☆ 4.7 Review

Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2023)

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Article Gastroenterology & Hepatology

Inflamed and non-inflamed classes of HCC: a revised immunogenomic classification

Carla Montironi et al.

Summary: This study characterizes the immunogenomic contexture of hepatocellular carcinoma (HCC) and defines inflamed and non-inflamed tumors. Two distinct patterns of CTNNB1 are associated with differential immune evasion and may help predict immune response in HCC.

GUT (2023)

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Review Gastroenterology & Hepatology

Conceptual Model for the Hepatocellular Carcinoma Screening Continuum: Current Status and Research Agenda

Amit G. Singal et al.

Summary: Hepatocellular carcinoma (HCC) has a poor prognosis with survival rates below 20% in 5 years, partly due to failures in the cancer screening process continuum. A conceptual model outlining discrete steps in the HCC screening process highlights delays or failures at each step and identifies factors contributing to these failures at the patient, provider, and health care system levels. Comparing HCC screening processes with breast and colorectal cancer screening can help identify opportunities for improvement and ultimately improve early detection of HCC.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

Association between ultrasound quality and test performance for HCC surveillance in patients with cirrhosis: a retrospective cohort study

Nicolas Chong et al.

Summary: This study found that impaired ultrasound visualization is associated with worse surveillance test performance in patients with cirrhosis. Severe visual limitations were linked to lower sensitivity, while moderate limitations were associated with an increased risk of false-positive results. Alternative blood-based biomarkers and imaging strategies are needed for patients at risk of ultrasound-based surveillance failure.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS (2022)

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Review Gastroenterology & Hepatology

Incidence of Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-analysis, and Meta-regression

Lorenzo A. Orci et al.

Summary: Nonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), and this study used meta-analysis to analyze the incidence rates of HCC in NAFLD patients. The results showed that NAFLD patients with cirrhosis have a similar risk of developing HCC compared to cirrhosis patients with other causes. However, the incidence of HCC in nonalcoholic steatohepatitis or simple steatosis patients is lower.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2022)

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Review Pharmacology & Pharmacy

Nonalcoholic steatohepatitis (NASH) cirrhosis: a snapshot of therapeutic agents in clinical development and the optimal design for clinical trials

Pankaj Aggarwal et al.

Summary: This article summarizes the natural history and development rates of major adverse liver outcomes (MALO) in patients with NASH cirrhosis, and provides examples of ongoing clinical trials. The article discusses FDA guidance on acceptable endpoints for NASH cirrhosis trials and offers practical advice on trial design. The data presented justify further development and investigation of therapeutic agents for the treatment of NASH cirrhosis.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2022)

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Review Gastroenterology & Hepatology

T cells: Friends and foes in NASH pathogenesis and hepatocarcinogenesis

Pierluigi Ramadori et al.

Summary: This article reviews the specific functions of various T-cell populations involved in NAFLD and NAFLD-driven HCC, illustrating their interactions with other immune cells and the influence of the metabolic microenvironment on immune cell functionality.

HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease

Jennifer R. Kramer et al.

Summary: Patients with NAFLD and diabetes have a high risk of developing HCC. The study found that the use of metformin was associated with a reduced risk of developing HCC, while combination therapy was associated with an increased risk. Glycemic control can be a useful biomarker for stratifying HCC risk in these patients.

HEPATOLOGY (2022)

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Meeting Abstract Oncology

Pembrolizumab plus best supportive care versus placebo plus best supportive care as second-line therapy in patients in Asia with advanced hepatocellular carcinoma (HCC): Phase 3 KEYNOTE-394 study

Shukui Qin et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Gastroenterology & Hepatology

HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis

Amit G. Singal et al.

Summary: In this systematic review and meta-analysis, HCC surveillance was found to be associated with improved early-stage detection, curative treatment receipt, and survival in patients with cirrhosis. However, there was significant heterogeneity in the pooled estimates, and there were fewer data quantifying potential surveillance-related harms. Available data suggest that HCC surveillance is of high value in patients with cirrhosis, although further studies evaluating benefits and harms are still needed.

