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BACKGROUND: Although tolvaptan treatment improves hyponatremia, only few studies have investigated whether tolvaptan actually benefits the survival of cirrhotic patients. This study evaluated the impact of tolvaptan on six-month survival of decompensated cirrhotic patients with and without hyponatremia. METHODS: Two hundred forty-nine decompensated cirrhotic patients with or without hyponatremia were enrolled in a multicenter cohort study. Patients were divided into two groups according to receiving either tolvaptan or placebo treatment for 7-day. Subsequently, the patients were followed up for 6 months. RESULTS: Two hundred thirty patients, including 98 with hyponatremia (tolvaptan vs. placebo: 69 vs. 29) finished the study. Tolvaptan did not alter serum sodium levels and survival outcome of decompensated cirrhotic patients without hyponatremia. However, tolvaptan treatment remarkably improved serum sodium levels and six-month survival in patients with hyponatremia. Following tolvaptan treatment, serum sodium levels were restored to normal in 63.8% of patients, whereas in patients receiving placebo, only 36.2% showed the same effect (P < 0.05). Compared to a six-month survival rate of 68.97% in patients receiving placebo, the survival rate in tolvapatan-treated patients was 89.94% (P < 0.05). Furthermore, six-month survival rate in the tolvaptan-treated hyponatremia patients with resolved serum sodium was 81.32%, whereas the survival in those with unresolved serum sodium was only 24% (P < 0.05). CONCLUSIONS: Tolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium. TRIALS REGISTRATION: Clinical trial one: ClinicalTrials.gov ID: NCT00664014 , Registered on April 14, 2008. Clinical trial two: ClinicalTrials.gov ID: NCT01349335 , Registered on March 5, 2010. Clinical trial three: ClinicalTrials.gov ID: NCT01349348 , Registered on May 4, 2011.
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Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Ascite/tratamento farmacológico , Benzazepinas/uso terapêutico , Hiponatremia/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/mortalidade , Adulto , Ascite/etiologia , Método Duplo-Cego , Feminino , Humanos , Hiponatremia/etiologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sódio/sangue , Taxa de Sobrevida , TolvaptanRESUMO
Introduction and aim. Hyponatremia is common in patients with decompensated cirrhosis and is associated with increased mortality. Tolvaptan, a vasopressor V2 receptor antagonist, can increase free water excretion, but its efficacy and safety in cirrhotic patients remain unclear. MATERIAL AND METHODS: We studied the usage and safety of tolvaptan in cirrhotic patients in a real-life, non-randomized, multicenter prospective cohort study. Forty-nine cirrhotic patients with hyponatremia were treated with tolvaptan 15 mg daily, and 48 patients not treated with tolvaptan in the same period served as controls. Improvement in serum sodium level was defined as an increase in serum sodium from < 125 to ≥ 125 mmol/L or from 125-134 to ≥ 135 mmol/L on day 7. RESULTS: Twenty-three (47%) patients in the tolvaptan group and 17 (35%) in the control group had normal serum sodium on day 7 (p = 0.25). Serum sodium improved in 30 (61%) patients in the tolvaptan group and 17 (35%) patients in the control group (p = 0.011). Adverse events occurred in 46-47% of patients in both groups, and tolvaptan was not associated with worsened liver function. No patient with normal serum sodium on day 7 died within 30 days of treatment, whereas 16% of those with persistent hyponatremia died (p = 0.0019). CONCLUSION: In conclusion, short-term tolvaptan treatment is safe and can improve serum sodium level in cirrhotic patients with hyponatremia. Normalization of serum sodium level is associated with better survival.
