Liver cancer international最新文献

Chronic liver diseases frequently progress to liver fibrosis, characterized by the accumulation of extracellular matrix (ECM) proteins and the formation of fibrous scars. This fibrous tissue disrupts normal liver architecture, impairing its physiological functions. Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure, often necessitating transplantation. Hepatic stellate cells (HSCs) are pivotal in collagen production and play a crucial role in the fibrotic process. Notably, mild to moderate fibrosis can be reversed upon removal of its causative agents, with recovery rates varying based on the cause and severity of fibrosis. Emerging anti-fibrotic therapies focus on inhibiting fibrogenic cell accumulation and preventing ECM deposition. This review highlights herbal extracts with proven effects on HSCs in vivo, showing potential in mitigating liver fibrosis. These extracts inhibit HSC proliferation and ECM release by targeting critical signalling pathways, including TGF-β, NF-κB, MAPK, STAT3 and NRF2. While many of these plants have been validated in pre-clinical studies, further research is needed to identify active compounds and establish clinical efficacy.

We read with great interest the recent article by Kim and Vutien, et al., which reports that substantial liver fat, measured via Vibration-controlled Transient Elastography (VCTE), is associated with a reduced risk of decompensation (aHR: 0.54, 95% CI: 0.32–0.90) and mortality (aHR: 0.52, 95% CI: 0.37–0.73) in metabolic dysfunction-associated steatotic liver disease (MASLD) patients [1]. This study brings valuable insights by examining liver fat's unique prognostic value independent of fibrosis, which has often been overshadowed by an isolated focus on fibrosis. Their findings align with previous meta-analyses showing that lower liver fat content in MASLD individuals with significant/advanced fibrosis is associated with an increased risk of composite adverse outcomes, including decompensation, hepatocellular carcinoma, and death (aHR: 42.2, 95% CI: 7.5–235.5) [2].

While commending the authors for this significant contribution, we suggest caution in interpreting steatosis quantification in populations with high variability in fibrosis levels [as indicated by interquartile range (IQR) of 6.4–17.9 (median 10.6 kPa)] in this study [1]. A large cohort study involving 9.8 million individuals, deemed to be at low risk of advanced fibrosis, illustrated that high Liver fat content, as measured by the surrogate Fatty Liver Index (FLI) was associated with a higher risk of cardiovascular events in MASLD (aHR: 1.39, 95% CI: 1.38–1.40 for FLI ≥ 30 and aHR: 1.52, 95% CI: 1.51–1.54 in FLI ≥ 60) [3]. Similarly, in a recent meta-analysis of 19 studies involving 147 411 participants, primarily from population-based studies, we found that higher liver fat levels in MASLD were associated with an increased risk of subclinical atherosclerosis (pooled OR: 1.27, 95% CI: 1.13–1.41 for mild steatosis and 1.68, 95% CI: 1.41–2.00 for moderate to severe steatosis) [4]. However, this association reversed in populations with a high prevalence of significant/advanced fibrosis, in parallel with increasing fibrosis levels [4].

This paradox may be explained by the ‘burnout’ NASH phenomenon. As liver disease progresses, alterations in portal circulation—such as reduced blood flow, portosystemic shunting, and loss of sinusoidal fenestrations—diminish hepatocyte interactions with insulin and lipoproteins, leading to decreased hepatic fat accumulation [5]. Additionally, while low levels of the insulin-sensitising and anti-steatotic adipocytokine adiponectin are linked with hepatic steatosis and inflammation, elevated adiponectin levels in later disease stages may contribute to reduced hepatic fat storage in advanced (burnt-out) MASH with liver dysfunction [6]. Consequently, individuals with significant/advanced fibrosis may exhibit lower liver fat levels, which could distort associations between steatosis and clinical outcomes, suggesting that fibrosis severity biases