JOURNAL OF HEPATOLOGY (2022)

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Review Gastroenterology & Hepatology

Treatment Candidacy for Pharmacologic Therapies for NASH

Ian A. Rowe et al.

Summary: NASH has become an important cause of cirrhosis and hepatocellular carcinoma, and there are currently more than 50 therapeutic agents in clinical development. Obeticholic acid has achieved interim histological improvement in fibrosis without worsening NASH in the phase 3 REGENERATE study, and long-term clinical outcomes are being followed. It is now a timely consideration of the current situation and future direction in NASH management.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2022)

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Article Oncology

Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial

Thomas Yau et al.

Summary: First-line nivolumab treatment did not significantly improve overall survival compared with sorafenib in patients with advanced hepatocellular carcinoma, but clinical activity and a favorable safety profile were observed in some patients.

LANCET ONCOLOGY (2022)

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Review Oncology

Immunotherapies for hepatocellular carcinoma

Josep M. Llovet et al.

Summary: Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related death globally. Traditional treatments involve specific drugs, but the emergence of immune checkpoint inhibitors has revolutionized the management of HCC.

NATURE REVIEWS CLINICAL ONCOLOGY (2022)

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Article Gastroenterology & Hepatology

Advancing the global public health agenda for NAFLD: a consensus statement

Jeffrey Lazarus et al.

Summary: Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects a significant portion of the global adult population, but has received little attention from the global public health community. This has led to a lack of inclusion of NAFLD in national and international strategies and policies for non-communicable diseases, highlighting the need for a more comprehensive public health response to the disease.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2022)

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Article Multidisciplinary Sciences

T cell immunity against liver cancer in mice

John C. McVey et al.

Summary: Non-alcoholic fatty liver disease (NAFLD) has a significant impact on liver cancer development and may impair antigen-specific CD8 (+) T cell immunity due to accumulated macrophages in the liver environment.

ISCIENCE (2022)

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Article Gastroenterology & Hepatology

Dynamic Changes in Ultrasound Quality for Hepatocellular Carcinoma Screening in Patients With Cirrhosis

Haley Schoenberger et al.

Summary: Nearly 1 in 5 patients with cirrhosis had moderately-severely limited ultrasound visualization for HCC nodules, particularly those with obesity or alcohol-related or nonalcoholic fatty liver disease cirrhosis. Ultrasound quality can change between exams, including improvement in many patients with limited visualization.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

CXCR2 inhibition enables NASH-HCC immunotherapy

Jack Leslie et al.

Summary: This study found that targeting neutrophils using a CXCR2 small molecule inhibitor can enhance the sensitivity of non-alcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) to immune checkpoint inhibition therapy (ICI). The combination therapy can reprogram the tumor immune microenvironment, increase the number of anti-tumor immune cells, and improve treatment outcomes.

GUT (2022)

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Article Gastroenterology & Hepatology

NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options

Friedrich Foerster et al.

Summary: Given the global increase in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are becoming important causes of hepatocellular carcinoma (HCC). HCCs caused by chronic inflammation mediated by lipotoxicity have unique characteristics, such as occurring in up to 50% of NAFLD-HCC patients without cirrhosis and having a lower annual incidence, leading to challenges in surveillance strategies. Locoregional treatments may be equally effective regardless of HCC etiology, but the effectiveness of systemic therapy is less clear. Tyrosine kinase inhibitors are likely equally effective, while there are initial signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC compared to viral HCC.

JOURNAL OF HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

Metformin treatment rescues CD8+T-cell response to immune checkpoint inhibitor therapy in mice with NAFLD

Simon Wabitsch et al.

Summary: Non-alcoholic steatohepatitis (NASH) negatively affects the efficacy of immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC). This study reveals that NASH alters the metabolism, function, and motility of hepatic CD8+ T cells, leading to reduced responsiveness to anti-PD-1 treatment. The efficacy can be rescued by metformin treatment.

JOURNAL OF HEPATOLOGY (2022)

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Review Oncology

Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis

Darren Jun Hao Tan et al.