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Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Benzazepinas/uso terapêutico , Hiponatremia/tratamento farmacológico , Cirrose Hepática/complicações , Sódio/sangue , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Benzazepinas/efeitos adversos , Biomarcadores/sangue , Estudos de Casos e Controles , China , Feminino , Humanos , Hiponatremia/sangue , Hiponatremia/etiologia , Hiponatremia/mortalidade , Estimativa de Kaplan-Meier , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Tolvaptan , Resultado do TratamentoRESUMO
BACKGROUND: It is difficult to diagnose spontaneous bacterial peritonitis (SBP) early in decompensated liver cirrhotic ascites patients (DCPs). The aim of the study was to measure serum procalcitonin (PCT) levels and peripheral blood leukocyte/platelet (WBC/PLT) ratios to obtain an early diagnostic indication of SBP in DCPs. METHODS: Our cohort of 129 patients included 112 DCPs (94 of whom had infections) and 17 cases with compensated cirrhosis as controls. Bacterial cultures, ascitic fluid (AF) leukocyte and peripheral WBC/PLT counts, and serum PCT measurements at admission were carried out prior to the use of antibiotics. Receiver operating characteristic (ROC) curves were generated to test the accuracies and cut-off values for different inflammatory markers. RESULTS: Among the 94 infected patients, 66 tested positive by bacterial culture, for which the positivity of blood, ascites and other secretions were 25.8%, 30.3% and 43.9%, respectively. Lung infection, SBP and unknown sites of infection accounted for 8.5%, 64.9% and 26.6% of the cases, respectively. Serum PCT levels (3.02 ± 3.30 ng/mL) in DCPs with infections were significantly higher than those in control patients (0.15 ± 0.08 ng/mL); p < 0.05. We used PCT ≥0.5 ng/mL as a cut-off value to diagnose infections, for which the sensitivity and specificity was 92.5% and 77.1%. The area under the curve (AUC) was 0.89 (95% confidence interval: 0.84-0.91). The sensitivity and specificity were 62.8% and 94.2% for the diagnosis of infections, and were 68.8% and 94.2% for the diagnosis of SBP in DCPs when PCT ≥2 ng/mL was used as a cut-off value. For the combined PCT and WBC/PLT measurements, the sensitivity was 76.8% and 83.6% for the diagnosis of infections or SBP in DCPs, respectively. CONCLUSION: Serum PCT levels alone or in combination with WBC/PLT measurements seem to provide a satisfactory early diagnostic biomarker in DCPs with infections, especially for patients with SBP.
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Infecções Bacterianas/diagnóstico , Calcitonina/sangue , Cirrose Hepática/complicações , Peritonite/complicações , Peritonite/diagnóstico , Precursores de Proteínas/sangue , Adulto , Idoso , Ascite/complicações , Ascite/diagnóstico , Ascite/microbiologia , Infecções Bacterianas/sangue , Infecções Bacterianas/microbiologia , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Contagem de Leucócitos , Cirrose Hepática/microbiologia , Masculino , Pessoa de Meia-Idade , Peritonite/sangue , Peritonite/microbiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Background and Aims: The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy. Methods: Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days. Results: Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count. Conclusions: Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.
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BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. However, there are little published data on risk factors and outcomes of LT for ACLF. METHODS: The objective of this study was to analyze preoperative, intraoperative, postoperative, and overall survival data on 100 consecutive cases with ACLF in order to try to determine for which patients LT are futile. RESULTS: One hundred consecutive patients with pathology-confirmed ACLF who underwent LT from June 2004 to September 2012 were enrolled. The preoperative data showed that all patients were in a serious condition with a median high model for end-stage liver disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed by a Sequential Organ Failure Assessment (SOFA) score of ≥9. The patients had either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3-, and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%, respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%, 72.1%, and 70.6%, respectively. However, the area under receiver operating characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552, 0.547, and 0.547, respectively. CONCLUSIONS: Both deceased and living donor LT are effective therapeutic options for patients with ACLF and the short- and long-term survival rates are encouraging. It is important to conduct more prospective and multi-center studies to define preoperatively which patients would benefit from LT.
