Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission. Thus, we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal.

Male C57BL/6J mice were divided into three groups: Western diet (WD) feeding, chow diet (CD) feeding, or diet reversal from WD to CD. After 16 weeks of feeding, RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of MASLD. Additionally, RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized.

WD-induced MASLD triggered persistent activation of the DNA damage response (DDR) and its primary transcription factor, P53, long after the resolution of the hepatic phenotype through dietary reversal. Elevated levels of P53 might promote apoptosis, thereby exacerbating metabolic dysfunction-associated steatohepatitis, as they strongly correlated with hepatocyte ballooning, an indicator of apoptosis activation. Moreover, P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver. Mechanistically, P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease (AEN). Consistently, P53, AEN, and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal.

The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD. Our findings provide new insights into the mechanisms of MASLD relapse, highlighting DDR signaling as a promising target to prevent MASLD recurrence.

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.

Natural products have been used effectively to treat different ailments since the advent of human history. Angiosperms contain numerous bioactive molecules that have been applied as medicines to treat various human diseases, including cancer. Jamun (Syzygium cumini) is an angiosperm belonging to the Myrtaceae family. This comprehensive review on Jamun includes information collected from Google Scholar, SciFinder, PubMed, ScienceDirect, and other websites on the internet, giving an account of its botanical profile, chemical composition, and medicinal properties. Ethnomedicinally, various parts of Jamun are used to treat various conditions and have been administered since ancient times in Ayurveda to treat arthritis, obesity, urinary diseases, asthma, bowel spasms, stomach pain, flatulence, diabetes, and dysentery. Several scientific studies also have demonstrated the pluripotent medicinal properties of Jamun, including anti-oxidant, anti-allergic, antiretinitis, antipyretic, antidiarrheal, antinociceptive, anticancer, antidiabetic, anti-obesity, antihyperlipidemic, anti-inflammatory, antimicrobial, diuretic, cardioprotective, chemopreventive, gastroprotective, immunomodulatory, hepatoprotective, wound healing, anthelmintic, and radioprotective. Jamun contains alkaloids, anthraquinones, catechins, cardiac glycosides, flavonoids, glycosides, steroids, phenols, tannins, and saponins. Numerous active phytochemicals have been isolated from its roots, stems, leaves, flowers, fruits, and seeds. Jamun increases glutathione, glutathione peroxidase, catalase, and superoxide dismutase expression and reduces lipid peroxidation levels to exert its beneficial effects on important organs and tissues. Jamun also protects against DNA damage induced by toxic agents including metals, chemicals and ionizing radiation. Jamun activates peroxisome proliferator-activated receptors alpha and gamma and increases fatty acid and glucose metabolism. Additionally, Jamun suppresses various genes at the molecular level. Thus, the scientific evaluation of Jamun is a step forward in validating its traditional use to treat various disorders and may pave the way for translational research for its medicinal use.

Cirrhosis is often characterized by decreased liver function, ranging from a compensated, typically asymptomatic phase to a decompensated phase characterized by the appearance of ascites or variceal bleeding, and ultimately hepatorenal syndrome (HRS) or hepatopulmonary syndrome (HPS). The latter two complications are associated with a poor prognosis and limited treatment efficacy. In cases of ascites or variceal bleeding resistant to medical therapy, transjugular intrahepatic portosystemic shunt (TIPS) is effective and safe. Shunting blood by TIPS diverts portal blood to the systemic circulation, potentially increasing systemic blood volume and benefiting renal function. However, TIPS could also divert nitric oxide to the systemic circulation, potentially worsening systemic hypotension and perfusion, which could be detrimental to renal function. Available evidence indicates that TIPS often improves renal function in patients with portal hypertension, with or without HRS. No studies have shown persistently decreased renal function after TIPS. However, these data are insufficient to support a recommendation for the use of TIPS specifically for HRS. In patients without pre-existing HPS, TIPS does not appear to significantly affect pulmonary gas exchange. Results of TIPS in HPS have been inconsistent; some studies have shown improvement, but effects were transient. No studies have shown a persistent decline in pulmonary function after TIPS. The evidence supports the need for large randomized controlled trials to investigate the beneficial effects of TIPS for HRS. Similar pulmonary function data are less clear regarding TIPS for HPS. The aim of the current report was to review the literature regarding the effects of TIPS on renal and pulmonary function in hepatic decompensation, with or without the development of HRS or HPS.

Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver diseases, such as acute liver failure, drug-induced liver injury, and viral hepatitis, bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver damage. Chronic liver diseases, including alcohol-related liver disease, chronic hepatitis C virus infection, metabolic dysfunction-associated fatty liver disease, and autoimmune liver diseases, are marked by persistent liver injury and inflammation. Bilirubin levels in chronic liver diseases provide insight into liver function, disease severity, and prognosis. As a versatile biomarker, bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their complications. This review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.

The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus, developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019, serves as a valuable reference for standardizing the prevention of mother-to-child transmission in China. As new evidence continues to emerge, it is essential to update these guidelines regularly to optimize clinical practice and research. To this end, the Infectious Disease Physician Branch of the Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of the Chinese Medical Association, in collaboration with multidisciplinary experts, have updated the guidelines based on the latest domestic and international research advancements and clinical practices, providing up-to-date guidance for clinicians and maternal and child healthcare workers.

The most prevalent form of dementia, Alzheimer’s disease (AD), is a neurological disorder that causes gradual memory loss. AD is characterized by amyloid-beta plaques, neurofibrillary tangles, and neuron loss. While preclinical and clinical trials are underway to reduce the generation and overall brain disease load, current treatment focuses on alleviating symptoms. Animal studies are essential for advancing our understanding of AD, identifying potential drug targets, and testing experimental therapies. An ideal animal model not only exhibits the same symptoms and pathological changes as a human disease but also follows the same sequence of pathological events. This review highlights the various inducing agents used to model AD in animals, such as streptozotocin, aluminium chloride, trimethyltin, lipopolysaccharide, scopolamine, and others, along with their underlying mechanisms. The outcomes of some studies that used such inducing agents to develop AD are discussed briefly. Among chemically induced models, streptozotocin and amyloid-beta are the most frequently used, while d-galactose, scopolamine, and aluminium-induced models are being used because they are non-invasive, reproducible, and compatible. However, none of the chemical/drug-induced models fully capture the scope of AD pathology and cognitive impairment. Overall, further research is necessary to establish the stability of the models in terms of consistency and reproducibility.

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.

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 incidence of autoimmune liver diseases (ALDs) and research on their pathogenesis are increasing annually. However, except for autoimmune hepatitis, which responds well to immunosuppression, primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy. Besides the known effects of the environment, genetics, and immunity on ALDs, the heterogeneity of target cells provides new insights into their pathogenesis. This review started by exploring the heterogeneity in the development, structures, and functions of hepatocytes and epithelial cells of the small and large bile ducts. For example, cytokeratin (CK) 8 and CK18 are primarily expressed in hepatocytes, while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes. Additionally, emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs. This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.