Bone marrow-derived mesenchymal stem cell therapy for decompensated liver cirrhosis:A meta-analysis

AIM: To assess the efficacy and safety of bone marrow-derived mesenchymal stem cell (BM-MSC) in the treatment of decompensated liver cirrhosis.

Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis:A prospective study

To assess the vitamin D (VD) deficiency as a prognostic factor and effect of replenishment of VD on mortality in decompensated cirrhosis. METHODSPatients with decompensated liver cirrhosis were screened for serum VD levels. A total of 101 VD deficient patients (< 20 ng/mL) were randomly enrolled in two groups: Treatment group (n = 51) and control group (n = 50). Treatment group received VD treatment in the form of intramuscular cholecalciferol 300000 IU as loading dose and 800 IU/d oral as maintenance dose along with 1000 mg oral calcium supplementation. The VD level, clinical parameters and survival of both the groups were compared for 6-mo. RESULTSPrevalence of vitamin D deficiency (VDD) in decompensated CLD was 84.31%. The mean (SD) age of the patients in the treatment group (M:F: 40:11) and control group (M:F: 37:13) were 46.2 (± 14.93) years and 43.28 (± 12.53) years, respectively. Baseline mean (CI) VD (ng/mL) in control group and treatment group were 9.15 (8.35-9.94) and 9.65 (8.63-10.7), respectively. Mean (CI) serum VD level (ng/mL) at 6-mo in control group and treatment group were 9.02 (6.88-11.17) and 29 (23-35), respectively. Over the period of time the VD, calcium and phosphorus level was improved in treatment group compared to control group. There was non-significant trend seen in greater survival (69% vs 64%; P > 0.05) and longer survival (155 d vs 141 d; P > 0.05) in treatment group compared to control group. VD level had no significant association with mortality (P > 0.05). In multivariate analysis, treatment with VD supplement was found significantly (P < 0.05; adjusted hazard ratio: 0.48) associated with survival of the patients over 6-mo. CONCLUSIONVD deficiency is very common in patients of decompensated CLD. Replenishment of VD may improve survival in patients with decompensated liver cirrhosis.

Development and validation of a prognostic nomogram for decompensated liver cirrhosis

BACKGROUND Decompensated liver cirrhosis(DLC)is a stage in the progression of liver cirrhosis and has a high mortality.AIM To establish and validate a novel and simple-to-use predictive nomogram for evaluating the prognosis of DLC patients.METHODS A total of 493 patients with confirmed DLC were enrolled from The First Affiliated Hospital of Nanchang University(Nanchang,Jiangxi Province,China)between December 2013 and August 2019.The patients were divided into two groups:a derivation group(n=329)and a validation group(n=164).Univariate and multivariate Cox regression analyses were performed to assess prognostic factors.The performance of the nomogram was determined by its calibration,discrimination,and clinical usefulness.RESULTS Age,mechanical ventilation application,model for end-stage liver disease(MELD)score,mean arterial blood pressure,and arterial oxygen partial pressure/inhaled oxygen concentration were used to construct the model.The Cindexes of the nomogram in the derivation and validation groups were 0.780(95%CI:0.670-0.889)and 0.792(95%CI:0.698-0.886),respectively.The calibration curve exhibited good consistency with the actual observation curve in both sets.In addition,decision curve analysis indicated that our nomogram was useful in clinical practice.CONCLUSION A simple-to-use novel nomogram based on a large Asian cohort was established and validated and exhibited improved performance compared with the Child-Turcotte-Pugh and MELD scores.For patients with DLC,the proposed nomogram may be helpful in guiding clinicians in treatment allocation and may assist in prognosis prediction.

Endoscopic ultrasound-guided intraportal injection of autologous bone marrow in patients with decompensated liver cirrhosis:A case series

BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.

Safety and efficacy of tenofovir in chronic hepatitis B-related decompensated cirrhosis

AIM To evaluate the safety and efficacy of tenofovir disoproxil fumarate(TDF) as a first-line therapy in decompensated liver disease. METHODS We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis group. We followed the patients for 12 mo and evaluated clinical outcomes, including biochemical, virological, and serological responses. We also evaluated changes in hepatic and renal function and compared the decompensated and compensated cirrhosis groups. RESULTS The 1-year complete virological response(CVR) and Hepatitis B e antigen(HBe Ag) seroconversion were seen in 70.2% and 14.2% in the decompensated cirrhosis group, respectively. The rates of HBe Ag seroconversion/loss and ALT normalization at month 12 were similar in both groups. TDF treatment was also effective for decreasing the level of hepatitis B virus(HBV) DNA in both groups, but CVR was higher in the compensated group(88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved Child-Turcotte-Pugh(CTP) and model for end-stage liver disease(MELD) scores in decompensated group(P < 0.001). Of the 57 decompensated patients, 39(68.4%) achieved CTP class A and 27(49.1%) showed improvement in the CTP score of 2 points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/d L increases in serum levels of creatinine in the decompensated and compensated cirrhosis group were 7.0% and 2.5%, respectively(P < 1.000).CONCLUSION TDF therapy in decompensated cirrhosis patients was effective for decreasing HBV DNA levels and improving hepatic function with relatively lower CVR than in compensated cirrhosis. Thus, physicians should carefully monitor not only renal function but also treatment responses when using TDF in decompensated cirrhosis patients.

