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BACKGROUND & AIMS: Whether non-selective ß-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH). METHODS: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach. RESULTS: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989). CONCLUSIONS: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42019144786. LAY SUMMARY: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective ß-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective ß-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.
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Varizes Esofágicas e Gástricas , Hipertensão Portal , Antagonistas Adrenérgicos beta/uso terapêutico , Ascite/complicações , Carvedilol/uso terapêutico , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/prevenção & controle , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Pressão na Veia Porta , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: In patients with non-alcoholic fatty liver disease (NAFLD), the impact of the severity of steatosis and inflammatory activity on the accuracy of liver stiffness measurement (LSM) by transient elastography (TE) and by two-dimensional shear wave elastography (2D-SWE) in staging liver fibrosis is still debated and scarce. We aimed to focus on this aspect. METHODS: We prospectively studied 104 patients requiring biopsy for the assessment of NAFLD. We used ordinary least squares regression to test for differences in the association between fibrosis and LSM by TE and 2D-SWE when other factors (steatosis and inflammatory activity) are considered. RESULTS: Among 104 patients, 102 had reliable LSM by TE, and 88 had valid LSM by 2D-SWE. The association between fibrosis based on histology and LSM was significantly stronger when 2D-SWE assessed LSM compared to TE (Spearman's correlation coefficient of .71; P < .001 vs .51, P < .001; Z = 2.21, P = .027). Inflammatory activity was an independent predictor of LSM by TE but not of LSM by 2D-SWE. After controlling for fibrosis, age, sex and body mass index, the inflammatory activity and the interaction between inflammatory activity and fibrosis independently explained 11% and 13% of variance in LSM by TE respectively. Steatosis did not affect the association of fibrosis and LSM by either method. CONCLUSION: Inflammatory activity on histology significantly affects LSM by TE, but not LSM by 2D-SWE in NAFLD. LSM by 2D-SWE reflects liver fibrosis more accurately than LSM by TE. Furthermore, the severity of steatosis on histology did not influence the association of LSM and fibrosis by either elastography method.
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Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Biópsia , Técnicas de Imagem por Elasticidade/métodos , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagemRESUMO
INTRODUCTION: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice. METHODS: This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH. RESULTS: A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 × 10/L ruled out CSPH in most etiologies. DISCUSSION: Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH.
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Técnicas de Imagem por Elasticidade/métodos , Hipertensão Portal/diagnóstico , Cirrose Hepática/complicações , Fígado/diagnóstico por imagem , Pressão na Veia Porta/fisiologia , Idoso , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND & AIMS: Renal function is a major determinant of prognosis in patients with cirrhosis. Current guidelines only contemplate serum creatinine (sCr) to assess kidney injury. However, there are formulas to estimate glomerular filtration rate (eGFR) which better measure renal function in patients listed for liver transplantation. There is no data available on whether these formulas predict prognosis in patients with acute kidney injury (AKI). METHODS: In 143 patients presenting with a first episode of AKI, we compared the prognostic value of renal function estimated using sCr or eGFR assessed with Modification of Diet in Renal Disease (MDRD-6), chronic kidney disease epidemiology (CKD-EPI) and Royal Free Hospital (RFH) for renal replacement therapy (RRT) within 30 days of AKI, and 30- and 90-day transplant-free survival. RESULTS: eGFR was calculated on values obtained before and at admission, at presentation of AKI (D0) and 48 hours after AKI (D2).15% of patients (more commonly in alcohol + metabolic etiology; P = .049 vs other) required RRT. Transplant-free survival at 30-and 90-day were 77% and 63%. Among sCr, MDRD-6, CKD-EPI and RFH-eGFR, the latter predicted best RRT (HR 0.937 95% CI 0.893-0.982, P = .007), 30-d (HR 0.936 95% CI 0.901-0.972, P = .001) and 90-d (HR 0.934 95% CI 0.908-0.972, P < .001) mortality/OLT. CONCLUSIONS: Renal function estimated using the RFH-eGFR calculated at D2 after AKI diagnosis is a strong predictor of RRT and of 30-d and 90-d transplant-free survival. Results suggest that in cirrhosis, RFH-eGFR may be a better indicator of prognosis in AKI than sCr.
