Palak Jitendrakumar Trivedi

• BSc (hons) MBBS MRCP (UK) PhD
• University of Birmingham

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biologic pathways to liver in...

Objective Hepatocellular carcinoma (HCC) is an infrequent yet critical event in primary biliary cirrhosis (PBC); however, predictive tools remain ill-defined. Our objective was to identify candidate risk factors for HCC development in patients with PBC. Design Risk factor analysis was performed in over 15 centres from North America and Europe spann...

Background and aims Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events. Methods We evaluated a cohort of PBC patients (n=386) attending the Liver Unit in Birmin...

Up to 25% of patients diagnosed with primary biliary cirrhosis (PBC) are of childbearing age. However, little is known about disease course during pregnancy. We performed a retrospective analysis of women with PBC during pregnancy using a representative large cohort of patients attending the Liver Center at Toronto Western hospital from January 197...

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the umbrella term of autoimmune liver disease, in which the end result is immune-mediated hepatocellular or hepatobiliary injury. All three conditions are associated with gut inflammation; PSC and AIH being strongly linked to infla...

Background After 1 year of ursodeoxycholic acid (UDCA), patients with primary biliary cholangitis (PBC) may have a normal GLOBE score despite high alkaline phosphatase (ALP) levels. Aim To assess the association between ALP and liver transplantation (LT)‐free survival according to the GLOBE score. Methods Among patients with a normal or elevated...

The UK-PBC audit is a collaborative project sanctioned by the British Association for the Study of the Liver (BASL), the British Society of Gastroenterology (BSG), UK-PBC and the PBC Foundation, established to benchmark current management of primary biliary cholangitis (PBC) in the UK National Health Service (NHS) against the BSG audit standards pu...

Background and Aims Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC) in the UK. A recent analysis of UK order data estimated that patient retention on OCA was around 69% at 24 months after the date of patients’ first Homecare order. There have been no published analyses into whether these retenti...

Background Patients with cirrhosis increasingly require major surgery carrying high morbidity and mortality. In Europe, surgical risk prediction remains a challenge, despite the availability of multiple prognostic systems (mainly US origin) in clinical practise to predict post-operative risk. In addition, there is lack of surgical outcome data in l...

Background and Aims The POISE randomized double-blind (DB) placebo-controlled trial and open label extension (OLE) demonstrated that obeticholic acid (OCA) reduced biomarkers associated with adverse clinical outcomes in patients with primary biliary cholangitis (PBC). The objective of this analysis was to evaluate event-free survival in OCA-treated...

Generic tacrolimus has been proposed to provide cost savings over innovator tacrolimus in transplantation whilst preserving clinical outcomes. Whilst increasing evidence supports this approach for renal transplantation, there remains a paucity of published studies in the field of liver transplantation. The aim of this study was to compare the clini...

The term 'PBC/AIH-overlap' has been applied when features of autoimmune hepatitis (AIH), be they biochemical, serological or histological, coexist with primary biliary cholangitis (PBC), either at first presentation or sequentially during disease course. Several treatment paradigms have been proposed, extrapolated from those of the primary conditio...

Background and aims The POISE randomized double-blind placebo-controlled trial demonstrated that obeticholic acid (OCA) reduced biomarkers associated with adverse clinical outcomes (ALP, bilirubin, AST, ALT) in patients with primary biliary cholangitis (PBC). The objective of this study was to evaluate time to first occurrence of liver transplant o...

Background and aims One-third of patients with primary biliary cholangitis (PBC) inadequately respond to ursodeoxycholic acid (UDCA). Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate/fenofibrate). Met...

Carcinogenesis of primary sclerosing cholangitis (PSC)‐associated cholangiocarcinoma (CCA) is largely unexplored. Improved understanding of the molecular events involved may guide development of novel avenues for rational clinical management. We aimed to assess the genetic alterations during progression of the neoplastic cascade from biliary dyspla...

Primary biliary cholangitis (PBC) is a debilitating chronic liver disease that progresses to cirrhosis with attendant complications in a substantial proportion of patients. It is a major cause of liver-related morbidity and mortality in the United Kingdom (UK). The British Society of Gastroenterology (BSG) published guidelines on PBC management, wh...

Background & Aims Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) was shown to predict outcomes of primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. Methods We performed an international, multicentre, retrospective follow-up stu...

Organ fibrosis is a shared endpoint of many diseases, yet underlying mechanisms are not well understood. Several pathways governed by the primary cilium, a sensory antenna present on most vertebrate cells, have been linked with fibrosis. Ciliopathies usually start early in life and represent a considerable disease burden. We performed massively par...

