L. Gheorghe

Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.

Aim The Romanian Society of Gastrointestinal Endoscopy developed a multicentre, prospective study to evaluate the frequency and epidemiological features of inflammatory bowel disease (IBD) in an adult population that refers to gastroenterology centres in Romania. Material and methods Eighteen centres with adequate diagnostic and therapeutic facilities uniformly distributed across Romania reported through a proforma the new and old IBD cases between 1 June 2002 and 1 June 2003. The rates of incidence and prevalence of ulcerative colitis (UC) and Crohns disease (CD) have been reported per 100 000 inhabitants. Epidemiological features and disease characteristics were analysed. Results During the study, 407 cases of UC (163 incident cases) and 254 cases of CD (85 incident cases) were identified. The incidence in the referral population was 0.97/100 000 and 0.50/100 000 for UC and CD, respectively, whereas the prevalences was 2.42/100 000 and 1.51/100 000 for UC and CD, respectively. A slight male predominance, wider age distribution and predominant urban residence were the main demographic features of incident cases; smoking and appendectomy/appendicitis were infrequent in UC, while a higher proportion of CD patients were smokers. Lower rates of severe, extensive or complicated IBD were noted as compared with the literature. Conclusion Incidence and prevalence rates of IBD in Romania are low. Predominant male involvement and a wider distribution of incident cases were the main demographic features in our population. IBD in our patients had a more ‘benign’ course as compared with the literature, with lower rates of severe, extensive or complicated disease and a small proportion of patients who need surgery.

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease.

Objectives To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. Methods Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). Results From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10–15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. Conclusion Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(−) profile, and probable diagnosis according with the scoring system for AIH.

Predictors of graft and patient survival in hepatitis C virus (HCV) recipients : Model to predict HCV cirrhosis after liver transplantation

Background. Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is almost universal, but the natural history of recurrent HCV in the allograft is highly variable. Our study had two aims: 1) to assess the impact of different pre- and postLT factors on graft and patient survival in HCV transplant recipients and 2) to create a model which may predict the patients at risk for HCV-related graft cirrhosis at 5 years postLT. Methods. A total of 168 LTs were considered for this study. Univariate and multivariate Cox proportional hazards regression model was used, as well as logistic regression analysis to create a model of prediction of HCV cirrhosis within 5 years after LT. Results. Predictive factors for both decreased graft and patient survival included patients recently transplanted (2000–2004), induction without azathioprine, short-term therapy with mycophenolate mofetil and prednisone (≤6 months), presence of early cholestasis, histologically proven early recurrence of hepatitis C. Recipient human leukocyte antigen DR3 positivity, presence of early cholestasis, and donor age >50 years were identified as independent predictors of graft cirrhosis within 5 years. A predictive model was established in order to calculate at 6 months a risk score for graft HCV cirrhosis within 5 years postLT using a formula that included the identified independent predictors. The area under receiver operating characteristic curve was 0.83, indicating a good ability to predict medium-term HCV allograft cirrhosis. Conclusion. This model may be a useful tool for better identifying high-risk HCV patients who should be selected for early initiation of antiviral therapy.

Homozygous familial hypercholesterolemia: specific indication for domino liver transplantation.

Background. Domino liver transplantation is one possibility to overcome the discrepancy between the small number of liver donors and the long waiting lists. Homozygous familial hypercholesterolemia (FHC) is a genetic disorder of lipoprotein metabolism defined by the absence or small number of functional low-density lipoprotein receptors (LDL-Rs) and the ensuing high levels of serum cholesterol. We report a case of a patient with FHC whose liver was used for domino transplantation in a patient with cirrhosis and hepatocellular carcinoma. Methods. The patient diagnosed with FHC received the large part of a split liver. The liver of the patient with FHC was then transplanted into the patient with cirrhosis and hepatocellular carcinoma. Quantification of extrahepatic LDL-R was performed by flow cytometry on monocytes, and the gene expression of LDL-R was assayed by reverse transcriptase-polymerase chain reaction on monocyte-derived macrophages and cultured fibroblasts isolated from the patients. Results. One year after surgery, the donor’s serum cholesterol (without treatment) was normal, and the recipient’s serum cholesterol (with simvastatin treatment) was slightly increased. Quantification of peripheral LDL-R on monocytes isolated from the patients revealed values of 6.7% in the patient with FHC and 71% in the patient with cirrhosis and hepatocellular carcinoma. The reverse transcriptase-polymerase chain reaction assay revealed the presence of gene expression for LDL-R. Conclusions. Domino transplantation can be efficiently used in a patient with marginal indications for transplantation using a liver from a patient with FHC. The slightly elevated serum cholesterol level in the recipient may be explained by the normal function of extrahepatic LDL-R.

