (and possibly phenylalanine) could be enzymatically clipped from the peptide and converted to catecholamines locally, through the canonical biosynthetic molecular pathway for catecholamines. Spatially and possibly temporally precise conversion of these terminal amino acids to catecholamines may allow them to be produced “on demand” in specific regions of the brain, spinal cord, or periphery. This hypothesis is readily testable by infusing stable isotopically labeled opioids into the brain or periphery of model organisms, and observing through liquid chromatography-mass spectrometry whether the terminal amino acids of these opioids are converted to catecholamines.

Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). Given their diverse physiological activities, we hypothesized that plasma fatty acids might influence the progression of sarcopenia. This study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with HCC.

In this single-center retrospective study, we registered 516 cases and analyzed 414 cases of liver cirrhosis and HCC. The skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar vertebra. The cutoff value for sarcopenia followed the criteria set by the Japan Society of Hepatology. Fatty acid concentrations were measured by gas chromatography.

Fatty acid levels, particularly omega-3 (n-3) polyunsaturated fatty acid (PUFA), were lower in patients with poor liver function (Child-Pugh grade B/C) and were negatively correlated with the albumin-bilirubin score (p<0.0001). The prognosis of HCC patients with low PUFA levels was significantly worse. Among the different fatty acid fractions, only n-3 PUFAs significantly correlated with skeletal muscle mass index (p=0.0026). In the multivariate analysis, the n-3 PUFA level was an independent variable associated with sarcopenia (p=0.0006).

A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China’s rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.

Harm caused by crude oil spillage and its associated environmental toxicants manifests slowly. This study examined the impact of crude oil environmental toxicants on neonates’ thyroid and cognitive functions in crude oil-producing communities.

The case-control study comprised 55 crude oil-exposed expectant mothers and 33 non-crude oil-exposed expectant mothers as controls. Serum Benzo Pyrene Dihydrodiol Epoxide (BPDE), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were assayed in expectant mothers and neonates. Intelligence quotient and APGAR scores were determined in the children using Fagan’s test of infant intelligence.

Serum TSH (p < 0.05) and BPDE (p < 0.001) were higher, while T3 and T3/T4 ratio were significantly lower (p < 0.001) in exposed pregnant women compared to the control. Cord blood TSH and T3/T4 ratio were lower (p < 0.001) while T4 and BDPE were higher (p < 0.001) in prenatally exposed neonates than prenatally non-exposed infants. Serum TSH correlated with BDPE (R2 = 0.080, p < 0.036) and APGAR score (R2 = 0.341, p < 0.012), while T3 and T4 were not associated with BDPE and APGAR score. TSH correlated with T3 (R2 = 0.0.082, p < 0.05), T3 correlated with T4 (R2 = 0.111, p < 0.013) and TSH (R2 = 0.082, p < 0.05). Exactly 54.5% (30/55) of prenatally exposed neonates had a low intelligence quotient compared to 36.4% (12/33) in prenatally non-exposed neonates.

Crude oil and associated environmental pollutants might significantly affect the thyroid function. Environmental surveillance, biomonitoring and environmental cleanup are emphasized. Future research on the mechanisms of the observed toxicological effects on thyroid hormones and targeted protection of pregnant women and their offspring is suggested.

Following complete peripheral nerve injury, collateral sprouting (CS) by adjacent nerves causes concentric shrinkage of the insensate area. Such take-over of insensate territory is unknown in proximal lesions such as stroke, spinal cord injury, and cauda equina syndrome, as peripheral nerves supplying insensate territories still maintain continuity from the cell body in the dorsal root ganglion (DRG) to the skin innervation territory. This preserved distal continuity opposes territory take-over by the expansion of adjacent sensate territories; sectioning peripheral nerves in insensate territories distal to DRGs disconnects nerve cell bodies from their skin territory, thus facilitating sensate territory expansion of adjacent nerves. Similar motor system applications in paralyzed territories include lower motor neurone lesioning and fasciectomies, facilitating motor territory expansion of adjacent nerves through CS. A search for evidence of previous conception of these hypotheses was conducted in the literature, using a combination of relevant terms from three categories (proximal neuraxial lesions, nerve-muscle interventions, collateral sprouting); however, this yielded no pertinent results, suggesting that these concepts are novel. Observations from the literature on peripheral nerve injury indicate a sound scientific basis for these hypotheses. Therefore, the suggested “weeding” interventions are likely to succeed in minimizing neurological deficits and improving patients’ quality of life. Various interventions to expand sensory/motor territories are considered; these include nerve lesioning distal to DRGs and removing fascial barriers between innervated and paralyzed muscles. Experience from such interventions will help expand our understanding of the speed and extent of CS-mediated neurological recovery as well as brain’s plastic abilities in reorienting after such procedures.

Metabolic-associated fatty liver disease (MAFLD) may increase the risk of cardiovascular events. In this study, we assessed the predictive value of pentraxin 3 (PTX3) for severe fibrosis and carotid intima-media thickness (CIMT) in patients with MAFLD.

188 patients (114 with MAFLD, 74 with dual etiology MAFLD and chronic hepatitis C) were included. All participants underwent clinical history and examination, metabolic parameter assessment, serum level evaluation of PTX3, Fibrosis-4 index and nafld fibrosis score scores, abdominal ultrasound, and CIMT assessment.

