1.Exploring the Efficacy of BMSC Transplantation via Various Pathways for Treating Cholestatic Liver Fibrosis in Mice.
Jun Jie REN ; Zi Xu LI ; Xin Rui SHI ; Ting Ting LYU ; Xiao Nan LI ; Min GE ; Qi Zhi SHUAI ; Ting Juan HUANG
Biomedical and Environmental Sciences 2025;38(4):447-458
OBJECTIVE:
To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice.
METHODS:
BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.
RESULTS:
BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation.
CONCLUSION
The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals
;
Mice
;
Mesenchymal Stem Cell Transplantation
;
Liver Cirrhosis/etiology*
;
Male
;
Cholestasis/therapy*
;
Mice, Inbred C57BL
;
Hepatic Stellate Cells
;
Mesenchymal Stem Cells
2.Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B.
Chuan JIANG ; Jinqing LIU ; Ronghua LI ; Keyu CHEN ; Wenting PENG ; Lei FU ; Shifang PENG
Journal of Central South University(Medical Sciences) 2023;48(5):698-706
OBJECTIVES:
Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).
METHODS:
This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.
RESULTS:
Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).
CONCLUSIONS
The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans
;
Hepatitis B, Chronic/complications*
;
Hepatitis B e Antigens/therapeutic use*
;
Alkaline Phosphatase
;
DNA, Viral
;
Retrospective Studies
;
Fibrosis
;
Hepatitis B virus/genetics*
;
Liver Cirrhosis/etiology*
;
Inflammation/drug therapy*
;
Antiviral Agents/therapeutic use*
;
Alanine Transaminase
3.Practice guidance for the use of terlipressin for liver cirrhosis-related complications (2021).
Chinese Journal of Hepatology 2022;30(8):859-865
Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis related complications has been recognized during recent years. This paper aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis related complications. Hepatobiliary Study Group of Chinese Society of Gastroenterology of Chinese Medical Association and Hepatology Committee of Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Overall, 10 major statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis related complications.
Electrolytes
;
Esophageal and Gastric Varices/drug therapy*
;
Gastrointestinal Hemorrhage/etiology*
;
Hepatorenal Syndrome/etiology*
;
Humans
;
Liver Cirrhosis/drug therapy*
;
Lypressin/adverse effects*
;
Terlipressin/adverse effects*
;
Vasoconstrictor Agents/adverse effects*
4.Research Progress in Chinese Medicine Preparations for Promoting Blood Circulation and Removing Blood Stasis for Cirrhotic Patients with Portal Vein Thrombosis Following Splenectomy.
Ding-Qi ZHANG ; Yong-Ping MU ; Ying XU ; Jia-Mei CHEN ; Ping LIU ; Wei LIU
Chinese journal of integrative medicine 2022;28(9):855-863
This article presented an overview of the therapeutic effects of Chinese medicine (CM) preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis (PVT) after splenectomy. Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension (CPH), this paper evaluated the incidence of PVT, and explored potential active components and mechanisms of CM preparations. Safflower Yellow Injection, Danshen Injection () Danhong Injection (), and Compound Danshen Dropping Pill () achieved good curative effect alone or combined with anticoagulant therapy. In addition, Compound Biejia Ruangan Tablet () and Anluo Huaxian Pill () can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis. Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH, we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.
Anticoagulants/therapeutic use*
;
Humans
;
Hypertension, Portal/drug therapy*
;
Liver Cirrhosis/surgery*
;
Medicine, Chinese Traditional/adverse effects*
;
Portal Vein
;
Risk Factors
;
Splenectomy/adverse effects*
;
Venous Thrombosis/etiology*
5.Umbilical needling therapy of I-Ching at 1 PM to 3 PM for cirrhosis ascites with syndrome of spleen-deficiency and fluid-retention.