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Doença Hepática Terminal/cirurgia , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Adulto , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Falência Hepática Aguda/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos , Resultado do TratamentoRESUMO
We experienced a case of a 36-year-old married man who was found to be hepatitis B virus (HBV) positive at 23 years of age. His liver function was repeatedly abnormal in the past 13 years. In November 2007 he presented with fatigue. Laboratory tests showed serum alanine aminotransferase concentration 255.3 U/l, positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antibody, HBV DNA 3.01 × 10(7) copies/ml; liver biopsy showed necroinflammatory scores 11 and fibrosis scores 4. After 20 weeks of treatment with Peg-IFN α-2b, laboratory tests showed HBV DNA <500 copies/ml and normal liver function. By week 52 of the treatment, HBsAg became negative. By week 92 of continuing treatment, HBsAb became weakly positive and Peg-IFN α-2b treatment was stopped. On follow-up, both HBsAg and HBsAb were negative 28 weeks after discontinuation of Peg-IFN α-2b. We then performed a second liver biopsy and histological examination revealed necroinflammtary scores 2 and fibrosis scores 2. We administered hepatitis B vaccine intramuscularly every 4 weeks combined with IFN α-1b 30 µg intramuscularly every other day. HBsAb was 244.8 IU/l at week 32 of this combined treatment. Follow-up showed that after discontinuation of the combined treatment HBsAb concentration declined rapidly but could be maintained above 100 IU/l by intermittent injections of hepatitis B vaccine. Findings from this case reveal that HBsAg loss may be not sufficient; however, HBsAg seroconversion together with maintenance of certain concentrations of HBsAb may be a better endpoint to HBV treatment.
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Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Adulto , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis (mPVTT) and cirrhotic portal hypertension (CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm. AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with radioactive seed strand for the treatment of mPVTT patients with CPH. METHODS: The clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data (success rate, relief of portal vein pressure and CPH symptoms, and adverse events), PVTT response, and patient survival were assessed through a 2-year follow-up. RESULTS: The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure (22.25 ± 7.33 mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo (range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%, and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo (95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage, and PVTT response were independent prognostic factors (P < 0.05). CONCLUSION: TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.
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BACKGROUND: The liver is one of the most important organs in the human body, with functions such as detoxification, digestion, and blood coagulation. In terms of vascular anatomy, the liver is divided into the left and the right liver by the main portal vein, and there are three hepatic efferent veins (right, middle, and left) and two portal branches. Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation, which may lead to an increase in the portal pressure gradient (PPG) and cause portal hypertension (PHT). In order to measure the increased pressure gradient of portal vein, the hepatic venous pressure gradient (HVPG) can be measured to reflect it in clinical practice. The accuracy of PPG measurements is directly related to patient prognosis. AIM: To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT. METHODS: From January 2017 to December 2019, 102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed. RESULTS: The mean HVPG of the middle hepatic vein was 17.47 ± 10.25 mmHg, and the mean HVPG of the right and left hepatic veins was 16.34 ± 7.60 and 16.52 ± 8.15 mmHg, respectively. The average PPG was 26.03 ± 9.24 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.15 and 0.02 (P = 0.164); 0.25 and 0.05 (P = 0.013); and 0.14 and 0.02 (P = 0.013), respectively. The mean wedged hepatic vein/venous pressure (WHVP) of the middle and left hepatic veins was similar at 29.71 ± 12.48 and 29.1 ± 10.91 mmHg, respectively, and the mean WHVP of the right hepatic vein was slightly lower at 28.01 ± 8.95 mmHg. The mean portal vein pressure was 34.11 ± 8.56 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.26 and 0.07 (P = 0.009); 0.38 and 0.15 (P < 0.001); and 0.26 and 0.07 (P = 0.008), respectively. The average free hepatic venous pressure (FHVP) of the right hepatic vein was lowest at 11.67 ± 5.34 mmHg, and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19 ± 4.88 and 11.67 ± 5.34 mmHg, respectively. The average inferior vena cava pressure was 8.27 ± 4.04 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.30 and 0.09 (P = 0.002); 0.18 and 0.03 (P = 0.078); and 0.16 and 0.03 (P = 0.111), respectively. CONCLUSION: Measurement of the middle hepatic vein HVPG could better represent PPG. Considering the high success rate of clinical measurement of the right hepatic vein, it can be the second choice.