The serum PTX3 was significantly elevated in patients with advanced fibrosis compared to those with mild/moderate fibrosis (1.8 vs 1.4, p = 0.006). The PTX3 level was independently associated with advanced fibrosis (odds ratio = 1.26, 95% confidence interval 1.008–1.040). In MAFLD patients, the PTX3 levels in patients with low fibrosis compared to those with advanced fibrosis were 1.4 (1–2.1) and 1.9 (1.3–3.8), respectively (p = 0.027). A significantly greater CIMT was noted in patients with elevated PTX3 levels (3.85 (3.42–4) vs 4.05 (3.7–4.67), p = 0.0001) compared to those with low PTX3 levels.

Serum PTX3 levels can accurately predict advanced fibrosis and CIMT in MAFLD patients. Thus, it could be useful for management and risk stratification.

Prostate cancer is virtually the most common type of cancer, leading to multiple complications within the male gender worldwide. However, prostatic complications have been increasing recently due to probable changes in lifestyles. Affected patients try every treatment technique to confront their cancer. Thus, radiation therapy has been demonstrated to be one of the most efficient lanes of long-term survivorship in men with malignant prostatic cancer. Although radiotherapy has the potential to seem irritating, due to the studies, metastasis-free survival, biochemical recurrence-free survival, and prostate cancer-specific survival have experienced a major increase in various cases of the disease. Subsequently, still, radiation therapy has revealed the superlative approach to avoiding the risk of cancer relapse and case mortalities. This manuscript would radically discuss novel approaches that could probably increase the lifespan and survivorship of patients owning to previous examinations.

Liver cancer, also identified as hepatic cell carcinoma, is the fifth most prevalent kind of malignancy globally and the fourth foremost cause of cancer-associated mortality. The development and progression of liver cancer are complex processes that involve multiple genetic and environmental factors. As the diagnosis of liver cancer is still worse, with late-stage patients facing a less than 20% 5-year survival rate, there is a critical need for the development of new and effective therapeutic approaches for liver cancer. Mitochondrial alterations and mitochondrial DNA (mtDNA) mutations have long been associated with cancer pathogenesis, including liver cancer. These alterations not only disrupt cellular bioenergetics but also deteriorate the situation by modifying tumor suppressors and oncogenic proteins. Excessive reactive oxygen species generation and flaws in mitochondrial enzymes are among the factors responsible for mitochondrial dysfunction. Additionally, perturbed microRNA levels have also been linked to mtDNA dysfunction and reactive oxygen species generation. Various pharmacological approaches to target mitochondrial dysfunction and mtDNA mutations in cancer have been proposed as potential therapeutic strategies. These approaches include targeting the electron transport chain, which is responsible for the production of adenosine triphosphate in the mitochondria, or transcriptional inhibition of various proteins involved in the mitochondrial biogenesis pathway. Overall, mtDNA is a crucial component of the cell, and alterations in mtDNA make it an attractive target for therapeutic interventions. Hence, we advocate that understanding the role of mtDNA in cancer pathogenesis is important for the development of targeted therapies for these disorders.

Chronic hepatitis B remains the primary cause of liver-related events in China. The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030. However, achieving this goal appears challenging due to the current low rates of diagnosis and treatment. The “Treat-all” strategy, which proposes treating all patients with detectable hepatitis B virus (HBV) DNA or even all patients with positive HBsAg, has been suggested to simplify anti-HBV treatment. In 2022, the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China, expanding antiviral indications and simplifying the treatment algorithm. According to this latest guideline, nearly 95% of patients with detectable HBV DNA are eligible for antiviral treatment. This review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022) and to identify gaps in achieving the “Treat-all” strategy in China.

Hepatic fibrosis (HF) is a critical step in the progression of hepatocellular carcinoma (HCC). Gene associated with retinoid-IFN-induced mortality 19 (GRIM19), an essential component of mitochondrial respiratory chain complex I, is frequently attenuated in various human cancers, including HCC. Here, we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF pathogenesis.

GRIM19 expression was evaluated in normal liver tissues, hepatitis, hepatic cirrhosis, and HCC using human liver disease spectrum tissue microarrays. We studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in vivo. We performed flow cytometry, immunofluorescence, immunohistochemistry, western blotting, and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced HF.

Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues, including hepatitis, cirrhosis, and HCC tissues. Hepatocyte-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in mice. In addition, GRIM19 loss caused chronic liver injury through reactive oxygen species (ROS)-mediated oxidative stress, resulting in aberrant NF-кB activation via an IKK/IкB partner in hepatocytes. Furthermore, GRIM19 loss activated NLRP3-mediated IL33 signaling via the ROS/NF-кB pathway in hepatocytes. Intraperitoneal administration of the NLRP3 inhibitor MCC950 dramatically alleviated GRIM19 loss-driven HF in vivo.

The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-кB signaling, providing potential therapeutic approaches for earlier HF prevention.

Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction.

mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk.

Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12–1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09–3.78] vs. 1.14 [0.80–1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41–12.07]).

The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.