275 research outputs found
Interventions for hereditary haemochromatosis: an attempted network meta-analysis
No full textBACKGROUND: Hereditary haemochromatosis is a genetic disorder related to proteins involved in iron transport, resulting in iron load and deposition of iron in various tissues of the body. This iron overload leads to complications including liver cirrhosis (and related complications such as liver failure and hepatocellular carcinoma), cardiac failure, cardiac arrhythmias, impotence, diabetes, arthritis, and skin pigmentation. Phlebotomy (venesection or 'blood letting') is the currently recommended treatment for hereditary haemochromatosis. The optimal treatment of hereditary haemochromatosis remains controversial. OBJECTIVES: To assess the comparative benefits and harms of different interventions in the treatment of hereditary haemochromatosis through a network meta-analysis and to generate rankings of the available treatments according to their safety and efficacy. However, we found only one comparison. Therefore, we did not perform the network meta-analysis and we assessed the comparative benefits and harms of different interventions using standard Cochrane methodology. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised clinical trials registers to March 2016 to identify randomised clinical trials on treatments for hereditary haemochromatosis. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with hereditary haemochromatosis. We excluded trials which included participants who had previously undergone liver transplantation. We considered any of the various interventions compared with each other or with inactive treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models with RevMan 5 based on available-participant analysis. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS: Three trials with 146 participants met the inclusion criteria of this review. Two parallel group trials with 100 participants provided information on one or more outcomes. The remaining trial was a cross-over trial, with no usable data for analysis. All the trials were at high risk of bias. Overall, all the evidence was of very low quality. All three trials compared erythrocytapheresis (removal of red cells only, instead of whole blood) versus phlebotomy. Two of the trials shared the same first author. The mean or median age in the three trials ranged from 42 to 55 years. None of the trials reported whether the included participants were symptomatic or asymptomatic or a mixture of both. Two trials were conducted in people who were haemochromatosis treatment-naive. The trial that provided most data for this review excluded people with malignancy, heart failure, and serious cardiac arrhythmias. We found no trials assessing iron-chelating agents.Only one of the trials with 38 participants reported no short-term mortality and no serious adverse events at the end of the short-term follow-up (eight months). Two trials reported the proportion of people with adverse events: 10/49 (20.4%) in the erythrocytapheresis group versus 11/51 (21.6%) in the phlebotomy group. One of these two trials provided data on adverse event rates (42.1 events per 100 participants with erythrocytapheresis versus 52.6 events per 100 participants with phlebotomy). There was no evidence of differences in the proportion of people with adverse events and the number of adverse events (serious and non-serious) between the groups (proportion of people with adverse events: OR 0.93, 95% CI 0.36 to 2.43; participants = 100; trials = 2; number of adverse events: rate ratio 0.80, 95% CI 0.32 to 2.03; participants = 38; trial = 1). There was no difference between the groups regarding short-term health-related quality of life (mean difference (MD) 1.00, 95% CI -10.80 to 12.80; participants = 38; trials = 1). This outcome was measured using EQ-VAS (range: 0 to 100 where a higher score indicates better health-related quality of life). None of the trials reported mortality beyond one year, health-related quality of life beyond one year, liver transplantation, decompensated liver disease, cirrhosis, hepatocellular carcinoma, diabetes, or cardiovascular complications during the long-term follow-up.The two trials that provided data for this review were funded by parties with no vested interest in the results; the source of funding of the third trial was not reported. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine whether erythrocytapheresis is beneficial or harmful compared with phlebotomy. Phlebotomy has less equipment requirements and remains the treatment of choice in people with hereditary haemochromatosis who require blood letting in some form. However, it should be noted that there is no evidence from randomised clinical trials that blood letting in any form is beneficial in people with hereditary haemochromatosis. Having said this, a trial including no treatment is unlikely to be conducted. Future trials should compare different frequencies of phlebotomy and erythrocytapheresis versus phlebotomy with and without different iron-chelating agents compared with each other, and with placebo. Such trials should include long-term follow-up of participants (e.g. using national record linkage databases) to determine whether treatments are beneficial or harmful in terms of clinical outcomes such as deaths, health-related quality of life, liver damage and its consequences, heart damage and its consequences, and other outcomes that are of importance to people with hereditary haemochromatosis
