Comparison of TIPS alone and combined with partial splenic embolization (PSE) for the management of variceal bleeding.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional radiological treatments for the complications of cirrhosis. This study aimed to investigate the effects of concomitant PSE on the long-term shunt patency and overall survival of TIPS-treated patients. METHODS: Forty-eight patients with TIPS insertion were enrolled and studied retrospectively. They were divided into TIPS+PSE (n = 16) and TIPS groups (n = 32), undergoing combined therapy using TIPS and PSE, and monotherapy using TIPS alone, respectively. RESULTS: The 5-year cumulative primary patency rate in the TIPS+PSE group was markedly higher than in the TIPS group (56.8% vs. 32.8%, p = 0.028), whereas the 5-year cumulative secondary patency rate (93.8% vs. 87.7%, p = 0.749) and overall survival rate (62.5% vs. 30.7%, p = 0.414) were not significantly different between the two groups. Cox-regression models revealed that group (hazard ratio [HR], 0.235; 95% CI, 0.084-0.665; p = 0.006), portal venous pressure decline (HR, 0.687; 95% CI, 0.563-0.838; p = 0.000), and baseline portal vein thrombosis (HR, 3.955; 95% CI, 1.634-9.573; p = 0.002) were significant predictors for shunt dysfunction, while only ascites (HR, 2.941; 95% CI, 1.250-6.920; p = 0.013) was a significant predictor for mortality. No severe adverse event was noted in the two groups except for the potential risk of splenic abscess development in the TIPS+PSE group. CONCLUSIONS: Concomitant PSE may help increase the long-term primary shunt patency rate, but not the overall survival of TIPS-treated patients. Further prospective studies are needed to validate these retrospective findings and to investigate the potential mechanisms. KEY POINTS: • Combined therapy using TIPS and PSE is associated with higher primary patency rates than TIPS alone. • Combined therapy using TIPS and PSE is associated with similar rates of secondary patency and overall survival of patients than TIPS alone. • Group (TIPS alone or TIPS+PSE), PVD, and baseline PVT are three independent predictors for shunt dysfunction, while ascites is the only independent predictor for mortality.

Tenofovir Versus Entecavir for the Treatment of Acute-on-Chronic Liver Failure due to Reactivation of Chronic Hepatitis B With Genotypes B and C.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) can be triggered by reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are now the most potent antiviral agents for CHB. This study aimed to compare the short-term safety and efficacy of TDF with ETV in the treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF]. PATIENTS AND METHODS: In total, 67 consecutive patients with HBV-ACLF were divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35) receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the primary endpoint was overall survival at 3 months. RESULTS: At 2 weeks, the TDF group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte-Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients; CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were comparable between the 2 groups, but markedly lower than at baseline (P<0.01); the TDF group had significantly higher cumulative survival rate than the ETV group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95% confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors for mortality. Both drugs were well tolerated. CONCLUSIONS: The short-term efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for mortality at 3 months.

Elective Transjugular Intrahepatic Portosystemic Shunt Using Viatorr Stent-Grafts: A Single-Center Experience from China.

Background and Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established approach for the management of variceal bleeding, refractory ascites, hepatic hydrothorax, and preoperative treatment of portal hypertension prior to major abdominal surgery in patients with compensated cirrhosis, and so on. This study aimed to investigate the safety and long-term efficacy of TIPS implantation using Viatorr TIPS stent-grafts. Material and Methods: A cohort of 59 patients undergoing TIPS placement using Viatorr TIPS stent-grafts were included, and the periprocedural events, and long-term mortality, shunt dysfunction, variceal rebleeding and incidence of hepatic encephalopathy (HE) were analyzed. Results: The technical success rate was 100%. The median portosystemic pressure gradient was reduced from 21 mmHg (interquatile range: 19-25) to 13 mmHg (interquatile range: 10-16) before and after TIPS, leading to a hemodynamic success rate of 72.9%. The cumulative rate of overall mortality was 34.2% at five years, and direct bilirubin (hazard ratio [HR] = 1.336, 95% confidence interval [CI]: 1.050-1.700, P = 0.018) and post-TIPS right atrial pressure (HR = 1.238, 95% CI: 1.015-1.510, P = 0.035) were independent predictors for mortality. The cumulative rates of shunt dysfunction and variceal rebleeding were 11.0% and 28.3% at five years, respectively, and portal venous pressure gradient (HR = 2.572, 95% CI: 1.094-6.047, P = 0.030) was the only independent predictor for shunt dysfunction. The cumulative four-year HE-free rate was 48.6%. No severe adverse event was noted during TIPS procedures. Conclusion: Elective TIPS implantation using Viatorr TIPS stent-grafts is generally safe, and the long-term efficacy is favorable for the treatment of cirrhotic patients with recurrent variceal bleeding or refractory ascites.