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Injúria Renal Aguda , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Creatinina , Taxa de Filtração Glomerular , Hospitais , Humanos , Cirrose Hepática/complicações , PrognósticoRESUMO
BACKGROUND & AIMS: Controlled attenuation parameter (CAP) for steatosis assessment has not been validated in compensated advanced chronic liver disease compensated advanced chronic liver disease (cACLD). We primarily aimed at assessing the accuracy of CAP for the diagnosis and quantification of steatosis in cACLD. Secondary aim: to assess the validity of non-invasive criteria for cACLD according to liver stiffness measurement (LSM). METHODS: This is a single-centre retrospective study including patients with cACLD defined as LSM ≥10 kPa, CAP measurement and liver biopsy (reference standard for steatosis and fibrosis) observed in 06/2015-06/2017. Steatosis was graded as S0 (<5%), S1 (5%-32%), S2 (33%-66%) and S3 (>66%). The diagnostic performance of CAP for any grade of steatosis and for high-grade steatosis (≥S2) was studied. RESULTS: Among 461 consecutive patients, 111 with LSM-based diagnosis of cACLD were included (63% male, median age 55 years, median body mass index 28.1 Kg/m2 , aetiology: 32% non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, 32% alcohol or viral + metabolic syndrome, 15% viral, 6% autoimmune, 4% alcohol, 11% others). Median LSM and CAP were 16.1 kPa and 277 dB/m respectively. On liver biopsy, steatosis was found in 88/111 patients (79%); 44 patients (43 with metabolic syndrome) had high-grade steatosis. CAP was accurate in identifying any grade of steatosis (area under the receiving operating characteristic curves 0.847; 95% CI 0.767-0.926, P < .0001), and ≥S2 steatosis (0.860; 95% CI 0.788-0.932, P < .0001). CAP performed similarly in patients with CAP- interquartile range (IQR) ≥ or <40 dB/m. CONCLUSIONS: Steatosis is frequent in patients with cACLD and metabolic syndrome. CAP diagnostic accuracy for any steatosis and high-grade steatosis is good in this population. A CAP-IQR ≥40 dB/m does not impair CAP diagnostic accuracy in cACLD.
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Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Biópsia , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos RetrospectivosRESUMO
Failure to control variceal bleeding with current recommendations occurs in 10 to 20% of cases. This systematic review and meta-analysis analyzes the experience, results, and complications of "bridge" therapies for failure to control acute variceal bleeding: balloon tamponade and esophageal stents. The main outcomes assessed were failure to control bleeding and mortality in the short-term and medium-term follow-up, and adverse events. Balloon tamponade studies had a pooled rate of short-term failure to control bleeding of 35.5%, and adverse events in over 20% of cases; 9.7% resulting in death. Stenting failed to control bleeding in the short term and medium term in 12.7 and 21.5% of cases of severe or refractory variceal bleeding, respectively, despite stent migration in 23.8% of cases. Medium-term mortality rates were similar in both therapies. Although only one trial compared these treatments, the available evidence consistently supports that stents serve as a better and safer bridge therapy in refractory acute variceal bleeding.
