Serum vascular cell adhesion molecule-1 predicts significant liver fibrosis in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is strongly associated with obesity, dyslipidemia and insulin resistance. NAFLD often presents as simple steatosis (NAFL) but can progress to non-alcoholic steatohepatitis (NASH) and fibrosis. Current non-invasive biomarkers are not tailored to identify significant (⩾F2) fibrosis, although recent guidelines recommend a stringent follow-up of this patient population. We and others have reported on the role of pathological angiogenesis in the pathogenesis of NAFLD, highlighting pro-angiogenic factors as potential diagnostic markers. OBJECTIVE: To investigate the applicability of angiogenic and endothelial dysfunction markers as non-invasive diagnostic tools for NASH or NASH-associated fibrosis in obese patients. METHODS: In a prospective cross-sectional study, male patients undergoing bariatric surgery (n=61) and control patients (n=35) were recruited. Serum protein levels and visceral adipose tissue gene expression of endothelial dysfunction and angiogenic markers were analyzed by multiplex bead-based assay and quantitative RT-PCR, respectively. For validation, we recruited a second cohort of patients undergoing bariatric surgery (n=40) and a cohort of NAFLD patients from our outpatient clinic (n=30). RESULTS: We identified serum vascular cell adhesion molecule-1 (VCAM-1) as an independent predictor for ⩾F2 fibrosis (median 14.0 vs 8.7 ng ml-1 in patients with and without significant fibrosis; P<0.0001) with an area under the receiver-operating characteristics (AUROC) curve of 0.80. The cutoff point of 13.2 ng ml-1 showed a sensitivity of 80% and specificity of 83%. In line with these results, VCAM-1 visceral adipose tissue gene expression was also elevated in patients with fibrosis (P=0.030). In the bariatric surgery and clinical validation cohorts, VCAM-1 displayed similar AUROCs of 0.89 and 0.85, respectively. CONCLUSIONS: VCAM-1 levels are able to accurately predict significant (⩾F2) fibrosis in NAFLD patients.

Recurrent rejections after liver transplantation for hepatocellular carcinoma with stem cell features in an adult patient.

Patients with hepatoblastoma featuring carcinoma characteristics have better outcomes after liver transplantation, than after chemotherapy and resection. Possibly this should be extrapolated to aggressive subtypes of hepatocellular carcinomas in non-cirrhotic livers, where early liver transplantation might also be indicated. However, the risks associated with liver transplantation and immunosuppressive treatment after liver transplantation are once again demonstrated by this case of a 32-year-old women with a negative personal and familial history of liver diseases. She underwent transplantation (DBD) for a hepatocellular carcinoma with stem cell features (HCC-HS; an aggressive 'hepatoblast subtype' of hepatocellular carcinoma) after chemotherapeutical downstaging techniques failed to sufficiently downstage the tumor. Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels. Together, these episodes stress the importance of therapeutic drug monitoring of tacrolimus. Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.

Pathophysiology and management of post resection liver failure.

Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and nonparenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

Diagnostic and prognostic scoring systems for autoimmune hepatitis: a review.

INTRODUCTION: Auto-immune hepatitis (AIH) is a rare condition which primarily affects young women. Several diagnostic scoring systems exist based on clinical, biochemical, immunologic and histologic characteristics of AIH. Additionally, prognostic parameters can be identified. The purpose of this literature review is to compare the clinical value, strengths and limitations of these diagnostic and prognostic scoring systems. METHODS: A literature search was performed in two databases and selected based on diagnostic and prognostic criteria. Only studies concerning AIH in adults were included. RESULTS: The backbone of scoring systems remains the revised AIH criteria published in 1999 and the simplified from 2008. The revised system shows a higher sensitivity, lower specificity and lower diagnostic accuracy compared to the simplified. Limitations to these scoring systems include limited diagnostic accuracy in acute or fulminant liver failure, insufficient inclusion of atypical auto-antibodies and lacking diagnostic power in presence of overlap syndromes. Concerning these overlap syndromes, the Paris criteria show a higher diagnostic accuracy compared to the scoring systems for AIH. Presently, no clinical prognostic scoring systems are available. However, a first system based on response to treatment accurately predicts long-term survival in AIH. CONCLUSION: Diagnostic scoring systems are useful in diagnosing AIH and have complementary value. However, they are no substitute for the gold standard of appropriate clinical assessment and are mostly useful in defining cohorts for research purposes. An evolution towards a more dynamic scoring system, using prognostic parameters and the progression of typical features, seems more valuable than the current diagnostic systems.

Comorbidities and concomitant medications in patients with chronic hepatitis C virus infection receiving second-generation direct-acting antiviral regimens in Belgium: an observational study.

