As the central organ of metabolism, the liver plays a pivotal role in the regulation of the synthesis and metabolism of various nutrients within the body. Ferroptosis, as a newly discovered type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides, is involved in the physiological and pathological processes of a variety of acute and chronic liver diseases. Ferroptosis can accelerate the pathogenetic process of acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, and autoimmune hepatitis; while it can slower disease progression in advanced liver fibrosis and hepatocellular carcinoma. This suggests that targeted regulation of ferroptosis may impact the occurrence and development of various liver diseases. This article reviews the latest research progress of ferroptosis in various liver diseases, including acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune hepatitis, liver fibrosis and hepatocellular carcinoma. It aims to provide insights for the prevention and treatment of acute and chronic liver diseases through targeting ferroptosis.
Humans ; Liver Diseases/etiology* ; Ferroptosis/physiology* ; Liver Neoplasms/pathology* ; Carcinoma, Hepatocellular/pathology* ; Liver Cirrhosis/etiology* ; Liver/pathology* ; Hepatitis, Autoimmune/metabolism* ; Liver Diseases, Alcoholic/metabolism*

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Esophageal Neoplasms/pathology* ; Prospective Studies ; Programmed Cell Death 1 Receptor/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Liver Diseases/etiology*

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.
Female ; Humans ; Middle Aged ; Carcinoma, Hepatocellular/diagnostic imaging* ; Jaundice, Obstructive/etiology* ; Liver Neoplasms/diagnostic imaging* ; Hepatic Duct, Common/pathology* ; Thrombosis/complications* ; Hemorrhage/complications*

A 66-year-old female patient was diagnosed with hepatocellular carcinoma accompanied by neuropathic pain induced by a metastatic tumor that compromised root and spinal canal. Although her pain was relieved following medical treatment, breakthrough pain occurring 1-2 times a day was still distressing. Neuropathic pain in her right lower limb caused discomfort and irritability and decreased her quality of life. We had limited options to adjust her prescription drug regime, due to the side effect of these drugs. Although acupuncture therapy was only performed at her home once a week, the efficacy was outstanding. The patient did not report any further instances of breakthrough pain, and she did not require additional bolus morphine. She could comfortably live in her familiar surroundings with her family and did not require any emergency room visits or admission into the hospital during the last month of her life. She had excellent quality of life in the terminal period of her life, and could even participate in a family function during this time. The present case report suggests that acupuncture may have a role in treating neuropathic pain induced by bone metastasis in patients with advanced cancer across clinical and in-home settings.
Acupuncture Therapy ; Aged ; Bone Neoplasms ; complications ; secondary ; Carcinoma, Hepatocellular ; pathology ; Female ; Home Care Services ; Humans ; Liver Neoplasms ; pathology ; Neoplasms ; pathology ; Neuralgia ; etiology ; therapy ; Quality of Life

BACKGROUNDLiver abscess is a serious complication following transcatheter arterial chemoembolization (TACE). Much attention has been paid to this condition as it may interfere with the treatment process and result in a poor prognosis of the patient. This study aimed to analyze the causes of liver abscess, a complication, after TACE for hepatic tumors and to summarize management approaches.

METHODSFrom June 2012 to June 2014, of 1480 consecutive patients who underwent TACE at our hospital, five patients developed liver abscess after TACE procedures for hepatic tumors. Of the five patients, each receiving conventional TACE, one underwent three sessions, two underwent two sessions, and the remaining two underwent one session of TACE. Demographic and clinical characteristics, together with management approaches and prognosis, were collected through a review of medical records.

RESULTSThese five patients were confirmed to have post-TACE liver abscess through clinical manifestations, laboratory, and imaging tests. After percutaneous drainage and anti-inflammatory treatments, the symptoms present in four patients with liver abscess significantly improved as evidenced by shrinkage or disappearance of the abscess cavity, and the patients recovered completely after sufficient drainage. The remaining patient experienced recurrent symptoms and abdominal abscess, achieved no significant improvement after treatment, and eventually died of severe infection and multiple organ failures.

CONCLUSIONSTACE must be implemented with extreme caution to avoid liver abscess. An effective management relies on an early diagnosis, prompt use of sufficient doses of appropriate antibiotics, and active implementation of abscess incision, drainage, and aspiration.

