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1.
Rev Med Suisse ; 17(748): 1453-1456, 2021 Sep 01.
Artigo em Francês | MEDLINE | ID: mdl-34468096

RESUMO

Treatment of hepatitis C has known major progress thanks to direct-acting antivirals resulting in the healing, defined by a viral clearance (sustained virological response [SVR]), in the vast majority of patients. However, there is a residual risk of progressive liver damage in a minority of patients, potentially leading to complications such as liver decompensation, hepatocellular carcinoma and/or death. This article discusses the current knowledge of residual liver disease after treatment, the impact of comorbidities and the factors potentially predicting patients at risk of complications and warranting surveillance.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia
2.
World J Gastroenterol ; 27(30): 5088-5099, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34497437

RESUMO

BACKGROUND: As a country with a high burden of hepatitis B, China has about 86 million cases of hepatitis B virus infection, ranking the first in the world. Currently, there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year. Consequently, how to control portal hypertension, improve liver functional reserve, and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention. Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt (TIPS), the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcohol-induced and immune cirrhosis, which may be related to the effective etiological treatment. AIM: To investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China (2019) in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS. METHODS: The clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively. According to different anti-viral drugs, the patients were divided into entecavir (ETV) (n = 70), tenofovir alafenamide fumarate (TAF) (n = 32), and tenofovir disoproxil fumarate (TDF) (n = 35) groups. The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma, survival, and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated. RESULTS: At 24 mo after surgery, the Child-Pugh score in the TAF group (6.97 ± 0.86) was lower than that in the TDF (7.49 ± 0.82; t = -2.52, P = 0.014) and ETV groups (7.64 ± 1.17; t = -2.92, P = 0.004). The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72 ± 1.5, which was lower than that in the TDF (10.74 ± 2.33; t = -2.09, P = 0.040) and ETV groups (10.97 ± 2.17; t = -2.93, P = 0.004). At 24 mo after surgery, the estimated glomerular filtration rate (eGFR) in the TAF group (104.41 ± 12.54) was higher than that in the TDF (93.54 ± 8.97) and ETV groups (89.96 ± 9.86) (F = 21.57, P < 0.001). CONCLUSION: At 24 mo after surgery, compared with TDF and ETV, TAF has significant advantages in the improvement of liver functional reserve and eGFR.


Assuntos
Doença Hepática Terminal , Hepatite B , Derivação Portossistêmica Transjugular Intra-Hepática , Antivirais/efeitos adversos , Doença Hepática Terminal/tratamento farmacológico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
3.
J Assoc Physicians India ; 69(8): 11-12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34472804

RESUMO

INTRODUCTION: Hepatic encephalopathy (HE) is a significant complication of severe chronic liver insufficiency characterized by altered sensorium, motor, and cognitive dysfunction. This was a cross-sectional multicenter, epidemiological study to understand the prescribing pattern for primary prophylaxis of overt HE (OHE) in patients with cirrhosis in India. METHODS: The study was conducted at eight centers across different geographical regions of India. A total of 200 patients (100%) were screened, of which 197 (98.50%) met all the inclusion criteria. The prescribing pattern of the physicians was studied by calculating the percentage (subject to availability of sufficient data) of OHE-naïve patients with cirrhosis who were prescribed with different classes of drugs as primary prophylaxis of HE (such as lactulose, rifaximin, neomycin, sodium benzoate, and L-ornithine L- aspartate). The risk factors responsible for initiation of primary prophylaxis of HE was also determined. RESULTS: All the 197 patients (100%) were prescribed with prophylactic treatment. The factors that were considered by treating physicians to pose a risk for precipitating OHE for which prophylaxis was initiated were constipation in 111 (56.35%), infections in 51 (25.89%) and gastrointestinal bleeding in 35 (17.77%). Of the total 197 patients, 122 (61.93%) patients were prescribed a monotherapy, and 75 (38.07%) were prescribed a combination therapy. Of the patients on combination therapy, 68 (34.52%) patients were prescribed with two primary prophylaxis agents (dual therapy), and seven (3.55%) patients were prescribed with three primary prophylaxis agents (triple therapy). Lactulose was the most commonly prescribed agent for primary prophylaxis, followed by rifaximin. CONCLUSION: These findings may guide recommendations on primary prophylaxis for OHE in patients with liver cirrhosis that may help reduce the occurrence of first episode of overt HE, and thereby prevent subsequent cognitive impairment in these patients.