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Oclusão com Balão/métodos , Hemorragia Gastrointestinal/terapia , Cirrose Hepática/complicações , Stents , Adulto , Idoso , Oclusão com Balão/efeitos adversos , Oclusão com Balão/mortalidade , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/mortalidade , Varizes Esofágicas e Gástricas/terapia , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Falha de TratamentoRESUMO
BACKGROUND & AIMS: Patients with hepatic venous pressure gradients (HVPGs) of 10 mm Hg or greater and chronic liver disease often are assumed to have cirrhosis. We investigated the association between HVPGs and cirrhosis, using histologic findings as the reference standard. We also assessed the prevalence and characteristics of patients with HVPGs of 10 mm Hg or greater without cirrhosis. METHODS: We performed a retrospective analysis of 157 consecutive patients, 89 with suspected cirrhosis and hepatic hemodynamic data collected from 2015 through 2017. Biopsy specimens collected had 10 or more portal tracts from each patient and were analyzed for features of cirrhosis. Biopsy specimens with histologic features of cirrhosis were excluded and the remaining biopsy specimens were re-reviewed by an expert pathologist. The fibrosis area was calculated digitally by image analysis. RESULTS: HVPG identified patients with cirrhosis with an area under the receiver operating characteristic curve of 0.879: 14 of 89 patients with HVPG of 10 mm Hg or greater (16%) had no histologic features of cirrhosis (METAVIR scores <4 and Ishak scores <6). The median HVPG was 11 mm Hg (range, 10-22 mm Hg). Based on METAVIR scores, 7 patients had fibrosis stage F3, 4 patients had fibrosis stage F2, and 3 patients had fibrosis stages F0 or F1. The mean area of fibrosis in livers was 16.2% ± 6.5%. All 14 patients had perisinusoidal fibrosis and 8 patients had hepatocyte ballooning. The most common diagnoses were nonalcoholic steatohepatitis (n = 5) and nodular regenerative hyperplasia (n = 4). An HVPG cut-off value of 12 mm Hg identified patients with cirrhosis with 92% specificity, misclassifying 5 patients with different etiologies of liver disease. CONCLUSIONS: In a retrospective analysis of 89 consecutive patients with chronic liver disease and an HVPG of 10 mm Hg or greater, 16% were not found to have cirrhosis upon biopsy analysis. Most of these patients had nonalcoholic steatohepatitis or nodular regenerative hyperplasia. Perisinusoidal fibrosis and hepatocyte ballooning might increase sinusoidal pressure. An HVPG cut-off value of 12 mm Hg or greater identified patients with cirrhosis with 92% specificity.
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Hipertensão Portal/diagnóstico , Cirrose Hepática/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Veias Hepáticas/fisiopatologia , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/patologia , Hipertensão Portal/fisiopatologia , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Pressão , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: In cirrhosis, hepatic venous pressure gradient (HVPG) and imaging body composition assessment can influence prognosis. We assessed whether adipose and skeletal muscle tissues reflect the severity of portal hypertension (PH), and whether they improve non-invasive prediction of decompensation and death. METHODS: We included 84 cirrhosis patients with HVPG and computed tomography (CT) within 12 weeks of HVPG at a single centre. L3 vertebra CT images were used for body composition indexes (cm2 /m2 ): total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), intramuscular adipose tissue index (IMATI), skeletal muscle index (SMI) and psoas muscle index (PMI). Correlations were calculated between indexes, HVPG and standard non-invasive tests for PH. Twelve-month decompensation and death predictors were determined. RESULTS: The following were the characteristics for the patients included in the study: male 61%; BMI 28 ± 5 kg/m2 ; alcoholic liver disease in 51%, non-alcoholic steatohepatitis in 24%; HVPG 14 ± 6 mm Hg; 45% compensated. The median follow-up was 11 (4-17) months. HVPG correlated with SATI (r = -0.282, P = 0.01), TATI (r = -0.220, P = 0.045) and SATI/VATI index (r = -0.240, P = 0.03). In compensated patients, lower VATI (HR 0.94 (0.90-0.99), P = 0.01) was associated with 12-month decompensation. Combining TATI and liver stiffness × spleen size over-platelet count risk score added discriminative capacity for 12-month decompensation (AUROC 0.91 vs 0.87). IMATI was independently associated with mortality in decompensated patients. MELD-Na combined with IMATI discriminated excellently for mortality (AUROC 0.94; P < 0.001). CONCLUSIONS: Hepatic venous pressure gradient inversely correlates with imaging markers of adipose tissue, while markers of sarcopenia were unrelated to PH. In compensated patients, TATI improves non-invasive prediction of decompensation. In decompensated patients, IMATI independently predicted mortality.