Palliative long-term abdominal drains vs large volume paracenteses for the management of refractory ascites in end-stage liver disease

BACKGROUND Long-term abdominal drains(LTAD)are a cost-effective palliative measure to manage malignant ascites in the community,but their use in patients with end-stage chronic liver disease and refractory ascites is not routine practice.The safety and cost-effectiveness of LTAD are currently being studied in this setting,with preliminary positive results.We hypothesised that palliative LTAD are as effective and safe as repeat palliative large volume paracentesis(LVP)in patients with cirrhosis and refractory ascites and may offer advantages in patients’quality of life.AIM To compare the effectiveness and safety of palliative LTAD and LVP in refractory ascites secondary to end-stage chronic liver disease.METHODS A retrospective,observational cohort study comparing the effectiveness and safety outcomes of palliative LTAD and regular palliative LVP as a treatment for refractory ascites in consecutive patients with end-stage chronic liver disease followed-up at our United Kingdom tertiary centre between 2018 and 2022 was conducted.Fisher’s exact tests and the Mann-Whitney U test were used to compare qualitative and quantitative variables,respectively.Kaplan-Meier survival estimates were generated to stratify time-related outcomes according to the type of drain.RESULTS Thirty patients had a total of 35 indwelling abdominal drains and nineteen patients underwent regular LVP.The baseline characteristics were similar between the groups.Prophylactic antibiotics were more frequently prescribed in patients with LTAD(P=0.012),while the incidence of peritonitis did not differ between the two groups(P=0.46).The incidence of acute kidney injury(P=0.014)and ascites/drain-related hospital admissions(P=0.004)were significantly higher in the LVP group.The overall survival was similar in the two groups(log-rank P=0.26),but the endpoint-free survival was significantly shorter in the LVP group(P=0.003,P<0.001,P=0.018 for first ascites/drain-related admission,acute kidney injury and drain-related complications,respectively).CONCLUSION The use of LTAD in the management of refractory ascites in palliated end-stage liver disease is effective,safe,and may reduce hospital admissions and utilisation of healthcare resources compared to LVP.

Spontaneous Bacterial Peritonitis and Short-Term Prognosis in a Group of Decompensated Cirrhotic Patients in Yaounde: A Cross-Sectional Study

Introduction: Spontaneous bacterial peritonitis (SBP) is among the most common infections in cirrhotic patients. Data on SBP are rare in Cameroon. This prompted us to carry out this study on patients with decompensated cirrhosis of the liver in Yaounde University Hospital Centre (YUHC). Methods: We carried out a cross-sectional study from December 2015 to June 2016 in three units of YUHC. All patients with decompensated liver cirrhosis were included. Our sampling was consecutive. Diagnosis of cirrhosis was performed, based on clinical, biological and ultrasound criteria. A neutrophil count greater than 250 cell/mm3 in ascites fluid defined an SBP. Data on socio-demography, clinical presentation, and outcomes were collected. Results: We included 34 decompensated cirrhotic patients (15 males). Patients mean age was 57.5 ± 2 years (SBP positive: 48.7 ± 21.3 versus without SBP: 59.8 ± 19.5, p = 0.22). SBP diagnosis was made in 6 (17.7%) patients. Compared to patients with decompensated liver cirrhosis and without SBP, positive SBP patients had a higher pulse rate (p = 0.002) and respiratory rate (p = 0.02). The patients with SBP were more likely to present these other clinical features: pulse rate >100 (RR: 4.2, [95% CI: 0.7 - 27.7];p = 0.02), presence of jaundice (RR: 3.4, [95% CI: 0.6 - 21.1];p = 0.09), being from female gender (RR: 3.2, [95% CI: 0.5 - 19.9]; p = 0.11), advanced liver disease (Child C class) (RR: 2.4, [95% CI: 0.4 - 14.5], p = 0.66), low-plasma albumin (less than 20 g/L) (RR: 1.7, [95% CI: 0.8 - 3.9], p = 0.08), respiratory rate > 30 (RR: 1.6, [95% CI: 0.6 - 3.3], p = 0.05) and fever/hypothermia (RR: 1.5, [95% CI: 0.6 - 3.4];p = 0.22). Evolution after a 72-hours antibiotherapy was stationary in four cases and unfavorable in two patients, resulting in death. Conclusion: SBP prevalence was 17.7%. SBP patients were younger, from female sex, tachycardia and polypnea, presenting with fever/hypothermia and signs of advanced liver disease than non-SBP patients. Improvement of our technical platform will be useful to determine the cause of cirrhosis and identify the different germs responsible for SBP.