Assuntos
Encefalopatia Hepática , Estudos Transversais , Fármacos Gastrointestinais/uso terapêutico , Encefalopatia Hepática/epidemiologia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/prevenção & controle , Humanos , Lactulose/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico
4.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360721

RESUMO

Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does not always protect against hepatocellular carcinoma (HCC). Angiopoietin-like protein-3 (ANGPTL-3) and angiopoietin-like protein-4 (ANGPTL-4) regulate the clearance of plasma lipids by inhibiting cellular lipase activity and possess emerging roles in tumourigenesis. We used ELISA and RT-qPCR to investigate ANGPTL-3 and ANGPTL-4 expression in HCV patients with characterised fibrosis throughout the natural history of hepatitis C and in long-term HCV infection in vitro, before and after DAA treatment. ANGPTL-3 was decreased in patients with advanced fibrosis compared to other disease stages, while ANGPTL-4 was progressively increased from acute infection to cirrhosis and HCC, peaking at the advanced fibrosis stage. Only ANGPTL-3 mRNA was down-regulated during early infection in vitro, although both ANGPTLs were increased later. DAA treatment did not alter ANGPTL-3 levels in advanced fibrosis/cirrhosis and in HCV infection in vitro, in contrast to ANGPTL-4. The association between ANGPTLs and fibrosis in HCV infection was underlined by an inverse correlation between the levels of ANGPTLs and serum transforming growth factor- ß (TGF-ß). Collectively, we demonstrate the pivotal role of advanced fibrosis in defining the expression fate of ANGPTLs in HCV infection and after treatment and propose a role for ANGPTL-3 as a contributor to post-treatment deregulation of lipid metabolism that could predispose certain individuals to HCC development.


Assuntos
Proteína 4 Semelhante a Angiopoietina/biossíntese , Proteínas Semelhantes a Angiopoietina/biossíntese , Antivirais/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Hepacivirus/metabolismo , Hepatite C Crônica , Cirrose Hepática , Linhagem Celular Tumoral , Feminino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Masculino
5.
World J Gastroenterol ; 27(29): 4831-4845, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34447229

RESUMO

Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts. Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients. The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments. Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence, the number of new infections. Antiviral treatments have decreased the rates of liver decompensation and as a result, lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection. The quality of life of chronically infected patients has also been improved significantly by modern treatment. Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis. Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation. This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Qualidade de Vida
6.
Medicine (Baltimore) ; 100(32): e26902, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397919

RESUMO

ABSTRACT: Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010-2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066-4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702-1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.


Assuntos
Encefalopatia Hepática/epidemiologia , Cirrose Hepática/tratamento farmacológico , Pontuação de Propensão , Inibidores da Bomba de Prótons/uso terapêutico , Idoso , Feminino , Encefalopatia Hepática/etiologia , Humanos , Incidência , Japão/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco
9.
Ann Intern Med ; 174(8): JC91, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34339226

RESUMO

SOURCE CITATION: China L, Freemantle N, Forrest E, et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med. 2021;384:808-17. 33657293.