Clinical Outcomes of Transjugular Intrahepatic Portosystemic Shunt (Tips) Creation Using Fluency Versus Viatorr Stent-Grafts: A Single-Centre Retrospective Study.

PURPOSE: To investigate the effects of transjugular intrahepatic portosystemic shunt (TIPS) creation using Fluency versus Viatorr stent-grafts on the long-term clinical outcomes. MATERIALS AND METHODS: This was a single-center retrospective study from January 2010 to October 2021 in 213 patients receiving TIPS with Fluency (Fluency group, n = 154) versus Viatorr (Viatorr group, n = 59) stent-grafts. Inclusion criteria were: age > 18 years old and TIPS creation for variceal hemorrhage. Exclusion criteria were: age > 80 years old, concomitant chronic heart or lung disease, active tuberculosis or human immunodeficiency virus infection, extrahepatic malignancy, alcohol dependence, TIPS created outside of our hospital, without any follow-up data, or decline to participate. The primary outcome was primary patency rate and its associated risk factors. RESULTS: The 5-year cumulative primary patency rate was significantly higher in Viatorr group than in Fluency group (89.0% vs. 19.6%, p < 0.001), whereas the 5-year cumulative transplant-free survival rate (62.3% vs. 62.2%, p = 0.636) was comparable between two groups. Cox-regression models revealed that group (hazard ratio [HR]4.029, 95% confidence interval [CI] 1.486-10.927, p = 0.006), use of bare stents (HR 3.307, 95% CI 1.903-5.747, p < 0.001), and baseline portal vein thrombosis (HR 0.248, 95% CI 0.149-0.412, p < 0.001) were significantly associated with shunt patency. Incidences of adverse events were not significantly different between two groups (p > 0.05). CONCLUSIONS: TIPS creation using Viatorr stent-grafts is superior to using Fluency stent-grafts in terms of higher long-term primary patency rate but similar transplant-free survival rate.

The Effect of Transjugular Intrahepatic Portosystemic Shunt Plus Partial Splenic Embolization for the Treatment of Patients with Recurrent Variceal Bleeding.

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional therapies effective for the management of variceal bleeding with cirrhosis. This study aimed to investigate the effect of TIPS plus PSE for the treatment of patients with cirrhosis and recurrent variceal bleeding. MATERIAL AND METHODS: This is a single-center, nonrandomized and retrospective study that included 32 patients undergoing TIPS alone (the TIPS group) and 16 patients undergoing TIPS plus PSE (the TIPS+PSE group). RESULTS: The 5-year cumulative rates of variceal rebleeding (20.0% vs. 37.9%, p = 0.027) and shunt stenosis (35.1% vs. 55.9%, p = 0.036) in the TIPS+PSE group were significantly lower than in the TIPS group, whereas the 5-year cumulative rates of shunt blockage (12.5% vs. 25.8%, p = 0.388), and all-cause mortality (37.5% vs. 69.3%, p = 0.414) were not statistically different between the two groups. The 2-year cumulative rate of remaining free of hepatic encephalopathy was also similar between the two groups (75.0% vs. 81.3%, p = 0.704). Cox-regression analyses showed that group and reduction of portal venous pressure before and after TIPS creation were associated with both variceal rebleeding and shunt stenosis, whereas only reduction of portal venous pressure (hazard ratio 0.648, 95% confidence interval: 0.444-0.946, p = 0.025) was associated with shunt blockage. No severe adverse event was observed in the two groups. CONCLUSION: TIPS+PSE is superior to TIPS alone in control of variceal rebleeding and shunt stenosis. Further prospective studies are warranted to confirm our findings.