Pharmacological interventions for acute hepatitis C infection
No full textBackground: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. Objectives: To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on the available-participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results: We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon-alpha versus pegylated interferon-alpha plus ribavirin. None of the trials compared direct-acting antivirals versus placebo or other interventions. The mean or median follow-up period in the trials ranged from six to 36 months. There was no short-term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow-up beyond one year, there were no further deaths. The number of serious adverse events was higher with pegylated interferon-alpha plus ribavirin than with pegylated interferon-alpha (rate ratio 2.74, 95% CI 1.40 to 5.33; participants = 237; trials = 2; I 2 = 0%). The proportion of people with any adverse events was higher with interferon-alpha and interferon-beta compared with no intervention (OR 203.00, 95% CI 9.01 to 4574.81; participants = 33; trials = 1 and OR 27.88, 95% CI 1.48 to 526.12; participants = 40; trials = 1). None of the trials reported health-related quality of life, liver transplantation, decompensated liver disease, cirrhosis, or hepatocellular carcinoma. The proportion of people with chronic HCV infection as indicated by the lack of sustained virological response was lower in the interferon-alpha group versus no intervention (OR 0.27, 95% CI 0.09 to 0.76; participants = 99; trials = 3; I 2 = 0%). The differences between the groups were imprecise or not estimable (because neither group had any events) for all the remaining comparisons. Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. Authors' conclusions: Very low quality evidence suggests that interferon-alpha may decrease the incidence of chronic HCV infection as measured by sustained virological response. However, the clinical impact such as improvement in health-related quality of life, reduction in cirrhosis, decompensated liver disease, and liver transplantation has not been reported. It is also not clear whether this finding is applicable in the current clinical setting dominated by the use of pegylated interferons and direct-acting antivirals, although we found no evidence to support that pegylated interferons or ribavirin or both are effective in people with acute HCV infection. We could find no randomised trials comparing direct-acting antivirals with placebo or other interventions for acute HCV infection. There is significant uncertainty in the benefits and harms of the interventions, and high-quality randomised clinical trials are required
Pharmacological interventions for non-alcohol related fatty liver disease (NAFLD): An attempted network meta-analysis
No full textBackground Non-alcohol related fatty liver disease (commonly called non-alcoholic fatty liver disease (NAFLD)) is liver steatosis in the absence of significant alcohol consumption, use of hepatotoxic medication, or other disorders affecting the liver such as hepatitis C virus infection, Wilson's disease, and starvation. NAFLD embraces the full spectrum of disease from pure steatosis (i.e. uncomplicated fatty liver) to non-alcoholic steatohepatitis (NASH), via NASH-cirrhosis to cirrhosis. The optimal pharmacological treatment for people with NAFLD remains uncertain. Objectives To assess the comparative benefits and harms of different pharmacological interventions in the treatment of NAFLDthrough a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis, and instead, assessed the comparative benefits and harms of different interventions using standard Cochrane methodology. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials. com to August 2016. Selection criteria We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with NAFLD. We excluded trials which included participants who had previously undergone liver transplantation. We considered any of the various pharmacological interventions compared with each other or with placebo or no intervention. Data collection and analysis We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on an available participant analysis with Review Manager. We assessed risk of bias according to the Cochrane risk of bias tool, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results We identified 77 trials including 6287 participants that met the inclusion criteria of this review. Forty-one trials (3829 participants) provided information for one or more outcomes. Only one trial was at low risk of bias in all domains. All other trials were at high risk of bias in one or more domains. Overall, all the evidence was very low quality. Thirty-five trials included only participants with nonalcohol related steatohepatitis (NASH) (based on biopsy confirmation). Five trials included only participants with diabetes mellitus; 14 trials included only participants without diabetes mellitus. The follow-up in the trials ranged from one month to 24 months. We present here only the comparisons of active intervention versus no intervention in which two or more trials reported at least one of the following outcomes: mortality at maximal follow-up, serious adverse events, and health-related quality of life, the outcomes that determine whether a treatment should be used. Antioxidants versus no intervention There was no mortality in either group (87 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the trial which reported the proportion of people