Summary: Compared with hepatocellular carcinoma due to other causes, patients with NAFLD-related hepatocellular carcinoma are older, have higher BMI, and are more likely to have metabolic comorbidities and cardiovascular disease. The surveillance rate is lower, but the proportion of patients without cirrhosis is higher.

LANCET ONCOLOGY (2022)

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Article Pharmacology & Pharmacy

Rifaximin Ameliorates Non-alcoholic Steatohepatitis in Mice Through Regulating gut Microbiome-Related Bile Acids

Jie Jian et al.

Summary: Rifaximin treatment has significant effects on improving hepatic steatosis, lobular inflammation, and fibrogenesis in mice with methionine and choline deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH). It achieves this by altering the gut microbiome and decreasing levels of deoxycholic acid (DCA) in the ileum. These findings suggest that rifaximin may be a promising approach for NASH therapy in humans.

FRONTIERS IN PHARMACOLOGY (2022)

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Article Oncology

Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312) : a multicentre, open-label, randomised, phase 3 trial

Robin Kate Kelley et al.

Summary: This study evaluated the combination of cabozantinib and atezolizumab versus sorafenib as first-line systemic treatment for advanced hepatocellular carcinoma. The combination treatment group showed better progression-free survival compared to the sorafenib group, but overall survival did not reach statistical significance. Common adverse events in the combination group included liver enzyme elevation, hypertension, and skin reactions. The study suggests that cabozantinib plus atezolizumab may be a treatment option, but further research is needed.

LANCET ONCOLOGY (2022)

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Article Biochemistry & Molecular Biology

Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma

Andrew X. Zhu et al.

Summary: This study analyzed tumor samples from patients with hepatocellular carcinoma and found that combination therapy with atezolizumab and bevacizumab was effective in treating this type of cancer. Patients with high expression of VEGF Receptor 2, regulatory T cells, and myeloid inflammation signatures showed better outcomes with the combination therapy compared to atezolizumab alone. These findings provide insights into baseline immune and genetic features that can identify patients who will benefit from the combination therapy of atezolizumab and bevacizumab in advanced hepatocellular carcinoma.

NATURE MEDICINE (2022)

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Review Medicine, General & Internal

Hepatocellular carcinoma

Arndt Vogel et al.

Summary: Hepatocellular carcinoma is a common cancer worldwide, with non-alcoholic fatty liver disease becoming a dominant cause. Treatment options are varied, including surgery, radiation, and medication. With the approval of new drugs and the development of immunotherapy, the outlook for hepatocellular carcinoma patients has improved, but the optimal sequencing of drugs and predictive biomarkers still need further research.

LANCET (2022)

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Review Oncology

Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Josep M. Llovet et al.

Summary: In this article, Llovet and colleagues review recent advances in hepatocellular carcinoma therapy and discuss the clinical workflows for selecting and monitoring patients. The article covers the molecular pathogenesis of HCC, molecular classes and determinants of heterogeneity, and effective systemic therapies including immunotherapy. The authors propose a flowchart of sequential therapies, explore mechanisms of resistance, and address the need for predictive biomarkers.

NATURE CANCER (2022)

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Review Immunology

Immune cell-mediated features of non-alcoholic steatohepatitis

Thierry Huby et al.

Summary: NASH is a serious chronic liver disorder with increasing prevalence globally. Metabolic disturbance and the role of immune cells are crucial in its onset and progression. Understanding the mechanisms by which immune cells contribute to NASH pathogenesis is essential for the development of innovative drugs targeting NASH.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Gastroenterology & Hepatology

Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma

Frank Juhling et al.

Summary: The study found that patients with chronic viral hepatitis and NASH share similar epigenetic and transcriptional modifications driving cancer risk. Chromatin readers were identified as targets to revert liver gene transcription in patients, reducing the risk of HCC. Proof-of-concept studies in a NASH-HCC mouse model showed that inhibiting chromatin reader bromodomain 4 can inhibit liver disease progression and hepatocarcinogenesis.

GUT (2021)

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Review Gastroenterology & Hepatology

Use of Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis: A Systematic Review and Meta-Analysis

Erin Wolf et al.

