When and how to use direct oral anticoagulants in patients with advanced chronic liver disease?

Direct oral anticoagulants (DOACs) emerged as effective and safe alternatives to traditional anticoagulants for the prevention and treatment of venous thromboembolic disease and the prevention of stroke in non-valvular atrial fibrillation. Patients with advanced chronic liver disease (ACLD) have a higher risk of thromboembolism and bleeding than patients with normal liver function. Therefore, anticoagulation and, in particular, direct oral anticoagulants play a central role. Portal vein thrombosis is a relatively frequent complication in patients with ACLD, but its treatment remains challenging. DOACs have been introduced in clinical practice and demonstrated similar efficacy and safety profiles compared with vitamin K antagonist and heparins. However, further data about the use of DOACs in patients suffering from ACLD are needed. This review summarizes current knowledge in terms of anticoagulation in patients with ACLD and focuses on the available data about the use of DOACs in this population.

Clinical Adverse Events after Endoscopic Resection for Colorectal Lesions: A Meta-Analysis on the Antibiotic Prophylaxis.

BACKGROUND: Post-polypectomy coagulation syndrome (PECS) is a well-known adverse event after endoscopic polypectomy for colorectal lesions. To date, there are no standardized guidelines for the antimicrobial prophylaxis. The aim of this meta-analysis is to evaluate the usefulness of antibiotics in patients undergoing endoscopic mucosal or submucosal resections. METHODS: A comprehensive literature search of PubMed, MEDLINE, EMBASE, and Web of Science databases was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies investigating the role of prophylactic antibiotic administration in reducing the PECS after endoscopic polypectomy were considered. The terms used to search were ("antimicrobial"OR"antibiotics"OR"prophylaxis"OR"prophylactic") AND ("resection"OR"polypectomy"OR"dissection") AND ("endoscopic"OR"mucosal"OR"submucosal") AND ("colon"OR"colorectal"OR"colonic"OR"rectum"). Data of included studies were collected and analysed. RESULTS: The literature search revealed 262 articles, 3 of whom were randomized trials and one was a retrospective study. Patients included were 850 (548 treated with antibiotics and 302 received no treatment). The overall incidence rate was 2.4 and 19.9% in treatment and control groups, respectively. The pooled analysis showed a reduction of 83% of postoperative events in the antibiotics group (relative risk 0.181; 95% CI 0.100-0.326, p < 0.001). CONCLUSIONS: In our meta-analysis, the antibiotic prophylaxis showed a positive effect in reducing the incidence of postoperative adverse events other than perforation and bleeding in patients treated with endoscopic mucosal resection and endoscopic submucosal dissection for colorectal lesions. Despite the low-level of evidence of this meta-analysis, the antibiotic prophylaxis should be taken into account. Further multicenter, large-sample, randomized controlled studies are needed to confirm our results and to evaluate whether specific subgroups of patients could actually benefit from an antibiotic prophylaxis.

Intestinal Endometriosis: Mimicker of Inflammatory Bowel Disease?

BACKGROUND/AIMS: Endometriosis of the intestinal tract (IE) is thought to mimic inflammatory bowel disease (IBD) both clinically and pathologically but robust data on a large unselected series are missing. Diagnostic problems arise both at colonoscopy as well as on resection specimens for IE when IBD-like features are encountered. The aim was to establish the frequency of IBD-like histology in IE and which type of histological lesions are shared by these two entities. METHODS: One hundred consecutive, unselected cases of surgically resected IE were collected and clinical features and histopathology reviewed and reevaluated. RESULTS: Seventy-five surgical specimens showed no histological alterations except for endometriosis foci. Twenty-two cases showed focal architectural alterations in the absence of significant inflammation. Three cases showed marked inflammatory and architectural mucosal changes making a differential diagnosis with IBD particularly challenging. On follow-up, however, these patients remained symptom-free and with no need for anti-inflammatory therapy after surgical resection of IE. CONCLUSIONS: Diagnostic problems may arise in women who have IBD-like symptoms and histology at colonoscopy but who lack a known diagnosis of endometriosis. Clinicians must be aware that the diagnosis of IBD in patients with IE should be reevaluated over time.

13C-galactose breath test and 13C-aminopyrine breath test for the study of liver function in chronic liver disease.

BACKGROUND AND AIMS: Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13 C-aminopyrine breath test ( 13 C-ABT) and 13 C-galactose breath test ( 13 C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease. METHODS: We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13 C-GBT and 13 C-ABT, and the results were expressed as a percentage of the administered dose of 13 C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13 C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis. RESULTS: On average, 13 C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13 C-ABT results from 30 to 120 minutes. 13 C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13 C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13 C-GBT and 13 C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis. CONCLUSIONS: In patients with chronic liver disease, both 13 C-GBT and 13 C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.

Helicobacter pylori infection is associated with greater impairment of cytochrome P-450 liver metabolic activity in anti-HCV positive cirrhotic patients.

