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Background This study aimed to evaluate the safety and efficacy of 125I brachytherapy combined with transarterial chemoembolization (TACE) and microwave ablation (MWA) for unresectable hepatocellular carcinoma (HCC) in high-risk locations. Patients and methods After 1:2 propensity score matching (PSM), this retrospectively study analyzed 49 patients who underwent TACE +MWA+125I brachytherapy (group A) and 98 patients who only received TACE +MWA (group B). The evaluated outcomes were progression-free survival (PFS), overall survival (OS), and treatment complications. Cox proportional hazards regression analysis survival was used to compare the two groups. Results The patients in group A showed a longer PFS than group B (7.9 vs. 3.3 months, P = 0.007). No significant differences were observed in median OS between the two groups (P = 0.928). The objective response rate (ORR), disease control rate of tumors in high-risk locations, and the ORR of intrahepatic tumors were 67.3%, 93.9%, and 51.0%, respectively, in group A, and 38.8%, 79.6% and 29.6%, respectively, in group B (P < 0.001, P = 0.025 and P = 0.011, respectively). TACE-MWA-125I (HR = 0.479, P < 0.001) was a significant favorable prognostic factor that affected PFS. The present of portal vein tumor thrombosis was an independent prognostic factor for PFS (HR = 1.625, P = 0.040). The Barcelona clinic liver cancer (BCLC) stage (BCLC C vs. B) was an independent factor affecting OS (HR = 1.941, P = 0.038). The incidence of complications was similar between the two groups, except that the incidence of abdominal pain was reduced in the group A (P = 0.007). Conclusions TACE-MWA-125I resulted in longer PFS and better tumor control than did TACE-MWA in patients with unresectable hepatocellular carcinoma in high-risk locations.

Background: The aim of this study was to explore the effects of endoplasmic reticulum (ER) stress on hepatitis B virus (HBV) replication and the antiviral effect of entecavir (ETV).Methods: Thapsigargin (TG) and stearic acid (SA) were used to induce ER stress in HepG2.2.15 cells and HepAD38 cells that contained an integrated HBV genome, while ETV was used to inhibit HBV replication. The expression levels of glucose-regulated protein 78 (GRP78) and phosphorylated eukaryotic translation initiation factor 2 subunit alpha (p-eIF2α) were measured by western blotting. Intracellular HBV DNA was determined by qPCR; HBsAg by western blotting; HBV RNA by real-time RT-qPCR; HBsAg and HBeAg in supernatants by enzyme-linked immunosorbent assay (ELISA); and HBV DNA in supernatants by qPCR.Results: TG and SA induced ER stress in HepG2.2.15 cells and HepAD38 cells from 12 to 48 h post treatment. However, 4-phenylbutyric acid (PBA) partly alleviated the TG-induced ER stress. Moreover, TG inhibited HBsAg, HBeAg, and HBV DNA secretion from 12 to 48 h, while different concentrations of SA inhibited HBsAg and HBV DNA secretion at 48 h. TG promoted intracellular HBV DNA and HBsAg accumulation and the transcription of the HBV 3.5-kb mRNA and S mRNA. PBA treatment restored the secretion of HBsAg and HBV DNA. Finally, ER stress accelerated extracellular HBV DNA clearance but delayed intracellular HBV DNA clearance after ETV treatment.Conclusions: Hepatocyte ER stress promoted intracellular HBV DNA and HBsAg accumulation by inhibiting their secretion. Our study also suggested that hepatocyte ER stress delayed intracellular HBV DNA clearance after ETV treatment.