Chinese Acupuncture & Moxibustion 2019;39(7):713-716
OBJECTIVE:
To observe the clinical efficacy of umbilical needling therapy of I-Ching at 1 PM to 3 PM for cirrhosis ascites with syndrome of spleen-deficiency and fluid-retention.
METHODS:
Forty-eight patients of cirrhosis ascites with syndrome of spleen-deficiency and fluid-retention were randomly divided into an observation group and a control group, 24 cases in each one. Both groups were treated with routine treatment of western medicine combined with TCM decoction. In addition, the patients in the observation group were treated with umbilical needling therapy of I-Ching at locations of , , and . The treatment was given at 1 PM to 3 PM, once a day; 10-d treatment was a course of treatment, and a total of 20-d treatment was given. The abdominal circumference, urine volume, body mass, liver function and prothrombin time were observed before and after treatment in the two groups, and the clinical efficacy of the two groups was compared.
RESULTS:
The total effective rate was 91.7% (22/24) in the observation group, which was higher than 87.5% (21/24) in the control group (<0.05). After treatment, the improvement of abdominal circumference, urine volume, body mass, liver function and prothrombin time between the two groups was significantly different (<0.05), the observation group was better.
CONCLUSION
Based on the western medicine treatment, the combination of TCM decoction and umbilical needling therapy of I-Ching shows significant efficacy for cirrhosis ascites with syndrome of spleen-deficiency and fluid-retention.
Ascites
;
etiology
;
therapy
;
Humans
;
Liver Cirrhosis
;
complications
;
Needles
;
Spleen
;
Syndrome
;
Umbilicus
6.Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.
Soon Jae LEE ; Yoo Kyung CHO ; Soo Young NA ; Eun Kwang CHOI ; Sun Jin BOO ; Seung Uk JEONG ; Hyung Joo SONG ; Heung Up KIM ; Bong Soo KIM ; Byung Cheol SONG
Clinical and Molecular Hepatology 2016;22(3):390-395
Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.
Abdomen/diagnostic imaging
;
Antiviral Agents/*therapeutic use
;
Drug Therapy, Combination
;
Endoscopy, Digestive System
;
Esophageal and Gastric Varices/complications/prevention & control
;
Female
;
Hepatitis C/complications/*drug therapy
;
Humans
;
Interferon-alpha/*therapeutic use
;
Liver Cirrhosis/*etiology
;
Male
;
Middle Aged
;
Polyethylene Glycols/*therapeutic use
;
Recombinant Proteins/therapeutic use
;
Ribavirin/*therapeutic use
;
Splenomegaly/complications/prevention & control
;
Tomography, X-Ray Computed
;
Ultrasonography
7.Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report.
Hae Won LEE ; Jin Du KANG ; Chang Woo YEO ; Sung Woon YOON ; Kwang Jae LEE ; Mun Ki CHOI
Journal of Korean Medical Science 2016;31(8):1345-1348
Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.
Adrenal Insufficiency/diagnosis/etiology
;
Adult
;
Brain/diagnostic imaging
;
Depression/etiology
;
Female
;
Hepatolenticular Degeneration/*complications
;
Humans
;
Hypopituitarism/complications/*diagnosis/drug therapy
;
Hypothyroidism/diagnosis/etiology
;
Liver Cirrhosis/complications/diagnostic imaging
;
Magnetic Resonance Imaging
;
Steroids/therapeutic use
;
Thyrotropin-Releasing Hormone/therapeutic use
8.Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report.
Hae Won LEE ; Jin Du KANG ; Chang Woo YEO ; Sung Woon YOON ; Kwang Jae LEE ; Mun Ki CHOI
Journal of Korean Medical Science 2016;31(8):1345-1348
Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.
Adrenal Insufficiency/diagnosis/etiology
;
Adult
;
Brain/diagnostic imaging
;
Depression/etiology
;
Female
;
Hepatolenticular Degeneration/*complications
;
Humans
;
Hypopituitarism/complications/*diagnosis/drug therapy
;
Hypothyroidism/diagnosis/etiology
;
Liver Cirrhosis/complications/diagnostic imaging
;
Magnetic Resonance Imaging
;
Steroids/therapeutic use
;
Thyrotropin-Releasing Hormone/therapeutic use
9.Cyanoacrylate injection versus band ligation for bleeding from cardiac varices along the lesser curvature of the stomach.
