Liver test abnormalities in patients admitted for severe psoriasis: prevalence and associated risk factors.

BACKGROUND: Few epidemiologic data are available regarding biologic liver abnormalities during psoriasis flares. OBJECTIVES: The aim of this study was to assess the prevalence of biological liver test abnormalities (LTA) in a psoriasis population and the risk factors associated with LTA. METHODS: A retrospective cross-sectional study in four hospital dermatology tertiary care centres included patients admitted for severe psoriasis flare between 1st January 2010 and 31st December 2011. During the same period, a control population was selected comprising patients admitted for contact and/or atopic eczema. Data were collected on hospital records and biology software. LTA was defined as serum AST and/or ALT and/or ALP concentration above the upper normal limit (UNL) and/or GGT concentration above 2 UNL. Prevalence of LTA with 95% confidence intervals (95% CI) was compared between the psoriatic and control populations. Factors associated with LTA at P < 0.05 were considered for the final multivariate logistic regression model. RESULTS: Two hundred and forty psoriasis patients and 96 eczema control patients were included. One hundred and fifty-five(64.6%) of the psoriasis patients were male, aged 55 years on average (±17.6); 192 (80.0%) had plaque-type psoriasis (PV) and 52 (21.6%) had localized (n = 32) or generalized (n = 20) pustular psoriasis (PP). Prevalence of LTA was 36% (95% CI, 30-42) in the psoriatic population, significantly higher than in controls (17%, 95% CI 9.5-25). Risk factors independently associated with LTA comprised PV (OR 3.79; 95% CI 1.48-9.65), PP (OR 3.80; 95% CI 1.40-10.25) and previously diagnosed liver disease (underlying hepatic steatosis, viral hepatitis or excessive alcohol consumption) (OR 3.88; 95% CI 2.02-7.45). No association was found with systemic antipsoriatic drug therapies. CONCLUSION: In severe psoriasis, liver impacting comorbidities and/or specific psoriatic inflammation, the latter mostly in PP cases, more than drug-related liver toxicity, appears to predominantly account for LTA. Clinicians should be aware of this, to avoid unjustified withdrawal of useful systemic drugs.

Association between IL28B polymorphism, TNFα and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance.

TNFα has been shown to play a role in hepatitis C virus (HCV)-induced insulin resistance (IR). Polymorphism of the IL28B gene that encodes IFN-lambda 3 may be associated with IR through modulation of TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty-three nondiabetic genotype 1 HCV-infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNFα (sTNFR1) and adipokines: leptin, adiponectin and IL-6. The HOMA-IR was positively correlated with serum levels of leptin (r = 0.35, P < 0.0001) and sTNFR1 (r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA-IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA-IR or sTNFR1 level. HCV-related IR may be mediated through TNFα independent of IL28B genotype.

Endoscopic features of low-phospholipid-associated cholelithiasis syndrome: A retrospective cohort study.

BACKGROUND AND OBJECTIVE: LPAC (low phospholipid-associated cholelithiasis) syndrome is a rare genetic form of cholelithiasis. ERCP (endoscopic retrograde cholangiopancreatography) is often used to remove gallstones in the bile duct. No published data is available on the role of ERCP in LPAC syndrome. PATIENTS AND METHODS: In this retrospective cohort study, we included patients diagnosed with LPAC syndrome in a single tertiary referral center between 2009 and 2021. Our aim was to assess the frequency, indications, modalities, results, and complications of ERCP, as well as predictive factors for ERCP, in LPAC syndrome. Independent factors associated with ERCP occurrence were identified using a multivariable Cox regression analysis. RESULTS: ERCP was required in 31.2 % of the 269 patients included for analysis. Among patients who required ERCPs, 78.6 % had the procedure before diagnosis (i.e., starting UDCA). Most common indications were choledocholithiasis (53.6 %) and acute cholangitis (29.5 %). Post ERCP pancreatitis, perforation and bleeding rates were 7.2 %, 2.6 %, and 1.3 %, respectively. Age and history of cholelithiasis in first-degree relatives were associated with a higher risk of ERCP (Hazard-ratio [HR]=1.30 [95 %confidence-interval [CI] 1.04-1.62] and HR=1.88 [95 %CI 1.15-3.07] respectively). Female gender and UDCA intake ≥ 1 year were associated with a lower risk of ERCP (HR=0.49 [95 %CI 0.29-0.82] and HR=0.44 [95 %CI 0.22-0.90] respectively). Median follow-up was 10.8 years. CONCLUSION: One-third of patients with LPAC syndrome undergo sphincterotomy. However, most procedures are performed before diagnosis and UDCA is associated with a lower risk of endoscopic procedure. Earlier diagnosis and treatment with UDCA may further reduce the need for ERCP in patients with LPAC syndrome.