TSG-6 Inhibits Oxidative Stress and Induces M2 Polarization of Hepatic Macrophages in Mice With Alcoholic Hepatitis via Suppression of STAT3 Activation.

Tumor necrosis factor (TNF)-α-stimulated protein 6 (TSG-6) is a secreted protein with diverse tissue protective and anti-inflammatory properties. We aimed to investigate its effective in treating mice with alcoholic hepatitis (AH) and the associated mechanisms. AH was induced in 8-10 week female C57BL/6N mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) injection of recombinant mouse TSG-6 or saline were performed in mice on day 10. Blood samples and hepatic tissues were collected on day 11. Biochemistry, liver histology, flow cytometry, and cytokine measurements were conducted. Compared to the normal control mice, the AH mice had significantly increased liver/body weight ratio, serum alanine aminotransferase (ALT) and aspartate aminotransferases (AST), hepatic total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), hepatic macrophage infiltration, serum and hepatic interleukin (IL)-6, and tumor necrosis factor (TNF)-α, which were markedly reduced by i.p. injection of rmTSG-6. Compared to the normal control mice, the hepatic glutathione (GSH), accumulation of M2 macrophages, serum, and hepatic IL-10 and TSG-6 were prominently reduced in the AH mice, which were significantly enhanced after i.p. injection of rmTSG-6. Compared to the normal control mice, hepatic activation of signal transducer and activator of transcription 3 (STAT3) was significantly induced, which was markedly suppressed by rmTSG-6 treatment. TSG-6 were effective for the treatment of AH mice, which might be associated with its ability in inhibiting hepatic oxidative stress and inducing hepatic M2 macrophages polarization via suppressing STAT3 activation.

Corrigendum: TSG-6 Inhibits Oxidative Stress and Induces M2 Polarization of Hepatic Macrophages in Mice With Alcoholic Hepatitis via Suppression of STAT3 Activation.

[This corrects the article DOI: 10.3389/fphar.2020.00010.].

Mesenchymal stem cells alleviate liver injury induced by chronic-binge ethanol feeding in mice via release of TSG6 and suppression of STAT3 activation.

BACKGROUND: Mesenchymal stem cells (MSCs) are a population of pluripotent cells that might be used for treatment of liver disease. However, the efficacy of MSCs for mice with alcoholic hepatitis (AH) and its underlying mechanism remains unclear. METHODS: MSCs were isolated from the bone marrow (BM) of 4-6-week-old male C57BL/6 N mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. The mice were given intraperitoneal injections of MSCs with or without transfection or AG490, recombinant mouse tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rmTSG-6), or saline at day 10. Blood samples and hepatic tissues were collected at day 11. Various assays such as biochemistry, histology, and flow cytometry were performed. RESULTS: MSCs reduced AH in mice, decreasing liver/body weight ratio, liver injury, blood and hepatic lipids, malondialdehyde, interleukin (IL)-6, and TNF-ɑ, but increasing glutathione, IL-10, and TSG-6, compared to control mice. Few MSCs engrafted into the inflamed liver. Knockdown of TSG-6 in MSCs significantly attenuated their effects, and injection of rmTSG-6 achieved similar effects to MSCs. The signal transducer and activator of transcription 3 (STAT3) was activated in mice with AH, and MSCs and rmTSG-6 inhibited the STAT3 activation. Injection of MSCs plus AG490 obtained more alleviation of liver injury than MSCs alone. CONCLUSIONS: BM-MSCs injected into mice with AH do not engraft the liver, but they secrete TSG-6 to reduce liver injury and to inhibit STAT3 activation.

Prednisone is not beneficial for the treatment of severe drug-induced liver injury: An observational study (STROBE compliant).

There is limited information about the effects of corticosteroids on severe drug-induced liver injury (DILI). This study aimed to investigate the efficacy and safety of prednisone in severe DILI.Ninety patients with severe DILI were enrolled and studied retrospectively. They were divided into prednisone (n = 66) and control groups (n = 24), undergoing the same treatment regimen except that patients in the prednisone group received a median daily dose of 40 mg prednisone. The primary endpoint was severity reduction (serum total bilirubin [TBIL] <86 µmol/L).During the study, the cumulative rates of severity reduction at 4-, 8-, and 12 days were comparable between the 2 groups (prednisone versus control: 7.6%, 33.3%, and 60.6% versus 12.5%, 37.5%, and 66.7%, P = .331), and were markedly lower in the high-dose group than in the low-dose group (0%, 28.6%, and 35.7% versus 9.6%, 34.6%, and 67.3%, P = .012) or in the control group (0%, 28.6%, and 35.7% versus 12.5%, 37.5%, and 66.7%, P = .023). The 30-day overall survival rate in the prednisone group was significantly higher than in the control group (100% versus 91.7%, P = .018). Serum bilirubin and transaminase values gradually decreased in both groups, which were not significantly different mostly. Cox-regression models revealed that baseline TBIL (hazard ratio: 0.235; 95% confidence interval: 0.084-0.665; P = .006) was the only predictor for severity reduction. No severe adverse event was noted in both groups.Prednisone therapy is safe but not beneficial, and even detrimental at a daily dose > 40 mg for the treatment of severe DILI.

Transjugular Intrahepatic Portosystemic Shunt:The Impact of Portal Venous Pressure Declines on Shunt Patency and Clinical Efficacy.

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) placement using the same-diameter covered stents can lead to differed declines of portal venous pressure declines (PVDs). This study aimed to compare the long-term shunt patency and clinical efficacy of TIPS placement that caused low PVDs (≤9 mmHg) and high PVDs (>9 mmHg). MATERIALS AND METHODS: A total of 129 patients treated by TIPS placement with 8 mm-diameter polytetrafluoroethylene covered stents were included and analyzed retrospectively. They were stratified into group A with low PVDs (n = 69) and group B with high PVDs (n = 60). RESULTS: The 6-year actuarial probabilities of remaining free of shunt dysfunction (47.2% vs 64.6%; p = 0.007) and variceal rebleeding (48.3% vs 63.9%; p = 0.038) were significantly lower in group A than in group B. The 6-year actuarial probability of remaining free of hepatic encephalopathy was significantly higher in group A than in group B (44.5% vs 32.5%; p = 0.010), though the 6-year cumulative survival rate was similar in both groups (A vs B: 65.5% vs 56.0%; p = 0.240). The baseline portal vein thrombosis (hazard ratio [HR]: 6.045, 95% confidence interval [CI]: 2.762-13.233; p = 0.000) and stent type (HR: 4.447, 95%CI: 1.711-11.559, p = 0.002) were associated with shunt dysfunction, whereas only ascites was associated with mortality (HR: 1.373, 95%CI: 1.114-3.215; p = 0.024). CONCLUSION: High PVDs (>9 mmHg) were associated with higher shunt patency, lower incidence of variceal rebleeding, but higher frequency of hepatic encephalopathy and similar survival rate than low PVDs (≤9 mmHg) after TIPS placement.

Portal Vein Thrombosis in Patients With Cirrhosis Undergoing Elective Transjugular Intrahepatic Portosystemic Shunt: Risk Factors, Warfarin Efficacy, and Clinical Outcomes.

Portal vein thrombosis (PVT) is a common complication in cirrhosis. The aim of this study was to determine risk factors for PVT, assess the efficacy of anticoagulant therapy, and evaluate the effects of PVT on patients with cirrhosis undergoing elective transjugular intrahepatic portosystemic shunt (TIPSS). A total of 101 patients with cirrhosis undergoing elective TIPSS were prospectively studied. After TIPSS, all patients received preventive therapy for PVT and were followed up at 3, 6, 12, and 24 months. Clinical outcomes were compared between patients who developed PVT after TIPSS and those who did not. Multivariate analysis showed that white blood cell count (relative risk [RR]: 0.377; 95% confidence interval [CI]: 0.132-0.579; P = .001), Child-Turcotte-Pugh score (RR: 1.547; 95% CI: 1.029-2.365; P = .032), and ascites (RR: 1.264; 95% CI: 1.019-1.742; P = .040) were independent predictors for PVT. Warfarin treatment within 12 months achieved significantly higher rates of complete recanalization than aspirin or clopidogrel in patients with PVT (54.5% vs 31.3%; P = .013), although adverse events were similar between the 2 groups ( P > .05). Patients without PVT had significantly lower 2-year cumulative rates of variceal rebleeding (15.9% vs 36.6%; P = .023), shunt dysfunction (27.0% vs 46.8%; P = .039), hepatic encephalopathy (24.1% vs 42.6%; P = .045), and hepatocellular carcinoma (11.4% vs 31.2%; P = .024) and markedly higher 2-year cumulative survival rates (89.8% vs 72.9%; P = .041) than those with PVT. The PVT is associated with poorer clinical outcomes in TIPSS-treated patients, and warfarin is both safe and more effective in recanalizing PVT than aspirin or clopidogrel.