Assuntos
Albuminas , Cirrose Hepática , China , Hospitais , Humanos , Cirrose Hepática/tratamento farmacológico
11.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 685-689, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34371540

RESUMO

Objective: To investigate the effect of anti-liver fibrosis treatment on the occurrence of liver cancer in patients with hepatitis B-related liver cirrhosis within three years. Methods: 1,049 cases with hepatitis B-related liver cirrhosis who were hospitalized in Beijing Ditan Hospital affiliated to Capital Medical University from October 2008 to August 2016 were enrolled. Clinical data were collected, and COX regression analysis was used to find the independent influencing factors for the occurrence of liver cancer in patients with hepatitis B-related liver cirrhosis within three years. According to whether the patients had received anti-liver fibrosis treatment for ≥ 6 months, they were divided into combination and antiviral group. There were 388 cases in combination group and 661 cases in antiviral group. In addition, the combination group received anti-liver fibrosis therapy with Chinese patent medicine on the basis of antivirus, and the antiviral group received antiviral treatment. The incidence of liver cancer within three years were compared between the two groups, and the incidence of liver cancer in patients with different Child-Pugh grades and mPAGE-B risks was further analyzed. The independent samples t-test, Mann Whitney U test, χ2 test or Fisher's exact probability method were used for data comparison. Results: Anti-liver fibrosis treatment was an independent protective factor to prevent liver cancer in patients with hepatitis B-related liver cirrhosis within 3 years (P < 0.05). The incidence of liver cancer in the combination group was lower than antiviral group within 3 years (10.3% vs. 15.4%, χ (2) = 5.480, P < 0.05). Child-Pugh stratified analysis showed that the risk of liver cancer was significantly reduced in Child-Pugh grade A patients (6.7% vs. 12.6%, χ (2) = 2.857, P = 0.040). Among high-risk patients with mPAGE-B, the incidence of liver cancer was significantly lower in combination group than control group (13.7% vs. 19.9%, χ (2) = 6.671, P = 0.031). Conclusion: Compared to antiviral therapy alone, combined anti-liver fibrosis and antiviral therapy can reduce the liver cancer occurrence risk in patients with hepatitis B-related liver cirrhosis for 3 years. Patients with Child-Pugh grade A and high-risk group by mPAGE-B scores are the dominant population to receive treatment.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Estudos Retrospectivos
12.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 716-720, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34371546

RESUMO

Spontaneous bacterial peritonitis (SBP) is a common complication in patients with liver cirrhosis, and it is also an important inducement for patients with liver cirrhosis to develop into an acute decompensated stage, and thereby has become the concern and difficulties of clinical treatment. SBP pathogenic bacteria varies with time and region, and the confirmed detection rate of Gram-positive bacteria and multidrug-resistant bacteria has been increasing year by year. Therefore, whether the antimicrobial treatment plan based on the previous guidelines is still applicable remains to be further explored. This paper focuses on introducing the pathogenic bacteria characteristics for cirrhosis combined with SBP in different study populations, different regions, different time, and different infection modes, and further summarizes empirical antimicrobial treatment plan according to the changes of SBP pathogenic bacteria, in order to provide theoretical basis for clinical treatment.


Assuntos
Infecções Bacterianas , Peritonite , Antibacterianos/uso terapêutico , Bactérias , Infecções Bacterianas/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Peritonite/tratamento farmacológico
13.
World J Gastroenterol ; 27(28): 4639-4652, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34366626

RESUMO

This review summarizes the safety and efficacy of statins in patients with cirrhosis. Due to concerns about the safety of statins in patients with impaired liver function, they have recently been investigated as a potential treatment option in cirrhosis. The most clinically significant adverse event is statin-related myopathy, and this may be related to the high serum statin concentrations in the setting of severely impaired liver function. Rhabdomyolysis is the most serious and potentially life-threatening manifestation. It has recently been demonstrated that the recommended dose of simvastatin in patients with decompensated cirrhosis would be 20 mg/d because higher values, such as 40 mg/d, are associated with many adverse events, especially muscle injury. Likewise, simvastatin should not be administered to patients with Model for End-stage Liver Disease score > 12 and/or Child-Pugh class C because of the high risk of severe muscle injury. Due to the pleiotropic effects, the focus on statins has shifted from being considered harmful to something useful. Through these effects, statins could prevent liver-related morbidity and mortality in cirrhotic patients. Observational studies in large populations of patients with cirrhosis have shown that treatment with statins to decrease high cholesterol levels was associated with a reduced risk of hepatic decompensation, hepatocellular carcinoma development and death. The few randomized controlled trials in patients with cirrhosis and portal hypertension showed that statins lower portal pressure, quite likely through a reduction in hepatic resistance. Another large randomized controlled trial in patients with variceal bleeding showed that simvastatin in addition to standard of care did not prevent rebleeding but improved survival rate. Despite these encouraging outcomes, the quality of the evidence regarding the use of statins is low or very low due to the observational characteristics of most of the studies involved. Therefore, it is advisable to perform further randomized controlled trials on a large series of patients with hard clinical endpoints, using different statin types and varying doses. The objectives would be to prevent liver-related morbidity and mortality rather than treating cirrhosis complications to take additional information that makes it possible to add statins to the standard of care of these patients.