Primary sclerosing cholangitis (PSC) is a rare immune-mediated cholestatic disease for which no medical therapy has been shown to slow disease progression. Consequently, liver transplantation is the only lifesaving intervention for patients, and despite being a rare disease, PSC is the lead indication for transplantation across several European cou...

Purpose of review: In this article, we provide a contemporary overview on PSC pathogenesis, with a specific focus on the role of mucosal immunity. Recent findings: The extent of enteric dysbiosis in PSC has been extensively quantified, with evidence of reduced bacterial diversity and enrichment of species capable of driving lymphocyte recruitmen...

Erratum for An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs. Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de...

Second line treatments in PBC : UK experience

Introduction Our aim was to compare the effectiveness of second-line therapies in primary biliary cholangitis (PBC), with regards Obeticholic acid (OCA) and non-licensed therapy (fibric acid derivatives; FA) across a nationwide cohort of patients (pts). Method Efficacy and safety data was accrued from 12 centres across the UK. Biochemical paramete...

Introduction The increased risk of colorectal cancer in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) justifies an enhanced surveillance strategy with annual colonoscopy and dye spray or protocol biopsies. As symptoms are frequently mild in PSC-IBD colitis can be missed unless colonoscopy and biopsies are u...

Introduction Primary sclerosing cholangitis (PSC) is a rare disorder and as such clinical care can be heterogeneous. We audited PSC management across the UK against audit standards set by the British Society of Gastroenterology (BSG). Method All UK PSC investigators were invited to complete an electronic questionnaire on the PSC patient cohort enc...

LINKED CONTENT This article is linked to Roberts et al papers. To view these articles, visit https://doi.org/10.1111/apt.16488 and https://doi.org/10.1111/apt.16562

Background The aim of this study was to quantify the global epidemiology of primary sclerosing cholangitis (PSC), alongside the incidence of liver transplantation, cancer and death, through robust systematic review of population-based data. Methods We searched MEDLINE and EMBASE up to and including June 30th 2020 to identify population-based studi...

Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and pr...

The cover image is based on the Original Article Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult‐to‐treat primary biliary cholangitis by Pierre‐Antoine Soret et al., https://doi.org/10.1111/apt.16336 image

Liver allografts have been considered to be immunologically privileged due to a degree of tolerogenicity, as manifest by the lower frequency of hyperacute rejection episodes despite positive T‐cell cross‐matches, a low incidence of graft loss due to chronic rejection, and the potential for hepatocyte regeneration after tissue injury. As an organ th...

Background: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA). Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC....

Introduction Fatigue is the most commonly reported symptom of the liver disease primary biliary cholangitis (PBC). It affects 40%–80% of patients, has no effective treatment and is associated with heightened mortality risk. The pathogenesis is unknown, but muscle bioenergetic abnormalities have been proposed to contribute. Directly observed exercis...

Background: Opportunity to redefine the care journeys for those living with primary biliary cholangitis (PBC) includes facilitating access to enhanced (PBC-dedicated) programmes by nonspecialist risk 'flagging' of patients. Objective: To develop a nonexpert PBC stratification tool to help care pathway choices (standard vs. enhanced) choices in P...

Background and aims: A variety of auto-antibody assays are available as part of the clinical care of patients with liver disease. We sought to better understand the clinical utility of immune-serological testing in patients with primary biliary cholangitis (PBC). Methods: We retrospectively analyzed data from 2846 patients investigated for liver...

Background & Aims Serum alkaline phosphatase (ALP) and the enhanced liver fibrosis (ELF) score are used as endpoints in trials of patients with primary sclerosing cholangitis (PSC). We aimed to quantify inter- and intra-individual variation in levels of ALP and the ELF score over time, and evaluated their association with fibrosis progression. Met...

Background & Aims There are insufficient population-level data on effects of primary sclerosing cholangitis (PSC) in patients with inflammatory bowel disease (IBD). Methods We identified incident cases of IBD, with PSC (PSC-IBD) and without, from April 2006 through to April 2016 and collected data on outcomes through April 2019. We linked data fro...

Background & Aims Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and able to impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence aft...

Objective: To determine maternal, obstetric and neonatal outcomes in a cohort of women with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) DESIGN: Retrospective cohort study. Setting: 10 specialist centres managing pregnant women with liver disease POPULATION: Women with a diagnosis of PBC and PSC and a pregnancy of ≥...

Objectives: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. Methods: The patient cohort from the GLOBAL PBC Study Gro...