Genotype Matters in Patients with Acute-on-chronic Liver Failure Due to Reactivation of Chronic Hepatitis B.

BACKGROUND: Acute-on-chronic liver failure (ACLF) can be caused by reactivation of chronic hepatitis B virus (HBV) infection (HBV-ACLF). It's unclear whether HBV genotypes affect the clinical and therapeutical outcomes of patients with HBV-ACLF. This study was to investigate the short-term antiviral response and overall survival in HBV-ACLF patients treated by tenofovir or entecavir. METHODS: Seventy-three consecutive patients with HBV-ACLF were stratified into genotype B group (n = 33) and C group (n = 40). They were prospectively followed-up. RESULTS: At 2 weeks, the genotype B group had significantly lower HBV-DNA load (P = 0.005), greater HBV-DNA decline (P = 0.026), higher proportion of patients with HBV-DNA < 500 IU/ml (P = 0.007), improved Child-Turcotte-Pugh (CTP; P = 0.032) and model for end-stage liver disease (MELD; P = 0.039) scores compared to the genotype C group. At three months, survivors in both groups had undetectable HBV-DNA loads, comparable CTP (P = 0.850) and MELD (P = 0.861) scores; the genotype C group had markedly lower overall survival rate than the B group (P = 0.013). The genotype (hazard ratio [HR]: 2.138; 95% confidence interval [CI]: 1.034-4.143; P = 0.041), MELD score (HR:1.664, 95%CI: 1.077-2.571; P = 0.022) and HBV-DNA decline (HR: 0.225, 95% CI: 0.067-0.758; P = 0.016) at 2 weeks were significantly associated with mortality at 3 months. No severe adverse event was noted. CONCLUSIONS: Genotype B was associated with better short-term antiviral response and clinical outcome compared to genotype C in patients with HBV-ACLF.

The Effect of Transarterial Chemoembolization in Combination With Kang'ai Injection on Patients With Intermediate Stage Hepatocellular Carcinoma: A Prospective Study.

BACKGROUND: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. OBJECTIVE: This study aimed to investigate the effect of combining TACE with Kang'ai (KA) injection for treating patients with intermediate stage HCC. METHODS: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA injection, and TACE group (n = 41) receiving repeated TACE alone. All patients were prospectively studied. Primary endpoints were overall survival (OS) and time to radiologic progression (TTP). RESULTS: The TACE + KA group had significantly longer median OS (27.0 vs 21.0 months, P = .038) and TTP (12.0 vs 10.0 months, P = .028) than TACE group. The 1-, 2-, and 3-year OS rates in the TACE + KA group were markedly higher than in TACE group (88.5%, 58.8%, and 20.8% vs 81.3%, 44.9%, and 6.7%, respectively, P = .038), while the 1- and 2-year TTP rates in the TACE + KA group were significantly lower than in TACE group (49.3% and 86.9% vs 75.3% and 100%, P = .028). TACE + KA group displayed significantly lower incidences of intrahepatic and extrahepatic metastases, as well as postembolization syndrome than TACE group ( P < .05). Multivariate analyses revealed group ( P = .023), maximum tumor size ( P = .019), and tumor number ( P = .034) as significant predictors for OS, and group ( P = .046), maximum tumor size ( P = .002) and α-fetoprotein level ( P = .020) as significant predictors for TTP. Both TACE and KA injection were well tolerated. CONCLUSION: TACE plus KA injection is more effective than TACE alone for treating patients with intermediate stage HCC in this nonrandomized study. Further research is warranted.

