Recurrence rate of hepatocellular carcinoma in patients with treated hepatocellular carcinoma and hepatitis C virus-associated cirrhosis after ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin therapy.

Introduction: Recent studies have suggested a higher recurrence rate of hepatocellular carcinoma (HCC) in patients with a history of HCC and hepatitis C virus (HCV)-associated cirrhosis treated with direct-acting antiviral (DAA) agents. Material and methods: We conducted a prospective analysis of 24 patients with HCV-associated cirrhosis and treated HCC who received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for 12 weeks. Prior therapies for HCC included resection (9/24 patients), radiofrequency ablation (RFA) (7/24) and trans-arterial chemoembolization (TACE) (8/24). All patients were eligible for treatment if they had no HCC recurrence 6 months after their last procedure. A control group was defined. All patients were followed every 6 months, with dynamic computed tomography and/or magnetic resonance imaging. Results: The sustained virological response rate per protocol was 21/24 (87.5%). The study group included 14 (59%) males, median age 64 years (51-77), 50% with associated non-alcoholic steatohepatitis and 24% with Child-Pugh A6 points. HCC recurrence rate/100 patient-years was lower in the DAA-HCC group versus control: 5.5 versus 24.6% patient-years for the resection+RFA group (p = 0.044), respectively, and 18.6 versus 72.7% patient-years for TACE group (p = 0.002). Survival without recurrence was higher in the resection+RFA group (45 compared to 18 months (p < 0.001)) and also in the TACE group (44 compared to 11.5 months (p = 0.002)). Conclusions: DAA therapy significantly reduced the recurrence rate of HCC and improved survival without recurrence in patients with treated HCV-associated HCC.

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

BACKGROUND: 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. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.

New Epidemiologic Data Regarding Hepatitis C Virus Infection in Romania.

BACKGROUND AND AIMS: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania. METHODS: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address. RESULTS: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanta (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramures (8.8/105) (p<0.001). CONCLUSIONS: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta.

Efficacy and safety of peginterferon alpha-2a (40KD) in HBeAg-positive chronic hepatitis B patients.

AIM: The study was designed to evaluate the efficacy and safety of peginterferon alpha-2a in HBeAg-positive chronic hepatitis B patients, nonresponders or relapsers after previous lamivudine or standard interferon therapy. METHODS: This prospective, national, multicentric, open label, not randomized trial enrolled 43 HBeAg-positive chronic hepatitis B patients with detectable HBsAg for at least 6 months prior to screening, positive HBeAg and negative anti-HBe, serum HBV DNA levels of at least 500,000 copies/mL by PCR assay, elevated ALT up to 10 x ULN, no response or relapse after previous lamivudine or standard interferon therapy. All eligible patients received pegIFN alpha-2a 180 micrograms weekly for 48 weeks with 24 weeks treatment free follow-up. There were two main efficacy assessments: HBeAg seroconversion and viral supression below 100,000 copies/mL. RESULTS: HBeAg seroconversion rate at the end-of-treatment was 4.65% (n=2; p less than 0.05) increasing to 11.62% 24 weeks after end of therapy (n=5; p less than 0.05). The rate of viral supression at levels below 100,000 copies/mL was 23.25% (n=10; p less than 0.05) at end-of-treatment, and 16.3% (n=7; p less than 0.05) at end of follow-up. ALT normalization was obtained in 20.9% (p less than 0.05) of patients at end-of-treatment, the percentage being significantly higher - 37.2% (p less than 0.05) at the end of follow-up. CONCLUSIONS: Even in a difficult-to-treat patient population with HBeAg-positive chronic hepatitis B, peginterferon alpha 2a proved to be efficient in a defined proportion of patients. The increase in HBeAg seroconversion rate from end-of-treatment (4.65%) to the end of follow-up period (11.62%) also proves the benefits of prolonged immunological effect of pegIFN alpha 2a.