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BACKGROUND: Peptic ulcer (PU) is more prevalent in patients with liver cirrhosis. The role of Helicobacter pylori (H. pylori) infection in the pathogenesis of PU in patients with cirrhosis is still not elucidated. AIM: To perform a meta-analysis on the prevalence of H. pylori infection and PU and their association in liver cirrhosis patients. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane, CNKI, Wangfang, and CQVIP databases from inception to July 10, 2020. Odds ratio (OR) and 95% confidence interval (CI) were pooled using a random-effects model. The statistical heterogeneity among studies (I 2-index), subgroup analyses, regression analysis, sensitivity analysis, and the possibility of publication bias were assessed. RESULTS: A total of 14 studies (13 cross-sectional studies; 1 cohort study) involving 2775 individuals (611 cases with PU and 2164 controls) were included in our meta-analysis. The prevalence of PU in patients with cirrhosis was 22%. The prevalence of H. pylori infection was 65.6% in cirrhotic patients with PU, and 52.5% in those without. The pooled overall OR was 1.73 (95%CI: 1.16-2.56, I 2 = 66.2%, P < 0.001, Z = 2.7, P z < 0.05). We did not find the cause of heterogeneity in the subgroup analyses and meta-regression analysis except for one study. Funnel plot did not show significant publication bias. The results of Begg's test and Egger's test indicated no evidence of substantial publication bias (P Begg = 0.732, P Egger = 0.557). CONCLUSION: There is a weakly positive association between H. pylori infection and PU in patients with liver cirrhosis. It is suggested that H. pylori infection may play a role in the pathogenesis of PU in liver cirrhotic patients.
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BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) is a matter of debate. Although it has been studied in many observational studies, the results remain controversial. Therefore, we performed a meta-analysis to assess the association between H pylori infection and risk of NAFLD. METHODS: We searched Pubmed, EMBASE, and Web of Science databases, from inception to September 10, 2020. Odds ratio (OR) and 95% confidence interval (CI) were pooled by random-effects model. The statistical heterogeneity among studies (I2-index), subgroup analyses, regression analyses, sensitivity analysis and the possibility of publication bias were assessed. RESULTS: A total of seventeen studies involving 91,958 individuals were included in our meta-analysis. Meta-analysis of data from cross-sectional and case-control studies showed that H pylori infection was associated with increased risk of prevalent NAFLD (nâ=â15; involving 74,561 middle-aged individuals; OR1.38, 95% CI 1.23-1.55, I2â=â86.8%, Pâ<â.001). The results of meta-regression implicated that the study type and the case-control ratio impacted the total effect size. Funnel plot did not show significant publication bias. Meta-analysis of data from longitudinal studies showed that H pylori infection was also associated with increased NAFLD incidence (nâ=â2; involving 17397 individuals; OR 1.21, 95% CI 1.01-1.44, I2â=â6.5%, Pâ=â.301). CONCLUSIONS: The results indicated that a positive association between H pylori infection and the risk of NAFLD. Further studies are required to strengthen the association and clarify the mechanism.
