Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and one of the deadliest cancers worldwide. As opposed to the majority of patients with HCC, approximately 20– 30% of cases of non-alcoholic steatohepatitis (NASH)-derived HCC develop malignant tumours in the absence of liver cirrhosis. NASH is characterized by metabolic dysregulation, chronic inflammation and cell death in the liver, which provide a favorable setting for the transformation of inflammation into cancer. This review aims to describe the pathogenesis and the underlying mechanism of the transition from inflammation to cancer in NASH.

Objectives: The present study aimed to evaluate the association between the concurrence of pre-existing chronic liver diseases (CLD) and worse prognosis in patients with HILI.Design: A case–control study.Setting: Tertiary hospital specialising in liver diseases in China.Participants: 145 hospitalised HILI patients were assessed with respect to prognosis by comparing HILI with or without pre-existing CLD from February 2007 to January 2017. Twenty-five HILI cases with pre-existing alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) and 200 ALD or NAFLD controls matched 1:8 for sex, age (±4 years old), body mass index (±2 kg/m²), the type of CLD, alcohol intake (±5 g/d) and the presence or absence of cirrhosis.Primary outcome measures: Mortality and chronicity in HILI patients with or without pre-existing CLD, and matched CLD patients.Results: Of the 193 714 hospitalised patients with liver diseases, 5703 patients met the diagnostic criteria for drug-induced liver injury (DILI), which was attributed toPolygonum multiflorumThunb. (PMT) in 145 patients. Among these HILI patients, 22.8% (33 of 145) had pre-existing CLD, including 17 (51.5%) with ALD, 8 (24.2%) with NAFLD, 5 (15.2%) with chronic viral hepatitis and 3 (9.1%) with autoimmune liver disease. Compared with HILI patients without CLD, HILI patients with pre-existing CLD showed higher mortality (0.9% vs 9.1%, p=0.037) and higher chronicity (12.5% vs 30.3%, p=0.016). Compared with matched ALD (136 patients) or NAFLD (64 patients) patients, HILI patients with pre-existing ALD showed higher chronicity (35.3% vs 11.8%, p=0.019). Multivariate logistic regression analysis found that concurrence of pre-existing CLD was an independent risk factor for both of chronicity and mortality (OR 3.966, 95% CI 1.501 to 10.477, p=0.005), especially the chronicity (OR 3.035, 95% CI 1.115 to 8.259, p=0.030).Conclusions: Concurrence of pre-existing CLD could be an independent risk factor for worse prognosis, especially chronicity, in PMT-related HILI.

Background and aims: Drug-induced liver injury (DILI) is a prevalent adverse reaction in clinical settings. However, there is limited research on age-related differences in DILI. We performed a large-scale retrospective study to delineate the characteristics of DILI across different age groups. Methods: We collected data on a total of 17,946 patients with confirmed DILI hospitalized at the Fifth Medical Center of the People’s Liberation Army (PLA) General Hospital in Beijing, China, from January 1, 2002, to December 31, 2022. The patients were stratified based on age into the following groups: children (< 18 years), young adults (18–44 years), middle-aged individuals (45–64 years), and elderly individuals (≥ 65 years). We gathered demographic information, medical histories, laboratory results, disease severity assessments, and mortality statistics for all patients. Results: Overall, the distribution of DILI cases across different age groups was as follows: 6.57% were children, 24.82% were young adults, 49.06% were middle-aged individuals, and 19.54% were elderly individuals. The percentage of females increased with age, rising from 36.47% in the pediatric group to 60.51% in the elderly group. Notably, central nervous system agents (15.44%) and anti-infectious agents (21.80%) were more commonly associated with DILI in children, while cardiovascular agents (10.58%) and herbal dietary supplements or traditional medicines (H/TMs) (26.29%) were more prevalent among elderly people with DILI. Among all age groups, hepatocellular-type DILI was more common in the pediatric group (p < 0.001), whereas cholestatic-type DILI and chronic DILI were more prevalent in the elderly group (p < 0.001). Acute liver failure (ALF) and fatal outcomes were more prevalent in the pediatric and elderly groups, particularly in the pediatric group (2.04%, p = 0.041; 0.85%, p = 0.007, respectively). Conclusions: Children and elderly individuals face a higher risk of adverse outcomes following DILI. Graphical

