There are limited data on pregnancy outcomes in women with cirrhosis. To address this gap, we examined the records of singleton births from Sweden’s National Patient Register (NPR), Cause of Death ...Register (CDR), and Medical Birth Register (MBR) between 1997 and 2011 to assess exposure and pregnancy‐related and liver‐related outcomes of pregnant women with cirrhosis. Exposure status was defined as having an International Classification of Diseases (ICD) code for cirrhosis obtained prior to or during pregnancy. Poisson regression with cluster‐robust standard errors was used to estimate relative risks (RRs) adjusted for maternal age, smoking, and body mass index (BMI). We identified 103 pregnancies in women with cirrhosis and compared these to 1,361,566 pregnancies in women without cirrhosis. Pregnancies in women with cirrhosis were at increased risk of caesarean delivery (36% versus 16%, respectively; adjusted RR aRR, 2.00; 95% confidence interval CI, 1.47‐2.73), low birth weight (15% versus 3%; aRR, 3.87; 95% CI, 2.11‐7.06), and preterm delivery (19% versus 5%; aRR, 3.51; 95% CI, 2.16‐5.72). Rates of maternal mortality during pregnancy (no cases), gestational diabetes, preeclampsia, small for gestational age, congenital malformations, and stillbirth were not increased when compared to the pregnant women without cirrhosis. There were 12 hospitalizations during pregnancy due to liver‐related events, including one case with bleeding esophageal varices. Conclusion: Women with cirrhosis are at increased risk for adverse pregnancy outcomes. However, severe maternal and fetal adverse events were rare in our study, and most pregnancies in women with cirrhosis ended without complications.
We investigated pregnancies in Sweden between 1997 to 2011 in women with cirrhosis defined by ICD‐coding in national registers. We found that in contrast to popular thinking, adverse events were rare and most pregnancies ended without maternal or fetal complications.
In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we ...carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻⁸) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC.
Autoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require ...further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.
Optimal involvement of palliative care (PC) services in the management of patients with decompensated cirrhosis and end‐stage liver disease (ESLD) is limited. This may result from both ignorance and ...the failure to recognize the spectrum and unpredictability of the underlying liver condition. Palliative care is a branch of medicine that focuses on quality of life (QoL) by optimizing symptom management and providing psychosocial, spiritual, and practical support for both patients and their caregivers. Historically, palliative care has been underutilized for patients with decompensated liver disease. This review provides an evidence‐based analysis of the benefits of the integration of palliative care into the management of patients with ESLD. Liver Transplantation 24 961–968 2018 AASLD.
For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant 'autoimmune ...disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH. For a majority of patients, these joint symptoms resolve within days of the introduction of immunosuppressive therapy. Rarer features at index presentation include a maculopapular skin rash and unexplained fever, which are features that tend to resolve quickly with treatment. Interestingly, joint pain and stiffness are also well recognised in the context of steroid withdrawal and cessation in AIH. The occasional co-presentation of AIH with coeliac disease is clinically important (1-6%), since for some patients, there is a risk of immunosuppression malabsorption, thus delaying effective treatment. Similarly, the co-existence of selective IgA deficiency (IgAD) can occur in patients with coeliac disease or in isolation. Selective IgAD as a co-existing extraheaptic feature seems to be more common in paediatric patients with AIH. For these patients, they are at an increased risk of respiratory and sinus infections. Although, typically associated with primary sclerosing cholangitis, the presence of inflammatory bowel disease (IBD; both Crohn's disease and ulcerative colitis) has been described in 2-8% of patients with AIH. Interestingly, for patients with autoimmune sclerosing cholangitis, a distinct pattern of IBD has been recently described. Other conditions have been reported at a lower frequency, including Sjogren's syndrome 1-7%, systemic lupus erythematosus 1-3% and glomerulonephritis 1%. Rarer still and at a frequency of <1% include fibrosing alveolitis, haemolytic anaemia, uveitis, mononeuritis multiplex, polymyositis and multiple sclerosis. In contrast, the reported associations between AIH and thyroiditis 8-23%, diabetes 1-10% and psoriasis 3% are commonly seen and notable in clinical practice.