Assuntos
Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão Portal , Neoplasias Hepáticas , Hemorragia Gastrointestinal , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Índice de Gravidade de Doença
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(7): 1002-1011, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34308849

RESUMO

OBJECTIVE: To investigate the protective effect of Bao Gan Ning (BGN), a traditional Chinese medicinal formula, against CCl4-induced liver fibrosis in mice and explore the mechanism. METHODS: C57BL/6 mice were randomly divided into control group, liver fibrosis model group, positive control group and the low-, middle-, and high-dose BGN groups (n=10). In all but the control group, the mice were subjected to daily intraperitoneal injection of 25% CCl4 (in olive oil) to induce liver fibrosis and intragastric gavage of corresponding drugs. After 8 weeks, serum levels of ALT and AST were detected. Pathological examination of the liver was performed using HE and Sirius Red staining and α-SMA immunohistochemistry. The expression level of indoleamine 2, 3-dioxygenase 1 (IDO1) and phenotypic changes of hepatic DCs in the liver were measured. Another 18 mice were randomly divided into AAV9-NC, AAV9-IDO1 and high-dose BGN + AAV-IDO1 groups (n=6) for corresponding treatment, and 4 weeks later the deposit of hepatic IDO1 and phenotypic changes of the hepatic DCs were analyzed. RESULTS: Compared with those in the model group, serum AST and ALT levels decreased significantly in BGN group (P < 0.01). Obvious liver fibrosis was observed in the model group, while the mice treated with BGN showed obviously reduced cell necrosis and collagen proliferation in the liver with significantly lowered the expression levels of hepatic α-SMA and IDO1 (P < 0.05). The percentages of CD11C + DCs, CD11C +CD80 + DCs, CD11C +CD86 + DCs, CD11C +CD40 + DCs, CD11C +MHCII + DCs, CD3 + T cells, and CD3 +CD4 + T cells all increased significantly in BGN group as compared with the model group (P < 0.05). In mice with adenovirus-mediated IDO1 overexpression in the liver, BGN treatment significantly lowered the expression level of IDO1 (P=0.000) and increased the percentages of hepatic CD11C +CD40 + DCs, CD11C +MHCII + DCs and CD3 +CD4 + T cells (P < 0.05). CONCLUSION: BGN can effectively inhibit liver fibrosis in mice possibly by lowering the expression level of IDO1 in the liver, thus improving the function of hepatic DCs and subsequently promoting proliferation of T cells.


Assuntos
Cirrose Hepática , Fígado , Animais , Células Dendríticas , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T
15.
Expert Opin Investig Drugs ; 30(8): 813-825, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34214406

