Assessment of Sarcopenia Related Quality of Life Using SarQoL® Questionnaire in Patients With Liver Cirrhosis.

Introduction: Sarcopenia, malnutrition, physical deconditioning, and frailty contribute to a significantly altered quality of life (QoL) in patients with cirrhosis and sarcopenia. Aim: To investigate the sarcopenia-linked alterations of QoL by SarQoL® questionnaire in patients with end-stage liver disease. Methods: Consecutive patients with liver cirrhosis, admitted to our department between May and August 2021, completed the SarQoL® questionnaire by themselves. They were evaluated for sarcopenia according to the 2019 European Working Group on Sarcopenia in Older People (EWGSOP) definition [hand grip cut-offs and skeletal muscle index (SMI) calculation at CT scan]. Results: A total of 71 patients with liver cirrhosis were included in the study, with a median age of 54 years. Sarcopenia was present in 31.2% of patients with Child-Pugh class A, in 58.3% with class B, and in 93.5% with class C. The SarQoL® score was statistically significant and lower in Child-Pugh class C vs. class B and class A (70.2 vs. 66.5 vs. 52.5 points, p = 0.0002). The SarQoL® score was evaluated according to different complications of cirrhosis, with statistically significant lower scores in patients with sarcopenia (p < 0.0001), in patients with ascites requiring paracentesis (p = 0.0006), and in patients with hepatic encephalopathy (p < 0.0001). A cut-off level of 75.9 points for SarQoL® score can accurately detect sarcopenia in patients with end-stage liver disease [area under the receiver operating characteristic (AUROC) curve of.823, SE of 92.1%, SP of 45.5%, positive predictive value (PPV) and negative predictive value (NPV) of 66 and 83.3%, respectively, correctly classified 73.2% of cirrhotic patients with sarcopenia]. Conclusions: The use of SarQoL® questionnaire in cirrhotic patients can, at the same time, evaluate the quality of life and identify subjects with sarcopenia and altered QoL.

Inflammatory Bowel Disease Management in a Romanian Tertiary Gastroenterology Center: Challenges of the COVID-19 Pandemic.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) patients management has been challenging during the ongoing coronavirus disease 2019 (COVID-19) pandemic, due to lockdowns, limitation of access to medical facilities and new recommendations regarding patient management. The implications of the COVID-19 pandemic on IBD patients' management were assessed in our Tertiary Gastroenterology Center in Bucharest, Romania. METHODS: Medical records of IBD patients admitted between 15th of March and 15th of August 2020 were retrospectively reviewed and compared to a control cohort of consecutive IBD patients admitted to our unit during the corresponding period of 2019. RESULTS: There was a highly significant shift towards one-day hospitalization during the referral period in 2020 for IBD cases (91% in 2020 vs 82.2% in 2019, p=0.0001). There was no statistically significant difference between the distribution of patient's gender, IBD phenotype or newly diagnosed IBD cases. A significantly lower proportion of admitted patients received 5-aminosalicylic acid (29% vs 41.2%, p=0.0001), whereas a substantially higher number of patients were prescribed biological therapy in 2020 in comparison to the corresponding 2019-time frame (79.5% vs 57.9%, p<0.0001). The distribution of the biological agent used was significantly different in 2019 in comparison to the 2020 period mainly due to the increase in vedolizumab prescription in 2020 (p<0.0001). During the study period in 2020, seven IBD patients (1.7%) were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection, all of them with mild symptoms without impact on the IBD course. CONCLUSIONS: The COVID-19 pandemic led to reorganizing medical care, limiting the hospital admissions in favor of severe IBD cases, favoring telemedicine for mild disease and optimization of treatment for moderate to severe IBD with an increased use of biologicals aimed to maximize the risk/benefit ratio. Incidence of SARS-Cov2 infection during the first wave of COVID-19 infection in our study group was 1.7% and did not adversely impact the IBD disease course.

The Prevalence of HCV Infection and Risk Factors in a Hospital- Based Population Screening, a First Step to the Micro-Elimination of HCV Infection in Medical Institutions from Romania - Results of the HepC ALERT Study.