Acute-on-chronic liver failure：recent update

Acute on chronic liver failure（ACLF） was first described in 1995 as a clinical syndrome distinct to classic acute decompensation.Characterized by complications of decompensation,ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between45%and 90%.Despite the clinical relevance of the condition,it still remains largely undefined with continued disagreement regarding its precise etiological factors,clinical course,prognostic criteria and management pathways.It is concerning that,despite our relative lack of understanding of the condition,the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%.This paper highlights our current understanding of ACLF,including its etiology,diagnostic and prognostic criteria and pathophysiology.It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates.The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters,while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF.

Hepatic recompensation according to Baveno VII criteria via transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology.It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease with portal hypertension.It represents a potential addition to the therapeutic modalities that could achieve hepatic recompensation in those patients based on Baveno VII criteria.

Pregnancy Complicated With a Giant Pancreatic Tumor and Decompensation of Liver Cirrhosis:A Case Report and Literature Review

Pregnancy with solid pseudopapillary tumor of the pancreas(SPTP)is rare.Because pregnancy hormones may cause tumor progression,the management and treatment of SPTP need to balance the safety of pregnant women and fetuses with surgical treatment.We reported a case of a giant pancreatic tumor diagnosed during pregnancy that was considered to be SPTP.Examinations also showed hepatitis B virus infection and severe decompensation of liver cirrhosis.Medical termination of pregnancy was performed.The patient has lived with the tumor until now without surgery.We retrieved the published case reports,summarized the clinical characteristics of pregnancy with SPTP,and explored its management during the perinatal period.Most patients with SPTP have a good prognosis with good maternal and fetal outcomes,and it is important to choose an appropriate treatment method and timing.However,pregnancy combined with decompensated liver cirrhosis needs to be terminated in a timely manner because of its high-risk status.

Hepatic encephalopathy with status epileptics: A case report

A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephalopathy with status epileptic us. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy. The status epilepticus was resolved after antiepileptic therapy （phenytoin sodium） and treatment for hepatic encephalopathy （Branched chain amino acids）. The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephalopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephalopathy.

Status epilepticus as an initial manifestation of hepatic encephalopathy:A case report

BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult without a clear history of cirrhosis.Liver transplantation (LT) is effective to alleviate symptoms, however, there arefew reports about LT in the treatment of status epilepticus with HE. To ourknowledge, this is the first report of status epilepticus present as initialmanifestation of HE.CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalizedfor generalized tonic-clonic seizures. She reported no history of episodes of HE,stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding.Neurological examination revealed a comatose patient, without papilledema.Laboratory examination suggested liver cirrhosis. Plasma ammonia levels uponadmission were five times normal. Brain computed tomography (CT) was normal,while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis andsplenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm,consistent with HE, and sharp waves during ictal EEG corresponding to clinicalsemiology of focal tonic seizures. The symptoms were reversed by continuousantiepileptic treatment and lactulose. She was given oral levetiracetam, and focalaware seizures occasionally affected her 10 mo after LT.CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE,and LT is effective to prevent the relapse.

Plasma copeptin concentration is a predictor of tolvaptan efficacy in patients with hepatic ascites

Aims:No solid evidence-based opinion was raised regarding predictors of the degree of ascites reduction with tolvaptan.This retrospective cohort study aimed to examine whether serum copeptin concentration is a useful predictor of this.Methods:The study population consisted of 80 patients with liver cirrhosis treated with tolvaptan for hepatic ascites effusions at Nara Medical University Hospital from May 2014 to December 2018.Forty-three patients who lost>1.5 kg of body weight in the first week after starting tolvaptan were classified as good responders and the remaining 37 as poor responders.Various laboratory parameters were measured immediately before the start of tolvaptan therapy to examine factors associated with predicting its efficacy.Results:In the univariate analysis,no significant differences with respect to age(67.6 vs.69.8 years,p>0.05),sex,body mass index(24.8 vs.23.7 kg/m^(2),p>0.05),Child-Pugh score(9.4 vs.9.7,p>0.05),and Model for End-stage Liver Disease score(11 vs.12,p>0.05)were found between the two groups.Conversely,aspartate transferase and alanine transaminase(ALT)levels were significantly lower in the good response group(52.9±56.3 vs.68.8±50.7 U/L,p<0.05;26.2±30.6 vs.40.5±33.5 U/L,p<0.01),whereas serum copeptin and serum sodium concentrations were significantly higher(57.1±15.0 vs.45.8±16.0 pg/mL,p<0.01;136.3±3.4 vs.133.8±5.8 mEq/L,p<0.05).In the multivariate analysis,serum copeptin concentration and ALT were statistically significant factors(p<0.01,p<0.05).Regression analysis of the association between the tolvaptan efficacy for refractory ascites and pretreatment serum copeptin concentration showed that a copeptin concentration cutoff of 45.9 pg/mL could predict treatment efficacy with a sensitivity,specificity,and area under the curve of 76.7%,59.5%,and 0.71%,respectively.Conclusion:Serum copeptin concentration may be a predictor of tolvaptan efficacy for refractory ascites effusion in Japanese patients with liver cirrhosis.