Sang Jung PARK ; Yong Kwon KIM ; Yeon Seok SEO ; Seung Woon PARK ; Han Ah LEE ; Tae Hyung KIM ; Sang Jun SUH ; Young Kul JUNG ; Ji Hoon KIM ; Hyunggin AN ; Hyung Joon YIM ; Jae Young JANG ; Jong Eun YEON ; Kwan Soo BYUN
Clinical and Molecular Hepatology 2016;22(4):487-494
BACKGROUND/AIMS: Practice guidelines recommend endoscopic band ligation (EBL) and endoscopic variceal obturation (EVO) for bleeding from esophageal varices and fundal varices, respectively. However, the optimal treatment for bleeding from cardiac varices along the lesser curvature of the stomach (GOV1) remains undefined. This retrospective study compared the efficacy between EBL and EVO for bleeding from GOV1. METHODS: Patients treated by EBL or EVO via cyanoacrylate injection for bleeding from GOV1 were enrolled. Patients diagnosed with hepatocellular carcinoma or treated with endoscopic injection sclerotherapy were excluded. RESULTS: The study included 91 patients treated for bleeding from GOV1. The mean age was 56.3±10.9 years (mean±SD), and 78 of them (85.7%) were men. Overall, 51 and 40 patients were treated with EBL and EVO, respectively. A trend for a higher hemostasis rate was noted in the EVO group (100%) than in the EBL group (82.6%, P=0.078). Varices rebled in 15 patients during follow-up. The rebleeding rate was significantly higher in the EBL group than in the EVO group (P=0.004). During follow-up, 13 patients died (11 in the EBL group and 2 in the EVO group); the survival rate was marginally significant between two groups (P=0.050). The rebleeding-free survival rate was significantly higher in the EVO group than in the EBL group (P=0.001). CONCLUSIONS: Compared to EBL, EVO offered significantly lower rebleeding rates, significantly higher rebleeding-free survival rates, and a trend for higher hemostasis and survival rates. EVO appears to be the better therapeutic option for bleeding from GOV1.
Adult
;
Aged
;
Carcinoma, Hepatocellular/complications
;
Cyanoacrylates/*therapeutic use
;
Disease-Free Survival
;
Endoscopy, Gastrointestinal
;
Female
;
Gastrointestinal Hemorrhage/etiology/mortality/*therapy
;
Humans
;
Ligation
;
Liver Cirrhosis/complications/diagnosis
;
Liver Neoplasms/complications
;
Male
;
Middle Aged
;
Proportional Hazards Models
;
Recurrence
;
Retrospective Studies
;
Sclerotherapy
;
Survival Rate
;
Treatment Outcome
10.Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis.
Hye Young JWA ; Yoo Kyung CHO ; Eun Kwang CHOI ; Heung Up KIM ; Hyun Joo SONG ; Soo Young NA ; Sun Jin BOO ; Seung Uk JEONG ; Bong Soo KIM ; Byoung Wook LEE ; Byung Cheol SONG
Clinical and Molecular Hepatology 2016;22(1):183-187
Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.
Abdomen/diagnostic imaging
;
Antiviral Agents/*therapeutic use
;
DNA, Viral/blood
;
Esophageal and Gastric Varices/complications/prevention & control
;
Guanine/*analogs & derivatives/therapeutic use
;
Hepatitis B virus/genetics
;
Hepatitis B, Chronic/complications/*drug therapy/virology
;
Humans
;
Liver Cirrhosis/*diagnosis/etiology
;
Male
;
Middle Aged
;
Polymerase Chain Reaction
;
Ultrasonography

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