Prediction of long-term clinical outcome in a diverse chronic hepatitis B population: Role of the PAGE-B score

An abundance of noninvasive scores have been associated with fibrosis and hepatocellular carcinoma (HCC) development. We aimed to compare the prognostic ability of these scores in relation to liver histology in chronic hepatitis B (CHB) patients. Liver biopsies from treatment-naïve CHB patients at one tertiary care centre were scored by a single hepato-pathologist. Laboratory values at liver biopsy were used to calculate the PAGE-B, REACH-B, GAG-HCC, CU-HCC and FIB-4 scores. Any clinical event was defined as HCC development, liver failure, transplantation and mortality. HCC and mortality data were obtained from national database registries. Of 557 patients, 40 developed a clinical event within a median follow-up of 10.1 (IQR 5.7-15.9) years. The PAGE-B score predicted any clinical event (C-statistic.86, 95% CI: 0.80-0.92), HCC development (C-statistic.91) and reduced transplant-free survival (C-statistic.83) with good accuracy, also when stratified by ethnicity, antiviral therapy after biopsy or advanced fibrosis. The C-statistics (95% CI) of the REACH-B, GAG-HCC, CU-HCC and FIB-4 scores for any event were.70 (0.59-0.81),.82 (0.75-0.89),.73 (0.63-0.84) and.79 (0.69-0.89), respectively. The PAGE-B event risk assessment improved modestly when combined with the Ishak fibrosis stage (C-statistic.87, 95% CI: 0.82-0.93). The PAGE-B score showed the best performance in assessing the likelihood of developing a clinical event among a diverse CHB population over 15 years of follow-up. Additional liver histological characteristics did not appear to provide a clinically significant improvement

ITPA polymorphisms are associated with hematological side effects during antiviral therapy for chronic HCV infection

Background/Objective Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV. Patients and Methods This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed. Results In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024). Conclusion Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently

Role of anticoagulant therapy in liver disease

Anticoagulant therapy is a cornerstone in the treatment of different liver diseases. In Budd-Chiari syndrome (BCS), survival rates have increased considerably since the introduction of a treatment strategy in which anticoagulation is the treatment of first choice. In all patients diagnosed with acute portal vein thrombosis (PVT), anticoagulant therapy for at least 3 months is indicated. Anticoagulation should also be considered in patients with chronic PVT and a concurrent prothrombotic risk factor. Current evidence suggests that patients with PVT in cirrhosis will benefit from treatment with anticoagulation as well. In severe chronic liver disease the levels of both pro- and anticoagulant factors are decreased, resetting the coagulant balance in an individual patient and making it more prone to deviate to a hypo- or hypercoagulable state. An increased activity of the coagulation cascade is not solely a feature of chronic liver disease; it influences the development of liver fibrosis as well. Several studies in animals and humans have shown that anticoagulation could prevent or improve fibrogenesis and even disease progression in cirrhosis. Anticoagulation is therefore a promising antifibrotic treatment modality

GI ischemia in patients with portal vein thrombosis: A prospective cohort study

Background and Aims GI ischemia is a concerning adverse event of portal vein thrombosis (PVT). Minimally invasive techniques, such as visible light spectroscopy (VLS), have greatly improved the ability to diagnose GI ischemia. The aim of this study was to assess the clinical presentation and characteristics of GI ischemia in patients with PVT. Methods Patients with noncirrhotic, nonmalignant PVT were included in this prospective cohort study. Clinical symptoms of GI ischemia were assessed by a structured questionnaire, VLS, and radiologic evaluation of the mesenteric vasculature. VLS measurements were compared with those in patients with cirrhosis and with a reference population. Results We included 15 patients with chronic PVT and 1 patient with acute PVT (median age 46.1 years [interquartile range [IQR], 30.9-53.7]; 44% male). Decreased mucosal oxygenation in at least 1 location of the GI tract was found in 12 patients (75%). Compared with the reference population (median 60.0 [IQR, 56.2-61.7]), VLS measurements were mostly decreased in the descending duodenum in patients with PVT (median 55.5 [IQR, 52.3-58.8]; P =.02) and patients with cirrhosis (median 52.0 [IQR, 46.5-54.0], P =.003). Symptoms typical for GI ischemia, such as postprandial pain and exercise-induced pain, were reported in 10 patients (63%) with PVT. In patients with extension of thrombosis into the superior mesenteric vein and splenic vein and/or presence of hypercoagulability, decreased VLS measurements were observed compared with historical control subjects. Conclusions In patients with chronic PVT, GI ischemia is frequent. VLS enables objective and quantitative determination of GI mucosal ischemia. Onset of abdominal symptoms such as postprandial pain should prompt the physician to re-evaluate extent, cause, and treatment of PVT

Prothrombotic genetic risk factors are associated with an increased risk of liver fibrosis in the general population: The Rotterdam Study

Background & Aims The coagulation system is known to be involved in fibrogenesis in patients with liver disease. We investigated whether common genetic prothrombotic risk factors are associated with an increased risk of fibrosis in the general population. Methods This investigation was part of the Rotterdam Study, an ongoing, population-based cohort study. Liver stiffness (LS) was measured using transient elastography (Fibroscan®) and associated with single nucleotide polymorphisms determining blood group type and presence of the Factor V Leiden (FVL) mutation or prothrombin G20210A gene variant. Results Reliable LS measurements and genetic data were obtained from 1055 Caucasian participants. LS ≥8.0 kPa, suggestive of clinically relevant fibrosis, was observed in 101 subjects (9.6%). Presence of FVL or prothrombin G20210A was independently associated with an increased risk of LS ≥8.0 kPa (OR 2.09, 95%CI 1.07-4.07, p = 0.03). Combination of blood group type non-O and the FVL mutation or prothrombin G20210A variant resulted in an even higher risk of LS ≥8.0 kPa (OR 3.36, 95%CI 1.50-7.56, p = 0.003). Presence of the FVL mutation or prothrombin G20210A variant in participants with blood group non-O was associated with a predicted probability of 14.3% (7.7-23.8) of LS ≥8.0 kPa. Conclusions Participants carrying the FVL mutation or prothrombin G20210A variant have an increased risk of clinically relevant liver fibrosis, which is even higher in blood group type non-O carriers. The fact that genetic prothrombotic risk factors are associated with an increased risk of liver fibrosis suggests that coagulation plays an important role in fibrogenesis in the general population