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A liver disease in which the body's immune system damages liver cells for unknown reasons.

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A meta-analysis was performed of RCTs comparing therapies that combine UDCA and corticosteroids with UDCA monotherapy. In this paper, we found that the combination therapy of UDCA and corticosteroids was more effective for PBC-AIH.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Acute infection with viral hepatitis C manifests most commonly no symptoms, but frequently results in chronic infection. Chronic hepatitis C is in most cases benign, but may progress to severe illness and liver‐related death. This review found no significant effect of glucocorticosteroids on chronic hepatitis, but the amount of data is sparse. Accordingly there is insufficient evidence to neither confirm nor exclude beneficial and harmful effects of glucocorticosteroids for hepatitis C. Further, the evidence is unclear as to whether glucocorticosteroids treatment can be safely administered for other diseases in patients with concomitant hepatitis C. The authors were unable to identify randomised clinical trials on glucocorticosteroids for acute hepatitis C.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

In response to a request from the public regarding antiviral regimens for the treatment of chronic hepatitis C virus (HCV) infection, a review was undertaken to evaluate the evidence regarding the potential benefits and adverse effects associated with currently available antiviral treatment regimens. This review did not address antiviral treatment for hepatitis C in pregnant women, or in patients receiving hemodialysis, or in those infected with HIV, or in patients after transplantation. The systematic review included 77 reports of eligible studies published from 1947 through April 2012. The full report, listing all studies, is available at www.effectivehealthcare.ahrq.gov/hepctreatment.cfm. This summary is provided to inform discussions with patients of options and to assist in decisionmaking along with consideration of a patient’s values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Comparative Effectiveness Review Summary Guides for Clinicians [Internet] - Agency for Healthcare Research and Quality (US).

Version: November 27, 2012

This report focuses on whether it is useful to order a hepatitis C virus (HCV) antibody test in either the general population of asymptomatic adults or selected high-risk subpopulations who have no history of liver disease or known liver function test abnormalities.

Systematic Evidence Reviews - Agency for Healthcare Research and Quality (US).

Version: March 2004

BACKGROUND: Antinuclear antibodies (ANA), smooth muscle antibodies (SMA) and antibodies to a soluble liver antigen/liver pancreas (anti-SLA/LP) are useful markers that can help clinicians to diagnose and classify autoimmune hepatitis (AIH).

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Chronic hepatitis B describes a spectrum of disease usually characterised by the presence of detectable hepatitis B surface antigen (HBsAg) in the blood or serum for longer than 6 months. In some people, chronic hepatitis B is inactive and does not present significant health problems, but others may progress to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The progression of liver disease is associated with hepatitis B virus (HBV) DNA levels in the blood. Without antiviral treatment, the 5-year cumulative incidence of cirrhosis ranges from 8 to 20%. People with cirrhosis face a significant risk of decompensated liver disease if they remain untreated. Five-year survival rates among people with untreated decompensated cirrhosis can be as low as 15%. Chronic hepatitis B can be divided into e antigen- (HBeAg) positive or HBeAg-negative disease based on the presence or absence of e antigen. The presence of HBeAg is typically associated with higher rates of viral replication and therefore increased infectivity.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: June 2013

These are the first World Health Organization (WHO) guidelines for the prevention, care and treatment of persons living with chronic hepatitis B (CHB) infection, and complement similar recently published guidance by WHO on the prevention, care and treatment of infection due to the hepatitis C virus (HCV).

World Health Organization.

Version: March 2015

To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa and ribavirin for the treatment of chronic hepatitis C virus (HCV) in three specific patient subgroups affected by recent licence changes: those eligible for shortened treatment courses [i.e. those with low viral load (LVL) and who attained a rapid virological response (RVR) at 4 weeks of treatment], those eligible for re-treatment following previous non-response or relapse, and those co-infected with human immunodeficiency virus (HIV).

Health Technology Assessment - NIHR Journals Library.

Version: April 2011

The field of HCV therapeutics continues to evolve rapidly and, since the World Health Organization (WHO) issued its first Guidelines for the screening, care and treatment of persons with hepatitis C infection in 2014, several new medicines have been approved by at least one stringent regulatory authority. These medicines, called direct-acting antivirals (DAAs), are transforming the treatment of HCV, enabling regimens that can be administered orally, are of shorter duration (as short as eight weeks), result in cure rates higher than 90%, and are associated with fewer serious adverse events than the previous interferon- containing regimens. WHO is updating its hepatitis C treatment guidelines to provide recommendations for the use of these new medicines.

