Study of liver cirrhosis over ten consecutive years in Southern China

AIM: To investigate the etiology and complications of liver cirrhosis (LC) in Southern China.

Endoscopic variceal ligation caused massive bleeding due to laceration of an esophageal varicose vein with tissue glue emboli

Endoscopic variceal obturation of gastric varices with tissue glue is considered the first choice for management of gastric varices, and is usually safe and effective. However, there is still a low incidence of complications and some are even fatal. Here, we present a case in which endoscopic variceal ligation caused laceration of the esophageal varicose vein with tissue glue emboli and massive bleeding after 3 mo. Cessation of bleeding was achieved via variceal sclerotherapy using a cap-fitted gastroscope. Methods of recognizing an esophageal varicose vein with tissue glue plug are discussed.

β-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation in mice

AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.RESULTS Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines(including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 si RNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phosphoIκBα and phosho-p65, were upregulated.CONCLUSION β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation.

Successful treatment of ileal ulcers caused by immunosuppressants in two organ transplant recipients

Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-yearold man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at postoperative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus wasfound in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant might be effective to treat these ulcers.

Acute diarrhea and metabolic acidosis caused by tuberculous vesico-rectal fistula

Acquired vesico-rectal fistula is an uncommon complication of pelvic malignant tumors,surgical injury,inflammatory disorders such as tuberculosis infection,radiotherapy and less commonly diverticulum of the urinary tract.The fistula is often identified by urinary tract abnormalities such as dysuria,recurrent urinary tract infection,pneumaturia,and fecaluria.Here,we report an unusual case of a patient with a vesico-rectal fistula of tuberculous origin,presenting with severe acute diarrhea,metabolic acidosis,hyperchloremia and hypokalemia while with only mild urinary tract symptoms.The patient was cured by tuberculostatic therapy.

Intestinal obstruction caused by extramedullary hematopoiesis and ascites in primary myelofibrosis

Primary myelofibrosis(PMF) is a clonal hematopoietic stem cell disorder. It is characterized by bone marrow fibrosis, extramedullary hematopoiesis with hepatosplenomegaly and leukoerythroblastosis in the peripheral blood. The main clinical manifestations of PMF are anemia, bleeding, hepatosplenomegaly, fatigue, and fever. Here we report a rare case of PMF with anemia, small bowel obstruction and ascites due to extramedullary hematopoiesis and portal hypertension. The diagnosis was difficult to establish before surgery and the differential diagnosis is discussed.

Sodium butyrate protects against lipopolysaccharideinduced liver injury partially via the GPR43/b-arrestin-2/NF-кB network

Background Butyrate acts as a regulator in multiple inflammatory organ injuries.However,the role of butyrate in acute liver injury has not yet been fully explored.In the present study,we aimed to investigate the association between butyrate and lipopolysaccharide(LPS)-induced acute liver injury and the signaling pathways involved.Methods LPS-induced acute liver injury was induced by intraperitoneal injection of LPS(5 mg/kg)in G-protein-coupled receptor 43(GPR43)-knockout(KO)and wild-type female C57BL/6 mice.Sodium butyrate(500mg/kg)was administered intraperitoneally 30min prior to LPS exposure.Liver injury was detected by serum markers,tissue morphology,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction(RT-PCR).Cell models were first treated with sodium butyrate(4μmol/mL),followed by LPS(1μg/mL)half an hour later in GPR43 small interfering RNA(siRNA)-transfected or control RAW264.7 cells.Cell-inflammation status was evaluated through detecting pro-inflammatory-factor expression by RT-PCR and also through checking toll-like receptor 4/nuclear factor-кB(TLR4/NF-кB)-element levels including TLR4,TRAF6,IKKb,IкBα,phospho-IкBα,p65,and phospho-p65 by Western blot.The interaction between GPR43 and barrestin-2 was tested by co-immunoprecipitation.Results Sodium butyrate reversed the LPS-induced tissue-morphology changes and high levels of serum alanine aminotransferase,aspartate transaminase,myeloperoxidase,TUNEL,and pro-inflammatory cytokines such as tumor necrosis factor-a and interleukin-6.The ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 siRNA RAW264.7 cells,compared with those of GPR43-positive controls.Sodium butyrate downregulated some elements of the TLR4/NF-кB pathway,including phospho-IкBαand phospho-p65,in RAW264.7 cells.Increased interactions between GPR43 and b-arrestin-2,and between b-arrestin-2 and IrBa were observed.Conclusion Sodium butyrate significantly attenuated LPS-induced liver injury by reducing the inflammatory response partially via the GPR43/b-arrestin-2/NF-кB signaling pathway.