Introduction Acute lower gastrointestinal bleeding (LGIB) presents challenges in emergency settings, with incidence influenced by demographic shifts and anticoagulant usage. The Oakland score aids in ...risk stratification for safe discharge based on clinical and laboratory parameters. However, external validation remains limited. Methods This study validated the Oakland score in a French cohort of patients with acute LGIB and assessed the discriminatory value of the score using the area under the curve (AUC) and then its sensitivity and specificity. Results A retrospective examination of 343 patient records that satisfied the inclusion criteria showed a median score of 14 points and good discriminatory capacity (area under the receiver operating characteristic (AUROC) curve: 0.83). There was low sensitivity (20.9%) for safe discharge but good specificity (98.5%) when using an 8-point threshold. With a 9-point threshold, the sensitivity was increased to 36.5%, while the specificity remained at 95%. Conclusion Identifying low-risk LGIB patients is accomplished without sacrificing sensitivity by increasing the Oakland score threshold to 9 points. This modification improves patient safety and resource allocation in the emergency room and has been verified by other large series. For wider implementation, additional validation and long-term outcome evaluations are required.
Low-phospholipid-associated cholelithiasis (LPAC) syndrome, a rare genetic form of intrahepatic cholelithiasis in adults, is still poorly understood. We report the results of the largest-ever ...case-control study of patients with LPAC syndrome aiming to assess the prevalence, clinical features, and comorbidities of the disease.
We included all LPAC cases diagnosed between 2001 and 2016 in 11 French centres. Controls consisted of all patients who underwent a cholecystectomy for common gallstone disease in a single non-academic centre over 1 year. A logistic regression analysis was used to identify the clinical features associated with LPAC syndrome across several patient strata with increasing levels of diagnostic confidence. The ratio between the incident cases of LPAC syndrome and the total number of cholecystectomies for gallstones was used to assess the relative prevalence of the disease.
In this study, 308 cases and 206 controls were included. LPAC syndrome accounted for 0.5–1.9% of all patients admitted with symptomatic gallstone disease. Age at first symptoms <40 years, absence of overweight, persistence of symptoms after cholecystectomy, intrahepatic micro- or macrolithiasis, common bile duct (CBD) lithiasis, and no history of cholecystitis were independently associated with LPAC diagnosis. ATP-binding cassette subfamily B member 4 (ABCB4) variants, present in 46% of cases, were associated with CBD lithiasis, chronic elevation of gamma-glutamyltransferase (GGT), and personal or family history of hepato-biliary cancer.
In this case-control study, LPAC syndrome accounted for approximately 1% of symptomatic cholelithiasis in adults. In addition to pre-established diagnostic criteria, normal weight, CBD lithiasis, and no history of cholecystitis were significantly associated with the syndrome. ABCB4 gene variations in patients with LPAC were associated with CBD lithiasis, chronic cholestasis, and a personal or family history of hepato-biliary cancer.
In the largest case-control study ever conducted in patients with LPAC syndrome, a rare genetic form of intrahepatic cholelithiasis in young adults, LPAC syndrome was found in approximately 1% of all patients admitted to the hospital for symptomatic gallstones and, in addition to the pre-established characteristics of the syndrome (age at first symptoms <40 years, recurrence of symptoms after cholecystectomy, and/or imaging evidence of intrahepatic microlithiasis), was associated with lower BMI, higher prevalence of common bile duct stones, and lower incidence of acute cholecystitis. ABCB4 gene variants, which were detected in about half of cases, were associated with common bile duct stones and a personal or family history of hepato-biliary cancer.
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•Low-phospholipid-associated cholelithiasis (LPAC) syndrome affects approximately 1% of adults with symptomatic cholelithiasis.•Normal weight, common bile duct stones, and lack of cholecystitis are clinical features significantly associated with this syndrome.•ABCB4 variants in patients with LPAC may be associated with an increased personal or family risk of hepato-biliary cancer.
Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome ...proliferator-activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition.
In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months.