Summary: The study found that HCC surveillance is underused in clinical practice, especially among patients with alcohol-associated or NASH-related cirrhosis and those not followed in subspecialty gastroenterology clinics. Interventions such as provider education, inreach including reminder systems, and population health outreach efforts can significantly increase HCC surveillance.

HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Steatohepatitis Impairs T-cell-Directed Immunotherapies Against Liver Tumors in Mice

Bernd Heinrich et al.

Summary: This study found that steatohepatitis reduces infiltration of CD4(+) T cells and effector memory cells in liver tumors, which decreases the efficacy of immunotherapeutic agents like M30 and aOX40 in inhibiting tumor growth. N-acetylcysteine can restore T-cell numbers in tumors and enhance the ability of M30 and aOX40 to slow tumor growth in mice.

GASTROENTEROLOGY (2021)

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Article Gastroenterology & Hepatology

rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis

Kevin Teo et al.

Summary: The genetic variant rs641738C>T near MBOAT7 is validated as a risk factor for the presence and severity of non-alcoholic fatty liver disease (NAFLD) in individuals of European descent. This variant is associated with higher liver fat, NAFLD diagnosis, and advanced fibrosis in Caucasian adults.

JOURNAL OF HEPATOLOGY (2021)

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Review Gastroenterology & Hepatology

Maladaptive regeneration - the reawakening of developmental pathways in NASH and fibrosis

Changyu Zhu et al.

Summary: Emerging data suggest that the reactivation of developmental pathways is associated with nonalcoholic steatohepatitis (NASH) and fibrosis in the liver injury response. This review discusses the role of these pathways in liver development and in the pathogenesis of NASH and fibrosis.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Review Gastroenterology & Hepatology

Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention

Daniel Q. Huang et al.

Summary: The prevalence of NAFLD-related HCC is projected to continue rising globally, with NASH expected to increase and obesity as a major risk factor. Urgent measures are needed to address this growing problem.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Article Medicine, General & Internal

Hepatocellular carcinoma

Josep M. Llovet et al.

Summary: Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global health challenge with rising incidence projected to exceed 1 million cases by 2025. Infection by hepatitis B and C viruses remains a major risk factor for HCC, while non-alcoholic steatohepatitis is emerging as a more common risk factor in Western countries. Advances in systemic therapies for HCC, including immunotherapies and targeted therapies, are expected to revolutionize the management of this disease.

NATURE REVIEWS DISEASE PRIMERS (2021)

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Article Gastroenterology & Hepatology

Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial

Etienne Garin et al.

Summary: This study compared the efficacy of personalized versus standard dosimetry in selective internal radiation therapy for advanced hepatocellular carcinoma, showing that personalized dosimetry significantly improved the objective response rate. The results suggest that personalized dosimetry may enhance outcomes in clinical practice and should be considered for future trials.

LANCET GASTROENTEROLOGY & HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease

Ramy Younes et al.

Summary: This study compared various non-invasive scoring systems in identifying risk and predicting long-term outcomes for patients with non-alcoholic fatty liver disease. NFS, HFS, and FIB-4 outperformed APRI and BARD in both cross-sectional identification of fibrosis and prediction of long-term outcomes, making them useful tools for clinical management of NAFLD patients at increased risk of fibrosis and liver-related complications or death.

JOURNAL OF HEPATOLOGY (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Multidisciplinary Sciences

Convergent somatic mutations in metabolism genes in chronic liver disease

Stanley W. K. Ng et al.

Summary: In patients with liver disease, mutations in FOXO1, CIDEB, and GPAM genes were found at a higher frequency, showing convergent evolution. Master regulators of metabolic pathways are a frequent target of convergent somatic mutation in alcohol-related and non-alcoholic fatty liver disease.

NATURE (2021)

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Article Medicine, General & Internal

Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease

Arun J. Sanyal et al.

Summary: In this study involving patients with nonalcoholic fatty liver disease, advanced fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death over a median of 4 years of follow-up. Advanced fibrosis was also related to an increased incidence of liver decompensation events.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Gastroenterology & Hepatology

Therapeutic pipeline in nonalcoholic steatohepatitis

Raj Vuppalanchi et al.