World Health Organization.

Version: April 2016

Study found that peginterferon alfa-2a or -2b in combination with ribavirin may be effective for the treatment of children and young people with chronic hepatitis C. The results suggest that this therapy is cost-effective compared with best supportive care. However, the available evidence is of poor quality.

Health Technology Assessment - NIHR Journals Library.

Version: October 2014

The objective of this report was to perform a systematic review of the beneficial and harmful effects of ledipasvir plus sofosbuvir (LDV/SOF) for the treatment of chronic hepatitis C virus (HCV) G1 infection in adults.

Common Drug Review - Canadian Agency for Drugs and Technologies in Health.

Version: July 2015

The study found that treating all patients with chronic hepatitis C without a prior non-invasive liver test (NILT) is cost-effective; however, recently approved interferon-free regimens were not included. For hepatitis B e antigen (HBeAg)-negative patients, this strategy is cost-effective only if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive patients, two NILTs applied sequentially were cost-effective but highly uncertain. No conclusive results could be obtained for alcoholic and non-alcoholic fatty liver disease. Most studies evaluating non-invasive fibrosis tests had a high risk of bias.

Health Technology Assessment - NIHR Journals Library.

Version: January 2015

Objective: To perform a systematic review of the beneficial and harmful effects of sofosbuvir in combination with other agents for the treatment of adults with chronic hepatitis C virus (CHC) infection (genotypes 1, 2, 3, or 4).

Common Drug Review - Canadian Agency for Drugs and Technologies in Health.

Version: October 2014

Prednisone/prednisolone (PRED) monotherapy and PRED plus azathioprine combination therapy were both viable induction therapies for adult autoimmune hepatitis treatment-naive patients and those who relapsed. In maintenance therapy, PRED plus azathioprine and azathioprine monotherapy were superior to PRED monotherapy. The results should be interpreted with caution due to loss of randomisation in the analysis. The authors' conclusions may be unreliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Recurrence of autoimmune liver disease in allografts has long been a topic of debate. We conducted a systematic review of the literature to examine the reported incidence of recurrence after liver transplantation of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH). The MEDLINE, EMBASE, and Cochrane electronic databases were used to identify articles. The inclusion criteria used were articles on patients with at least 90 days of posttransplantation follow-up, histologic criteria for diagnosis of PBC and AIH recurrence, radiologic or histologic criteria or both for diagnosis of PSC recurrence, and exclusion of other causes of liver disease causing similar histologic findings. Incidence in individual studies was combined to calculate the overall recurrence. Risk factors were analyzed whenever crude data were available. Funnel plots were used to assess publication bias. Out of 90 articles identified, 43 met criteria for systematic review (PBC, 16; PSC, 14; AIH, 13). The calculated weighted recurrence rate was 18% for PBC, 11% for PSC, and 22% for AIH. No difference was found in PBC and AIH recurrence by type of primary immunosuppression. There were not enough data to assess this issue in PSC studies. There was evidence of publication bias among PSC and AIH studies but not among PBC studies. In conclusion, recurrence of autoimmune liver disease after liver transplantation appears to be a real concern. As these patients are followed long-term, recurrence of disease may become the primary cause of morbidity.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2006