with serious adverse events (87 participants; 1 trial; very low quality evidence). There was no evidence of difference in the number of serious adverse events between antioxidants and no intervention (rate ratio 0.89, 95% CI 0.36 to 2.19; 254 participants; 2 trials; very low quality evidence). None of the trials reported health-related quality of life. Bile acids versus no intervention There was no evidence of difference in mortality at maximal follow-up (OR 5.11, 95% CI 0.24 to 107.34; 659 participants; 4 trials; very low quality evidence), proportion of people with serious adverse events (OR 1.56, 95% CI 0.84 to 2.88; 404 participants; 3 trials; very low quality evidence), or the number of serious adverse events (rate ratio 1.01, 95% CI 0.66 to 1.54; 404 participants; 3 trials; very low quality evidence) between bile acids and no intervention. None of the trials reported health-related quality of life. Thiazolidinediones versus no intervention There was no mortality in either group (74 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the two trials which reported the proportion of people with serious adverse events (194 participants; 2 trials; very low quality evidence). There was no evidence of difference in the number of serious adverse events between thiazolidinediones and no intervention (rate ratio 0.25, 95% CI 0.06 to 1.05; 357 participants; 3 trials; very low quality evidence). None of the trials reported health-related quality of life. Source of funding Twenty-six trials were partially-or fully-funded by pharmaceutical companies that would benefit, based on the results of the trial. Twelve trials did not receive any additional funding or were funded by parties with no vested interest in the results. The source of funding was not provided in 39 trials. Authors' conclusions Due to the very low quality evidence, we are very uncertain about the effectiveness of pharmacological treatments for people with NAFLD including those with steatohepatitis. Further well-designed randomised clinical trials with sufficiently large sample sizes are necessary
Liver test abnormalities in patients with HIV mono-infection: assessment with simple noninvasive fibrosis markers
No full textBACKGROUND: Patients with HIV mono-infection may develop chronic liver disease due to a number of factors including hepatic steatosis. We estimated the prevalence and predictors of hepatic steatosis and fibrosis in a cohort of HIV-mono-infected patients with persistently deranged liver function tests. METHODS: Of 2398 consecutive patients at one UK clinical center, 156 (6.5%) had persistently abnormal transaminases in at least two measurements six months apart. We used APRI and FIB4 scores to determine the presence of significant and/or advanced fibrosis in this group as well as its potential associations. RESULTS: Mean age was 47.5±8.5 years and 91% (142/156) were males. Diabetes mellitus was present in 11% of patients; hypertension in 18%; and dyslipidemia in 52%. Almost all were on antiretroviral therapy (ART) (97%) and most were virologically suppressed (94%). Steatosis was detected by ultrasound in 71% of patients. The prevalence of FIB4≤1.45, 1.46-3.24 and >3.25 was 67%, 29% and 4%, respectively, and that of APRI≤0.5, 0.51-1.49 and >1.5 was 52%, 45% and 3% respectively. In multivariate analysis, only cumulative ART exposure was associated with FIB4>1.45 (odds ratio [OR] 1.008, 95% confidence interval [CI] 1.000-1.016), while APRI>0.5 was associated with higher alanine aminotransferase levels (OR 1.033, 95%CI 1.015-1.510). Twenty patients had a liver biopsy, of whom 13 had non-alcoholic fatty liver disease (NAFLD). CONCLUSIONS: Elevated transaminases are often present in HIV-mono-infected patients and this may be associated with NAFLD and/or ART. Non-invasive screening for the presence of NAFLD and fibrosis in all HIV-mono-infected patients as part of their routine clinical management should be further explored
EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update
No full textNon-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years
Identification of patients with advanced fibrosis due to nonalcoholic fatty liver disease: Considerations for best practice
No full textNonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) prevalence has increased in the past two decades, resulting in a significant but under-recognised public health burden. This impacts the prevalence of advanced fibrosis, end-stage liver disease and associated extrahepatic manifestations. To understand the challenges in recognising patients with advanced fibrosis due to NASH and develop a standardised approach to screen these patients, the authors of this document provided their opinions and expertise from practice and published evidence to identify key challenges and current approaches for diagnosing NASH. The severity of liver fibrosis due to NASH is the main indicator of associated morbidity and mortality outcomes. Therefore, identifying patients with, or at risk of, advanced fibrosis due to NASH and linking them to appropriate care is critical. This can be challenging due to a lack of awareness of NASH among healthcare professionals and a lack of standardised protocols for identifying patients. Simple noninvasive tests may provide an opportunity to facilitate early identification of these patients. This article proposes a simple, universally applicable diagnostic algorithm for use in clinical practice, that includes sequential use of noninvasive tests, ideally a biological marker and an imaging technique, which may help to facilitate early diagnosis of these patients. In the opinion of the authors, early detection of advanced fibrosis is fundamental in the efforts to halt the progression of NASH and diagnostic algorithms may facilitate pre-emptive interventions to curtail the disease