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Cirrose Hepática/diagnóstico , Pressão na Veia Porta , Sarcopenia/complicações , Gordura Subcutânea/patologia , Adiposidade , Adulto , Idoso , Biomarcadores , Composição Corporal , Índice de Massa Corporal , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Índice de Gravidade de Doença , Gordura Subcutânea/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Measurement of hepatic venous pressure gradient (HVPG) effectively mirrors the severity of portal hypertension (PH) and offers valuable insights into prognosis of liver disease, including the risk of decompensation and mortality. Additionally, HVPG offers crucial information about treatment response to nonselective beta-blockers and other medications, with its utility demonstrated in clinical trials in patients with PH. Despite the widespread dissemination and validation of noninvasive tests, HVPG still holds a significant role in hepatology. Physicians treating patients with liver diseases should comprehend the HVPG measurement procedure, its applications, and how to interpret the results and potential pitfalls.
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Hipertensão Portal , Pressão na Veia Porta , Humanos , Hipertensão Portal/fisiopatologia , Hipertensão Portal/diagnóstico , Veias Hepáticas/fisiopatologia , Prognóstico , Índice de Gravidade de DoençaRESUMO
Background & Aims: Sarcopenia is associated with increased morbidity and mortality in patients with cirrhosis, but its definition in current literature is very heterogeneous. We performed a systematic review and meta-analysis to assess the association between mortality and sarcopenia evaluated by computed tomography (CT) in patients with cirrhosis, both overall and stratified for the criteria used to define sarcopenia. Methods: Medline, Embase, Scopus, and Cochrane Library were searched up to January 2023. We included studies assessing sarcopenia presence with CT scans and providing data on the risk of mortality. Adjusted hazard ratios (HRs) and 95% CIs were pooled using a random-effects model. Results: Thirty-nine studies comprising 12,827 patients were included in the meta-analysis. The summary prevalence of sarcopenia was 44% (95% CI 38-50%). The presence of sarcopenia (any definition) was an independent predictor of mortality with an adjusted HR of 2.07 (95% CI 1.81-2.36), and the result was consistent in all subgroup analyses. The prognostic role of the EASL/AASLD criteria was confirmed for the first time with an HR of 1.86 (95% CI 1.53-2.26) (n = 14 studies). The cut-offs used to define sarcopenia based on psoas muscle parameters varied among studies, thus, a subgroup analysis was not feasible. There was no substantial heterogeneity for the main estimates and no significant risk of publication bias. Conclusions: Sarcopenia on CT is associated with a 2-fold higher risk of mortality in patients with cirrhosis. The cut-offs proposed by EASL/AASLD are prognostically relevant and should be the recommended criteria used to define sarcopenia in clinical practice. Impact and implications: Sarcopenia assessed by the reference standard (computed tomography scan) is an independent predictor of mortality in patients with cirrhosis, with a 2-fold increase in the risk of death in all sensitivity analyses. This finding is particularly valid in patients from Europe and North America, and in transplant candidates. Stratifying for the parameters and cut-offs used, we confirmed for the first time the prognostic impact of the definition proposed by EASL/AASLD, supporting their use in clinical practice. Psoas muscle assessment is promising, but data are still limited and too heterogeneous to recommend its routine use at present.
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BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.