Objective The clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC. Methods The NNT was calculated based on the untreated...

Autoimmune hepatitis is widely assumed by health-care professionals to be a disease that is easily controlled through the use of corticosteroids and immunosuppressants but recent studies in the UK indicate highly variable treatment regimens and often unsatisfactory treatment outcomes, such as dependence on long-term high-dose steroids and ongoing n...

Objectives: Magnetic resonance (MR) risk scores and liver stiffness (LS) have individually been shown to predict clinical outcomes in primary sclerosing cholangitis (PSC). The aim of this study was to assess their complementary prognostic value. Methods: Patients with PSC from 3 European centers with a 3-dimensional MR cholangiography available...

Background: Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. Aims: To assess the utility of baseline fibrosis stage in predicting long-term outcomes in the context of biochemical...

Autoimmune hepatitis is widely assumed by health-care professionals to be a disease that is easily controlled through the use of corticosteroids and immunosuppressants but recent studies in the UK indicate highly variable treatment regimens and often unsatisfactory treatment outcomes, such as dependence on long-term high-dose steroids and ongoing n...

Background & aims: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochem...

Introduction Primary sclerosing cholangitis[PSC] is the classical hepatobiliary manifestation of inflammatory bowel disease[IBD] for which liver transplantation[LT] is the only curative therapy.In this study,we provide pooled incidence rates[IR] and time trends of (1)colorectal cancer[CRC], (2)flares in IBD activity and (3)colectomy rates post LT,...

Background & aims: Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the ef...

The use of ECD grafts has been associated with acute kidney injury (AKI) after liver transplantation. However, the relation between graft quality and development of CKD remains unknown. The aim of this study was therefore to analyse the impact of extended criteria (ECD) grafts for chronic kidney disease (CKD) after liver transplantation. All patien...

Background & aims: Primary sclerosing cholangitis (PSC) has a variable, often progressive, course. Magnetic resonance cholangiography (MRC) is used in the diagnosis of PSC. Magnetic resonance risk scoring systems, called Anali without and with gadolinium, are used to predict disease progression, determined by radiologic factors. We aimed to assess...

Primary biliary cholangitis/cirrhosis (PBC) is a rare autoimmune liver disease for which therapies are limited to the licensed agents ursodeoxycholic acid (UDCA) and obeticholic acid (OCA). The low prevalence of PBC represents a significant barrier to conducting large controlled clinical outcome trials. Fibric acid derivatives exert potent anti‐cho...

Background After liver transplantation primary sclerosing cholangitis (PSC), the condition returns in the transplanted liver in a subset of patients (recurrent primary sclerosing cholangitis, rPSC). Aim To define risk factors for rPSC. Methods We searched Pubmed, Embase, Web of Science, and Cochrane library for articles published until March 2018...

Background Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) for which liver transplantation [LT] is the only curative therapy. We provide pooled incidence rates (IR) and time trends of (1) colorectal cancer (CRC), (2) colectomy, and (3) IBD activity post LT through systematic revi...

Background Primary sclerosing cholangitis (PSC) is a chronic inflammation of the bile ducts leading to fibrosis and eventually cirrhosis. Aetiology of PSC remains unknown and no specific treatment can delay or arrest the progressive course of the disease with orthotopic liver transplantation (OLT) remaining the only curative option. Nonetheless, re...

We sought to identify factors 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. Analysing data from 1001 patients recruited to the UK‐PSC research cohort, we evaluated clinical variables for their asso...

Autoimmune hepatitis (AIH) is a corticosteroid responsive, autoimmune liver disease arising consequent to immunogenetic and environmental risk factors. The clinical course reflects relapsing and remitting, hepatocyte targeted, immunologic damage, countered by reparative responses to cell injury. Appropriate and timely immunosuppressive therapy driv...

Background & aims: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group). Methods: We collected demographic and clinical data from 785 patients (8...

The principal targets for anti-chemokine therapy in inflammatory bowel disease (IBD) have been the receptors CCR9 and CXCR3 and their respective ligands CCL25 and CXCL10. More recently CCR6 and its ligand CCL20 have also received attention, the expression of the latter in enterocytes being manipulated through Smad7 signalling. These pathways, selec...

Understanding the role of modest alcohol consumption in patients with non-alcohol induced fatty liver disease (NAFLD) remains a significant challenge, with no clear guidance on counselling regarding alcohol use. Conventionally, the strong association of alcohol excess and development of complications related to chronic liver disease, including hepa...

BACKGROUND: Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes. AIM: To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA)...