Hepatitis C: The beginning of the end-key elements for successful European and national strategies to eliminate HCV in Europe.

Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely "silent pandemic," its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high-level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.

Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study.

The present study was designed to determine the seroprevalence of hepatitis B and C virus (HBV, HCV) infections and risk factors in the Turkish general population. Participants were enrolled from urban and rural areas of the predetermined 23 EUROSTAT NUTS 2 region. A two-stage stratified sampling method was used to select participants from these regions (n = 5460; 50.9% females; mean (SD) age: 40.8 (14.7) years). Sociodemographics, clinical characteristics and risk factors were recorded at home visits. The seropositivity rates for hepatitis B surface antigen (HBsAg), anti-HCV, anti-HBs and anti-HBc total were 4.0%, 1.0%, 31.9% and 30.6%, respectively. Among HBsAg-positive cases, 94.5% were anti-HBe-positive, 70.2% were HBV-DNA-positive and 2.8% were anti-HDV total positive; 99.1% of HBV infections were of genotype D. Close contact with a hepatitis patient (OR 3.24; 95% CI 2.25-4.66; p < 0.001), living in the southeastern region (OR 2.74; 95% CI 1.7-4.45; p < 0.001), male gender (OR 1.77; 95% CI 1.28-2.46; p < 0.001), being married (OR 1.62; 95% CI 1.02-2.57; p 0.038), educational level less than high school (OR 1.53; 95% CI 1.04-2.26; p 0.03), orodental interventions (OR 1.54; 95% CI 1.01-2.35; p 0.047) and a history of non-disposable syringe use (OR 1.4; 95% CI 1.01-1.96; p 0.045) were significant determinants of HBsAg positivity. Age ≥50 years (OR 2; 95% CI 1.09-4.3; p 0.026) was the only significant predictor of anti-HCV positivity. In conclusion, our findings revealed an HBsAg positivity in 4% and anti-HCV positivity in 1% of the adult population and at least one-third of the population has been exposed to HBV infection in Turkey.

Aorto-enteric fistula: a dilemma for the endoscopist as a rare cause of gastro-intestinal bleeding.

A 78-year-old man with a history of aorta-femoral graft operation was admitted to the hospital with symptoms of syncope, melena and haematemesis. He reported several episodes of melena during the previous year for which he underwent repeated gastro-intestinal endoscopic examinations, which were unable to show the site of the gastro-intestinal bleeding. The third upper gastro-intestinal endoscopic examination disclosed a yellowish ulcerative lesion with irregular borders in the third part of the duodenum, which was considered to be a fistula, between the aorta and the duodenum. The patient underwent an explorative operation that revealed an intact aortic graft, firmly adherent to the duodenal wall, and the duodenum that was eroded in the third portion. The duodenum was transected and a duodenoduodenostomy was performed. Although re-bleeding did not occur, the patient died of sepsis eight days after the operation. Aorto-enteric fistulae can be missed due to the common practice of limiting the endoscopic examination to the second part of the duodenum and not considering them in the differential diagnosis of gastro-intestinal bleeding because of their rarity. Possibly, a number of prior endoscopic examinations may be inconclusive until a correct diagnosis is reached in most of the cases.

Adrenomedullin in cirrhotic and non-cirrhotic portal hypertension.

AIM: Adrenomedullin (ADM) is a potent vasodilator peptide. ADM and nitric oxide (NO) are produced in vascular endothelial cells. Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH). The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown. plasma ADM levels were studied in patients with NCPH, compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups. METHODS: There were 4 groups of subjects. Group 1 consisted of 27 patients (F/M: 12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age: 41+/-12 years), group 2 consisted of 14 patients (F/M: 6/8) with compensated (Child-Pugh A) cirrhosis (mean age: 46+/-4), group 3 consisted of 16 patients (F/M: 6/10) with decompensated (Child-Pugh C) cirrhosis (mean age: 47+/-12). Fourteen healthy subjects (F/M: 6/8) (mean age: 44+/-8) were used as controls in Group 4. ADM level was measured by ELISA. NO was determined as nitrite/nitrate level by chemoluminescence. RESULTS: ADM level in Group 1 (236+/-61.4 pg/mL) was significantly higher than that in group 2 (108.4+/-28.3 pg/mL) and group 4 (84.1+/-31.5 pg/mL) (both P<0.0001) but was lower than that in Group 3 (324+/-93.7 pg/mL) (P=0.002). NO level in group 1 (27+/-1.4 micromol/L) was significantly higher than that in group 2 (19.8+/-2.8 micromol/L) and group 4 (16.9+/-1.6 micromol/L) but was lower than that in Group 3 (39+/-3.6 micromol/L) (for all three P<0.0001). A strong correlation was observed between ADM and NO levels (r=0.827, P<0.0001). CONCLUSION: Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated, Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis, and were significantly higher than those in patients with NCPH. Portal hypertension plays an important role in the increase of ADM and NO. Parenchymal damage in cirrhosis may contribute to the increase in these parameters.