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Varizes Esofágicas e Gástricas , Varizes , Humanos , Varizes Esofágicas e Gástricas/tratamento farmacológico , Varizes Esofágicas e Gástricas/prevenção & controle , Hemorragia Gastrointestinal , Ligadura , Antagonistas Adrenérgicos beta/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Varizes/tratamento farmacológicoRESUMO
BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated. METHODS: Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used. RESULTS: We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5 cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in <5%. Hepatic encephalopathy occurred in 15%-30% within three months. In the HCC treatment-response studies, major complication rates were low with no mortality. In the studies that evaluated the response to transarterial chemoembolization, complete response rate of patients with TIPS varied from 16% to 75%. Liver transplantation rate varied from 8% to 80%, with >40% rate in half of the studies. CONCLUSIONS: In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Varizes Esofágicas e Gástricas , Hipertensão Portal , Neoplasias Hepáticas , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Ascite/etiologia , Estudos Prospectivos , Varizes Esofágicas e Gástricas/complicações , Resultado do Tratamento , Hipertensão Portal/etiologia , Hipertensão Portal/cirurgiaRESUMO
Non-invasive tests (NITs) and liver stiffness measurement (LSM) in particular, have entered clinical practice over 20 years ago as point-of-care tests to diagnose liver fibrosis in patients with compensated chronic liver disease. Since then, NITs use has evolved thanks to a large number of studies in all major etiologies of liver disease, and they have become important tools to stratify the risk of portal hypertension and liver-related events. The Baveno VII consensus workshop provided several novel recommendations regarding the use of well-established and novel NITs in the specific setting of portal hypertension screening, diagnosis and follow-up. The Baveno VII expert panels paid special attention to summarizing the existing data into simple clinical rules able to guide clinicians in their practice. The "rule of five" for LSM is a tool to stratify the risk of liver-related events, and LSM alone or in combination with platelet count, can be used now to rule-in and rule-out compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension, as well as to rule-out high-risk varices. Use of NITs in obese subjects with non-alcoholic fatty liver disease (NAFLD) and patients with viral hepatitis C that has been successfully treated, require specific knowledge. This review will update the reader on these aspects.
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Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Hipertensão Portal , Hepatopatia Gordurosa não Alcoólica , Humanos , Varizes Esofágicas e Gástricas/complicações , Hipertensão Portal/etiologia , Fígado/patologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
BACKGROUND: Refractory ascites is a severe complication of liver cirrhosis and treatment options consist in large volume paracentesis, transjugular intrahepatic portosystemic shunt, alfapump®, peritoneovenous shunt and permanent indwelling peritoneal catheter. AIM: Our aim was to assess the efficacy, mortality and complications of each treatment. METHODS: We performed a systematic review using Pubmed and Embase. Frequencies were summarized with Comprehensive Meta-Analysis Software. RESULTS: Seventy-seven studies were included. In patients with transjugular intrahepatic portosystemic shunt, 1-year mortality was 33% (95% CI 0.29-0.39, I2=82.1; τ2 = 0.37; p<0.001) with lower mortality in newer studies (26% vs. 44%). At 6 months, mortality in patients with alfapump® was 24% (95% CI 0.16-0.33, I2=0.00; τ2 = 0.00; p = 0.83), 31% developed acute kidney injury (95% CI 0.18-0.48, I2=44.0; τ2 = 0.22; p = 0.15). Mortality at 12 months was 44% (95% CI 32%-58%, I2=76.7, τ2 = 0.44, p<0.001) in peritoneovenous shunts and 45% (95% CI 38%-53%, I2=61.4, τ2 = 0.18, p = 0.003) in large volume paracentesis, respectively. Overall mortality in patients with permanent indwelling catheters was 66% (95% CI 33%-89%, I2=82.5, τ2 = 1.57, p = 0.001). DISCUSSION: Mortality in patients with transjugular intrahepatic portosystemic shunt was lower in newer studies, probably due to a better patient selection. Acute kidney injury was frequent in patients with alfapump®. Permanent indwelling catheters seemed to be a good option in a palliative setting.
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Injúria Renal Aguda , Derivação Portossistêmica Transjugular Intra-Hepática , Injúria Renal Aguda/complicações , Ascite/etiologia , Ascite/terapia , Humanos , Cirrose Hepática/complicações , Paracentese/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Advanced chronic liver disease is considered a reversible condition after removal of the primary etiological factor. This has led to a paradigm shift in which portal hypertension (PH) is a reversible complication of cirrhosis. The pharmacologic management of PH is centered on finding targets to modify the natural history of cirrhosis and PH. AREAS COVERED: This paper offers an overview of the use of pharmacological strategies in early clinical development that modify PH. Papers included were selected from searching clinical trial sites and PubMed from the last 10 years. EXPERT OPINION: A paradigm shift has generated a new concept of PH in cirrhosis as a reversible complication of a potentially curable disease. Decreasing portal pressure to prevent decompensation and further complications of cirrhosis that may lead liver transplantation or death is a goal. Therapeutic strategies also aspire achieve total or partial regression of fibrosis, thus eliminating the need for treatment or screening of PH.