BACKGROUND AND AIMS: Elimination of hepatitis C worldwide is more feasible if micro-elimination screening strategies are adopted. We aimed to screen hepatitis C virus (HCV) in specific high-risk populations in certain sub-regions of Romania and link them to antiviral treatment. METHODS: A multicenter prospective study was conducted among the hospitalized or ambulatory adult patients from March 2019 to March 2020 in more than 20 medical institutions from 4 Romanian cities (Bucharest, Iasi, Timisoara, Cluj-Napoca). A rapid diagnostic test for HCV diagnosis was performed to all admitted patients and the positive ones were sent to gastroenterology departments for confirming the active infection, staging and treatment prescription. RESULTS: In total, 25,141 subjects signed the informed consent and were consequently enrolled into the study. The prevalence of anti-HCV antibodies was 1.39% (95%CI: 1.25-1.54) and increased with the number of risk factors presented by one subject. There was a positive association between the presence of anti-HCV antibodies and female gender (p<0.001), rural area of residence (p<0.001), advanced age (p<0.001), as well as a negative association with the education level (p<0.001). CONCLUSIONS: In a hospital-based screening micro-elimination program in Romania, HCV prevalence was lower than previously reported. This is a first step towards a cost-effective screening in a well-defined group of persons at risk and provides sufficient capacity to deliver access to HCV treatment and linkage to care in Romania.

The Role of Beta-7 Integrin and Carbonic Anhydrase IX in Predicting the Occurrence of de Novo Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients.

Background: Liver transplant (LT) recipients are at increased risk for developing metabolic syndrome. Early detection of NAFLD and other components of the metabolic syndrome is an important step in reducing morbidity and mortality. Methods: We assessed 60 liver transplant recipients for clinical and biological features, performed abdominal ultrasound and transient elastography (TE) Fibroscan© with controlled attenuation parameter (CAP), calculated non-invasive scoring systems APRI, FIB-4, NAFLD score, cardiovascular risk (Framingham risk score) and for the presence of metabolic syndrome and performed two biomarkers: beta 7 integrin and carbonic anhydrase IX. Results: Sixty liver transplant recipients underwent clinical and biochemical evaluation, abdominal ultrasound and TE with CAP. The median age was 56.5 years and the median time from transplantation 35 months. The Spearman correlation coefficient of beta 7 integrin and the liver stiffness measurement values obtained via Fibroscan© we obtained a moderate correlation r=0.31, but a significant association (p=0.01). The univariate analysis showed significant association between both biomarkers and liver fibrosis assessed with a cut-off value of advanced fibrosis of 8.7 kPa. The carbonic anhydrase IX showed a better correlation when compared to the liver stiffness with a correlation coefficient of 0.43 and p-value=0.0007 and a moderate correlation when compared to both FIB-4 (r=0.27) and APRI (r=0.27) score for liver fibrosis but with a significant p value=0.04, respectively 0.03. CONCLUSION: We consider very important for our patients the development of new non-invasive biomarkers for early diagnosis of NAFLD and NASH, as the "gold-standard" of liver biopsy is not easily accepted in clinical practice. Also NAFLD and NASH are dynamic processes that need prospective and repeated assessments, a need that cannot be met by the classical liver biopsy.

Prevalence of anemia and iron deficiency in Romanian patients with inflammatory bowel disease: a prospective multicenter study.

BACKGROUND AND AIMS: Anemia is the most frequent systemic complication in inflammatory bowel diseases. It affects the quality of life and can interact with working capacity. Our objectives were to identify the prevalence of anemia, its main causes and its management in patients with inflammatory bowel disease from Romania. METHODS: We conducted a multicenter prospective study from March 2013 to August 2014. We enrolled 291 patients from three referral centers: 115 (39.52%) with Crohn's disease (CD) and 176 (60.48%) with ulcerative colitis (UC). We defined anemia according to the WHO criteria. RESULTS: Median age of the patients was 41 years and the median time period since diagnosis was 3 years (0.75-7). The median activity index for UC (UCAI) was 4 and the median CD activity index (CDAI) was 96. More patients with CD were on antiTNFα therapy (p < 0.01), corticosteroids (p =0.18) or azathioprine (p=0.05) and required surgery for their underlying disease at study enrollment (p < 0.01). Anemia was present in 31.27% of the patients, more often in those with CD (35.65%) than with UC (28.41%) (not statistically significant); 53.26% of the patients had iron deficiency while 4.12% had folic acid and 8.59% vitamin B12 deficiency; 9.62% of the patients had received anti-anemic therapy at inclusion in the study or in the last three months prior to study enrollment. CONCLUSIONS: About one in three Romanian patients with inflammatory bowel disease has anemia, which is frequently associated with iron deficiency. About 30% of the patients with anemia are under therapy and the most frequent route for iron supplementation is the oral one. This might contribute to the high prevalence of iron deficiency and the low level of compliance.

Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: a comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol.

BACKGROUND AND AIMS: Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohn's disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes. METHODS: Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors. RESULTS: In L biopsies from patients with CD, higher expression levels were found for IL-4 (p=0.009) and IL-12p35 (p=0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p=0.03), chemokines SCYA3 (p=0.05), SCYA4 (p=0.01) and glutathione S-transferase P1 (p=0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p=0.01) and IL-12p35 (p=0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p=0.009) and SCYA8 (p=0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD. CONCLUSIONS: RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy.

Higher titers of anti-Saccharomyces cerevisiae antibodies IgA and IgG are associated with more aggressive phenotypes in Romanian patients with Crohn's disease.

BACKGROUND AND AIMS: Serological markers have been widely used for diagnostic purposes and disease stratification in inflammatory bowel diseases (IBD). The aim of this study was to investigate the seroprevalence and the correlations of anti-Saccharomyces cerevisiae antibodies (ASCA) titers with different clinical phenotypes in Romanian patients with Crohn's disease (CD). METHODS: The study included 107 CD and 86 ulcerative colitis (UC) patients from the Gastroenterology Departments of three University Hospitals, and 60 healthy subjects. ASCA IgA and IgG titers were determined using ELISA test. For CD patients the phenotype was established according to the Montreal classification. The differences in ASCA titers for different CD phenotypes were assessed using the Mann-Whitney U test. RESULTS: ASCA prevalence was 33.6% in CD group, 12.8% in UC group and 6.6% in the control group. Significantly higher IgA (p=0.05) and IgG (p=0.03) titers were found in patients from the Montreal A1+A2 groups (age at onset below 40) compared with the older patients (A3). Higher titers were found in patients with extensive ileo-colonic lesions (L3) and upper gastrointestinal tract involvement (L4) than in patients having only colonic disease (L2). Significantly higher IgA (p=0.03) and IgG (p=0.03) titers were observed in patients with stenosing (B2) and penetrating (B3) disease compared with the nonstricturing, nonpenetrating (B1) phenotype. No correlation between ASCA titers and disease duration was found. CONCLUSION: ASCA seropositivity in Romanian CD patients is lower than in Western Europe. Higher ASCA IgA and IgG titers are associated with a younger age at diagnosis and more aggressive phenotypes.

Weight-based dosing regimen of peg-interferon α-2b for chronic hepatitis delta: a multicenter Romanian trial.

BACKGROUND: Antiviral therapy for chronic hepatitis D (delta) is not yet satisfactory, although it appears to be the only means to alter the progressive natural course of chronic hepatitis D virus (HDV) infection. AIM: To assess safety and efficacy, evaluated by virological, biochemical and histological end-of-treatment (EOT) and end-of-follow-up (EOF) response to peg-interferon α-2b 1.5 µg/kg body weight weekly in a Romanian cohort of naïve patients with chronic hepatitis delta. RESULTS: 49 Caucasian patients (55.1% men, 44.9% females) with a mean age of 37.95 years received study medication; per-protocol population consisted of 36 subjects. Virological EOT response was present in 33.3% and EOF response was maintained in 25% of patients. 50% of study population showed normalization of ALT level at EOT and 25% at EOF. A combined biochemical and virological response was observed in 19.4% of patients at EOT and in 16.7% at EOF. At baseline, the necroinflammation quantified by histological activity index (HAI) score was 9.72 and the mean fibrosis score was 2.03; there was a significant decrease of HAI score to 7.44 (p=0.01) at EOT, but not for fibrosis score (1.33, p=0.37). However, only 8.3% of patients at EOT and 19.4% at EOF had progressive histological disease. CONCLUSIONS: Treatment with peg-interferon α-2b succeeded in obtaining a negative HVD RNA in 25% of patients after 104 weeks of follow-up, although combined biochemical and virological response was present in only 16.7%. Necroinflammation decreased significantly in treated patients. Longer treatment periods with pegylated interferon or combination regimen peg interferon-nucleotide analogues should be tested in order to increase efficacy.