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Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Humanos , Incidência , Estudos Observacionais como Assunto , PrevalênciaRESUMO
BACKGROUND: The impact of type 2 diabetes mellitus (T2DM) on the prognosis and complications of liver cirrhosis is not fully clarified. AIM: To clarify the mortality and related risk factors as well as complications in cirrhotic patients with T2DM. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from their inception to December 1, 2020 for cohort studies comparing liver transplant-free mortality, hepatocellular carcinoma (HCC), ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy (HE) in cirrhotic patients with vs without T2DM. Odds ratios (ORs) were combined by using fixed-effects or random-effects models with RevMan software. RESULTS: The database search generated a total of 17 cohort studies that met the inclusion criteria. Among these studies, eight reported the risk of mortality, and eight reported the risk of HCC. Three studies provided SBP rates, and two documented ascites rates. Four articles focused on HE rates, and three focused on variceal bleeding rates. Meta-analysis indicated that T2DM was significantly associated with an increased risk of liver transplant-free mortality [OR: 1.28, 95% confidence intervals (CI): 1.16-1.41, P < 0.0001] and HCC incidence (OR: 1.82, 95%CI: 1.32-2.51, P = 0.003). The risk of SBP was not significantly increased (OR: 1.16 95%CI: 0.86-1.57, P = 0.34). Additionally, T2DM did not significantly increase HE (OR: 1.31 95%CI: 0.97-1.77, P = 0.08), ascites (OR: 1.11 95%CI: 0.84-1.46, P = 0.46), and variceal bleeding (OR: 1.34, 95%CI: 0.99-1.82, P = 0.06). CONCLUSION: The findings suggest that cirrhotic patients with T2DM have a poor prognosis and high risk of HCC. T2DM may not be associated with an increased risk of SBP, variceal bleeding, ascites, or HE in cirrhotic patients with T2DM.
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BACKGROUND: Reflux esophagitis (RE) is increasing in prevalence in China. There are very few studies on the prevalence and factors related to RE in patients with chronic liver diseases. The aims of this study were to determine the prevalence of RE by endoscopy in patients with chronic liver diseases and the possible related predictors of RE. METHODS: A total of 1,280 patients with chronic liver disease and 29 patients with acute hepatitis A or E were prospectively evaluated. There were 879 and 401 patients with liver cirrhosis or chronic hepatitis, respectively. RE was classified by endoscopy according to the Los Angeles classification scheme. RESULTS: RE was diagnosed in 36.4% (469/1280) of the chronic liver disease patients, which was significantly higher than in the acute hepatitis patients (10.3% [3/29], P < 0.001). RE accounted for 43.0%, 9.7%, and 60.2% of patients with liver cirrhosis, chronic hepatitis(mild and medium), and liver failure, respectively. A high prevalence of RE existed in patients with liver failure and/or Child B and C liver cirrhosis, with typical symptoms of RE in 21.3% of the patients (100/469). There was a significant relationship between gender, age, ascites, and RE. CONCLUSIONS: The high prevalence of RE among upper endoscopies of patients with severe chronic liver disease was demonstrated. Asymptomatic RE was more common in cirrhotic and liver failure patients. The role of RE in variceal bleeding, however, needs to be demonstrated.
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Esofagite Péptica/etnologia , Esofagite Péptica/epidemiologia , Hepatopatias/complicações , Hepatopatias/etnologia , Adolescente , Adulto , Idoso , China/epidemiologia , Doença Crônica , Endoscopia do Sistema Digestório , Feminino , Hepatite Crônica/complicações , Hepatite Crônica/etnologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/etnologia , Falência Hepática/complicações , Falência Hepática/etnologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to determine if Golgi protein-73 (GP73) is up-regulated in hepatocellular carcinoma (HCC), and to explore the possibility of using GP73 in diagnosis and treatment of HCC. METHODS: Serum GP73 was detected by a quantitative ELISA assay. A total of 372 serum samples were included, among them 43 from healthy donors (Normal), 110 from either chronic hepatitis or cirrhosis (CH/LC), and 219 from HCC patients. The levels of GP73 were compared among the 3 groups. The received operating curve (ROC), sensitivity and specificity of GP73 for HCC patients were calculated. RESULTS: The average level of GP73 expression in normal, CH/LC and HCC groups were (22.1 ± 8.5) ng/ml, (81.4 ± 57.2) ng/ml and (271.5 ± 202.3) ng/ml, respectively. Serum GP73 levels were significantly higher in patients with HCC compared to those with CH/LC (P < 0.001). The GP73 area under ROC was 0.857. Put 100 ng/ml as the optimal cut-off point, GP73 had a sensitivity of 76.7% and a specifically of 73.2%. GP73 level had a significantly higher sensitivity than AFP (32.0%) in diagnosis of early HCC (P < 0.001). Moreover, GP73 level was elevated in the serum (72.5%, 108/149) of individuals with HCC who had serum AFP level less than 400 ng/ml. Following-up study of 4 HCC patients with low level AFP indicated that GP73 was associated with treatment and prognosis of HCC. CONCLUSION: Higher level of GP73 can be found in the serum of patients with HCC than those without. GP73 is better than AFP for the diagnosis of early HCC and in evaluating treatment result in patients with normal AFP. Further studies may help to validate both the role and mechanism of GP73 in diagnosis of HCC.