Background
Concurrent extrahepatic autoimmune disease (CEHAID) associated with autoimmune hepatitis (AIH) have been incorporated into the diagnostic criteria stipulated by the International ...Autoimmune Hepatitis Group (IAIHG). Large comprehensive cohort data on the extrahepatic autoimmunity in AIH remain scanty.
Aim
To systematically assess features and clinical impact of CEHAID on AIH.
Methods
Clinical records of 562 patients with AIH from two tertiary centres in the UK were retrospectively reviewed.
Results
Prevalence of CEHAID in patients with AIH was 42%. Autoimmune thyroid disease was the commonest CEHAID associated with AIH (101/562, 18%). Autoimmune skin diseases were more prevalent in AIH‐2 than AIH‐1 (21.9% vs 7%, P=.009). Personal history of CEHAID was more commonly found in AIH patients with than without first‐degree family history of CEHAID 48/86 (55.8%) vs 169/446 (37.9%), P=.002. AIH patients with CEHAID were more often women (85.2% vs 76.1%, P=.008), had higher post‐treatment IAIHG score (22 vs 20, P<.001), less reactivity to smooth muscle antibodies (49.8% vs 65%, P<.001), more likely to have mild fibrosis at diagnosis (20.9% vs 6.5%, P<.001) and less often had ascites (6.3% vs 13.6%, P=.008) and coagulopathy (1.18 vs 1.27, P=.013) at presentation. Presence of CEHAID, however, did not significantly affect disease progression, prognosis and survival in AIH.
Conclusions
Our study confirms the strong association of CEHAID with AIH. Association between personal and familial extrahepatic autoimmunity especially among first‐degree relatives was evident. Presence of CEHAID may influence clinical phenotype of AIH at presentation, but without notable impact on the long‐term clinical outcomes.
SUMMARY
Background
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that results in substantial morbidity and mortality with many unanswered clinical and research questions. ...Improved understanding of disease pathogenesis, including the extra‐hepatic manifestations of AIH, may allow targeted treatments with greater efficacy and fewer associated adverse events.
Aim
To identify the spectrum of unanswered clinical and research questions facing care providers in the management of patients with autoimmune hepatitis (AIH).
Methods
The International Autoimmune Hepatitis Group initiated a series of research workshops to start to address these questions. Key issues were discussed in small group sessions with collation of all discussions to be summarised in this manuscript.
Results
Key issues were identified as: the need for better understanding of disease pathogenesis, standardisation of the methods and assays used to evaluate autoantibodies in AIH, refinement of the histopathological criteria for “typical” or “compatible” AIH, focus on the interaction with non‐alcohol related fatty liver disease, how to treat acute severe AIH, better assessment of quality of life in adults and paediatrics, standardising use of standard, third‐line and experimental therapies in AIH and search for biomarkers early in the disease course that predict outcome.
Conclusion
This workshop has outlined the key unanswered clinical and research questions to help to define the research agenda in AIH.
We sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for ...use in a real‐world clinical setting. Analyzing data from 1,001 patients recruited to the UK‐PSC research cohort, we evaluated clinical variables for their association with 2‐year and 10‐year outcome through Cox‐proportional hazards and C‐statistic analyses. We generated risk scores for short‐term and long‐term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty‐six percent of the derivation cohort were transplanted or died over a cumulative follow‐up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10‐year outcome (hazard ratio HR = 3.05; C = 0.63; median transplant‐free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2‐year and 10‐year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK‐PSC risk scores were well‐validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase‐to‐platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)‐DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK‐PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real‐world scoring system to identify those patients most likely to die or require liver transplantation.
Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control ...disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH.
We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC.
There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal.
Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.
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