Assuntos
Drogas em Investigação , Hipertensão Portal , Ensaios Clínicos como Assunto , Drogas em Investigação/uso terapêutico , Fibrose , Humanos , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Transplante de Fígado , Pressão na Veia PortaRESUMO
Background: Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment.While data for mycophenolate mofetil (MMF) in patients intolerant to azathioprine is encouraging, MMF seems of less benefit in patients with insufficient response to first line treatment, but analyzed data on this issue is limited. Aim: To evaluate the efficacy and safety of MMF as a second-line therapy in patients with AIH. Methods: Retrospective analysis of a monocentric database of AIH patients who received medical care from 2000 to 2022. Clinical, immunological and biochemical parameters were assessed at different time points including last follow-up. Results: Overall, 144 patients with AIH were identified. Fifty out of 144 (35%) AIH patients received MMF. Forty (80%) received MMF due to first line treatment intolerance, while ten (20%) due to insufficient response to first line treatment.Remission with MMF monotherapy was 81.5% in the intolerance group versus 30% in the insufficient response group. Patients switched to MMF because of an insufficient response, more often needed additional prednisolone doses higher than 5 mg/day, a switch to third-line treatment or combination regiments, to achieve disease control. Conclusions: Patients treated with MMF because of intolerance to first line treatment show a good disease control under MMF in the majority of cases. Efficacy is considerably lower in the patients switched to MMF because of an insufficient response to first line treatment.
RESUMO
Patients with compensated advanced chronic liver disease have different prognoses depending on the presence of portal hypertension. Current non-invasive diagnostic methods allow identification of clinically significant portal hypertension. Portosystemic collaterals on imaging or liver stiffness of more than 20 to 25 kPa by using transient elastography identifies patients with clinically significant portal hypertension. Patients with liver stiffness of less than 20 kPa and platelet count of greater than 150 g/L can avoid endoscopy. This rule could be expanded using spleen stiffness. Methods to risk stratify for portal hypertension in compensated advanced chronic liver disease and successfully treated chronic hepatitis C and B are subject of research.
Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Hipertensão Portal , Humanos , Hipertensão Portal/diagnóstico , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Baço/diagnóstico por imagemRESUMO
Factors and outcomes associated with decompensation of liver disease and liver failure in obese patients who underwent modern bariatric surgery are unclear. We present here a cohort of seventeen consecutive patients referred because of decompensation of liver disease following laparoscopic bariatric surgery. All patients showed signs of malnutrition (sarcopenia in 76.5%). In ten (58.8%), decompensation was associated with alcohol ingestion, which started after bariatric surgery in six patients. One patient died and three patients required liver transplantation, in one case preceded by transjugular intrahepatic portosystemic shunt (TIPS). However, thirteen patients achieved stabilization or full re-compensation with medical therapy and nutritional support. Our cases underline the risk of alcohol intake and malnutrition after laparoscopic bariatric surgery as causes of severe liver decompensation and underline the need for careful interdisciplinary care of these patients after surgery to early identify and treat alcohol misuse, malnutrition, and liver disease.
Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Desnutrição , Obesidade Mórbida , Cirurgia Bariátrica/efeitos adversos , Gastrectomia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Desnutrição/etiologia , Obesidade Mórbida/cirurgia , Redução de PesoRESUMO
Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding. Recent evidence indicates that NSBBs could prevent liver decompensation in patients with compensated cirrhosis. Despite solid data favouring NSBB use in cirrhosis, some studies have highlighted relevant safety issues in patients with end-stage liver disease, particularly with refractory ascites and infection. This review summarises the evidence supporting current recommendations and restrictions of NSBB use in patients with cirrhosis.