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Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Proteínas de Membrana/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Feminino , Complexo de Golgi/metabolismo , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem , alfa-Fetoproteínas/metabolismoRESUMO
OBJECTIVE: To investigate the clinical significance of liver function and autoantibodies in patients with acute or chronic drug-induced liver injury. METHODS: 51 patients with drug-induced liver injury were divided into acute drug induced liver injury group and chronic drug induced liver injury group, liver function and autoantibodies were compared between these two groups. RESULTS: There was no significant difference (P more than 0.05) in alanine aminotransferase [(412.1+/-387.5) U/L and (376.0+/-319.7) U/L], aspartate aminotransferase [(352.5+/-457.9) U/L and (198.8+/-142.7) U/L], total bilirubin [(109.7+/-104.80)micromol/L and(102.4+/-135.7)micromol/L], direct bilirubin [(66.4+/-73.3)micromol/L and (61.2+/-72.1)micromol/L], alkaline phosphatase [(133.4+/-50.1) U/L and (147.4+/-97.3) U/L], gamma-glutamyltransferase [(139.9+/-134.1) U/L and (180.6+/-227.9) U/L], and albumin [(41.3+/-4.9) g/L and (39.8+/-5.3)g/L] between these two groups, however, the level of globulin [(25.1+/-5.3) g/L and (28.6+/-5.1) g/L] was significantly different between these two groups (P less than 0.05). The titers of Anti-nuclear antibody (ANA) and smooth muscle antibody (SMA) were less than or equal to 1:320 in patients with acute drug induced liver injury. The titers of ANA, antimitochondrial antibody (AMA), and SMA were more than or equal to 1:320 in most of the patients with chronic drug induced liver injury. CONCLUSION: Liver function has no value in the diagnosis of acute or chronic drug induced liver injury. High titer autoantibodies are found in patients with chronic drug induced liver injury.
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Autoanticorpos/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Fígado/patologia , Doença Aguda , Adulto , Anticorpos Antinucleares/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Diagnóstico Diferencial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Fígado/fisiopatologia , Testes de Função Hepática , Masculino , Microssomos/imunologia , Pessoa de Meia-Idade , Músculo Liso/imunologiaRESUMO
BACKGROUND: Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis. However, few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites. AIM: To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism. METHODS: A total of 75 cirrhotic patients with refractory ascites were enrolled in the study (50 in a rifaximin and 25 in a control group). Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics (19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics). All patients received conventional treatment for refractory ascites, while patients in the rifaximin group received oral rifaximin-α 200 mg four times daily for at least 2 wk. The ascites grade, fasting weight, liver and kidney function, and inflammatory factors in the plasma were evaluated before and after treatment. In addition, the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment. The patients were followed for 6 mo. RESULTS: Compared with the control group, the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin (P = 0.011 and 0.009, respectively). The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group (P = 0.048). The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group (P = 0.024). The abundance of Roseburia, Haemophilus, and Prevotella was significantly reduced after rifaximin treatment, while the abundance of Lachnospiraceae_noname, Subdoligranulum, and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics. The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics. CONCLUSION: Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites. A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria, thus improving the systemic inflammatory state.