Objective: To describe comorbidities and concomitant medications in patients initiating treatment for hepatitis C virus (HCV) infection with direct-acting antiviral (DAA) regimens in Belgium. Methods: This was a noninterventional, observational, multicenter study of data from patient charts. Adult patients with HCV infection receiving second-generation DAA therapy were included. Comorbidities were assessed at the time of HCV treatment initiation. Concomitant medications were recorded at the time of diagnosis and at treatment initiation. Potential clinically relevant drug-drug interactions (DDIs) were assessed based on information available at www.hep-druginteractions.org. The primary objective was to describe concomitant medication use ; secondary objectives were to describe modifications in concomitant therapies and comorbidities. Results: 405 patients were included. A total of 956 comorbidities were reported by 362 patients (median, 2 ; range, 0-15). The most common comorbidities were hypertension (27.2%) ; HIV coinfection (22.5%), and type 2 diabetes mellitus (14.3%). Overall, 1455 concomitant medications were being taken by 365 patients (90.1% ; median, 3 ; range 0-16). The most common concomitant medications were psycholeptics (28.6%), antiviral agents (24.2%), and medications for acid-related disorders (21.0%) Overall, 74/365 (20.3%) patients receiving a concomitant medication required an adaptation to their concomitant medication. The medications that most frequently required change were drugs for acid-related disorders (n = 14) and antiviral drugs (n = 5) ; those that were most frequently stopped were lipid-modifying drugs (n = 25) and drugs for acid-related disorders (n = 13). Conclusion: Physicians are aware of the potential for DDIs with DAAs, but improved alignment between clinical practice and theoretical recommendations is required.

The potential of glycomics as prognostic biomarkers in liver disease and liver transplantation.

The study of glycomics is a novel and fascinating approach for the development of biomarkers. It has become clear that in the field of liver disease specific glycomic patters are present in specific disease states, which has led to the development of diagnostic biomarkers. In this manuscript, we will describe two new applications of this technology for the development of prognostic biomarkers. The first biomarker is associated with the risk of hepatocellular carcinoma development in patients with compensated cirrhosis. The second biomarker is present in perfusate and is related to the risk of primary non function occurrence after liver transplantation. The technology used for these biomarkers could easily be implemented on routine capillary electrophoresis equipment.

Update on liver transplantation for cholangiocarcinoma : a review of the recent literature.

Cholangiocarcinoma (CC) represent 3% of all gastrointestinal tumours and can be classified anatomically in 3 types: intrahepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinomas. Resection is the treatment of choice but is only achieved in a few cases (<20%) because of invasion of the biliary tract and/or vascular structures. The outcome of advanced CC is poor with an overall survival (OS) of maximum 15 months with chemotherapy. In the 1990s, CC was regarded as a contraindication for liver transplantation (LT). LT has recently been proposed as potentially curative option for ICC and PCC. Careful patient selection has changed OS. This article provides an update on current status of LT for patients with unresectable CC.

Hepatitis C virus (HCV) prevalence estimation in the adult general population in Belgium : a meta-analysis.

BACKGROUND AND STUDY AIMS: Although multiple HCV prevalence studies were recently performed in the general population from Belgium, they suffer from a lack of geographical representativeness, an insufficient number of participants or a lack of inclusion of high prevalence groups. The aim of this study is to provide robust information on the HCV burden. METHODS: Recently performed HCV prevalence studies in the general, adult population were included in this study, based on well-defined selection criteria. A meta-analysis was performed to estimate the seroprevalence, the prevalence of participants with viremia and the prevalence estimation for people with viremia which were unaware of their status. RESULTS: Eight studies fulfilled the criteria for inclusion of the quantitative prevalence estimation. Based on the meta-analysis on these 8 studies, we estimated an HCV seroprevalence of 1.01% [95% CI : 0.66-1.42%], representing a total of 90,722 adult, HCV seropositives of which 64,412 individuals (0.71%) were confirmed seropositive. Based on the RNA presence, an estimated viremic prevalence of 0.33% [95% CI : 0.21-0.47 %] was determined, corresponding with 29,642 individuals. This is 46,0% of the true HCV seropositive residents. Further, based on the availability of patient information in 5 out of the 8 studies, a prevalence of 0.18% [95% CI : 0.07-0.33] representing 16,168 individuals from the adult Belgian population are unaware of their HCV status. CONCLUSIONS: We believe that the quantitative measurement by the meta-analysis will be more reliable for their use in the design of a screening strategy or in the development of prevention campaigns as compared to the prevalence estimations performed at local level.