Summary: The therapeutic pipeline for NASH is expanding with insights into disease pathophysiology, offering potential solutions to resolve steatohepatitis or reverse fibrosis. However, there may be some clinical challenges in the use of these emerging therapies.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Review Gastroenterology & Hepatology

Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma

Josep M. Llovet et al.

Summary: Locoregional therapies, including local ablation and transarterial chemoembolization, play a crucial role in the management of hepatocellular carcinoma. Recent studies have shown potential benefits of combining these local therapies with systemic treatments, such as molecular therapies, to enhance therapeutic effects.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Associations Among Adipose Tissue Immunology, Inflammation, Exosomes and Insulin Sensitivity in People With Obesity and Nonalcoholic Fatty Liver Disease

Anja Fuchs et al.

Summary: Insulin resistance in people with obesity and NAFLD is associated with SAAT inflammation and both plasma and SAAT-derived exosomes, which may impact insulin sensitivity in these patients.

GASTROENTEROLOGY (2021)

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Article Gastroenterology & Hepatology

Yttrium-90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study

Riad Salem et al.

Summary: The LEGACY study evaluated the efficacy of yttrium-90 glass microspheres in treating solitary, unresectable HCC <= 8 cm, showing promising response rates and durable responses in a multicenter setting.

HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis

Roser Pinyol et al.

Summary: This study revealed higher rates of ACVR2A mutations (10%) in NASH-related hepatocellular carcinoma (HCC), along with a novel mutational signature that distinguishes NASH-HCC from HCCs of other etiologies.

JOURNAL OF HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores

Cristiana Bianco et al.

Summary: This study utilized polygenic risk scores (PRS) to investigate the causal relationship between hepatic fat and HCC, improving the accuracy of HCC detection and helping to stratify HCC risk in individuals with dysmetabolism. The PRS showed robust predictions for HCC in both high-risk individuals and the general population.

JOURNAL OF HEPATOLOGY (2021)

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Article Multidisciplinary Sciences

NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Dominik Pfister et al.

Summary: The study investigated the impact of NASH on immunotherapy response in HCC patients and found that NASH-HCC may be less responsive to immunotherapy. Aberrant T cell activation caused by NASH-related tissue damage led to impaired immune surveillance in HCC patients.

NATURE (2021)

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Article Multidisciplinary Sciences

Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH

Michael Dudek et al.

Summary: Liver resident CD8 T cells play an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis. These cells display specific phenotypic and metabolic characteristics in the liver, making them susceptible to metabolic stimuli and leading to auto-aggressive responses. This study sheds light on the mechanisms underlying liver damage in NASH and highlights the distinction between auto-aggressive and protective T cell immunity.

NATURE (2021)

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Review Medicine, General & Internal

Association of Obesity With Survival Outcomes in Patients With Cancer A Systematic Review and Meta-analysis

Fausto Petrelli et al.

Summary: Obesity is associated with increased mortality in cancer patients overall, but patients with obesity and certain types of cancer such as lung cancer, renal cell carcinoma, and melanoma may have better survival outcomes compared to non-obese patients with the same cancers. Weight-reducing strategies could potentially help reduce mortality in these patients.

JAMA NETWORK OPEN (2021)

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Review Gastroenterology & Hepatology

Sinusoidal endotheliopathy in nonalcoholic steatohepatitis: therapeutic implications

Samar H. Ibrahim

Summary: Liver sinusoidal endothelial cells (LSECs) play a crucial role in the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD) by undergoing capillarization and expressing adhesion molecules. They regulate hepatic immune cell populations by mediating leukocyte subset adhesion in NAFLD, highlighting their role in the inflammatory response.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2021)

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Review Gastroenterology & Hepatology

Evidence-Based Management of Hepatocellular Carcinoma: Systematic Review and Meta-analysis of Randomized Controlled Trials (2002-2020)

Philipp K. Haber et al.