Triple therapy with ursodeoxycholic acid, budesonide and mycophenolate mofetil in patients with features of severe primary biliary cirrhosis not responding to ursodeoxycholic acid alone.

BACKGROUND/AIMS: To assess the benefit of the UDCA-budesonide combination in association with mycophenolate mofetil (MMF) in patients with primary biliary cirrhosis (PBC) at high risk of developing cirrhosis or liver failure. METHODS: Inclusion criteria for this three-year open study were: 1) suboptimal biochemical response to one-year UDCA therapy at 13-15 mg/kg/d; 2) significant interface hepatitis without cirrhosis at liver biopsy. Treatment regimen included UDCA (13-15 mg/kg/d), budesonide (6 mg/d) and MMF (1.5 g/d). All patients underwent a control biopsy at three years. RESULTS: Fifteen patients fulfilled the inclusion criteria. Six patients (41%) normalized biochemistries and seven (47%) had a partial but significant biochemical response, as defined by a serum bilirubin less than 17 micromol/L, alanine aminotransferase less than 70 UI/L and alkaline phosphatase less than 250 UI/L. Histological activity and fibrosis were markedly improved. Side effects were minimal or absent. CONCLUSIONS: Triple therapy with UDCA, budesonide and MMF may provide benefit in non-cirrhotic PBC patients with features of severe disease not responding to UDCA.

[A case of autoimmune hepatitis]. / Un cas d'hépatite auto-immune.

Autoimmune hepatitis (AIH) is a disorder of unknown aetiology that occurs in children and adults of all ages with a female predominance. The spectrum of presentation is wide, ranging from no symptoms to acute liver failure. The diagnosis is based on high level or serum gammaglobulins, characteristic circulating autoantibodies and histologic abnormalities (necrosis and inflammation) in the absence of other causes. AIH is classified on the basis of the autoantibody pattern: type 1 (antinuclear and/or smooth muscle antibodies) is the classic form whereas type 2 (liver-kidney microsome 1 antibody) is much less common and occurs mainly in childhood. Mixed forms of AIH that share features with other putative autoimmune liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis, have been described. Because of therapeutic issues, it is important to distinguish AIH from other forms of hepatitis and the use of diagnostic scoring systems may be helpful. Treatment basis of AIH have not changed for the last 30 years. Initial treatment consists of corticosteroids associated with azathioprine. Budesonide may be at least as effective as systemic corticosteroids and reduces the frequency of side effects in non-cirrhotic patients. Long-term treatment consists of azathioprine. This treatment is rapidly effective but usually only suspensive since relapse after treatment withdrawal is the rule (80 % of cases). The probability of relapse is lower in case of complete biochemical response defined by normalization of transaminases, gamma-globulins and IgG and in case of histological response defined by the lack of interface hepatitis. The frequency of side effects justifies an attempt of drug discontinuation provided that criteria of clinical, biochemical and histological remission are achieved after at least 2 years of treatment.

[Liver disease and pregnancy]. / Pathologies hépatiques et grossesse.

Liver dysfunction during pregnancy can be related or not to pregnancy itself. The purpose of this review is to summarize the possible causes of liver dysfunction during pregnancy and their management. Liver dysfunction during pregnancy can be chronic or acute, independent or specific to pregnancy. Management of liver disease can be different during pregnancy. The knowledge of liver dysfunction during pregnancy is of help for a better management of the mother in order to avoid maternal and fetal mortality and morbidity.

HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry.