Association of recently described adipokines with liver histology in biopsy-proven non-alcoholic fatty liver disease: a systematic review.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising, as is the prevalence of obesity and type 2 diabetes. It is increasingly recognized that an impaired pattern in adipokine secretion could play a pivotal role in the development of NAFLD. We performed a systematic review to evaluate the potential link between newly described adipokines and liver histology in biopsy-proven NAFLD patients. A computerized literature search was performed in PubMed, EMBASE and Web of Science electronic databases. Thirty-one cross-sectional studies were included, resulting in a total of seven different investigated adipokines. Studies included in this review mainly had a good methodological quality. Most adipokines were suggested to be involved in the inflammatory response that develops within the context of NAFLD, either at hepatic or systemic level, and/or hepatic insulin resistance. Based on literature, clinical studies suggest that chemerin, resistin and adipocyte-fatty-acid-binding protein potentially are involved in NAFLD pathogenesis and/or progression. However, major inconsistency still exists, and there is a high need for larger studies, together with the need of standardized assays to determine adipokine levels.

IgG4-related cholangitis: Case report and literature review.

CASE PRESENTATION: We describe a case of a patient who presents with jaundice, elevated cholestatic liver enzymes, an extreme weight loss and a midcholedochal stricture very suspect for a cholangiocarcinoma. In the conviction of malignancy, although the absence of anatomopathological prove, the patient underwent a choledochal resection. The anatomopathological specimen revealed no malignancy. In the year following resection, the patient keeps presenting with bile duct strictures and further weight loss. Ultimately the diagnosis of Ig G4-related cholangitis is withheld. Therapy with corticosteroids is initiated with a spectacular clinical, biochemical and radiographical result. DISCUSSION: IgG4-related cholangitis is the biliary presentation of IgG4-related disease, a recently discovered entity of fibroinflammatory masses which can affect virtually every organ in the body. It is characterized by a dense lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis and a presence of > 30 IgG4-positive plasma cells per high power field. Main differential diagnosis contains cholangiocarcinoma and primary sclerosing cholangitis. Corticoids are cornerstone of therapy, with azathioprine frequently used as a maintenance in case of relapse. CONCLUSIONS: With this case we want to draw the attention to a rather uncommon cause of biliary obstruction, easily mistaken for a cholangiocarcinoma.

Cutaneous infection by Alternaria infectoria in a liver transplant recipient: a case report.

We report the case of a 65-year-old man who developed multiple crusty ulcerative skin lesions on both lower extremities six months after liver transplantation. The causative pathogen was identified as Alternaria Infectoria, an opportunistic fungal agent. The patient was successfully treated with fluconazole for 27 weeks, with complete regression of the lesions. Due to the lack of well-designed clinical studies it is difficult to determine the best treatment course regarding solid organ transplant recipients presenting with invasive fungal infections. And for now, the clinician must lean upon case-reports or retrospective analyses to compose the most suited therapy for his patient. Based upon literature, it seems that the combination of a broad spectrum azole and reducing the dose of immunosuppressive drugs is the cornerstone of treating invasive fungal infections in solid organ transplant patients.

Acute hepatitis after treatment for hair loss with oral green tea extracts (Camellia Sinensis).

Nutritional additives based on green tea have been claiming various beneficial health effects. However, several case reports on hepatotoxicity after the intake of green tea derivatives containing Camellia Sinensis have been published. We report a patient with an acute hepatitis after intake of an oral green tea derivative claiming protection against hair loss, showing a histological image compatible with drug induced hepatitis. Other important causes of hepatitis were excluded. After cessation of this nutritional additive there was a rapid and sustained recovery. We raise concern about the safety of nutritional additives with few proven beneficial effects and want to emphasize the importance of accurate and thorough history taking, with attention for over the counter drugs and herbal products.

Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by infliximab treatment in rheumatoid arthritis.

OBJECTIVES: To analyse the effect of infliximab on IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies, and determine whether baseline autoantibody titres (IgM RF and anti-CCP antibodies) are associated with changes in acute phase reactants. PATIENTS AND METHODS: 62 patients with refractory RA were treated with infliximab combined with methotrexate. At baseline and week 30, serum samples were tested for IgM RF by two agglutination assays, and for anti-CCP antibodies by an ELISA. Percentage change in C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was calculated. RESULTS: At baseline and week 30 RF titres were reduced significantly during infliximab treatment (p<0.001 and p = 0.038, respectively), whereas anti-CCP antibodies were unchanged (p = 0.240). Baseline IgM RF titres, but not anti-CCP antibodies, correlated inversely with changes in CRP and ESR during treatment. Patients with a marked decrease in acute phase reactants had lower IgM RF titres than those with a smaller decrease in CRP and ESR; no significant differences were found for anti-CCP antibodies. CONCLUSION: The differential effect of infliximab treatment on IgM RF and anti-CCP antibodies, and the different predictive value on changes in acute phase reactants during infliximab treatment support the existing evidence that RF and anti-CCP antibodies are independent autoantibody systems in RA.