Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review.

AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients. METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 µg/wk) or PegIFN alpha 2b (1 or 1.5 µg/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk. RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and C vs those with Child-Pugh class A: 22% vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2% vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001). CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders.

Role of interleukin-28B polymorphism as a predictor of sustained virological response in patients with chronic hepatitis C treated with triple therapy: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Chronic hepatitis C represents an important health problem. The aim of our meta-analysis was to establish the role of reference single nucleotide (rs) 12979860 allele of interleukin-28B (IL28B) CC versus CT+TT genotype (the most researched allele of IL28B) as a predictor of sustained virological response (SVR) in patients with chronic hepatitis C treated with triple therapy. METHODS: The PubMed, MEDLINE, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases as well as abstract books from important gastroenterology and hepatology meetings were searched for all studies published until 15 July 2012 that analysed the relationship between the polymorphism of IL28B and SVR in patients with chronic hepatitis C, genotype 1, treated with pegylated interferon + ribavirin + direct antiviral agents (telaprevir or boceprevir). The following keywords were used: IL28B polymorphism, chronic hepatitis C, sustained virological response, SVR, triple therapy, telaprevir, boceprevir. RESULTS: Odds ratios (ORs) with 95 % confidence intervals were pooled from five study populations (1,641 cases) using a random-effects model. The SVR rate was significantly higher in patients with the CC genotype of IL28B than in those with non-CC genotypes (CT and TT): OR = 3.91 (95 % CI 2.11-7.28), p < 0.0001. Higher SVR rates were obtained in chronic hepatitis C patients with the CC genotype of IL28B, regardless of their therapeutic status (naïve patients: OR = 3.99 [95 % CI 1.67-9.51], p < 0.0001; and previously treated ones: OR = 2.15 [95 % CI 1.35-3.43], p = 0.001). CONCLUSION: IL28B polymorphism seems to influence the SVR rate in patients with chronic hepatitis C treated with triple therapy, but further studies are needed to clarify the mechanism and the influence of other factors on the SVR rates.

Predictive factors for severe evolution in acute pancreatitis and a new score for predicting a severe outcome.

BACKGROUND: Acute pancreatitis (AP) is an acute inflammation of the pancreas with an unpredictable evolution. The aim of this study was to assess the factors associated with severe evolution of AP and to create a new score for predicting a severe outcome. METHODS: The initial group included 334 patients hospitalized in 2006-2009. The validation group included 195 patients admitted in 2010-2011. AP was classified according to the Atlanta criteria. RESULTS: In the initial group, C-reactive protein (CRP), creatinine, white blood count, body mass index (BMI), age and male gender were correlated with severe evolution of AP. Using only parameters available in emergency, by multiple regression analysis we obtained in the initial group the following score for predicting severe evolution of AP: Prediction pancreatic severity I score (PPS I score) = -1.038 + 0.119 × creatinine (mg/dL) + 0.012 × BMI (kg/m²) + 0.027xwhite blood count/1000 (cells/mm³) + 0.195 × gender (1-women, 2-men) + 0.005 × age (years). For a cut-off value >0.325, PPS I score had 71.8% accuracy (AUC=0.790) for predicting a severe evolution of AP. In the validation group the accuracy was 71.7%. Since CRP was proven to be a good predictor of severe evolution in AP, we calculated another score, PPS II, obtained using PPS I and CRP: PPS II score = -0.192 + 0.760 x PPS I + 0.003 x CRP (mg/L). For a cut-off value >0.397, PPS II score had 87.1% accuracy (AUROC=0.942) in the initial group and 75.3% accuracy in the validation group for predicting severe AP. CONCLUSIONS: PPS I and especially PPS II score are accurate predictors of severe outcome in patients with AP.

Can ARFI elastography predict the presence of significant esophageal varices in newly diagnosed cirrhotic patients?

AIM: To establish an algorithm which includes the liver stiffness (LS) and/or spleen stiffness (SS) assessed by ARFI for the prediction of significant esophageal varices-EV (at least grade 2). MATERIAL AND METHODS: Our study included 145 newly diagnosed cirrhotic patients admitted in our Department between September 2009-August 2011. 62 patients (42.7%) had significant EV. We performed 10 ARFI measurements in each patient, both in the liver and in the spleen; median values were calculated, expressed in meters/second. In 24 consecutive newly diagnosed cirrhotic patients admitted between September 2011-December 2011, we prospectively analyzed the value of the new score for predicting significant EV. RESULTS: The LS and SS assessed by ARFI elastography, and the percentage of patients with ascites were stastically significant higher in patients with significant EV as compared with those without EV or grade 1 EV. By multiple regression analysis we obtained the following formula for predicting significant EV: prediction of significant EV (Pred EV(2-3)) score: -0.572 + 0.041 x LS (m/s) + 0.122 x SS (m/s) + 0.325 x ascites (1-absent, 2-present). The best Pred EV(2-3) cut-off value for predicting significant EV was > 0.395 (AUROC = 0.721, accuracy = 69.6%). The accuracy in the group of patients in which the value of this score was prospectively analyzed was similar with that obtained in the first cohort of patients (70.8 vs. 69.6%). In conclusion, the proposed Pred EV(2-3) score had a enough good value for predicting significant EV.

A new scoring system for prediction of fibrosis in chronic hepatitis C.

BACKGROUND: Liver biopsy (LB) is still considered to be the gold standard for assessment of liver fibrosis. OBJECTIVES: To evaluate the effectiveness of various non-invasive methods for predicting liver fibrosis, including transient elastography (TE), APRI score, Lok score, Forns score, FIB-4 score, Fibrosis Index, King score, and Bonacini score, in comparison with the effectiveness of LB and to create a new scoring system for fibrosis prediction. PATIENTS AND METHODS: This study included 212 patients with chronic HCV hepatitis. LB, TE, and various biological tests were performed during a single hospital visit. Using established formulae, data from these tests were used to create scores for assessment of liver fibrosis. RESULTS: The results of all the tests showed significant correlation with histological fibrosis. TE results (r = 0.62), King score (r = 0.57), and APRI score (r = 0.56) showed the closest correlation with severity of fibrosis. The following formula was derived from our data by multiple regression: Predicted liver fibrosis score (PLF score) = 0.956 + 0.084 × TE - 0.004 × King score + 0.124 × Forns score + 0.202 × APRI score. A direct correlation (r = 0.68) was found between the PLF score and liver fibrosis. The cut-off values of the PLF score for various stages of fibrosis were: F ≥ 1, 1.77 (Area under ROC curve (AUROC) = 0.76); F ≥ 2, 2.18 (AUROC = 0.78); F ≥ 3, 2.47 (AUROC = 0.86); and F = 4, 2.98 (AUROC = 0.97). CONCLUSIONS: We found that our newly developed PLF score, which is derived from the scores of multiple tests, is more strongly correlated with fibrosis than each component score used individually. The PLF score is more effective than TE for predicting severe fibrosis, but they have similar effectiveness in predicting liver cirrhosis.

Response to standard of care antiviral treatment in patients with HCV liver cirrhosis - a systematic review.

BACKGROUND: Patients with HCV liver cirrhosis are a category difficult to treat. The aim of this study was to establish the sustained virological response (SVR) rates in HCV patients with liver cirrhosis treated with standard of care therapy (Pegylated Interferon and Ribavirin for 48 weeks in genotypes 1 and 4 and 24 weeks in genotypes 2 and 3). METHODS: Searching the PubMed, Medline, Lilacs, Scopus, Ovid and Medscape databases we identified all the articles published until February 2011 that included only HCV cirrhotic patients. These studies evaluated the SVR after standard of care treatment: Pegylated Interferon alpha 2a (doses ranging between 135-180 µg/week) or Pegylated Interferon alpha 2b (1 or 1.5 µg/kg/week) and Ribavirin (doses ranging between 800-1200 mg/day). We used the following key words: HCV, liver cirrhosis, sustained virological response (SVR). RESULTS: The overall SVR rate was 33.3% (95%CI-confidence interval=30.6-36.2%). SVR was significantly higher in patients with genotypes 2 and 3 (422 patients) as compared to those with genotypes 1 and 4 (692 patients): 55.4% (95%CI=50.7-60.1) versus 21.7% (95%CI=18.7-25), p < 0.0001. CONCLUSION: The overall SVR rate in cirrhotic patients treated with standard of care therapy is 33.3%, but lower in cases affected by genotypes 1 and 4 (21.6%) which makes them a priority regarding the development of more potent drugs for effective treatment.