It remains unclear whether alcohol intake and cardiometabolic factors are simultaneously associated with liver fibrosis progression in Japanese obese patients. This study investigated factors influencing liver fibrosis progression using the Aspartate Aminotransferase/Platelet Ratio Index (APRI), which does not include age. We conducted a cross-sectional study of 26 737 obese (BMI ≥ 25 kg/m²) adults undergoing health checkups. Steatotic liver disease (SLD) was diagnosed via ultrasonography. Clinical characteristics were analysed according to BMI category and APRI to identify risk factors for advanced liver fibrosis (APRI > 1.0). The prevalence of type 2 diabetes, hypertension, and SLD increased with increasing BMI. On multivariable analysis in male, significant risk factors for advanced liver fibrosis included increased BMI (BMI 30–34.9 kg/m²: OR 2.64, 95% CI 1.89–3.69, p < 0.001; BMI 35–39.9 kg/m²: OR 2.67, 95% CI 1.89–3.69, p = 0.002; BMI ≥ 40 kg/m²: OR 3.51, 95% CI 1.24–9.96, p = 0.018), SLD (OR 2.13, 95% CI 1.49–3.05, p < 0.001), moderate alcohol intake (OR 1.36, 95% CI 1.03–1.79, p = 0.031), heavy alcohol intake (OR 4.31, 95% CI 2.90–6.40, p < 0.001), high blood pressure (OR 1.30, 95% CI 1.01–1.67, p = 0.044), and high fasting blood glucose (OR 1.61, 95% CI 1.12–2.28, p = 0.008). In female, only age > 65 years (OR 3.02, 95% CI1.93–4.73, p < 0.001), BMI, and high uric acid (OR 2.06, 95% CI 1.15–3.68, p = 0.015) were extracted. In an obese male, alcohol intake and cardiometabolic factors were associated with liver fibrosis progression based on APRI, independent of elevated BMI and SLD.

Aspirin and NSAIDs may be beneficial in chronic liver diseases. We explored the effect of exposure to anti-inflammatory drugs in patients with chronic liver disease with regard to adverse liver events, cancers and mortality. A cohort of patients with chronic liver disease 2005–2020 (n = 21 439) was studied. All patients were hospitalised in Region Stockholm. Data from the Patient Register, Prescribed Drug Register, Death Certificate Register, Cancer Register, two laboratories and Stockholm Center for Health Data were combined. We analysed death, adverse liver events, liver cancers and all cancers in relation to drug exposure. During follow-up 10 279 patients (47.9%) died. There was a reduced risk for all cancers combined when patients were exposed to aspirin (aHR 0.68; 95% CI 0.63–0.73) and NSAIDs (aHR 0.80; 95% CI 0.75–0.86) and a reduced risk of liver cancer in patients exposed to aspirin (aHR 0.48; 95% CI 0.41–0.57) and to NSAIDs (aHR 0.71; 95% CI 0.62–0.82). There was a reduced overall mortality risk for patients exposed to NSAIDs (aHR 0.68; 95% CI 0.64–0.72) and a reduced mortality risk for patients exposed to aspirin (aHR 0.86; 95% CI 0.82–0.91) after adjusting for comorbidities and severity of the liver disease. Patients with alcohol-associated liver disease exposed to aspirin had reduced mortality risk (aHR 0.82; 95% CI 0.76–0.89) and exposure to NSAIDs also reduced the mortality risk (aHR 0.74; 95% CI 0.69–080). Exposure to aspirin or NSAIDs in patients with chronic liver diseases was associated with reduced cancer risks including risk for liver cancer and decreased overall mortality risk.

Carcinoid tumours are slow-growing neuroendocrine neoplasms mainly affecting the gastrointestinal tract, the respiratory tree, ovaries and kidneys. Approximately 20% of patients with carcinoid tumour are affected by carcinoid syndrome, characterised by chronic diarrhoea and/or flushing in the presence of systemically elevated levels of specific markers as serotonin or 5-hydroxyindolacetic acid. Skin manifestations include flushing of the face, neck and anterior surface of the chest but after repeated and prolonged relapses, the skin lesions become fixed, acquiring a bluish-red tint with telangiectasias. Patients may also develop pellagra skin symptoms including erythema, xerosis, scaling, hyperkeratosis and pigmentation, caused by a deficiency of tryptophan, due to its high consumption for serotonin synthesis.