Summary: A review of 49 high-quality phase III randomized controlled trials in hepatocellular carcinoma conducted between 2002 and 2020 found that 9 had positive results, suggesting that immunotherapies may be more effective in viral etiologies.

GASTROENTEROLOGY (2021)

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Meeting Abstract Oncology

Molecular markers of response to anti-PD1 therapy in advanced hepatocellular carcinoma.

Philipp K. Haber et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Gastroenterology & Hepatology

Epidemiology and risk-stratification of NAFLD-associated HCC

George N. Ioannou

Summary: NAFLD is projected to be the leading cause of hepatocellular carcinoma and is associated with risk factors such as obesity, diabetes, Hispanic ethnicity, and genetic polymorphisms. Lipotoxicity and oxidative DNA damage may lead to hepatocarcinogenesis, especially in the absence of cirrhosis. Validated models to identify high-risk patients for hepatocellular carcinoma in NAFLD are currently unavailable.

JOURNAL OF HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention

Naomi F. Lange et al.

Summary: This review highlights the increasing burden of hepatocellular carcinoma associated with nonalcoholic fatty liver disease and non-alcoholic steatohepatitis worldwide. Preventive strategies including lifestyle factors and chemopreventive treatments are crucial in combating this trend. The role of adjuvant therapies for tertiary prevention of HCC is briefly reviewed.

JOURNAL OF HEPATOLOGY (2021)

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Article Oncology

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study

Zhenggang Ren et al.

Summary: The study aimed to assess the efficacy of sintilimab plus IBI305 versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma in China, showing significant overall survival and progression-free survival benefits with acceptable safety profiles.

LANCET ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis

Aleksandra Deczkowska et al.

Summary: Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans. The study identified the significant role of cDC1 in NASH and confirmed their importance in liver pathology.

NATURE MEDICINE (2021)

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Editorial Material Medicine, General & Internal

Hepatocellular Carcinoma - Origins and Outcomes

Robin K. Kelley et al.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Gastroenterology & Hepatology

Outcomes after curative therapy for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: a meta-analysis and review of current literature

Ken M. Chin et al.

Summary: The study found that NAFLD-HCC patients undergoing curative therapy, such as liver resection, had improved disease-free survival and overall survival compared to non-NAFLD HCC patients. However, there were higher rates of peri-and post-operative complications reported in NAFLD-HCC patients, and significant inter-study heterogeneity limited further analysis.

HPB (2021)

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Article Oncology

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma

Tim F. Greten et al.

Summary: The standard of care for advanced HCC has been transformed by the combination of immunotherapy and anti-VEGF therapy, showing improved overall survival rates. The use of immunotherapy in later stages of treatment has been proven safe and effective, with ongoing research focusing on novel combinations of ICI and TKI for earlier intervention in HCC treatment.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Multidisciplinary Sciences

NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Dominik Pfister et al.

Summary: The text discusses the impact of NASH on the development of HCC and the effect of immunotherapy, revealing the accumulation of exhausted and unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, anti-PD1 treatment led to an increase in HCC, with CD8(+) T cells contributing to this increase.

NATURE (2021)

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Article Gastroenterology & Hepatology

Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease

Ju Dong Yang et al.

HEPATOLOGY (2020)

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Article Surgery

Bariatric surgery is associated with reduction in non-alcoholic steatohepatitis and hepatocellular carcinoma: A propensity matched analysis

Minyoung Kwak et al.

AMERICAN JOURNAL OF SURGERY (2020)

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Article Surgery

Liver transplant for hepatocellular carcinoma in the United States: Evolving trends over the last three decades

Marc Puigvehi et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2020)

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Article Cardiac & Cardiovascular Systems

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AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease: Expert Review

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NEW ENGLAND JOURNAL OF MEDICINE (2020)

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NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Senolytic CAR T cells reverse senescence-associated pathologies

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Hepatitis C-Related Hepatocellular Carcinoma Incidence in the Veterans Health Administration After Introduction of Direct-Acting Antivirals

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Inadequate Hepatocellular Carcinoma Screening in Patients With Nonalcoholic Steatohepatitis Cirrhosis