Significance of anti-sacharomices cerevisiae antibodies (ASCA) in patients with inflammatory bowel diseases in Romania.

INTRODUCTION: Anti-Sacharomyces cerevisiae antibodies (ASCA) represent the immunologic marker correlated with Crohn's disease because of their high specificity (80-95%). The aim of this study is to confirm their value in a Romanian population with IBD. MATERIAL AND METHODS: A prospective longitudinal study was performed, which included patients admitted to Center of Gastroenterology and Hepatology Fundeni, Bucharest, in 2000 with ulcerative colitis (33 patients) - UC group, or Crohn's disease (40 patients) - CD group, and a control group (C) consisting of 22 healthy subjects. ASCA determination from serum samples was performed in the Erasmus University by ELISA technique. RESULTS: ASCA+ prevalence in CD group was 5 in 40 patients (12.5%), in UC group 0/33 (0%), 1/21 C group (4.9%), p=0.05. ASCA+ phenotype was found only in patients with CD diagnosed before the age of 40 years (A1), p=0.04. Also, ASCA+ phenotype correlated significantly with the colonic (L2) or ileocolonic (L3) extension (p=0.05). ASCA+ status did not correlate with the evolutive pattern of CD (stricturing, penetrating or non- stricturing non-penetrating), and neither did the clinical severity. CONCLUSIONS: ASCA+ prevalence in CD patients is much lower compared with North-American or West-European studies (12.5% versus 40-70%). In Romanian patients, ASCA assessment may be helpful in achieving a diagnosis of Crohn's disease, especially in those younger than 40 years, or in those with colonic or ileocolonic extension.

Prevalence and significance of perinuclear anti-neutrophil antibodies (pANCA) in Romanian patients with Crohn's disease and ulcerative colitis.

INTRODUCTION: Antineutrophil cytoplasmic antibodies (ANCA) are known as a serologic marker of immune disturbances in IBD. The most specific are perinuclear ANCA (pANCA). The aim of this study was to investigate their significance for the diagnosis of inflammatory bowel disease (IBD) in Romania. MATERIAL AND METHODS: A prospective longitudinal study, comprising all patients admitted to our Center in 2000 with ulcerative colitis--UC group (33 patients) and with Crohn's disease--CD group (40 patients). The control group (C) included 22 healthy individuals, with similar age and sex distribution. ANCA was tested in serum by indirect immunofluorescence at Leuven University, Belgium. RESULTS: ANCA prevalence in UC group was 12/33 (36.4%), in CD group was 6/40 (15%), while in the C group all sera tested negative (p=0.004). All ANCA antibodies in patients with IBD were perinuclear type. In the UC group, the prevalence of pANCA was higher in females compared to males (52.9% versus 16.7%, p=0.04). The phenotype pANCA+ did not correlate with disease extension, severity, the evolutive form or complications. In the CD group, the phenotype pANCA+, although more frequently found in colonic involvement and in non-obstructive non-fistulizing forms to associate with pANCA+, did not reach statistical significance (p=0.59). A higher severity of CD was associated with higher pANCA titers (p=0.05). CONCLUSION: pANCA prevalence in UC in Romania was lower in comparison with other studies (36.4% versus 50-80%). The highest prevalence was found in females with UC. In CD, pANCA+ was associated with a higher severity. pANCA assessment remains at a research level, further in-vestigations being necessary in order to demonstrate its clinical importance.

Successful local fibrinolytic treatment and balloon angioplasty in superior mesenteric arterial embolism: a case report and literature review.

We present the case of a 72-year-old man with atrial fibrillation who developed an embolic occlusion of the superior mesenteric artery. He was successfully treated with local fibrinolysis using streptokinase associated with angioplasty. Such local treatments without the need of surgery are very rarely reported in the literature because of the great difficulty in selecting patients without intestinal necrosis, but represent an important option in the algorithm for the management of acute mesenteric ischemia. The patient was in good condition without recurrent embolism during the six months follow-up.