This study addresses the need for precise histopathological assessment of liver biopsies in Metabolic dysfunction-Associated Steatohepatitis (MASH) cirrhosis, where assessing nuanced drug effects on fibrosis becomes pivotal. The study describes a framework for the development and validation of an Artificial Intelligence (AI) model, leveraging SHG/TPE microscopy along with insights from an expert hepatopathologist, to precisely annotate fibrous septa and nodules in liver biopsies in MASH cirrhosis. A total of 25 liver biopsies from the Belapectin trial (NCT04365868) were randomly selected for training, and an additional 10 for validation. Each biopsy underwent three sections: Smooth Muscle Actin (SMA) and Sirius Red (SR) staining for septa and nodule annotation by pathologists and an unstained section for SHG/TPE imaging and AI annotation using qSepta and qNodule algorithms. Re-training of qSepta and qNodule algorithms was executed based on pathologist annotations. Sensitivity and positive predictive value (PPV) were employed to evaluate concordance with pathologist annotations, both pre- and post-training and during validation. Post-re-training by pathologist annotations, the AI demonstrated improved sensitivity for qSepta annotations, achieving 91% post-training (versus 84% pre-training). Sensitivity for qSepta in the validation cohort also improved to 91%. Additionally, PPV significantly improved from 69% pre-training to 85% post-training and reached 94% during validation. For qNodule annotations, sensitivity increased from 82% post-training to 90% in the validation cohort, while the PPV was consistent at 95% across both training and validation cohorts.This study outlines a strategic framework for developing and validating an AI model tailored for precise histopathological assessment of MASH cirrhosis, using pathologist training and annotations. The outcomes emphasise the crucial role of disease-specific customisation of AI models, based on expert pathologist training, in improving accuracy and applicability in clinical trials, marking a step forward in understanding and addressing the histopathological evaluation of MASH cirrhosis.

African individuals with metabolic dysfunction-associated steatotic liver disease (MAFLD) may have unique genetic factors that influence the clinical manifestations of MAFLD. The paucity of both epidemiological data on MAFLD within Africa and the lack of genetic research thereof have disadvantaged the population, as extrapolated data out the region has been utilised to direct health care policy and management of the disease. This unique cohort of MAFLD individuals within Africa requires further epidemiological and genomic research to advance precision medicine within the realm of clinical hepatology. With the anticipated increase in non-communicable disease that sub-Saharan African may experience in the near future, a robust large study within Africa may provide insight as to whether MAFLD prevalence may be expected to significantly add to this impending health burden; furthermore, a genetic research component may provide insight into whether protective genetic variants are present or whether there is a lack of pathogenic variants, thereby allowing clinicians and policy strategists to have a better understanding of the disease prevalence and manifestations in African individuals. The aim of this publication was to review the current prevalence trends of MAFLD within Africa and the knowledge of the genetic landscape of MAFLD individuals of African descent.

Radiotherapy has been proven to act synergistically with immunotherapy to prime the immune response against the immunosuppressive tumour microenvironment. Stereotactic body radiation therapy (SBRT) produces a greater variety of tumour-associated antigens. This can elicit an even stronger anti-tumour immune response, especially when combined with immune checkpoint inhibitors to prevent T cell exhaustion. This response is particularly useful in hepatocellular carcinoma patients due to a naturally immunosuppressive environment. SBRT has provided excellent local control rates in patients with hepatocellular carcinoma (HCC). Retrospective and prospective clinical trials involving advanced-stage HCC patients support combining SBRT with immune checkpoint inhibitors. Actively recruiting phase III randomised controlled trials are currently testing this promising combination in HCC patients. This mini-review outlines the rationale for combining the two modalities in HCC patients. Current guidelines for HCC and successes in the field using the combination treatment will also be discussed.

Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing liver-related cause of mortality, affecting about 25% of the adult world population. Despite this, fundamental questions regarding the underlying mechanisms remain incompletely answered. In mice, whole-body knockout (KO) of Na⁺/H⁺ exchanger NHE1 (SLC9A1) was suggested to be protective against NASH. However, the translatability of this finding is confounded by the fact that global NHE1 KO affects ubiquitous processes in tissues outside of the liver. Here, we aimed to determine the role of hepatocyte NHE1 in NAFLD. We generated a hepatocyte-specific NHE1 KO (NHE1 HKO) mouse and determined the impact of NHE1 loss on liver metabolism and NAFLD characteristics following methionine–choline-deficient (MCD) diet. Loss of hepatocyte NHE1 does not protect against NAFLD development, but rather seems to impair basal ROS balance in the mouse liver.