Journal of Clinical and Translational Hepatology

The high mortality rate in hepatocellular carcinoma (HCC) is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage, with surgical treatment options unavailable. Conversion therapy, which involves both locoregional and systemic treatments, has the potential to downstage tumors in selected patients with initially unresectable HCC, thereby making surgical treatment a possibility and potentially increasing long-term survival. To optimize the conversion rate, it is necessary to maximize successful conversions and clearly define the target population for conversion treatment through a collaborative effort...

Hepatocyte nuclear factor 1β (HNF1β) is essential for biliary development, while its genetic defect triggers the dysplasia of interlobular bile ducts, leading to life-threatening hepatitis and cholestasis. To date, this disorder has mainly been documented in neonates. Here, we report a case of cholestasis in an adult patient caused by a de novo HNF1β mutation. A liver biopsy revealed remarkable shrinkage of the portal area accompanied by a decrease or absence of interlobular bile ducts, veins, and arteries in the portal area...

BACKGROUND AND AIMS: Liver iron overload can induce hepatic expression of bone morphogenic protein (BMP) 6 and activate the BMP/SMAD pathway. However, serum iron overload can also activate SMAD but does not induce BMP6 expression. Therefore, the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain unclear. This study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD pathway. METHODS: A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin (Holo-Tf)...

Exosomes are 60-120 nm diameter double-membrane lipid organelles discharged by cells. Various studies have shown that exosomes exert multiple functions in both physical and diseased processes, such as intercellular information exchange, immune response, and disease progression. Repeated chronic injury to the liver often leads to inflammation and liver fibrosis (LF), a disorder that, if unchecked, may progress to cirrhosis, liver failure, portal hypertension, and even hepatocellular carcinoma. As an essential component of host innate immunity against pathogen invasion, macrophages play an important role in modulating inflammation homeostasis by finely tuning the polarization process of macrophages into either M1 or M2 subtypes in response to different microenvironments...

BACKGROUND AND AIMS: As sepsis progresses, immune cell apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ failure. We previously reported that adenosine deaminases acting on RNA-1 (ADAR1) reduced intestinal and splenic inflammatory damage during sepsis. However, the roles and mechanism of ADAR1 in sepsis-induced liver injury remain unclear. METHODS: We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with sepsis to investigate the effects of ADAR1 on immune cell activities...

BACKGROUND AND AIMS: SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown. METHODS: Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine...

BACKGROUND AND AIMS: While the incidence rates of hepatocellular carcinoma (HCC) are increasing, there are limited comprehensive data on demographic-specific incidence and mortality trends in the USA. We aimed to evaluate recent trends in HCC incidence and mortality among different demographic groups in the USA. METHODS: Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control's United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA...

Liver fibrosis is a reversible condition that occurs in the early stages of chronic liver disease. To develop effective treatments for liver fibrosis, understanding the underlying mechanism is crucial. The NOD-like receptor protein 3 (NLRP3) inflammasome, which is a part of the innate immune system, plays a crucial role in the progression of various inflammatory diseases. NLRP3 activation is also important in the development of various liver diseases, including viral hepatitis, alcoholic or nonalcoholic liver disease, and autoimmune liver disease...

Hepatocellular carcinoma (HCC) is an aggressive tumor that usually occurs in patients with chronic liver disease and cirrhosis. Surgical resection is an optimal treatment for HCC, but the 5-year recurrence rates are significantly high. The majority of recurrent HCCs occur through intrahepatic metastasis with local tumor progression, and less than 20% of recurrences are extrahepatic metastases. HCC with gastric metastasis is extremely rare, and it is easily misdiagnosed as primary gastric cancer with liver metastasis...

BACKGROUND AND AIMS: Accumulating evidence highlights the association between the gut microbiota and liver cirrhosis. However, the role of the gut microbiota in liver cirrhosis remains unclear. METHODS: We first assessed the differences in the composition of the bacterial community between CCl4-induced liver cirrhosis and control mice using 16S rRNA sequencing. We then performed a two-sample Mendelian randomization (MR) analysis to reveal the underlying causal relationship between the gut microbiota and liver cirrhosis...

No abstract text is available yet for this article.

Focal nodular hyperplasia is a benign tumor of the liver that is often found incidentally with imaging. The purpose of this review is to discuss the pathophysiology, rare complications that can occur due to these lesions, and management options. A literature review was performed on clinical trials and case reports involving focal nodular hyperplasia complications and management of these, as well as the proposed pathogenesis underlying these tumors. Although exposure to oral contraceptive pills and endogenous hormones have been thought to play a role in the development of these lesions, this has not been proven...

BACKGROUND AND AIMS: We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4 -mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid (tauro-THBA) in cholestasis. METHODS: Serum bile acid profiles were evaluated in 13 ABCB4 -mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS)...

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single tumor. The fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for cHCC-CCA. However, the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment. A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma, a mixed enhancement pattern on imaging, and a discrepancy between the elevation of tumor marker and the imaging enhancement pattern...

BACKGROUND AND AIMS: Stress granules (SGs) as membrane-less cytoplasmic foci formed in response to unfavorable external stimuli could promote cancer cells to adapt to hostile environments. Hepatocellular carcinoma (HCC) is prone to be highly aggressive once diagnosed, which markedly reduces patient survival time. Therefore, it is crucial to develop valid diagnostic markers to prognosticate HCC patient prognosis, which promotes individualized precision therapeutics in HCC. Considering the pro-tumorigenic activity of SGs, it is of great potential value to construct a prognostic tool for HCC based on the expression profiles of SG-related genes (SGGs)...

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis...

[This corrects the article DOI: 10.14218/JCTH.2021.00474.].

BACKGROUND AND AIMS: Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells (HSCs) and leads to a poor outcome. Artesunate (Art) is an ester derivative of artemisinin that can induce ferroptosis in HSCs, and activated transcriptional factor 3 (ATF3) is an ATF/CREB transcription factor that is induced in response to stress. In this study, we examined the role of the Rho-associated protein kinase 1 (ROCK1)/ATF3 axis in Art-induced ferroptosis in HSCs...

BACKGROUND AND AIMS: Several first-line immune checkpoint inhibitor (ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma (uHCC). This network meta-analysis (NMA) aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC. METHODS: A comprehensive literature search was performed in various databases from database inception to May 2022. The phase 3 trials evaluating first-line single-agent ICIs, molecular-target agents (MTAs), or their combinations in uHCC were included...

BACKGROUND AND AIMS: Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking. METHODS: A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers...