Irina Girleanu

Natural course of nonmalignant partial portal vein thrombosis in cirrhotic patients

Background/Aim: Portal vein thrombosis (PVT) has a high incidence in patients with liver cirrhosis and determines a poor prognosis of hepatic disease. The aim of our study was to define the natural course of partial PVT in cirrhotic patients, including survival and decompensation rates. Patients and Methods: We performed a prospective, cohort study, in a tertiary referral center. There were 22 cirrhotic patients with partial nonmalignant PVT, without anticoagulant treatment, who were followed-up between January 2011 and October 2013. All patients were evaluated by Doppler abdominal ultrasound and computed tomography. Kaplan–Meier method was used to determine the difference in clinical events between the study subgroups. Results: After a mean follow-up period of 20.22 months, partial PVT improved in 5 (22.73%), was stable in 11 (50%), and worsened in 6 (27.27%) patients. Hepatic decompensation rate at 6 and 18 months was higher in patients with worsened PVT than in those with stable/improved PVT (50% vs. 25%, P < 0.0001 and 100% vs. 56.25%, P < 0.0001, respectively). The survival rate at 6 months was 66.66% in worsened PVT group vs. 81.25% (P = 0.005) in stable/improved group, and 16.66% vs. 81.25% (P < 0.0001) at 18 months, respectively. Multivariate analysis showed that Model of End-Life Disease was the independent predictor of hepatic decompensation [hazard ratio (HR) 1.42; 95% confidence interval (CI): 1.08−1.87, P = 0.012] and survival (HR 1.76; 95% CI: 1.06−2.92, P = 0.028). Conclusions: Nonmalignant partial PVT remained stable/improved in over half of cirrhotic patients and aggravated in more than one fourth in whom it negatively influenced the survival and decompensation rates.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI). METHODS We conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran’s Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS). RESULTS Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Clostridium difficile infection and inflammatory bowel disease.

Over the past 15 years, Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) has increased both in incidence and severity. Traditional risk factors for CDI are similar in IBD and non-IBD populations, but there is a significant proportion of IBD patients which have distinctive characteristics. Patients with ulcerative colitis (UC) are more susceptible to CDI and have more severe outcomes than those with Crohns disease (CD). CDI may be difficult to distinguish from an IBD flare due to similar clinical presentation, and therefore screening for CDI is recommended at every flare in such patients. Several studies showed worse clinical outcomes in IBD patients with CDI, including longer hospital stay, higher colectomy and mortality rates than in those without CDI. Vancomycin and metronidazole appear to have similar efficacy in patients with moderate disease, but vancomycin is preferred in severe disease. Measures must be taken to prevent the spread of infection. Clinicians should have a high index of suspicion for CDI when evaluating a patient with IBD flare, as rapid detection and prompt treatment of infection improve outcomes. This review summarizes the available literature on epidemiology, risk factors, clinical aspects, diagnostic methods, treatment, outcome, and prevention of CDI in IBD patients.

Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

Helicobacter pylori (H. pylori) is one of the most common chronic bacterial infections in humans, affecting half of worlds population. Therapy for H. pylori infection has proven to be both effective and safe. The one-week triple therapy including proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H. pylori infection in countries with low clarithromycin resistance. Generally, this therapy is well-tolerated, with only a few and usually minor side effects. However, rare but severe adverse effects such as pseudomembranous colitis have been reported, Clostridium difficile (C. difficile) infection being the main causative factor in all cases. We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid, clarithromycin 500 mg bid, and amoxicillin 1 g bid to eradicate H. pylori infection. A limited colonoscopy showed typical appearance of pseudomembranous colitis, and the stool test for C. difficile toxins was positive. Rapid resolution of symptoms and negative C. difficile toxins were obtained in both patients with oral vancomycin. No relapse occurred during a four and eleven-month, respectively, follow up. These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H. pylori eradication therapy.