Successful endoscopic treatment of an unusual cause of lower gastrointestinal bleeding using the OVESCO system.

The great majority of foreign bodies swallowed and entering the stomach are usually passed through the entire gastrointestinal tract uneventfully. The ones that remain can cause perforation, obstruction or bleeding. The risk of perforation is increased with long sharp metal objects, animal bones, in subjects with intestinal diseases (Crohn's disease, intestinal stenosis), and in patients with adhesions due to prior abdominal surgery. For a long time, toothpick impaction in the lower gastrointestinal tract has been managed by surgery. Nowadays with the development of endoscopy, a variety of ingested foreign bodies have been successfully managed by endoscopy. We report the case of a male patient, with a toothpick impacted in the rectosigmoid junction, which was diagnosed and successfully managed by colonoscopy.

ERCP in Romania in 2006; a National Programme seems mandatory.

BACKGROUND: Endoscopic retrograde cholangio-pancreato-graphy (ERCP) is a procedure used in the diagnosis and treatment of biliary and pancreatic diseases, more preferable to open surgery in terms of a lower risk of morbidity and mortality and costing much less. METHODS: This was a retrospective, multicenter study, in which we tried to involve the largest medical centers in Romania. They were asked to complete a questionnaire detailing the number of ERCPs performed in 2006, the type of and accessibility to radiology equipment, indications for ERCP, the availability of skilled endoscopists for ERCP and if there were any training pro-grammes. RESULTS: The number of ERCP procedures performed in 2006 by the participating centers was 2647. There was a strong correlation between the availability of radiology equipment, the number of days allocated by the radiology department for the procedure, and the number of ERCPs performed. Gallstone removal accounted for most (50%) of the therapeutic ERCP indications. CONCLUSIONS: For a large country such as Romania, a total number of 2647 ERCPs for 2006 is too low. Various important factors such as lack of access to equipment and few skilled ERCP endosco-pists were identified as possible causes. The number of ERCPs performed in Romania should be reorganized to perform 20000 per year in 5 years from now (2012) and give our population access to proper intervention endoscopy. The National Gastroenterology Society should actively encou-rage training in interventional endoscopy, and collaborate with Ministry of Health to have a National Task-force for Endoscop.

Ultrasound assisted liver biopsy for the staging of diffuse chronic hepatopathies.

Liver biopsy is the most accurate method for the staging and grading of diffuse hepathopathies. In viral hepatitis staging is required in order to assess firstly if the patient should be treated or not and, secondly, to assess the prognosis. In alcoholic and non-alcoholic steato-hepatitis we only appreciate the prognosis by staging, because the therapy is the same. In this study we analyze the experience of our centre in performing ultrasound-assisted liver biopsies in diffuse chronic hepatopathies. Between 1993-2003 we performed 1460 ultrasound-assisted liver biopsies, all on inpatients, in 93.8% of the cases for the evaluation of viral hepatitis. In the last few years we used sedation with midazolam i.v., the saturation of O(2) being recorded. In the 10 years of the study we encountered one major complication (haemo-peritoneum) (0.07%), treated by conservative methods. The minor complications we encountered, pain and discomfort, were always alleviated by minor analgesics. Vaso-vagal reactions were frequent before we started using midazolam (8.05%), but were no longer present after we performed sedation. None of the liver biopsies was followed by the death of the patient. In 1.37% of the cases we obtained inadequate liver specimens. We performed multiple passages in 0.96% of the cases. In conclusion, ultrasound-assisted liver biopsy is still the "gold standard" of hepatologic evaluation, being a safe and accurate method for staging the diffuse chronic hepatopathies.