Epidemiology of viral hepatitis in the Mediterranean basin.

The prevalence of viral hepatitis is high and remains a serious public health challenge throughout the world. New molecular biology techniques provided a better understanding of the viruses over the last decades. Novel therapeutic options seem to be promising but preventing measures including donor screening, immunization against hepatitis A virus (HAV) and hepatitis B virus (HBV), universal use of disposable syringes and implementation of better hygienic conditions play a major role in the control of viral hepatitis. The Mediterranean basin has special demographic and socioeconomic features. We reviewed in this article the seroepidemiological features of viral hepatitis in this particular region. Improving general conditions led to a tendency to be infected in older ages with HAV. Hepatitis B and C virus still remain to be the major causes of chronic hepatitis. The seroprevalence of hepatitis D virus, which was once endemic in the Mediterranean region seem to decrease nowadays whereas hepatitis E virus is still prevalent in some areas. Other viruses such as hepatitis G virus (HGV), TT virus (TTV) and SEN virus do not seem to be a major problem and their clinical importance remains to be determined in further studies.

Risk factors for hepatocellular carcinoma in Turkey.

The contribution of hepatitis B, hepatitis C, and excess alcohol intake to the development of hepatocellular carcinoma in Turkey was assessed. The study was conducted through a questionnaire sent to seven major medical referral centers in different regions of Turkey and is based on 207 patients seen in the period 1994-1997. Of the seven centers, two were located in West Turkey (54 patients), two were in Central Turkey (85 patients), and two were in south and southeast Turkey (68 patients). In 196 of the 207 patients (94.7%), there was a history of chronic liver disease, and in 180 patients (87%) liver cirrhosis was documented. Of the 207 patients, 116 (56%) had hepatitis B, 48 (23.2%) had hepatitis C, and 33 (15.9%) had a history of excess alcohol intake. Anti-delta testing was available in 69 of 116 patients with hepatitis B, and anti-HDV was positive in 13 of these patients (13/69, 18.8%). Of the 33 patients with a history of heavy alcohol intake, 18 had concomitant chronic viral hepatitis infection, and alcohol alone was the etiology of hepatocellular carcinoma in only 15 cases (7.2%). The distribution of etiologic factors was not homogenous in different geographical regions in Turkey. In central, south, and southeastern Turkey, the predominant etiology of hepatocellular carcinoma was hepatitis B, whereas in western Turkey the impact of hepatitis B, hepatitis C, and alcohol was similar. This study indicates that hepatitis B virus infection is the leading cause of hepatocellular carcinoma in Turkey, followed by hepatitis C infection and alcoholic liver disease.

Influence of the metabolic complications of liver cirrhosis on dietary intake.

The role of the nutrition is discussed in relation to chronic liver disease. An outline of the general principles involved in regulating nutrition in patients with advanced liver disease is given followed by an evaluation of the effects of malnutrition on the outcome of the disease. Major problems faced over the course of advanced liver disease are carbohydrate intolerance, sodium and fluid retention which may progress to hepatorenal syndrome, and hepatic encephalopathy. Interest on diet regulation in such cases has been recently reemphasized in multicenter studies particularly in the liver transplant setting and alcoholic liver disease. Controversies exist regarding albumin infusion after paracenthesis, low protein diet in hepatic encephalopathy and water restriction before sodium. The effect of nutrition on the outcome of liver disease and survival is not well established. However patients with better nutritional state do much better after transplant.

Thrombophilia and inflammatory bowel disease: does factor V mutation have a role?