Helicobacter pylori gastric infection has been associated with various digestive and extradigestive diseases. In liver disease bacterial infections have been associated with impairment of cytochrome P-450 liver metabolic activity. Moreover, infection by Helicobacter spp. seems to be linked with the development of hepatocellular carcinoma (HCC) in mice. Our aims were to evaluate the influence of H. pylori infection on cytochrome P-450 liver metabolic activity as assessed by means of monoethylglycinexylidide (MEGX) test and to assess the prevalence of H. pylori infection in patients with HCC. Ninety-six hepatitis C virus (HCV) -positive cirrhotic patients, 36 of whom had HCC, were tested for H. pylori infection by means of anti-H. pylori IgG. Patients underwent the MEGX test. Characteristics of the patients were then analyzed on the basis of the presence of H. pylori infection. Seroprevalence of H. pylori infection was similar between cirrhotic patients without (68%) or with (63.8%) HCC. Mean MEGX values were significantly (P < 0.0001) lower in H. pylori infected patients (18.2 +/- 13.9 ng/ml) as compared to the noninfected ones (46.9 +/- 17.1 ng/ml), independently of Child-Pugh's classification. These differences persisted even after subdividing patients according to the presence of HCC. In conclusion, in anti-HCV positive cirrhotic patients H. pylori infection is associated to an impairment of cytochrome P-450 liver metabolic activity. Seroprevalence of H. pylori infection in HCC patients is similar to that observed in tumor-free cirrhotics.

Previous hepatitis B virus infection is associated with worse disease stage and occult hepatitis B virus infection has low prevalence and pathogenicity in hepatitis C virus-positive patients.

BACKGROUND: Anti-hepatitis C virus (anti-HCV) patients with chronic liver disease (CLD) frequently show markers of previous hepatitis B virus (HBV) infection. Moreover, they may carry occult HBV infection. These features might influence clinical and biochemical features as well as stage of disease. AIM: To assess the prevalence and clinical associations of previous (positivity for anti-HBs and/or anti-HBc antibodies) and occult HBV infection (positivity for HBV-DNA by nested-PCR) in the serum of anti-HCV-positive, HCV-RNA-positive, HBsAg-negative patients with various degrees of CLD seen at a tertiary referral centre. PATIENTS: A total of 119 patients fulfilled the inclusion criteria (84 chronic hepatitis and 35 liver cirrhosis). RESULTS: Forty-eight patients (40.3%) showed markers of previous HBV infection. This feature was more frequent (P = 0.02) among cirrhotics (57%) as compared to chronic hepatitis patients (33%). Chronic hepatitis patients positive for markers of previous HBV infection had worse histology as compared to negative ones (grading: 6.4 +/- 2.7 versus 4.6 +/- 3.0, P = 0.004; staging: 1.6 +/- 1.2 versus 1.0 +/- 1.0, P = 0.01). Eight patients were positive for HBV-DNA in serum (6.7%). No difference in the presence of occult HBV infection was seen between various degrees of liver disease (7.1% of chronic hepatitis, 5.7% of cirrhosis) and among patients who were positive (10.4%) or negative (4.2%) for markers of previous HBV infection. No significant biochemical, virological, or histological difference was observed between age, age at infection, duration of infection, marker patterns of previous HBV infection-matched HBV-DNA-positive and negative chronic hepatitis patients. CONCLUSIONS: Our findings suggest that previous HBV infection among anti-HCV patients is associated with worse disease stage. In these patients, the prevalence of occult HBV infection is low and there is no difference in distribution among patients with or without markers of previous HBV infection. Furthermore, it does not seem to be associated with disease stage. Lastly, at least among patients with chronic hepatitis, it does not seem to affect the severity of disease.

Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease.

BACKGROUND: The aspartate aminotransferase-alanine aminotransferase ratio (AST/ALT ratio) has been used to noninvasively assess the severity of disease in patients with chronic liver disease (CLD). We previously demonstrated that progressive liver functional impairment is associated with an increase in the AST/ALT ratio. OBJECTIVES: To evaluate the reproducibility and transportability of the AST/ALT ratio in a large cohort of patients with different degrees of hepatitis C virus (HCV)-related CLD, to confirm the correlation between progressive impairment of liver function and increase in the AST/ALT ratio, to evaluate whether diagnostic accuracy of the ALT/AST ratio can be improved by using it with other biochemical variables, and to assess the 1-year prognostic capability of the AST/ALT ratio in patients with liver cirrhosis. PATIENTS AND METHODS: We retrospectively evaluated 252 patients with HCV-related CLD. The AST/ALT ratio was correlated with the degree of liver fibrosis in patients with chronic hepatitis and with the Child-Pugh score in patients with cirrhosis. All patients had undergone monoethylglycinexylidide (MEGX) testing to evaluate liver function. We assessed the prognostic ability of the AST/ALT ratio in a subset of 63 cirrhotic patients who were followed up for at least 1 year. RESULTS: The AST/ALT ratio was more frequently 1 or higher in cirrhotic patients (P<.001). There was a significant correlation between MEGX values and the AST/ALT ratio (r(s) = -0.621, P<.001). Multivariate stepwise logistic analysis showed that AST/ALT ratio, platelet count (PLT), MEGX values, and prothrombin activity were independently associated with the presence of cirrhosis. Combined assessment of the AST/ALT ratio and/or PLT obtained 97.0% positive predictive value and 97.9% negative predictive value for the diagnosis of cirrhosis. The AST/ALT ratio had 81.3% sensitivity and 55.3% specificity in identifying cirrhotic patients who died within 1-year of follow-up. CONCLUSIONS: The AST/ALT ratio is both reproducible and transportable in patients with HCV-related CLD. The AST/ALT ratio is correlated with both histologic stage and clinical evaluation. Progressive liver functional impairment is reflected by an increase in the AST/ALT ratio. Noninvasive evaluation by means of the combined AST/ALT ratio and PLT assessment misclassifies only a few cirrhotic patients. In cirrhotic patients, the AST/ALT ratio provides medium-term prognostic information that is no different from that provided by established prognostic scores.