Primary sclerosing cholangitis (PSC) is strongly associated with several human leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and multiple polymorphic candidate genes in the HLA complex, identifying the alleles responsible for these associations has proven difficult. We aimed to evaluate whether studying populations of admixed or non-European descent could help in defining the causative HLA alleles. When assessing haplotypes carrying HLA-DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic cholangitis), we observed that every haplotype in the Scandinavian PSC population carried HLA-DQB1*06:03. In contrast, only 65% of HLA-DRB1*13:01 haplotypes in an admixed/non-European PSC population carried this allele, suggesting that further assessments of the PSC-associated haplotype HLA-DRB1*13:01-DQA1*01:03-DQB1*06:03 in admixed or multi-ethnic populations could aid in identifying the causative allele.

A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.

A-Type lamins, arising from the LMNA gene, are intermediate filaments proteins that belong to the lamina, a ubiquitous nuclear network. Naturally occurring mutations in these proteins have been shown to be responsible for several distinct diseases that display skeletal and/or cardiac muscle or peripheral nerve involvement. These include familial partial lipodystrophy of the Dunnigan type and the mandibuloacral dysplasia syndrome. The pathophysiology of this group of diseases, often referred to as laminopathies, remains elusive. We report a new condition in a 30-yr-old man exhibiting a previously undescribed heterozygous R133L LMNA mutation. His phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, hepatic steatosis, hypertrophic cardiomyopathy with valvular involvement, and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient's cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations. This observation broadens the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the unreported possibility of hypertrophic cardiomyopathy and skin involvement. It emphasizes the fact that the diagnosis of genetic alterations in A-type lamins requires careful and complete clinical and morphological investigations in patients regardless of the presenting signs.

Effect of fat-emulsion phospholipids on serum lipoprotein profile during 1 mo of cyclic total parenteral nutrition.

Changes in serum lipoprotein determined by selective precipitation were investigated in 11 adult patients during 1 mo of parenteral nutrition. Patients were divided into two groups that received a similar nutrient regimen except for Intralipid (IL) phospholipid, which was higher in group A (10% IL, n = 5) than in group B (20% IL, n = 6), 139 +/- 15 vs 71 +/- 0.5 mg.kg-1.d-1 (P less than 0.01). Lipoprotein X (LPX) detected soon after IL infusions were started reached its highest concentrations in group A. LPX concentrations correlated with phospholipid intakes on days 7 and 15 but not on day 29. Significant increases in the cholesterol and phospholipid content of low-density-lipoprotein-very-low-density-lipoprotein fractions were observed only in group A. It is suggested that these changes were induced by the twofold-higher intake of phospholipids in group A. With regard to the possible involvement of LPX in lipid overloading of the reticuloendothelial system and hepatocytes, administration of 20% IL seems preferable to 10% IL.

Hepatocellular carcinoma and focal hepatic glycogenosis after prolonged azathioprine therapy.

A 22-year-old woman without predisposing liver disease developed focal hepatic glycogenosis and hepatocellular carcinoma after 6 years of azathioprine therapy for Crohn's disease. Hepatocellular carcinoma without cirrhosis has previously been described during immunosuppression, but this is the first report of disseminated focal hepatic glycogenosis after long-term azathioprine therapy.

Chronic cholestasis and macronutrient excess in patients treated with prolonged parenteral nutrition.

The mechanism of chronic cholestasis observed during prolonged parenteral nutrition remains unclear. We studied liver function tests in 18 consecutive gastroenterological adult patients submitted to 18 mo (median; range 6-66 mo) of parenteral nutrition. Seven patients (group B) developed a cholestatic nonobstructive jaundice, culminating after 3 mo, (1-4 mo) whereas 11 patients (group A) did not develop chronic abnormalities on liver function tests during parenteral nutrition. Liver biopsies obtained at 4 mo (3-6 mo) in 6 group B patients demonstrated bile duct proliferation in the portal area, with extensive fibrosis, cholestasis, and focal necrosis of hepatocytes. Initial intakes of calories, fat, and protein were higher (p less than 0.01) in group B than in group A patients and, when reduced, were associated with reversal of jaundice and improvement in liver function tests and histological findings. These data suggest that the development and course of cholestasis are influenced by excess parenteral intake of protein and mixed-energy sources.