Reply to: Correspondence on "EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update"
No full textEtiology and severity of liver disease in HIV-positive patients with suspected NAFLD : lessons from a cohort with available liver biopsies
No full textBackground:Spectrum of liver injury among HIV-positive people is wide; in particular, prevalence of nonalcoholic fatty liver disease (NAFLD) seems to be higher compared with HIV-negative people.Methods:We retrospectively evaluated all liver biopsies performed at Royal Free Hospital from 2000 to 2017 in HIV monoinfected patients with abnormal transaminases, to assess the underlying cause of liver disease and to characterize the extent of fibrosis. We furthermore evaluated the diagnostic accuracy of FIB4 and FibroScan as noninvasive tools for fibrosis assessment.Results:Ninety-seven patients were included. Most common histological findings were NAFLD (28%), nonspecific changes (26%), and normal histology (13%). Twenty percent of the patients had significant fibrosis and 11% had advanced fibrosis. FIB4, at a cutoff of 1.3, had a specificity of 82% and negative predictive value (NPV) of 95% for exclusion of advanced fibrosis. FibroScan was available in 28% patients and 33% had a liver stiffness ≥7.5 kPa. FibroScan showed a specificity of 77% and NPV of 94% for exclusion of significant fibrosis. Among patients with NAFLD (n = 27), 18% had advanced fibrosis, whereas the majority (56%) did not have any fibrosis. The NPV of FIB4 for advanced fibrosis in these patients was 93%.Conclusions:Among HIV-positive patients with elevated transaminases, a surprisingly high number of patients had nonsignificant changes or even normal histological findings. The prevalence of NAFLD was lower than reported in other series. Use of noninvasive tools with a high NPV for significant fibrosis can help reduce the number of required biopsies
Evaluating the association of serum ferritin and hepatic iron with disease severity in non‐alcoholic fatty liver disease
No full textBackground & Aims
Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non‐alcoholic fatty liver disease (NAFLD). However, it is unclear whether it reflects hepatic inflammation or true iron‐overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD.
Methods
We selected 468 patients with biopsy‐proven NAFLD from 2 European centres. Iron, hepatic and metabolic parameters were collected at the time of liver biopsy. Iron deposits in hepatocytes and reticuloendothelial cells were assessed and graded. Diagnosis of non‐alcoholic steatohepatitis (NASH) and fibrosis staging were performed.
Results
A total of 122 (26%) patients had hyperferritinemia, whereas stainable hepatic iron was found in 116 (25%) patients (38% predominantly in hepatocytes, 20% in reticuloendothelial cells and 42% in both). Subjects with stainable hepatic iron, particularly those with a mixed pattern, had higher serum ferritin and transaminases but only a mixed pattern of iron deposition was among the variables significantly associated with presence of NASH. Serum ferritin was not associated with presence of NASH, however it increased with worsening fibrosis stage (F3 compared to F0‐F1), and significantly decreased in stage F4.
Conclusions
A mixed pattern of hepatic iron deposition is associated with the presence of steatohepatitis, while serum ferritin increases with worsening fibrosis up to pre‐cirrhotic stage. In individual NAFLD patients, serum ferritin could be evaluated as part of non‐invasive diagnostic panels but not on its own
Prospective evaluation of anticoagulation and transjugular intrahepatic portosistemic shunt for the management of portal vein thrombosis in cirrhosis.
No full textAbstract
BACKGROUND:
There is no established management algorithm for portal vein thrombosis (PVT) in cirrhotic patients. The aim of our study was to prospectively evaluate anticoagulation and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT.
METHODS:
Cirrhotics with non-malignant PVT were included. Low weight molecular heparin anticoagulation was considered in all; TIPS was indicated if thrombosis progressed or anticoagulation was contraindicated. Patients who were not anticoagulated nor received TIPS served as controls.
RESULTS:
Fifty-six patients (of whom 21 controls) were included. PVT was occlusive in 11/35, with extension to the superior mesenteric or splenic vein in 13/35. In the study group 33 patients were anticoagulated, with a recanalization rate of 36% (12/33) compared with 1/21 among controls. A time interval between appearance of thrombosis and anticoagulation < 6 months predicted chance of repermeation. Thrombus progression occurred in 15/21 non anticoagulated patients and in 5/33 anticoagulated patients (P < 0.001). TIPS was placed in six patients. There were five variceal bleedings and two intestinal venous ischaemia episodes in the control group, compared with one variceal bleeding episode in the study group.
CONCLUSIONS:
In cirrhotics with PVT, a treatment algorithm using anticoagulation and TIPS achieves a good chance of complete repermeation, reduces portal hypertensive complications, and decreases the rate of thrombosis progression
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