Adult ; Aged ; Carcinoma, Hepatocellular ; therapy ; Chemoembolization, Therapeutic ; adverse effects ; Humans ; Liver ; pathology ; Liver Abscess ; diagnosis ; etiology ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Retrospective Studies

Aged ; Bile Duct Diseases ; complications ; diagnostic imaging ; pathology ; Bile Duct Neoplasms ; diagnosis ; Carcinoma, Hepatocellular ; complications ; diagnostic imaging ; pathology ; Diagnosis, Differential ; Humans ; Jaundice, Obstructive ; etiology ; Klatskin Tumor ; diagnosis ; Liver Neoplasms ; complications ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Thrombosis ; complications ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed

BACKGROUND: The incidence and etiology of hepatocellular carcinoma (HCC) vary widely according to race and geographic regions. The insertional mutagenesis of adeno-associated virus 2 (AAV2) has recently been considered a new viral etiology of HCC. The aim of this study was to investigate the frequency and clinical characteristics of AAV2 in Korean patients with HCC. METHODS: A total of 289 unrelated Korean patients with HCC, including 159 Hepatitis-B-related cases, 16 Hepatitis-C-related cases, and 114 viral serology-negative cases, who underwent surgery at the Samsung Medical Center in Korea from 2009 to 2014 were enrolled in this study. The presence of AAV2 in fresh-frozen tumor tissues was investigated by DNA PCR and Sanger sequencing. The clinical and pathological characteristics of AAV2-associated HCC in these patients were compared with previous findings in French patients. RESULTS: The AAV2 detection rate in Korean patients (2/289) was very low compared with that in French patients (11/193). Similar to the French patients, the Korean patients with AAV2-related HCC showed no signs of liver cirrhosis. The Korean patients were younger than the French patients with the same AAV2-associated HCC; the ages at diagnosis of the two Korean patients were 47 and 39 yr, while the median age of the 11 French patients was 55 yr (range 43-90 yr). CONCLUSIONS: AAV2-associated HCC was very rare in Korean patients with HCC. Despite a limited number of cases, this study is the first to report the clinical characteristics of Korean patients with AAV2-associated HCC. These findings suggest epidemiologic differences in viral hepatocarcinogenesis between Korean and European patients.
Adult ; Asian Continental Ancestry Group ; Capsid Proteins/genetics ; Carcinoma, Hepatocellular/etiology/*pathology/virology ; DNA, Viral/chemistry/genetics/metabolism ; DNA-Binding Proteins/genetics ; Dependovirus/*genetics/isolation & purification/pathogenicity ; Female ; Humans ; Incidence ; Inverted Repeat Sequences/genetics ; Liver Neoplasms/etiology/*pathology/virology ; Male ; Middle Aged ; Parvoviridae Infections/complications/epidemiology ; Polymerase Chain Reaction ; Republic of Korea ; Sequence Analysis, DNA ; Viral Proteins/genetics

OBJECTIVETo explore the effect of colon cancer cell-derived interleukin-1α on the migration and proliferation of human umbilical vein endothelial cells as well as the role of IL-1α and IL-1ra in the angiogenesis process.

METHODSWestern blot was used to detect the expression of IL-1α and IL-1R1 protein in the colon cancer cell lines with different liver metastatic potential. We also examined how IL-1α and IL-1ra influence the proliferation and migration of umbilical vascular endothelial cells assessed by PreMix WST-1 assay and migration assay, respectively. Double layer culture technique was used to detect the effect of IL-1α on the proliferation and migration of vascular endothelial cells and the effect of IL-1ra on the vascular endothelial cells.

RESULTSWestern blot analysis showed that IL-1α protein was only detected in highly metastatic colon cancer HT-29 and WiDr cells, but not in the lowly metastatic CaCo-2 and CoLo320 cells.Migration assay showed that there were significant differences in the number of penetrated cells between the control (17.9±3.6) and 1 ng/ml rIL-1α group (23.2±4.2), 10 ng/ml rIL-1α group (31.7±4.5), and 100 ng/ml rIL-1α group (38.6±4.9), showing that it was positively correlated with the increasing concentration of rIL-1α (P<0.01 for all). The proliferation assay showed that the absorbance values were 1.37±0.18 in the control group, and 1.79±0.14 in the 1 ng/ml rIL-1α group, 2.14±0.17 in the 10 ng/ml rIL-1α group, and 2.21±0.23 in the 100 ng/ml rIL-1α group, showing a positive correlation with the increasing concentration of rIL-1α(P<0.01 for all). IL-1ra significantly inhibited the proliferation and migration of vascular endothelial cells (P<0.01). The levels of VEGF protein were (1.697±0.072) ng/ml, (3.507±0.064)ng/ml and (4.139±0.039)ng/ml in the control, HUVECs+ IL-1α and HUVECs+ HT-29 co-culture system groups, respectively, showing a significant difference between the control and HUVECs+ 10 pg/ml rIL-1α groups and between the control and HUVECs+ HT-29 groups (P<0.01 for both).