Background: Evidence concerning long-term outcome of robotic liver resection (RLR) and laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) patients is scarce. Methods: This study enrolled all patients who underwent RLR and LLR for resectable HCC between July 2016 and July 2021. Propensity score matching (PSM) was employed to create a 1:3 match between the RLR and LLR groups. A comprehensive collection and analysis of patient data regarding efficacy and safety have been conducted, along with the evaluation of the learning curve for RLR. Results: Following PSM, a total of 341 patients were included, with 97 in the RLR group and 244 in the LLR group. RLR group demonstrated a significantly longer operative time (median [IQR], 210 [152.0–298.0] min vs. 183.5 [132.3–263.5] min; p = 0.04), with no significant differences in other perioperative and short-term postoperative outcomes. Overall survival (OS) was similar between the two groups (p = 0.43), but RLR group exhibited improved recurrence-free survival (RFS) (median of 65 months vs. 56 months, p = 0.006). The estimated 5-year OS for RLR and LLR were 74.8% (95% CI: 65.4–85.6%) and 80.7% (95% CI: 74.0–88.1%), respectively. The estimated 5-year RFS for RLR and LLR were 58.6% (95% CI: 48.6–70.6%) and 38.3% (95% CI: 26.4–55.9%), respectively. In the multivariate Cox regression analysis, RLR (HR: 0.586, 95% CI (0.393–0.874), p = 0.008) emerged as an independent predictor of reducing recurrence rates and enhanced RFS. The operative learning curve indicates that approximately after the 11th case, the learning curve of RLR stabilized and entered a proficient phase. Conclusions: OS was comparable between RLR and LLR, and while RFS was improved in the RLR group. RLR demonstrates oncological effectiveness and safety for resectable HCC.

Reactive oxygen species (ROS) are not only used as a therapeutic reagent in chemodynamic therapy (CDT), to stimulate the release of antineoplastic drugs, they can also be used to achieve a combined effect of CDT and chemotherapy to enhance anticancer effects. Herein, we synthesized a pH-responsive prodrug (PEG_2k-NH-N-DOX), ROS-responsive prodrug (PEG_2k-S-S-CPT-ROS), organic CDT agents (TPP-PEG_2k-LND, TPP-PEG_2k-TOS), and T1-enhanced magnetic resonance imaging contrast agents (Gd-DTPA-N16-16), and used them to encapsulate combrestatinA4 (CA4) to prepare traceable pH/ROS dual-responsive multifunctional nanoparticles (TLDCAG NPs) with endogenous ROS burst and spatiotemporally controlled multiple drug release ability. Firstly, TLDCAG NPs were accumulated in the tumor cell microenvironment via an enhanced permeability and retention (EPR) effect. Secondly, CA4 was released and specifically destroyed angiogenesis to facilitate the interaction between the tumor and the remaining TLDCG NPs. After accumulating in tumor cells, the TLDCG NPs could be destroyed under acidic conditions to quickly release doxorubicin (DOX), TPP-PEG_2k-LND, and TPP-PEG_2k-TOS. Thirdly, TPP-PEG_2k-LND and TPP-PEG_2k-TOS quickly targeted mitochondria, induced endogenous ROS bursts, reduced the mitochondrial membrane potential, and induced tumor cell apoptosis. Endogenous ROS can not only be used as a therapeutic reagent for CDT, but also can cut off the thioketal bond in PEG_2k-S-S-CPT-ROS and release camptothecin (CPT). Finally, TLDCAG NPs were traced by magnetic resonance imaging (MRI). Furthermore, in vitro and vivo results indicate that the TLDCAG NPs have vigorous antitumor activity and negligible systemic toxicity. Therefore, the TLDCAG NPs provide an efficient strategy for enhancing antitumor efficacy.

Background/Aims: Herb-induced liver injury (HILI) can lead to chronic liver injury, liver transplantation, or even death. This study aimed to identify the predictors of poor HILI outcomes, especially chronic HILI. Materials and Methods: Clinical data of 488 patients with HILI were retrospectively analyzed from a Chinese center between January 2010 and January 2014. Logistic regression and C-statistic were used to identify risk factors and prognostic models for HILI outcomes. Results: In all patients, 69 (14.1%) developed chronic HILI, and 20 (4.1%) died due to liver injury or underwent liver transplantation. To predict the fatal HILI prognosis, the model for end-stage liver disease (MELD) with a C-statistic of 0.981 (95%CI 0.968-0.995) was better than Hy’s law (C-statistic 0.569; 95%CI 0.449-0.689). The latency, course of peak alanine aminotransferase decreasing ≥50% after discontinuation of herb application, peak triglyceride value, and platelet count at liver injury onset were identified as independent risk factors for chronicity with the adjusted odds ratios of 1.268 (95% confidence interval [CI] 1.034-1.554), 2.303 (95%CI 1.588-3.340), 0.580 (95%CI 0.343-0.978), and 0.183 (95%CI 0.091-0.368), respectively. A prognostic model for chronic HILI based on these four factors yielded the best prediction with a C-statistic of 0.812 (95%CI 0.755-0.868), compared with MELD (C-statistic 0.506; 95%CI 0.431-0.581) and Hy’s law (C-statistic 0.418; 95%CI 0.343-0.492). Conclusion: Model for end-stage liver disease can be used to predict the fatal prognosis of HILI. A long latency, slow recovery, and low triglyceride value and platelet counts are important determinants for chronic HILI. Cite this article as: Zhu Y, Niu M, Wang JB, et al. Predictors of poor outcomes in 488 patients with herb-induced liver injury. Turk J Gastroenterol 2019; 30: 47-58.