The prevalence of malnutrition and the evolution of nutritional status in patients with moderate to severe forms of Crohn's disease treated with Infliximab.

BACKGROUND & AIMS: Malnutrition is variably encountered in adult patients with Crohn's disease. We evaluated the nutritional status at the beginning and during Infliximab treatment in patients with Crohn's disease. METHODS: Patients with moderate/severe flares of disease treated with Infliximab for induction and maintenance of remission were included in a prospective observational study. Body Mass Index and Nutritional Risk Index were calculated in each patient at 0, 6 weeks and than every 8 weeks for one year. RESULTS: From 30 patients treated with Infliximab 59.3% had low BMI, 35.7% being undernourished. The severity of Crohn's disease did not correlate with low BMI but did correlate with Nutritional Risk Index (p = 0.001). In all patients that responded to Infliximab treatment progressive weight gain was observed, all but one patient reaching normal BMI after one year. Mean weight gain was significantly more elevated (p = 0.001) and time needed to reach normal BMI was longer in the undernutrition group (p = 0.01). Clinical remission was the principal factor associated with weight gain (p = 0.001), while there was no influence of endoscopic remission on nutritional status. CONCLUSIONS: In patients with moderate/severe forms of Crohn's disease malnutrition is frequently encountered. Induction and maintenance treatment with Infliximab determines weight gain and corrects malnutrition in all patients with clinical remission.

Access to peginterferon plus ribavirin therapy for hepatitis C in Romania between 2002-2009.

BACKGROUND: An overall prevalence rate of HCV infection in Romanian adult population was recently estimated to be 3.23%. The proportion of treated patients with chronic hepatitis C in our country has never been assessed. AIMS: 1) to analyze the quality and quantity of antiviral therapy delivery; 2) to determine the proportion of patients being annually and ever treated with antiviral therapy in Romania and 3) to identify barriers against treatment of HCV infected-population in Romania. RESULTS: The number of annually treated patients remained relatively stable between 2002 and 2007 (1,813 patients treated with pegylated interferon and ribavirin in 2002 and 2,446 in 2007). There was a doubled increase in reimbursed treatment in 2008 and 2009 (4,503 and respectively 4,701 treated patients) due to a special campaign organized to increase awareness and prevention of HCV transmission. The median time to therapy approval varies from county to county; overall it is 10.23 months. A total number of 25,318 patients with chronic C hepatitis were treated between 2002-2009, corresponding to a cumulative proportion of 4.1% of the prevalent cases of HCV infection treated in Romania until 1st January 2010. The main limiting factor of access to antiviral therapy for hepatitis C in Romania remains the lack of funds. CONCLUSIONS: This is the first analysis of the nationwide practice for treatment of hepatitis C in Romania. Increased public health efforts are required to improve access to antiviral therapy for hepatitis C in Romania.

Improvement of hepatic encephalopathy using a modified high-calorie high-protein diet.

BACKGROUND AND AIM: Protein-calorie malnutrition (PCM) occurs in 20-60% of patients with hepatic cirrhosis and is associated with the development of life-threatening complications. We evaluated the effect of a modified, casein-vegetable-based, high-protein high-calorie (HPHC) diet on the outcome of cirrhotic patients with hepatic encephalopathy (HE). METHODS: One hundred and fifty three consecutive cirrhotic patients with overt HE were included in this study. An HPHC diet based on better-tolerated vegetable and milk-derived proteins was initiated in order to ensure the adequate protein-energy requirements of 30 kcal/kg/day and 1.2g proteins/kg/day. Serial (daily) assessments were done, including mental status, asterixis, a conventional Number Connection Test (NCT), bowel movements and blood ammonia level. The assessment of the mental status was performed using the West Haven scale. Favorable evolution or response to HPHC diet was defined as an improvement in HE stage with 1 or more (Delta > or =1 stage) after 14 days of diet. RESULTS: During the HPHC diet, 122 patients (79.7%) improved in terms of response definition. A significant decrease in blood ammonia level was observed after 14 days (p<0.0001) in all patients, whatever the improvement of the mental status. A significant improvement in the NCT scores was also noted (p<0.0001). More patients with advanced HE (West Haven stage 3) precipitated by various factors showed a Delta = -2 improvement of their mental status during the modified HPHC diet compared with patients in lower initial stages (50% vs 18.9%, p=0.002). More patients in Child-Pugh B class had a Delta = -2 decrease in the grade of HE compared with patients in Child-Pugh C class (61.7% vs. 14%, p=0.001). CONCLUSIONS: Almost 80% of patients in our study improved their mental status during the casein-vegetable-based HPHC diet, showing that dietary protein restriction is not required for the improvement of HE. A higher rate of improvement was noted in patients with severe impairment of mental status related to precipitating factors and in patients with well preserved liver function. The daily eating pattern consisting of 4 snack-meals and a late evening meal may contribute to HE improvement by equal protein distribution during the day.

