Giampaolo Bresci

Hepatitis B and C Virus Infection in Crohn's Disease

Patients with Crohns disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-&agr; (IFN-&agr;) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00–2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04–11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61–3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37–3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37–3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06–1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-&agr; for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.

The Italian Registry of Therapeutic Apheresis: granulocyte-monocyte apheresis in the treatment of inflammatory bowel disease. A multicentric study.

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte–monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohns disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohns disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered.

Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis

AIM To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS Sixty-nine ulcerative colitis patients (39 F, 30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency, clinical activity index (CAI), C reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), values at baseline, use of immunosuppressant, duration of disease, and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS In the univariate analysis, CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390, 95% Confidence interval (CI): 0.176-0.865, Wald 5.361, P = 0.0160] and low CAI levels at baseline (4 < CAI < 7) (OR = 0.770, 95% CI: 0.425-1.394, Wald 3.747, P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo.

Transarterial chemoembolization for the treatment of hepatocellular carcinoma: a review.

According to the current European Association for the Study of Liver guidelines, transarterial chemoembolization (TACE) is the recommended first-line therapy for patients with intermediate-stage (Barcelona Clinic Liver Cancer-B class) hepatocellular carcinoma (HCC). The efficacy of this therapy is supported by robust evidence; however, there is still a lack of standardization in treatment methodology, and TACE protocols are widely variable. Moreover, TACE can be associated with a number of contraindications. Despite these limitations, research on TACE is still ongoing with the aim of optimizing the use of this methodology in the current management of HCC. In particular, TACE represents a control in comparative studies, and it is currently being investigated in combination schemes, for example, with sorafenib. In this review, we briefly describe the current scenario and the clinical innovations regarding TACE for the treatment of HCC.

Clinical epidemiology of chronic viral hepatitis B: A Tuscany real-word large-scale cohort study

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)-infected patients in the Tuscan public health care system. METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

Clinical outcomes with long-term sorafenib treatment of patients with hepatocellular carcinoma: a multicenter real-life study

AIM This multicenter field-practice study evaluates outcomes of long-term sorafenib in hepatocellular carcinoma (HCC) patients. METHODS Consecutive HCC patients on sorafenib were enrolled. We evaluated those receiving sorafenib for ≥12 months. RESULTS Out of 800 patients on sorafenib, 81 (10%) received long-term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6). Only 21 (26%) reported grade 3/4 adverse events. Complete response was reported in 11 patients (14%). Median overall survival was 34.8 months (95% CI: 29.9-44.3). Only baseline Child-Pugh class was associated with survival. CONCLUSION Sorafenib could result in long-term control of HCC in a relevant proportion of patients. Given the availability of regorafenib in the second-line setting, an earlier introduction of systemic therapy may be considered according to clinical indications.

Epidemiological, demographic and clinical data of chronic viral hepatitis C in Tuscany

Abstract Background: Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries’ economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy. Methods: We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress. Results: Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44 ± 15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin’s lymphoma in 10.5%). Conclusions: Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.

OC.11.4 LONG TERM EFFICACY OF GRANULOCYTE-MONOCYTE-APHERESIS IN ULCERATIVE COLITIS. THE ITALIAN REGISTRY OF THERAPEUTIC APHERESIS

G A A b st ra ct s These cases were divided into two groups according to the period of availability of infliximab (IFX): pre-IFX (N=94, Jan. 1975 Jun. 2001) and post-IFX (N=88, Jul. 2001 Jun. 2009). Results: The perianal lesions were observed in 36.3% of CD patients, more common in male, and diagnosed at younger age than CD without perianal lesions. Fistula was the most prevalent lesion, followed by abscess, fissure, and stricture. Perianal lesions preceded abdominal symptoms such as pain and diarrhea in 25% of the cases. In post-IFX group, the remission rates with non-specific conservative management, specific medical treatment, surgical treatment, and combined surgical and medical treatment were 17%, 73%, 58%, and 72%, respectively. The remission rate of combined treatment in post-IFX group was significantly higher than that in pre-IFX group. Cumulative relapse rates in 1, 3, and 5 years were 9.4%, 31.3%, and 41.7%, respectively. Medical maintenance treatment was the only significant factor that lowers the relapse rates (p<0.01). Conclusions: These results suggest that initial medical treatment is effective and maintenance therapy lowers the recurrence rates in CD patients with perianal lesions.

W1327 Long Term Efficacy of Granulocyte-Monocyte-Apheresis in Ulcerative Colitis. the Italian Registry of Therapeutic Apheresis

G A A b st ra ct s These cases were divided into two groups according to the period of availability of infliximab (IFX): pre-IFX (N=94, Jan. 1975 Jun. 2001) and post-IFX (N=88, Jul. 2001 Jun. 2009). Results: The perianal lesions were observed in 36.3% of CD patients, more common in male, and diagnosed at younger age than CD without perianal lesions. Fistula was the most prevalent lesion, followed by abscess, fissure, and stricture. Perianal lesions preceded abdominal symptoms such as pain and diarrhea in 25% of the cases. In post-IFX group, the remission rates with non-specific conservative management, specific medical treatment, surgical treatment, and combined surgical and medical treatment were 17%, 73%, 58%, and 72%, respectively. The remission rate of combined treatment in post-IFX group was significantly higher than that in pre-IFX group. Cumulative relapse rates in 1, 3, and 5 years were 9.4%, 31.3%, and 41.7%, respectively. Medical maintenance treatment was the only significant factor that lowers the relapse rates (p<0.01). Conclusions: These results suggest that initial medical treatment is effective and maintenance therapy lowers the recurrence rates in CD patients with perianal lesions.