The effects of hepatocyte steatosis on hepatitis B virus (HBV) DNA replication and HBV-related antigen secretion are incompletely understood. The aims of this study are to explore the effects and mechanism of hepatocyte steatosis on HBV replication and secretion. Stearic acid (SA) and oleic acid (OA) were used to induce HepG2.2.15 cell steatosis in this study. The expressions of glucose-regulated protein 78 (GRP78), phosphorylation of protein kinase R-like endoplasmic reticulum (ER) kinase (p-PERK), and eukaryotic translation initiation factor 2α (p-eIF2α) were detected by Western blotting (WB). HBV DNA, HBsAg, and HBeAg in the supernatant were determined by real-time fluorescent polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Intracellular HBV DNA, HBsAg level, and HBV RNA were measured by real-time fluorescent PCR, WB, and real-time quantitative reverse transcriptase-PCR, respectively. The results showed that SA and OA significantly increased intracellular lipid droplets and triglyceride levels. SA and OA significantly induced GRP78, p-PERK, and p-eIF2α expressions from 24 to 72 h. 4-phenylbutyric acid (PBA) alleviated ER stress induced by SA. SA promoted intracellular HBsAg and HBV DNA accumulation; however, it inhibited the transcript of HBV 3.5 kb mRNA and S mRNA. The secretion of HBsAg and HBV DNA inhibited by SA or OA could be partially restored by pretreatment with PBA but not by inhibiting GRP78 expression with siRNA. Hepatocyte steatosis inhibits HBsAg and HBV DNA secretion via induction of ER stress in hepatocytes, but not via induction of GRP78.

AIM To investigate the protective effect of prostaglandin E1 (PGE1) against endoplasmic reticulum (ER) stress-induced hepatocyte apoptosis, and to explore its underlying mechanisms. METHODS Thapsigargin (TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinoma-derived cell line HepG2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RT-PCR. Apoptotic index and cell viability of L02 cells and HepG2 cells were determined with flow cytometry and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. RESULTS Pretreatment with 1 μmol/L PGE1 protected against TG-induced apoptosis in both L02 cells and HepG2 cells. PGE1 enhanced the TG-induced expression of C/EBP homologous protein (CHOP), glucose-regulated protein (GRP) 78 and spliced X box-binding protein 1 at 6 h. However, it attenuated their expressions after 24 h. PGE1 alone induced protein and mRNA expressions of GRP78; PGE1 also induced protein expression of DNA damage-inducible gene 34 and inhibited the expressions of phospho-PKR-like ER kinase, phospho-eukaryotic initiation factor 2α and CHOP. Treatment with protein kinase A (PKA)-inhibitor H89 or KT5720 blocked PGE1-induced up-regulation of GRP78. Further, the cytoprotective effect of PGE1 on hepatocytes was not observed after blockade of GRP78 expression by H89 or small interfering RNA specifically targeted against human GRP78. CONCLUSION Our study demonstrates that PGE1 protects against ER stress-induced hepatocyte apoptosis via PKA pathway-dependent induction of GRP78 expression.

Wild mushroom poisoning is often reported to cause acute liver or renal failure. However, acute rhabdomyolysis caused by wild mushroom poisoning has rarely been reported. We describe 7 patients of 1 family with Russula subnigricans Hongo poisoning. Their clinical manifestations varied from gastrointestinal symptoms to rhabdomyolysis, with 1 fatality. Our report provides supporting evidence that rhabdomyolysis may result from ingestion of R subnigricans mushrooms. A key to survival for patients with rhabdomyolysis caused by R subnigricans poisoning may be early recognition and intensive supportive care.

Rationale: Acute liver failure (ALF) induced by amatoxin-containing mushrooms accounts for more than 90% of deaths in patients suffering from mushroom poisoning. However, due to the fact that most hospitals cannot identify the species of mushrooms involved, or detect amatoxins, the early diagnosis of amatoxin intoxication remains a significant challenge in clinical practice. Patient concerns: Two patients were had ingested wild mushrooms 15 hours before admission. Six hours prior to admission they experienced nausea, vomiting, weakness, abdominal pain and diarrhea. The species of mushrooms they had consumed could not be identified. Diagnoses: According to their delayed gastroenteritis, the two patients were clinically diagnosed with amatoxin poisoning. One week after the patients were discharged, the species of the mushrooms was identified as Amanita fuliginea and the diagnosis was confirmed. Interventions: The two patients were treated with silibinin, penicillin G and plasma exchange. Outcomes: Although the two patients progressed to ALF they fully recovered and were discharged on day 10 after admission. Lessons: Our case reports suggested that patients with unidentified wild mushroom intoxication with delayed gastroenteritis could be clinically diagnosed with amatoxin poisoning; in such cases, liver coagulation function should be frequently evaluated. Early diagnosis and treatment are crucial for survival in patients with ALF induced by amatoxin poisoning.