Predictors of Shunt Dysfunction and Overall Survival in Patients with Variceal Bleeding Treated with Transjugular Portosystemic Shunt Creation Using the Fluency Stent Graft.

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is an established method for portal hypertension. This study was to investigate the long-term safety, technical success, and patency of TIPS, and to determine the risk factors and clinical impacts of shunt dysfunction. MATERIALS AND METHODS: A total of 154 consecutive patients undergoing embolotherapy of gastric coronary vein and/or short gastric vein and TIPS creation were prospectively studied. Follow-up data included technical success, patency and revision of TIPS, and overall survival of patients. RESULTS: During the study, the primary and secondary technical success rates were 98.7% and 100%, respectively. Sixty-three patients developed shunt dysfunction, 30 with shunt stenosis and 33 with shunt occlusion. The cumulative 60-month primary, primary assisted, and secondary patency rates were 19.6%, 43.0%, and 93.4%, respectively. The cumulative 60-month overall survival rates were similar between the TIPS dysfunction group and the TIPS non-dysfunction group (68.6% vs. 58.6%, P = .096). Baseline portal vein thrombosis (P < .001), use of bare stents (P = .018), and portal pressure gradient (PPG) (P = .020) were independent predictors for shunt dysfunction, hepatocellular carcinoma (P < .001), and ascites (P = .003) for overall survival. The accuracy of PPG for shunt dysfunction was statistically significant (P < .001), and a cutoff value of 8.5 had 77.8% sensitivity and 64.8% specificity. CONCLUSIONS: The long-term safety, technical success, and patency of TIPS were good; baseline portal vein thrombosis, use of bare stents, and PPG were significantly associated with shunt dysfunction; shunt dysfunction has little impact on patients' long-term survival because of high secondary patency rates.

Telbivudine versus lamivudine and entecavir for treatment-naïve decompensated hepatitis B virus-related cirrhosis.

The long-term effects of telbivudine (TBV) on decompensated hepatitis B virus (HBV)-related cirrhosis were still not established. This study aimed to investigate the efficacy and safety of TBV in such cohort of patients as compared to lamivudine (LAM) and entecavir (ETV). We retrospectively evaluated 130 treatment-naïve patients with HBV-related decompensated cirrhosis who started treatment with TBV (n = 31), LAM (n = 45) or ETV (n = 54). After 24 months of treatment, cumulative virological response (VR) rates (HBV DNA <500 copies/mL) were 83.7, 65.3 and 89.1 % in TBV, LAM and ETV groups, respectively (p = 0.009). Reduction in HBV DNA levels in TBV was -3.66 ± 0.56, significantly higher than LAM (-3.34 ± 0.59; p < 0.05) and lower than ETV group (-3.98 ± 0.52; p < 0.05). The rates of HBeAg loss or seroconversion and normalization of alanine aminotransferase (ALT) were similar among the groups. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease score in TBV were significantly improved compared to at baseline without difference among the groups. TBV resulted in similar cumulative rates of survival and incidence of hepatocellular carcinoma (HCC) to LAM and ETV. Frequencies of complications from cirrhosis, including variceal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis, were comparable among the groups. Four patients (16.7 %) in TBV displayed virological breakthrough, lower than LAM and higher than ETV (p = 0.004). Cox regression analysis showed that baseline HBV DNA (hazard ratio 0.743; 95 % confidence interval 0.582-949, p = 0.017) was an independent predictor for VR at 24 months. Long-term therapy with TBV was effective and safe in HBV-related decompensated cirrhosis.

Portal vein thrombosis before and after transjugular intrahepatic portosystemic shunt placement: An observational study (STROBE compliant).