RESUMO

Introduction: Accumulating evidence supports a bidirectional association between nonalcoholic steatohepatitis (NASH) and type 2 diabetes (T2D). There is a clinical challenge to consider pharmaceutical strategies targeting the metabolic dysfunction common to NASH and T2D pathogenesis.Areas covered: By using PubMed, we performed a literature search to review the potential beneficial effect of anti-diabetic and metabolic investigational drugs on NASH.Expert opinion: Since insulin resistance is central in the pathophysiology of both T2D and NASH, there is an urgent need for new insulin sensitizers. Peroxisome proliferator-activated receptor (PPAR) agonists, especially PPARγ and pan-PPARs agonists, have shown some beneficial effects on both NASH and liver fibrosis, but their routine use should be limited by their safety profile. Incretin-based therapies, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the polyagonists (GLP-1, GIP, glucagon) under development are the most promising anti-diabetic drugs for NASH treatment, mainly due to their action on body weight loss. Preliminary, preclinical and early phase studies suggest that SGLT2 inhibitors and fibroblast growth factor (FGF)19 and FGF21-based therapies are promising targets for NASH and T2D treatment. The common weakness for all of these drugs is their limited effect on liver fibrosis, potentially due to short-term trial design.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Drogas em Investigação/farmacologia , Humanos , Resistência à Insulina , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Projetos de Pesquisa
16.
BMC Gastroenterol ; 21(1): 296, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284732

RESUMO

BACKGROUND AND AIMS: Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. METHODS: Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. RESULTS: In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). CONCLUSIONS: In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.


Assuntos
Antibacterianos , Infecções Bacterianas , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana , Alemanha/epidemiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico
17.
Acta Gastroenterol Belg ; 84(2): 333-342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34217185

RESUMO

Background and aim: Spontaneous bacterial peritonitis is a potentially life-threatening infection in patients with liver cirrhosis and ascites. Its prevention is vital to improve prognosis of cirrhotic patients. The main objective of this systematic review was to evaluate what is the most efficacious and safest antibiotic prophylactic strategy. Methods: Studies were located by searching PubMed and Cochrane Central Register of Controlled Trials in The Cochrane Library until February 2019. Randomized controlled trials evaluating primary or secondary spontaneous bacterial peritonitis prophylaxis in cirrhotic patients with ascites were included. The selection of studies was performed in two stages: screening of titles and abstracts, and assessment of the full papers identified as relevant, considering the inclusion criteria. Data were extracted in a standardized way and synthesized qualitatively. Results: Fourteen studies were included. This systematic review demonstrated that daily norfloxacin is effective as a prophylactic antibiotic for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis. Once weekly ciprofloxacin was not inferior to once daily norfloxacin, with good tolerance and no induced resistance. Trimethoprim-sulfamethoxazole and norfloxacin have similar efficacy for primary and secondary prophylaxis of spontaneous bacterial peritonitis, however, trimethoprim-sulfamethoxazole was associated with an increased risk of developing an adverse event. Rifaximin was more effective than norfloxacin in the secondary prophylaxis of spontaneous bacterial peritonitis, with a significant decrease in adverse events and mortality rate. Conclusions: Continuous long-term selective intestinal decontamination with norfloxacin is the most widely used prophylactic strategy in spontaneous bacterial peritonitis, yet other equally effective and safe options are available.


Assuntos
Infecções Bacterianas , Peritonite , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Ascite , Humanos , Cirrose Hepática/tratamento farmacológico , Norfloxacino
18.
Georgian Med News ; (314): 125-128, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34248041

RESUMO

Hepatorenal syndrome is a severe complication of liver cirrhosis which is difficult to treat because of a very fast course and lack of adequate dosing recommendations due to the stage of the disease. In this study we aimed to refine the treatment of hepatorenal syndrome type I by modifying the dose of terlipressin, depending on the stage of acute kidney injury (AKI). Objective - to improve the treatment method of hepatorenal syndrome type I in patients with alcoholic liver cirrhosis by selecting the dose of terlipressin depending on the stage of acute kidney injury. For this study were enrolled 161 patients with diagnosis alcoholic liver cirrhosis, complicated with the hepatorenal syndrome. All patients were were randomly divided into control (group 1) (n=79) and study (group 2) (n=82) groups depending on the treatment received (terlipressin in the standard dosage or modified by the response-guided titration method). If the serum creatinine level decreased less than 25% from the baseline, the dose of terlipressin was gradually increased but did not accede 12 mg/24 hours. The stage of AKI was diagnosed using the criteria of Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury, 2012. The risk of short term mortality (within the first 29 days) was prognosed by Model for End-Stage Liver Disease (MELD) score. The kidney function improved better in persons with a modified dose of terlipressin: the complete response rate in them was 81.7%. The response rate in those who received the standard treatment, was 66.7% only (p˂0.05). It was found that the effective dosage of terlipressin is 3 mg/24 for AKI stage I; 6 mg/24 - for AKI stage II; 12 mg/24 - for AKI stage III. The relapse of the disease occurred only in 23.2% patients with modified treatment against 40.1% in the control group (p˂0.05). Short term survival was also significantly higher in the study group - 54.9%, while in the control group it was 37% only (p˂0.05). Thus, correction of terlipressin dosage could improve the results of the treatment and reduce mortality in patients with hepatorenal syndrome type I.