The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001). Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group. Results regarding changes in pruritus, fatigue, and noninvasive measures of liver fibrosis, including liver stiffness and Enhanced Liver Fibrosis score, were consistent with the results of the primary outcome. Two patients in each group had complications from end-stage liver disease. The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group. Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group.
Among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731 .).
Summary
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.
Methods
PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second‐line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed‐effect model.
Results
Among 58 patients included, half received OCA as second‐line and fibrates as third‐line therapy (Group OCA‐Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate‐OCA). The mean duration of triple therapy was 11 months (range 3‐26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%‐31%), an effect that was stronger in OCA‐Fibrate than in Fibrate‐OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4‐8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma‐glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris‐2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8‐16.7) and 9.2 (95% CI 3.4‐25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA‐Fibrate but not in Fibrate‐OCA group.
Conclusions
Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult‐to‐treat PBC.
Triple therapy with UDCA, OCA, and Fibrate was associated with a 3.4 (95%CI 1.4‐8.2) odds ratio of achieving normal levels of alkaline phosphatase (ALP).
In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a ...non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated.
This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0.
A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio OR 6.85; 95% CI 2.23–21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59–30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09–24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <–0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%.
In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort.
The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
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•In patients with acute-severe autoimmune hepatitis treated with corticosteroids, the LT-free survival rate is 66%.•INR at the introduction of corticosteroids and the evolution of INR and bilirubin values after 3 days of therapy are highly predictive of LT or death.•The SURFASA score -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin) combines these 3 variables.•The SURFASA score can rapidly identify non-responders to corticosteroid therapy who require referral for LT.
Entecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment ...failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present before treatment in patient #1. HBs Ag immune escape mutations were present before treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). These results provided a unique insight into the evolution of HBV quasispecies during entecavir treatment, addressing the whole HBV genome and not only the Pol/RT domain. Our results suggest that mutations selected outside of the Pol/RT domain could contribute to entecavir treatment failure, not by an increased level of resistance, but by an immune escape mechanism, in synergy with immunosuppressive drugs.
Entecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment ...failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present as major mutations before and after treatment in patient #1. HBs Ag immune escape mutations were present as major mutations before and after treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). We demonstrated that PVR to entecavir does not require selection of any resistance mutation in the whole HBV genome. Our results demonstrate that major mutations can be selected outside of the Pol/RT domain before or during entecavir treatment. These mutations could contribute to entecavir treatment failure by other mechanisms than an increased level of resistance.
Non-invasive diagnosis and follow-up of primary biliary cholangitis Corpechot, Christophe; Heurgue, Alexandra; Tanne, Florence ...
Clinics and research in hepatology and gastroenterology,
January 2022, 2022-01-00, 20220101, 2022-01, Letnik:
46, Številka:
1
Journal Article
Recenzirano
Odprti dostop
•A liver biopsy is generally not required for the diagnosis of PBC.•PBC staging can be based on blood tests, ultrasound, and liver stiffness measurement.•Response to first-line treatment of PBC is ...based on blood tests (Paris-2 criteria) assessed after 6 to 12 months.•Autoimmune hepatitis features associated with PBC should be investigated in the event of a significant increase in transaminases or an inadequate response to treatment.•Liver transplantation for PBC should be considered specifically in patients with a total bilirubin level permanently ≥ 80 µmol/l or with severe, intractable pruritus.
Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the intra-hepatic bile ducts 1. It is characterised biologically by chronic cholestasis associated with the presence of specific autoantibodies, and histologically by lesions of nonsuppurative destructive cholangitis. If left untreated it can progress to cirrhosis, portal hypertension and liver failure. Diagnosis, staging and follow-up are largely based on non- or minimally-invasive assessment (blood tests, ultrasound, liver stiffness measurement). Histological examination of the liver and upper gastrointestinal endoscopy are sometimes necessary, but their indications remain limited. The purpose of this chapter is to provide the clinicians with what should be known about the non-invasive assessment of PBC and to provide specific recommendations for clinical practice.
Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive ...obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan (R) correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD. (c) 2021 Elsevier Masson SAS. All rights reserved. .101775 SAS. All rights reserved.
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