Portal vein thrombosis (PVT) is common in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study had 3-fold aims: to assess risk factors for PVT; to determine the efficacy of anticoagulant therapy; to investigate the impact of PVT on clinical outcomes in TIPS-treated cirrhosis.Between June 2012 and February 2016, 126 TIPS-treated patients with cirrhosis were enrolled and studied prospectively. Enrolled patients were screened for PVT before TIPS and at 3, 6, 12, and 24 months post-TIPS. All patients received warfarin (1.5-3.0 mg/day) or aspirin (100 mg/day) or clopidogrel (75 mg/day) post-TIPS. Results of patients with and without PVT (baseline and de novo) were compared.White blood cell (WBC) counts (odds ratio (OR): 0.430, 95% confidence interval (CI): 0.251-0.739, P = .002) and Child-Turcotte-Pugh (CTP) score (OR: 2.377, 95% CI: 1.045-5.409, P = .039) were significant baseline predictors for PVT in TIPS-treated patients with cirrhosis. Warfarin resulted in markedly greater rates of complete recanalization than aspirin or clopidogrel (P < .05) in patients with PVT. Patients with PVT had markedly higher 2-year cumulative rates of variceal rebleeding, shunt dysfunction, hepatic encephalopathy, and hepatocellular carcinoma, and prominently lower overall survival than those without PVT (P < .05).In TIPS-treated patients with cirrhosis, lower WBC count and higher CTP score were independent baseline predictors for PVT; patients with PVT had worse clinical outcomes than those without; warfarin may be more effective in recanalizing PVT than aspirin or clopidogrel.

Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study.

BACKGROUND & AIM: Search for an effective therapy for patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) remains an important issue. This study investigated the efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation in patients with HBV-ACLF. METHODS: 45 consecutive entecavir-treated HBV-ACLF patients were prospectively studied. Among these patients, 11 received both plasma exchange (PE) and a single transplantation of UC-MSCs (group A), while 34 received only PE (group B). The primary endpoint was survival at 24 months. RESULTS: Compared with group B, levels of albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin time (PT), international normalized ratio (INR) and model for end-stage liver disease score in group A improved significantly at 4 weeks after transplantation (p < 0.05). Levels of albumin, PT and INR in group A were also markedly improved at 24 months (p < 0.05). Group A had significantly higher cumulative survival rate at 24 months (54.5 % v.s. 26.5 %, p = 0.015 by log rank test). Between the two groups, levels of creatinine, White blood cell, hemoglobin and platelet were similar. HBeAg loss and hepatocellular carcinoma incidence were similar at 24 months. Group assignment (relative risk: 2.926, 95%confidence interval: 1.043-8.203, p = 0.041) was an independent predictor for survival at 24 months. Success rate of UC-MSC transplantation was 100 % in group A. No severe adverse event was observed in any patient. CONCLUSION: UC-MSC transplantation is safe and effective for HBV-ACLF patients treated with PE and entecavir. It further improves the hepatic function and survival.

Umbilical cord-derived mesenchymal stem cells inhibit growth and promote apoptosis of HepG2 cells.

Hepatocellular carcinoma is the fifth most common type of cancer worldwide and remains difficult to treat. The aim of this study was to investigate the effects of mesenchymal stem cells (MSCs) derived from the umbilical cord (UC­MSCs) on HepG2 hepatocellular carcinoma cells. UC­MSCs were co­cultured with HepG2 cells and biomarkers of UC­MSCs were analyzed by flow cytometry. mRNA and protein expression of genes were determined by reverse transcription­polymerase chain reaction and flow cytometry, respectively. Passage three and seven UC­MSCs expressed CD29, CD44, CD90 and CD105, whereas CD34 and CD45 were absent on these cells. Co­culture with UC­MSCs inhibited proliferation and promoted apoptosis of HepG2 cells in a time­dependent manner. The initial seeding density of UC­MSCs also influenced the proliferation and apoptosis of HepG2 cells, with an increased number of UC­MSCs causing enhanced proliferation inhibition and cell apoptosis. Co­culture with UC­MSCs downregulated mRNA and protein expression of α­fetoprotein (AFP), Bcl­2 and Survivin in HepG2 cells. Thus, UC­MSCs may inhibit growth and promote apoptosis of HepG2 cells through downregulation of AFP, Bcl­2 and Survivin. US-MSCs may be used as a novel therapy for treating hepatocellular carcinoma in the future.