Assuntos
Injúria Renal Aguda , Doença Hepática Terminal , Síndrome Hepatorrenal , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Doença Hepática Terminal/tratamento farmacológico , Síndrome Hepatorrenal/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Índice de Gravidade de Doença , Vasoconstritores/uso terapêutico
19.
World J Gastroenterol ; 27(24): 3581-3594, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239271

RESUMO

BACKGROUND: Fasudil, as a Ras homology family member A (RhoA) kinase inhibitor, is used to improve brain microcirculation and promote nerve regeneration clinically. Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis. AIM: To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide (TAA). METHODS: C57BL/6 mice were administered TAA once every 3 d for 12 times. At 1 wk after induction with TAA, Fasudil was intraperitoneally injected once a day for 3 wk, followed by hematoxylin and eosin staining, sirius red staining, western blotting, and quantitative polymerase chain reaction (qPCR), and immune cell activation was assayed by fluorescence-activated cell sorting. Furthermore, the effects of Fasudil on hepatic stellate cells and natural killer (NK) cells were assayed in vitro. RESULTS: First, we found that TAA-induced liver injury was protected, and the positive area of sirius red staining and type I collagen deposition were significantly decreased by Fasudil treatment. Furthermore, western blot and qPCR assays showed that the levels of alpha smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor beta 1 (TGF-ß1) were inhibited by Fasudil. Moreover, flow cytometry analysis revealed that NK cells were activated by Fasudil treatment in vivo and in vitro. Furthermore, Fasudil directly promoted the apoptosis and inhibited the proliferation of hepatic stellate cells by decreasing α-SMA and TGF-ß1. CONCLUSION: Fasudil inhibits liver fibrosis by activating NK cells and blocking hepatic stellate cell activation, thereby providing a feasible solution for the clinical treatment of liver fibrosis.


Assuntos
Células Estreladas do Fígado , Metaloproteinase 2 da Matriz , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Animais , Células Estreladas do Fígado/patologia , Células Matadoras Naturais , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta1
20.
Liver Int ; 41(9): 1999-2008, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242466

RESUMO

Non-alcoholic steatohepatitis has emerged as a major public health problem, and the burden of non-alcoholic steatohepatitis cirrhosis is projected to increase by 64%-156% by 2030. The threat is aggravated by the fact that are currently no approved drugs for the treatment of non-alcoholic steatohepatitis. In this paper, we review the main challenges to drug development in patients with non-alcoholic steatohepatitis cirrhosis, and describe the opportunities brought by the advances in the understanding of the clinical and pathophysiological nuances of cirrhosis. The design of therapeutic regimens for non-alcoholic steatohepatitis cirrhosis will vary according to the specific cirrhosis substage (compensated vs decompensated), and the specific mechanistic basis of therapy, targeted either at improving aetiology-specific pathways and/or at more general aetiology-agnostic processes. The understanding of the probabilistic expectations for the whole range of potential outcomes, rooted at different mechanistic drivers at each specific substage, will be essential in order to choose adequate estimands and therapeutic strategies for clinical trials and individual patients with non-alcoholic steatohepatitis cirrhosis. Finally, we provide a summary of the main pitfalls and uncertainties in the design of clinical trials for non-alcoholic steatohepatitis cirrhosis and discuss potential biomarkers for use in trials and practice for these patients.


Assuntos
Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Humanos , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
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