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Angiopoietin-2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease

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High incidence of hepatocellular carcinoma and postoperative complications in patients with nonalcoholic steatohepatitis as a primary indication for deceased liver transplantation

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Models estimating risk of hepatocellular carcinoma in patients with alcohol or NAFLD-related cirrhosis for risk stratification

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NATURE MEDICINE (2019)

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NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2019)

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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LIVER CANCER (2019)

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Performance of Hong Kong Liver Cancer staging system in patients of hepatocellular carcinoma treated with surgical resection: An Indian validation study

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MOLECULAR CELL (2019)

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Meeting Abstract Cardiac & Cardiovascular Systems

Distribution of Coronary Flow Capacity Is Different Among the Groups by Abnormal CFR/HMR in Nonobstructive Coronary Artery Disease Patients

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The TM6SF2 E167K genetic variant induces lipid biosynthesis and reduces apolipoprotein B secretion in human hepatic 3D spheroids

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SCIENTIFIC REPORTS (2019)

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Review Immunology

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FRONTIERS IN IMMUNOLOGY (2019)

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Preclinical Models for Studying NASH-Driven HCC: How Useful Are They?

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CELL METABOLISM (2019)

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Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial

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Review Gastroenterology & Hepatology

The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

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The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases

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Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease

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HEPATOLOGY (2018)

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The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017Part 2: Management and special groups

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Editorial Material Gastroenterology & Hepatology

Editorial: NAFLD-related hepatocellular carcinoma - increasing or not? With or without cirrhosis?

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Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis

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Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases

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Review Gastroenterology & Hepatology

Lipotoxicity and the gut-liver axis in NASH pathogenesis

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Pharmacotherapy for NASH: Current and emerging

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Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030

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A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer

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JOURNAL OF HEPATOLOGY (2018)

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EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma

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Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial

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Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells

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SCIENCE (2018)

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Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4+ T cell apoptosis promoting HCC development

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CELL DEATH & DISEASE (2018)

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Review Gastroenterology & Hepatology

Systematic review with meta-analysis: risk of hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis compared to other liver diseases

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ALIMENTARY PHARMACOLOGY & THERAPEUTICS (2018)

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GASTROENTEROLOGY (2018)

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Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis

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SCIENCE TRANSLATIONAL MEDICINE (2018)

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NATURE COMMUNICATIONS (2018)

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HEPATIC ONCOLOGY (2018)

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The PNPLA3 Variant Associated With Fatty Liver Disease (I148M) Accumulates on Lipid Droplets by Evading Ubiquitylation

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INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY (2017)

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SCIENTIFIC REPORTS (2017)

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Survival after treatment with curative intent for hepatocellular carcinoma among patients with vs without non-alcoholic fatty liver disease

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ALIMENTARY PHARMACOLOGY & THERAPEUTICS (2017)

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Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice

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ENDOCRINE (2017)

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Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma

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Article Gastroenterology & Hepatology

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans Is Associated With Nonalcoholic Fatty Liver Disease

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CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2016)

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Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma

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Article Gastroenterology & Hepatology

The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent

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Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes

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The Severity of Nonalcoholic Fatty Liver Disease Is Associated With Gut Dysbiosis and Shift in the Metabolic Function of the Gut Microbiota

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Article Gastroenterology & Hepatology

Clinical Patterns of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease: A Multicenter Prospective Study

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HEPATOLOGY (2016)

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Article Oncology

Outcomes After Stereotactic Body Radiotherapy or Radiofrequency Ablation for Hepatocellular Carcinoma

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Article Gastroenterology & Hepatology

A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer

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NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis

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NATURE MEDICINE (2016)

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Clinical Presentation, Risk Factors, and Treatment Modalities of Hepatocellular Carcinoma: A Single Tertiary Care Center Experience

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Article Gastroenterology & Hepatology

Temporal Trends of Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma in the Veteran Affairs Population

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EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY (2015)

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GASTROENTEROLOGY (2015)

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Review Gastroenterology & Hepatology

Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy

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Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial

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LANCET ONCOLOGY (2015)

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Article Gastroenterology & Hepatology

Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study

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LIVER INTERNATIONAL (2015)

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Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

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NATURE (2015)

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Impact of Steatosis on Prognosis of Patients with Early-Stage Hepatocellular Carcinoma After Hepatic Resection

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ANNALS OF SURGICAL ONCOLOGY (2015)

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ER Stress Cooperates with Hypernutrition to Trigger TNF-Dependent Spontaneous HCC Development

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CANCER CELL (2014)

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Metabolic Activation of lntrahepatic CD8+ T Cells and NKT Cells Causes Nonalcoholic Steatohepatitis and Liver Cancer via Cross-Talk with Hepatocytes

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CANCER CELL (2014)

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Improved survival outcomes in patients with non-alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002-2012 United Network for Organ Sharing data

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CLINICAL TRANSPLANTATION (2014)

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Article Gastroenterology & Hepatology

Continuation of Metformin Use After a Diagnosis of Cirrhosis Significantly Improves Survival of Patients With Diabetes

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HEPATOLOGY (2014)

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Article Gastroenterology & Hepatology

Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene

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Hepatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team

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JOURNAL OF HEPATOLOGY (2014)

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Article Gastroenterology & Hepatology

Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma

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JOURNAL OF HEPATOLOGY (2014)

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Article Genetics & Heredity

Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease

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NATURE GENETICS (2014)

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CLINICAL CANCER RESEARCH (2013)

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Review Gastroenterology & Hepatology

Statins Are Associated With a Reduced Risk of Hepatocellular Cancer: A Systematic Review and Meta-analysis

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Article Gastroenterology & Hepatology

Characterization of Gut Microbiomes in Nonalcoholic Steatohepatitis (NASH) Patients: A Connection Between Endogenous Alcohol and NASH

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Article Gastroenterology & Hepatology

Role of Vascular Endothelial Growth Factor in the Pathophysiology of Nonalcoholic Steatohepatitis in Two Rodent Models

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HEPATOLOGY (2013)

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Article Gastroenterology & Hepatology

Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma

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JOURNAL OF GASTROENTEROLOGY (2013)

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Article Immunology

Hepatic Stellate Cells Preferentially Induce Foxp3+ Regulatory T Cells by Production of Retinoic Acid

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JOURNAL OF IMMUNOLOGY (2013)

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Article Biology

A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma

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MEDICAL MOLECULAR MORPHOLOGY (2013)

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Failure Rates in the Hepatocellular Carcinoma Surveillance Process

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CANCER PREVENTION RESEARCH (2012)

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The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease

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CELL CYCLE (2012)

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Review Gastroenterology & Hepatology

Association Between Nonalcoholic Fatty Liver Disease and Risk for Hepatocellular Cancer, Based on Systematic Review

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CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2012)

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Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia-Pacific trial

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EUROPEAN JOURNAL OF CANCER (2012)

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Excess body weight and the risk of primary liver cancer: An updated meta-analysis of prospective studies

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EUROPEAN JOURNAL OF CANCER (2012)

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Review Gastroenterology & Hepatology

Fibrosis-dependent mechanisms of hepatocarcinogenesis

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HEPATOLOGY (2012)

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Article Medicine, General & Internal

Association Between Sustained Virological Response and All-Cause Mortality Among Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis

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JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2012)

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Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial

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MYC Phosphorylation, Activation, and Tumorigenic Potential in Hepatocellular Carcinoma Are Regulated by HMG-CoA Reductase

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The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma

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Coffee, Decaffeinated Coffee, and Tea Consumption in Relation to Incident Type 2 Diabetes Mellitus A Systematic Review With Meta-analysis

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Integrative Transcriptome Analysis Reveals Common Molecular Subclasses of Human Hepatocellular Carcinoma

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Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial

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A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4+CD25+Foxp3+ T cells

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Statins induce mammalian target of rapamycin (mTOR)-mediated inhibition of Akt signaling and sensitize p53-deficient cells to cytostatic drugs

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A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease

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