Prevalence of hepatitis C in Romania: different from European rates?

(13%) would result. Actually, the majority of cases without dilatation of HA (using both Caselitz and Buscarini’s thresholds) had both color-spots and hypervascularization, thus further supporting our statement that intra-hepatic parameters have a better sensitivity and accuracy than extrahepatic ultrasonography parameters due to their ability to permit the diagnosis of even very small AVMs in their early stage of development. Evidently the presence of more severe vascular involvement determines an angiodynamic remodelling and gross abnormalities which can be detected on B-mode ultrasonographic study (mainly enlargement of HA in the extrahepatic tract and ‘double channel aspect’ in the portal spaces). In conclusion, in this first controlled, prospective study, we have demonstrated that the diagnosis of HAVMs in HHT can reliably be made by merely using intra-hepatic parameters and does not require evidence of extrahepatic abnormalities. The latter are useful to grade the haemodynamic impact of HAVMs and the possible effect on liver angioarchitecture and clinical significance. We disagree with Dr. Buscarini’s final comment in which she states that ‘‘Doppler US diagnosis of liver VMs in HHT requires a combination of extrahepatic and intra-hepatic findings, which can provide a diagnostic accuracy ranging between 95% and 99% for different observers” [7] because in the absence of a standard reference technique, data on sensitivity and accuracy cannot be considered reliable.

Diagnostic Delay in Romanian Patients with Inflammatory Bowel Disease: Risk Factors and Impact on the Disease Course and Need for Surgery

BACKGROUND The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures. METHODS A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohns disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients. RESULTS The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]. CONCLUSIONS A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery.

The prevalence and risk factors of hepatitis B virus infection in an adult population in Romania: a nationwide survey.

Aim The prevalence and risk factors of hepatitis B virus (HBV) infection in the general population in Romania are still largely unknown. Methods A nationwide cross-sectional survey among a Romanian adult population (18–69 years) was conducted during 2006–2008 using a stratified, multistage sampling design. A total of 17 600 individuals were enrolled randomly into the study; the prevalence of chronic HBV infection (HBsAg-positive and anti-HBcAb-positive samples) was assessed on 13 127 individuals (74.6%) and a history of previous HBV infection (anti-HBcAb-positive, but HBsAg-negative samples) was assessed on 12 470 individuals (70.5%). A questionnaire was used to collect information on the sociodemographic characteristics of the participants and the potential risk factors for HBV transmission. Results The overall prevalence rate of HBV chronic infection among all the participants tested was 4.4% (confidence interval: 4.0–4.8%), with significant differences (P=0.0001) between participants from the main geographical regions of residence (Moldavia 4.5%, Muntenia and Dobrogea 5.4%, and Transylvania and Banat 3.1%). The total prevalence of previous HBV infection of all participants was 27.0% (confidence interval: 26.2–27.8%). The proportion of individuals with previous HBV infection, as well as with chronic HBV infection, showed a statistically significant increasing trend with age. The personal history of blood or blood product transfusion, surgical interventions, tattooing, and alcohol consumption greater than 60 g/day were risk factors associated with both anti-HBcAb and HBsAg seropositivity. Conclusion A prevalence rate of 4.4 and 27.0% for HBsAg and anti-HBcAb, respectively, represents a high figure within the European Union and a strong motivation for developing adequate strategies for prevention, active detection, and treatment of HBV infection in Romania.

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy

Pegylated interferon‐alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug‐induced Sweets syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweets syndrome in association with pegylated interferon‐alpha therapy.

Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis†

Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real‐life data are still needed in order to confirm this profile.

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.