Assuntos
Antibacterianos/uso terapêutico , Ascite/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Peritonite/tratamento farmacológico , Rifaximina/uso terapêutico , Idoso , Antibacterianos/farmacologia , Ascite/imunologia , Ascite/microbiologia , Ascite/mortalidade , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Resistência a Medicamentos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/microbiologia , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Peritonite/imunologia , Peritonite/microbiologia , Peritonite/mortalidade , Rifaximina/farmacologia , Resultado do TratamentoRESUMO
BACKGROUND: Computed tomography (CT), liver stiffness measurement (LSM), and magnetic resonance imaging (MRI) are non-invasive diagnostic methods for esophageal varices (EV) and for the prediction of high-bleeding-risk EV (HREV) in cirrhotic patients. However, the clinical use of these methods is controversial. AIM: To evaluate the accuracy of LSM, CT, and MRI in diagnosing EV and predicting HREV in cirrhotic patients. METHODS: We performed literature searches in multiple databases, including PubMed, Embase, Cochrane, CNKI, and Wanfang databases, for articles that evaluated the accuracy of LSM, CT, and MRI as candidates for the diagnosis of EV and prediction of HREV in cirrhotic patients. Summary sensitivity and specificity, positive likelihood ratio and negative likelihood ratio, diagnostic odds ratio, and the areas under the summary receiver operating characteristic curves were analyzed. The quality of the articles was assessed using the quality assessment of diagnostic accuracy studies-2 tool. Heterogeneity was examined by Q-statistic test and I 2 index, and sources of heterogeneity were explored using meta-regression and subgroup analysis. Publication bias was evaluated using Deek's funnel plot. All statistical analyses were conducted using Stata12.0, MetaDisc1.4, and RevMan5.3. RESULTS: Overall, 18, 17, and 7 relevant articles on the accuracy of LSM, CT, and MRI in evaluating EV and HREV were retrieved. A significant heterogeneity was observed in all analyses (P < 0.05). The areas under the summary receiver operating characteristic curves of LSM, CT, and MRI in diagnosing EV and predicting HREV were 0.86 (95% confidence interval [CI]: 0.83-0.89), 0.91 (95%CI: 0.88-0.93), and 0.86 (95%CI: 0.83-0.89), and 0.85 (95%CI: 0.81-0.88), 0.94 (95%CI: 0.91-0.96), and 0.83 (95%CI: 0.79-0.86), respectively, with sensitivities of 0.84 (95%CI: 0.78-0.89), 0.91 (95%CI: 0.87-0.94), and 0.81 (95%CI: 0.76-0.86), and 0.81 (95%CI: 0.75-0.86), 0.88 (95%CI: 0.82-0.92), and 0.80 (95%CI: 0.72-0.86), and specificities of 0.71 (95%CI: 0.60-0.80), 0.75 (95%CI: 0.68-0.82), and 0.82 (95%CI: 0.70-0.89), and 0.73 (95%CI: 0.66-0.80), 0.87 (95%CI: 0.81-0.92), and 0.72 (95%CI: 0.62-0.80), respectively. The corresponding positive likelihood ratios were 2.91, 3.67, and 4.44, and 3.04, 6.90, and2.83; the negative likelihood ratios were 0.22, 0.12, and 0.23, and 0.26, 0.14, and 0.28; the diagnostic odds ratios were 13.01, 30.98, and 19.58, and 11.93, 49.99, and 10.00. CT scanner is the source of heterogeneity. There was no significant difference in diagnostic threshold effects (P > 0.05) or publication bias (P > 0.05). CONCLUSION: Based on the meta-analysis of observational studies, it is suggested that CT imaging, a non-invasive diagnostic method, is the best choice for the diagnosis of EV and prediction of HREV in cirrhotic patients compared with LSM and MRI.
Assuntos
Varizes Esofágicas e Gástricas/diagnóstico , Hemorragia Gastrointestinal/epidemiologia , Cirrose Hepática/complicações , Fígado/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Imageamento por Ressonância Magnética , Estudos Observacionais como Assunto , Curva ROC , Medição de Risco/métodos , Tomografia Computadorizada por Raios XRESUMO
Based on reviews of the literature and experts' consensus, the Chinese Society of Hepatology developed guidelines for the diagnosis and treatment of liver cirrhosis, in order to improve clinical practice. In addition to what has been covered in previously published guidelines on the management of cirrhosis complications, these guidelines add new sections and provide updates. The guidelines emphasize the early diagnosis of the cause and assessment of complications. Comprehensive treatments including etiological treatment and complication management should be initiated immediately. In addition, regular monitoring, especially surveillance of hepatocellular carcinoma, is crucial for managing patients.