Portal vein thrombosis in cirrhotic patients - it is always the small pieces that make the big picture

Portal vein thrombosis (PVT) is a frequent and serious complication in patients with liver cirrhosis (LC). Recently, a new classification of PVT was proposed, although the functional component was not completed included. The status of liver disease (compensated/decompensated) should be added to this classification. Reduced portal flow velocity and the acquired hypercoagulable status associated with LC are the main risk factors for PVT development, although endothelial dysfunction may play an important role that needs to be further evaluated. The European Association for the Study of the Liver and the American Association for the Study of Liver Disease recommend that the anticoagulant treatment should be consider in cirrhotic patients with PVT. Low molecular weight heparin and vitamin K antagonists proved their efficacy and relatively safety in PVT treatment, although in addition to recanalization rates, more complex end-points such as mortality and decompensation rate should be evaluated. The new oral anticoagulant therapies offers the advantage of oral administration in the absence of laboratory monitoring, however, there are a few reports regarding their use in cirrhotic patients, most of them referring to compensated isolated cases. Transjugular intrahepatic portosystemic shunt could be an alternative if thrombosis progresses despite anticoagulatant therapy and/or when PVT is associated with portal hypertension complications. The aim of this editorial is to discuss the different aspects of pathophysiology, clinical relevance, diagnosis and management of PVT in patients with LC.

Clostridium difficile infection in hospitalized octogenarian patients

To evaluate the risk factors and outcome of Clostridium difficile infection in hospitalized octogenarian patients.

Efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with ribavirin for the treatment of Hcv genotype 1b compensated cirrhosis in patients aged 70 years or older

Abstract Advanced age has been a major limitation of interferon-based treatment for chronic hepatitis C virus (HCV) infection because of its poor response and tolerability. Direct-acting antiviral (DAA) drug regimens are safe and highly effective, allowing administration of treatment also in elderly. This study aims to assess the efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with ribavirin for the treatment of patients aged ≥70 years with HCV genotype 1b compensated cirrhosis. A total of 1008 patients with HCV genotype 1b compensated cirrhosis were prospectively treated with PrOD + ribavirin for 12 weeks, between December 2015 and July 2016. Sustained virologic response 12 weeks after the end of treatment (SVR12), adverse effects (AEs), comorbidities, discontinuation, and death rates were recorded. Efficacy and safety of therapy were assessed in patients aged ≥70 years and compared with data from patients <70 years. There were 117 patients aged ≥70 years, preponderantly females (58.9%), mean age 73.3 ± 2.8 years (range 70–82), and 37 (31.6%) were treatment-experienced. Comorbidities were reported in 60.6% of patients ≥70 years and in 39.8% of those <70 years (P < .001). SVR12 rates based on intention-to-treat and per-protocol analyses were 97.4% and 100%, respectively, in patients ≥70 years, compared to 97.8% and 99.6%, respectively, in patients <70 years (P = ns and P = ns). Severe AEs were reported in 4 (3.4%) patients ≥70 years, compared to 23 (2.6%) in those <70 years (P = ns). One death was recorded in a patient aged 79 years (0.9%) and 6 deaths (0.8%) in those <70 years (P = ns). Treatment with PrOD + ribavirin in patients 70 years of age or older with HCV genotype 1b compensated cirrhosis proved as effective, safe, and well tolerated, as it did in younger patients.

Chronic hepatitis C virus infection: a new modifiable cardio-metabolic risk factor ?

Chronic hepatitis C infection is a systemic disease that leads to a high risk of cirrhosis and hepatic carcinoma, as well as extrahepatic related disorders, immune–related and metabolic alterations such as glucose metabolism impairment and steatosis, thus being a new cardio-metabolic risk factor. It has been shown that, due to chronic inflammation, HCV infection has a direct effect on the arterial wall, initiating endothelial dysfunction which is the first step in atherosclerotic processes with proatherogenic effects and numerous cardiovascular events. The recent data emphasize that HCV infection can induce insulin resistance in the liver and peripheral tissues through multiple mechanisms which interfere with insulin signaling, inducing the production of several proinflammatory cytokines, and modify the lipid metabolism with the result of hepatic steatosis, which is more pronounced in patients with HCV. The emergence of new direct acting, interferon-free antiviral treatment, leading to HCV cure in most cases with a satisfactory safety profile is, according to numerous studies, improving the glucose metabolism disorders and lowering the number of cardiovascular events in patients who obtained sustained viral response, thiugh further studies are needed to clarify definitively the role of HCV infection in cardiovascular and metabolic alterations, as well as the impact of viral eradication on cardiovascular outcomes.