CONCLUSIONSOur findings indicate that colon cancer cell-derived IL-1α plays an important role in the liver metastasis of colon cancer through increased VEGF level of the colon cancer cells and enhanced vascular endothelial cells proliferation, migration and angiogenesis, while IL-1ra can suppress the effect of IL-1α and inhibit the angiogenesis in colon cancer.

Blotting, Western ; Caco-2 Cells ; Cell Line, Tumor ; Cell Movement ; physiology ; Cell Proliferation ; physiology ; Coculture Techniques ; Colonic Neoplasms ; blood supply ; metabolism ; pathology ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Interleukin 1 Receptor Antagonist Protein ; metabolism ; physiology ; Interleukin-1alpha ; metabolism ; physiology ; Liver Neoplasms ; secondary ; Neovascularization, Pathologic ; etiology

OBJECTIVE: To investigate the outcomes of percutaneous unilateral metallic stent placement in patients with a malignant obstruction of the biliary hila and a contralateral portal vein steno-occlusion. MATERIALS AND METHODS: Sixty patients with a malignant hilar obstruction and unilobar portal vein steno-occlusion caused by tumor invasion or preoperative portal vein embolization were enrolled in this retrospective study from October 2010 to October 2013. All patients were treated with percutaneous placement of a biliary metallic stent, including expanded polytetrafluoroethylene (ePTFE)-covered stents in 27 patients and uncovered stents in 33 patients. RESULTS: A total of 70 stents were successfully placed in 60 patients. Procedural-related minor complications, including self-limiting hemobilia (n = 2) and cholangitis (n = 4) occurred in six (10%) patients. Acute cholecystitis occurred in two patients. Successful internal drainage was achieved in 54 (90%) of the 60 patients. According to a Kaplan-Meier analysis, median survival time was 210 days (95% confidence interval [CI], 135-284 days), and median stent patency time was 133 days (95% CI, 94-171 days). No significant difference in stent patency was observed between covered and uncovered stents (p = 0.646). Stent dysfunction occurred in 16 (29.6%) of 54 patients after a mean of 159 days (range, 65-321 days). CONCLUSION: Unilateral placement of ePTFE-covered and uncovered stents in the hepatic lobe with a patent portal vein is a safe and effective method for palliative treatment of patients with a contralateral portal vein steno-occlusion caused by an advanced hilar malignancy or portal vein embolization. No significant difference in stent patency was detected between covered and uncovered metallic stents.
Adult ; Aged ; Aged, 80 and over ; Biliary Tract Neoplasms/surgery ; Cholangitis/etiology ; Cholestasis/*surgery ; Female ; Hemobilia/etiology ; Humans ; Kaplan-Meier Estimate ; Liver/blood supply/pathology/surgery ; Liver Neoplasms/surgery ; Male ; Middle Aged ; Palliative Care/methods ; Polytetrafluoroethylene ; Portal Vein/pathology/*surgery ; Retinal Vein Occlusion/*surgery ; Retrospective Studies ; Stents/*adverse effects ; Treatment Outcome

BACKGROUND/AIMS: Spinal metastases often severely limit the quality of life by causing severe pain and neurological deficits. The purpose of this study was to evaluate the palliative effect of radiotherapy (RT) for spinal metastases from hepatocellular carcinoma (HCC) and to identify factors predictive of survival in HCC patients with spinal metastases who received RT. METHODS: A retrospective analysis was performed on 192 patients with spinal metastases from HCC who received RT. RESULTS: Of 192 patients with spinal metastases from HCC, an overall pain response to palliative RT occurred in 187 patients (97.4%), with a complete pain response (CR) in 41 patients (21.4%) and a partial response in 151 patients (78.6%). A higher biologically effective dose (BED) and more advanced RT techniques were identified as predictive factors for a CR. The 1- and 2-year overall survival (OS) rates were 18.1% and 6.3%, respectively, and the median survival time was 4.5 months. A long OS was associated with good performance status, controlled primary HCC, absence of extrahepatic metastases, and a higher BED. CONCLUSIONS: RT provided effective palliation for patients with painful spinal metastases from HCC. Our results provide information regarding pain control, survival outcomes, and predictive factors for the prognosis of HCC patients with spinal metastases treated with RT.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/mortality/*pathology ; Female ; Humans ; Liver Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Pain/etiology/radiotherapy ; Pain Management/methods ; Palliative Care/*methods ; Retrospective Moral Judgment ; Spinal Neoplasms/mortality/radiotherapy/*secondary ; Survival Analysis ; Treatment Outcome ; Young Adult