[A case of esophageal papillomatosis in adults]. / Un cas de papillomatose oesophagienne de l'adulte.

The authors report the case of a 60 year-old woman patient with esophageal papillomatosis, revealed by slowly progressive dysphagia and digestive hemorrhage. Multiple warty tumors were found at endoscopy, starting at approximately 23 cm from the dental ridge, increasing in size into the lower esophagus where they were responsible for stenosis. Pathological examination demonstrated epithelial proliferation with lengthened papillae, hyperkeratosis, hyperacanthosis and severe dysplasia. No extra-esophageal papillomata were discovered. Subtotal esophagectomy was performed and pathological examination with immune markers suggested a human papilloma virus (HPV) infection. However, search for HPV DNA was negative. To our knowledge, this constitutes the fifth case reported in the literature. The principal problem posed by this rare disease is the possible association with and/or progression to carcinoma, the diagnosis of which may be difficult, and particularly, with verrucous carcinoma. With this diagnostic uncertainty in mind, the authors suggest total surgical removal of the esophagus in this situation.

[Nodular regenerative hyperplasia of the liver and primary biliary cirrhosis. A fortuitous association?]. / Hyperplasie nodulaire régénérative du foie et cirrhose biliaire primitive. Une association fortuite?

We report here in a case of primary biliary cirrhosis associated with nodular regenerative hyperplasia of the liver in a white woman revealed by digestive hemorrhage due to ruptured esophageal varices. The diagnosis of primary biliary cirrhosis was based on the following: elevated serum IgM, high titer of antimitochondrial antibody (anti M2), typical histopathological picture of stage I/II disease. The diagnosis of nodular regenerative hyperplasia was supported by the demonstration of disseminated small hepatic nodules without perinodular fibrosis. This association may be a supplementary argument in favor of a possible autoimmune origin of nodular regenerative hyperplasia of the liver.

[Non-surgical treatment of biliary stenoses after hepatic transplantation]. / Traitement non chirurgical des sténoses biliaires après transplantation hépatique.

We report the initial and long-term results of non surgical procedures performed for the treatment of biliary strictures in liver transplant patients. Twelve liver transplant patients with biliary strictures underwent 16 interventional radiological procedures. Initial technical success was achieved in 11 of 12 patients (91%). Within long-term, with a follow-up of 27 months, primary success rate (only one procedure) was 58% (7 of 12 patients). Three restenoses occurred. They were all treated by interventional radiological procedures. The secondary success rate (one or more procedures) was 83% (10 of 12 patients). Two complications occurred including one pancreatitis and one cholangitis. Non surgical management may be performed for patients with biliary strictures after liver transplantation.

[Autoimmune hepatitis: diagnostic and therapeutic up-to-date]. / Hépatites auto-immunes : actualités diagnostiques et thérapeutiques.

Autoimmune hepatitis is a disorder of unknown aetiology that occurs in children and adults of all ages with a female predominance. The spectrum of presentation is wide, ranging from no symptoms to acute liver failure. The diagnosis is based on high level serum gammaglobulins, characteristic circulating autoantibodies and histologic abnormalities (necrosis and inflammation). Autoimmune hepatitis is classified on the basis of the autoantibody pattern: type 1 (antinuclear and/or smooth muscle antibodies) is the classic form whereas type II (liver-kidney microsome 1 antibody) is much less common and occurs mainly in childhood. Mixed forms of autoimmune hepatitis that share features with other putative autoimmune liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis, have been described. Because of therapeutic issues, it is important to distinguish autoimmune hepatitis from other forms of hepatitis and the use of diagnostic scoring systems may be helpful. The treatment of autoimmune hepatitis has not changed for the past 30 years. It consists of corticosteroids associated with azathioprine. This treatment is rapidly effective but usually only suspensive. Relapse after treatment withdrawal is the rule (80% of cases). The main risk factor of recurrence is the degree of residual inflammation on liver biopsy. The frequency of side effects justifies an attempt of drug discontinuation provided that criteria of clinical, biochemical and histological remission are achieved after at least 2 years of treatment.