The emergence of tumor necrosis factor-α (TNF-α)-targeted therapies as a key therapeutic option for patients with rheumatic, digestive, and dermatologic autoimmune diseases has been associated with increasing reports of liver damage in patients with hepatitis B virus (HBV) infection. We studied the current evidence on the use of anti-TNF agents in patients with HBV through a systematic analysis of cases reported in the MEDLINE and EMBASE databases using the MeSH term "hepatitis B virus" combined with the terms "infliximab," "etanercept," "adalimumab," "certolizumab," "golimumab," and "anti-TNF agents," and summarize the results here. We analyzed 257 patients with positive HBV markers who received anti-TNF therapy (255 identified in the search strategy and 2 new cases), 89 HBsAg+ carriers, and 168 anti-HBc+ persons. HBV reactivation was reported in 35 (39%) HBsAg+ carriers. The percentage of reactivation was higher in patients previously treated with immunosuppressive agents (96% vs. 70%, p=0.033) and lower in those who received antiviral prophylaxis (23% vs. 62%, p=0.003). Acute liver failure was reported in 5 patients, 4 of whom died. Infliximab was associated with a higher rate of induced liver disease (raised transaminase levels, clinical signs, viral reactivation, and acute liver failure) compared with etanercept. In anti-HBc+ persons, reactivation was reported in 9 (5%) cases, including 1 patient who died due to fulminant liver failure.In summary, our search of the current evidence identified 257 reported HBV+ patients treated with anti-TNF agents, with a significant percentage of liver damage in HBsAg+ carriers, including raised transaminase levels (42%), signs and symptoms of liver disease (16%), reappearance of serum HBV-DNA (39%), and death related to liver failure (5%). The rate of reactivation in anti-HBc+ persons was 7-fold lower than in HBsAg+ carriers. The increasing number of reported cases of HBV reactivation following TNF-targeted therapies and the associated morbidity and mortality demand specific preventive strategies.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Epidemiological studies have evaluated the association between tumour necrosis factor alpha (TNF-α)- 308G/A and (TNF-α)- 238G/A polymorphisms, and the risk of autoimmune liver disease (AILD), yet the results are conflicting. To derive a more precise estimation of the relationship, we performed this meta-analysis. A systematic review was conducted to identify all eligible studies of TNF-α polymorphisms and AILD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between the two TNF-α polymorphisms and AILD risk. A total of 15 eligible studies were identified. Overall, positive associations of -308G/A polymorphism with AILD risk were found (A vs G allele: OR =1.45, 95%CI = 1.13- 1.86; AA vs GG: OR = 2.74, 95%CI = 1.51- 4.96; GA vs GG: OR = 1.46, 95%CI = 1.11- 1.92;dominant model: OR = 1.57, 95%CI = 1.18- 2.10; recessive model: OR = 2.22, 95%CI = 1.31- 3.76). In subgroup analysis by ethnicity, a significantly higher risk was found in Caucasians. In subgroup analysis by AILD category, significant association was observed in autoimmune hepatitis and primary sclerosing cholangitis, especially in Caucasians. Patients carrying TNF-α-238A allele had a slightly decreased risk of developing AILD (OR = 0.65, 95%CI = 0.48- 0.87). However, we found both TNF-α polymorphisms were not associated with primary biliary cirrhosis risk, even in subgroup analysis. Our meta-analysis suggests that the TNF-α-308G/A and -238G/A polymorphisms may contribute to AILD susceptibility in Caucasians,especially for autoimmune hepatitis and primary sclerosing cholangitis. Nevertheless, we found both TNF-α polymorphisms were unlikely to be associated with the risk of primary biliary cirrhosis

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Alcohol is the most widely used psychotropic drug in the industrialised world; it has been used for thousands of years as a social lubricant and anxiolytic. In the UK, it is estimated that 24% of adult men and 13% of adult women drink in a hazardous or harmful way. Levels of hazardous and harmful drinking are lowest in the central and eastern regions of England (21–24% of men and 10–14% of women). They are highest in the north (26–28% of men, 16–18% of women). Hazardous and harmful drinking are commonly encountered amongst hospital attendees; 12% of emergency department attendances are directly related to alcohol whilst 20% of patients admitted to hospital for illnesses unrelated to alcohol are drinking at potentially hazardous levels. Continued hazardous and harmful drinking can result in dependence and tolerance with the consequence that an abrupt reduction in intake might result in development of a withdrawal syndrome. In addition, persistent drinking at hazardous and harmful levels can also result in damage to almost every organ or system of the body. Alcohol-attributable conditions include liver damage, pancreatitis and the Wernicke’s encephalopathy. Key areas in the investigation and management of these conditions are covered in this guideline.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: 2010

The guideline covers the identification and assessment of suspected cirrhosis, monitoring to detect complications and management of complications such as ascites and hepatorenal syndrome and referral for tertiary care.

NICE Guideline - National Guideline Centre (UK).

Version: July 2016

In the Veterans Health Administration (VHA), there has been a marked increase in the prevalence of cirrhosis from chronic hepatitis C infection with a corresponding increase in the number of hepatocellular cancer (HCC) diagnoses. From 1996 to 2006, the prevalence of cirrhosis among Veterans with chronic hepatitis C infection rose from 9 to 18.5%, and the prevalence of HCC rose from 0.07 to 1.3%. In the general population, the incidence of HCC rose between 1992 and 2005 from 3.1/100,000 to 5.1/100,000, with localized tumors accounting for most of the increase. While, on average, the 5-year survival of HCC is low (13 to 16.5%), the survival of early-stage disease has risen.

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: January 2014

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