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

BACKGROUND: Metastatic pathological fractures of the spine are a major problem for cancer patients; however, there is no consensus on treatment strategy. The purpose of this study was to evaluate various treatment options by analyzing their patterns for metastatic pathological fractures of the spine. METHODS: In this study, 54 patients (male:female = 36:18) who were diagnosed with metastatic pathological fractures of spine were recruited. Demographic data, origin of cancer, type of treatment, and results were obtained from electronic medical records. Treatment options were divided into radiotherapy (RT), vertebroplasty (VP) or kyphoplasty (KP), operation (OP), and other treatments. Treatment results were defined as aggravation, no response, fair response, good response, and unknown. The survival time after detection of pathologic fractures was analyzed with the Kaplan-Meier method. RESULTS: The mean age of the patients was 62.3 years. Hepatocellular carcinoma was the most common cancer of primary origin (n = 9), followed by multiple myeloma (n = 8). RT was the most common primary choice of treatment (n = 29, 53.7%), followed by OP (n = 13, 24.1%), and VP or KP (n = 10, 18.5%). Only 13 of 29 RT cases and 7 of 13 OP cases demonstrated a fair or good response. The mean survival time following detection of pathological spinal fractures was 11.1 months for 29 patients, who died during the study period. CONCLUSIONS: RT was the most common primary choice of treatment for metastatic pathological fractures of the spine. However, the response rate was suboptimal. Although OP should be considered for the relief of mechanical back pain or neurologic symptoms, care should be taken in determining the surgical indication. VP or KP could be considered for short-term control of localized pain, although the number of cases was too small to confirm the conclusion. It is difficult to determine the superiority of the treatment modalities, hence, a common guideline for the diagnosis and treatment of metastatic pathological fractures of the spine is required.
Carcinoma, Hepatocellular/mortality/pathology ; Female ; Humans ; Liver Neoplasms/mortality/pathology ; Male ; Middle Aged ; Multiple Myeloma/mortality/pathology ; Retrospective Studies ; Spinal Fractures/etiology/mortality/*radiotherapy/*surgery ; Spinal Neoplasms/*complications/secondary ; Spine ; Treatment Outcome

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity> or =grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV(5Gy)-rV(35Gy): normal liver volume receiving or =grade 2 occurred in 10 patients (13%): grade 2 in 9 patients and grade 3 in 1 patient. On univariate analysis, baseline Child-Pugh (CP) score (5 vs. 6-8), normal liver volume, and planning target volume were the significant clinical predictors. All dosimetric parameters were significant: rV(20Gy) was the most significant predictor. On multivariate analysis, baseline CP score (hazard ratio, 0.026; P=0.001) was the only significant predictor. In conclusion, SABR using 3 fractions in primary and metastatic liver cancers produces low hepatic toxicity, especially in patients with a baseline CP score of 5. However, further studies are needed to minimize hepatic toxicity in patients with baseline CP scores> or =6.
Aged ; *Dose Fractionation ; Female ; Hepatitis/*etiology/pathology/prevention & control ; Humans ; Liver Neoplasms/complications/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Metastasis ; Radiation Injuries/*etiology/pathology/prevention & control ; Radiosurgery/*adverse effects/*methods ; Radiotherapy Dosage ; Treatment Outcome

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