Assuntos
Carcinoma Hepatocelular , Gastroenterologia , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , China/epidemiologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Neoplasias Hepáticas/terapiaRESUMO
OBJECTIVE: To investigate the incidence, clinical features and prognostic implications of ischemic hepatitis in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage. METHODS: By retrospective review of the medical records of all 264 inpatients with upper gastrointestinal hemorrhage of hepatitis B related liver cirrhosis from January 1st 2007 to November 30th 2008, 11 patients with ischemic hepatitis (IH) were identified. The clinical features and prognostic implications were compared between the IH patients and 30 patients without ischemic hepatitis (control group). RESULTS: The incidence of ischemic hepatitis was 4.17% in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage. The patients in IH group were younger than those in control group, the average age was (43.1+/-5.7) in IH group and (52.3+/-11.1) in control group (P=0.013). The serum alanine aminotransferase and aspartate aminotransferase were increased more than 20-fold above the upper limit of normal values, and returned to normal values within 10 days. Compared to the control group, total bilirubin, lactate dehydrogenase, alkaline phosphates, gamma-glutamyltransferase, blood urea nitrogen, creatinine, and white blood cells were increased, while serum cholinesterase was decreased in IH group (P<0.05). The fatality rate of ischemic hepatitis was much higher than that of control group (54.5% vs 16.7%, P=0.041). The main causes of death in IH group were infection, hepatorenal syndrome and hepatic encephalopathy. The patients in IH group lost 200 to 3600 milliliter blood, and hemorrhagic shock occurred in 63.6% (7/11) of IH patients. Therefore the bleeding volume was not correlated with the occurrence rate of ischemic hepatitis. CONCLUSION: Ischemic hepatitis may occur secondary to upper gastrointestinal hemorrhage in hepatitis B related liver cirrhosis. The risk factors of ischemic hepatitis in cirrhositic patients with upper gastrointestinal hemorrhage are young and with hemorrhagic shock, and poor liver function. It is important to use antibiotics in time to improve the prognosis of these patients.
Assuntos
Hemorragia Gastrointestinal/complicações , Hepatite B/complicações , Hepatite/patologia , Isquemia/patologia , Cirrose Hepática/complicações , Fígado/irrigação sanguínea , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Feminino , Hepatite/epidemiologia , Hepatite/etiologia , Humanos , Isquemia/epidemiologia , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.
Assuntos
Doença Hepática Terminal/complicações , Gastroenterologia/normas , Encefalopatia Hepática/terapia , Cirrose Hepática/complicações , Sociedades Médicas/normas , China , Consenso , Doença Hepática Terminal/terapia , Gastroenterologia/métodos , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/terapia , Prognóstico , Prevenção Secundária/métodos , Prevenção Secundária/normas , Fatores de TempoRESUMO
AIM: To study and determine the resting energy expenditure (REE) and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS: A total of 100 patients with liver diseases were categorized into three groups: 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were assessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS: The REE of the severe chronic hepatitis group (20.7 +/- 6.1 kcal/d per kg) was significantly lower than that of the acute hepatitis group (P = 0.014). The respiratory quotient (RQ) of the severe chronic hepatitis group (0.84 +/- 0.06) was significantly lower than that of the acute hepatitis and cirrhosis groups (P = 0.001). The glucose oxidation rate of the severe hepatitis group (39.2%) was significantly lower than that of the acute hepatitis group and the cirrhosis group (P < 0.05), while the fat oxidation rate (39.8%) in the severe hepatitis group was markedly higher than that of the other two groups (P < 0.05). With improvement of liver function, the glucose oxidation rate increased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is significantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These results warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.