Influence of age on clinical presentation, therapeutic options, and prognosis in anti-HCV positive cirrhotic patients with hepatocellular carcinoma.

BACKGROUND: Hepatitis C virus infection-related cirrhosis is a major risk factor for the development of hepatocellular carcinoma. Hepatocellular carcinoma in anti-hepatitis C virus positive cirrhotics shows an increasing prevalence with ageing, although it is not clear whether the age of the patients can be considered a critical factor in the overall assessment of severity of disease or in the choice of therapeutic procedures and prognosis. OBJECTIVE: To evaluate the influence of older age on modality of presentation, therapeutic choices, outcome, and survival in anti-hepatitis C virus patients with hepatocellular carcinoma. METHODS: We retrospectively evaluated 75 anti-hepatitis C virus positive cirrhotic patients with hepatocellular carcinoma consecutively referred to our unit. Patients were sub-divided into two sub-groups according to their age (<65 or >or=65 years) at tumor diagnosis. The characteristics of the patients and of hepatocellular carcinoma, therapeutic procedures, and survival were then analyzed. RESULTS: Median age of the patients was 68 years and mean duration of infection was 24 years. Clinical characteristics of older hepatocellular carcinoma patients were no different from those of younger ones. Hepatocellular carcinoma was more frequently of diffuse type in patients aged <65 years. However, therapeutic options were no different between the two sub-groups of patients, and a similar proportion of patients did not undergo therapy in either group. Overall, 1- and 2-year survival rates were 73% and 51%, respectively. After a mean follow-up of 21 months a higher number of patients aged <65 years died (p=0.002). Moreover, Kaplan-Meier curves showed longer survival in patients aged >or=65 years (p=0.002). Lastly, diffuse type of hepatocellular carcinoma and tumor staging were the variables independently associated with worse survival in multivariate regression analysis. CONCLUSIONS: Hepatocellular carcinoma appears in older anti-hepatitis C virus positive cirrhotic patients showing long duration of infection. Older age of the patients does not seem to influence therapeutic options, and more importantly does not exclude patients from treatment. Lastly, older patients seem to have better prognosis most likely due to hepatocellular carcinoma characteristics, since hepatocellular carcinoma seems to present with more unfavourable characteristics in younger cirrhotic patients.

Monitoring of liver metabolic function during interferon-alpha therapy and its relationship to treatment outcome in chronic hepatitis C patients.

BACKGROUND/AIMS: Interferon is considered the cornerstone in the therapy of chronic hepatitis C patients. Experimental studies have shown that interferon administration may influence liver metabolic activity. However, data concerning the monitoring of liver metabolic function during a therapeutic course of interferon in chronic hepatitis C patients are scanty. The MEGX (monoethylglycinexylidide) test has been used in diagnostic and prognostic assessment of chronic liver disease as a quantitative liver function test. In this study our aim was to non-invasively monitor liver function in chronic hepatitis C patients during a course of interferon-alpha therapy and to evaluate whether the presence of modifications in liver metabolic function might influence the therapeutic outcome. METHODOLOGY: We studied 22 patients with biopsy-proven chronic hepatitis C before, during (1st, 3rd and 6th month of therapy), and three months after interferon-alpha (3 million units thrice weekly for six months) using MEGX test to monitor liver function. RESULTS: During the longitudinal study no significant differences were observed between pretreatment MEGX30 values and those obtained during interferon treatment or at the end of follow-up, both considering patients together or grouped according to treatment outcome (Responders vs. Non-responders). Analysis of the MEGX30 variations during therapy showed that they were evenly distributed between responder and non-responder patients. Furthermore, during interferon therapy none of the patients reached a MEGX30 value compatible with severely impaired liver function. CONCLUSIONS: Our results suggest that although a discrete prevalence of modifications in liver metabolic function occurs in chronic hepatitis C patients during interferon therapy they do not seem to have clinical relevance or influence therapeutic outcome.