Effectiveness and tolerability of pegylated Interferon alpha-2a and ribavirin combination therapy in Romanian patients with chronic hepatitis C: from clinical trials to clinical practice.

BACKGROUND AND AIM: Pegylated interferon alpha in combination with ribavirin represents nowadays the gold standard therapy in patients with chronic hepatitis C. The aim of this study was to assess early (EVR) and sustained virological response (SVR), tolerability and baseline predictive factors for SVR in patients with chronic hepatitis C treated with peginterferon alpha-2a and ribavirin combination therapy in day-to-day clinical practice. METHODS: The analysis included 174 consecutive patients with chronic hepatitis C (naive, relapsers and non-responders after standard therapy) managed in two expertise gastroenterology centers in Romania, mainly on an outpatient basis. The combination therapy was initiated between 1st of June 2002 - 30th of June 2003. RESULTS: The mean age of the study population was 47 years; 41% were men, mean BMI was 26.5 kg/sq.m. Only 7.5% of them had bridging fibrosis/cirrhosis on liver biopsy. EVR and SVR were noted in 78.7% and 51.1%, respectively. Multivariate analysis showed two independent variables associated with SVR: absence of bridging fibrosis/cirrhosis and absence of hepatic steatosis. The rate and profile of side effects associated with pegylated interferon alpha-2a and ribavirin in our clinical setting were all predictable, based on previous experience in the literature. Side effects resulted in interferon and ribavirin dose reductions in 9.2% and, respectively, 25.3%, but permanent discontinuation of the combination therapy was required in only 5.74% of patients. CONCLUSION: Combination antiviral therapy can be safely and successfully used outside clinical trials. To achieve high response rates and tolerability, similar or better than those reported in clinical trials, hepatitis C patients have to be managed in expertise centers, by experienced physicians, aiming at minimizing side effects, optimizing dosing, and enhancing compliance.

Natural history of compensated viral B and D cirrhosis.

AIM: The aim of this study was to define the natural long-term course of HDV compensated cirrhosis. METHODS: 166 consecutive patients with compensated HDV-related cirrhosis diagnosed since 1994 were followed up until the first decompensation and then until death, liver transplantation or 31st of December 2004. The survival during follow-up and the survival according to the type of first decompensation were calculated using the Kaplan Meier method. Survival curves were compared using the log-rank test. RESULTS: 56 females (33.7%) and 110 males (66.3%) with a mean age of 40.7+/-7.9 years were included in the study. The mean Child Pugh and MELD score at the first episode of hepatic decompensation was 8.6+/-2.08 and 15.19+/-5.42, respectively. The median survival was 58.3 months since the diagnosis of compensated cirrhosis and the mean time to first decompensation was 21+/-19 months. The probability of survival after the diagnosis of compensated cirrhosis was 94.3%, 82.5%, and 51.5% at 1, 2, and 5 years, respectively. Ascites was the most frequent first decompensation (80.7%), followed by jaundice (30.1%), portal hypertensive gastrointestinal bleeding (PHGIB) (28.9%), hepatic encephalopathy (HE) (12%), hepatocellular carcinoma (HCC) (12%), portal vein thrombosis (8.4%), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome. 86 patients (51.8%) presented more than one complication at initial decompensation. Survival was worse in patients with jaundice and SBP (p=0.001), followed by patients with HE (p=0.05) and patients who presented more than one initial complication (p=0.03). In the multivariate survival analysis only PHGIB as first decompensation and MELD score>15 were independent predictors of death. CONCLUSION: HDV-related cirrhosis in Romania is an aggressive disease with a median time to decompensation less than 2 years and a median survival less than 5 years. Jaundice, the main clinical consequences of portal hypertension and HCC are the most frequent causes of decompensation and more than half the patients present two or more concomitant initial complications.

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 Crohn's 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.