BACKGROUND: An increased tendency for thromboembolism is a well known problem of inflammatory bowel disease (IBD). Microvascular thrombosis has also been claimed as a pathogenic factor in IBD. Recently a point mutation in the gene coding factor V (FV Leiden) has been identified in various thromboembolic diseases, but the role in IBD is unknown. OBJECTIVE: To determine the frequency of FV Leiden in IBD patients and compare with a group of controls. METHODS: Sixty-three IBD patients [43 ulcerative colitis (UC) patients and 20 Crohn's disease (CD) patients] and 36 healthy controls were included in the study. Only one of the UC patients had a history of cerebral thromboembolism. The extracted DNA from frozen blood was subjected to polymerase chain reaction for the amplification of FV gene. The amplicons were hybridized both with the mutant and wild-type probes to detect FV mutation. Readings of optical density above 0.3 were considered as positive results. According to the patterns of ELISA, heterozygosity and homozygosity for normal and mutant alleles were determined. RESULTS: Eight (18%) of UC patients were heterozygous normal and one (2%) patient had homozygous mutation. Eight (45%) of the 20 CD patients had a heterozygous pattern and one (5%) had a homozygous pattern. In the control group four (11%) subjects showed a heterozygous genotype. FV Leiden was found to be statistically more frequent in CD patients (P < 0.005) (odds ratio 6.5, 95% confidence interval 1.3-18.), but not in the UC patients as compared with controls (P> 0.05). There was no significant correlation between FV Leiden presence and disease activity, gender or disease duration for both UC and CD. CONCLUSION: The results suggest that FV Leiden is more frequent in CD patients, but not in the UC patients as compared with controls. The high rate of factor V mutation in our CD patients suggests the need for further studies to confirm a relationship between this mutation and aetiology of the disease.

The distribution of HLA-DRB alleles in ulcerative colitis patients in Turkey.

Recently described distinct associations of HLA class II genes with ulcerative colitis (UC) suggest a genetic heterogeneity for disease susceptibility. In this study, HLA-DRB alleles of UC patients (n = 59) from Turkey were investigated and compared with healthy controls (n = 244). Using molecular genotyping by polymerase chain reaction (PCR) and sequence-specific oligonucleotide hybridization, we have shown a positive association of UC patients with the HLA-DRB1*1502 allele (10/59 vs. 16/244; P = 0.02; OR: 2.9) and a negative association with the DRB1*13 allele (7/59 vs. 64/244; P = 0.03; OR: 0.38) compared to controls. HLA-DRB1*0701 was significantly increased in perinuclear antineutrophil cytoplasmic antibody (pANCA)-positive UC patients compared to pANCA-negative patients (8/32 vs. 0/27; P = 0.005), whereas DRB1*1502 was observed more frequently in pANCA-negative patients (8/27 vs. 2/32; P = 0.03). These results extended the reported positive association of DRB1*1502 with UC to another population and supported the genetic susceptibility associated with HLA genes for disease development.

Clostridium difficile acquisition rate and its role in nosocomial diarrhoea at a university hospital in Turkey.

Infection with Clostridium difficile can present with various clinical pictures ranging from an asymptomatic carrier state to pseudomembranous colitis and plays an important part in the etiology of nosocomial diarrhoea. To identify risk factors for C. difficile colonization and diarrhoea in hospitalized subjects, patients admitted to a general medicine ward at Marmara University hospital during a one year period were entered into the study. Of the 202 patients, nosocomial diarrhoea developed in 45 (22.3%). Fourteen patients (6.9%) were colonized with C. difficile during their hospitalization period. Ten of the colonized patients (71.4%) developed diarrhoea and were found to be positive by toxin assay. Pseudomembranous colitis was confirmed endoscopically in 3 of the patients with diarrhoea. Administration of beta lactam agents such as ampicillin and cephalosporins; gastrointestinal manipulations and admission to the intensive care unit were found as major risk factors for C. difficile colonization.

Refractory duodenal ulcer healing and relapse: comparison of omeprazole with Helicobacter pylori eradication.

OBJECTIVE: To investigate differences between omeprazole and Helicobacter pylori eradication in patients with duodenal ulcers refractory to H2-receptor antagonists and to compare the recurrence rates after the two treatments. DESIGN AND METHODS: Forty-five patients with endoscopically proven duodenal ulcers refractory to H2-receptor antagonists and H. pylori infection were randomly assigned to 8 weeks of treatment with omeprazole 40 mg/day or 4 weeks of treatment with colloidal bismuth subcitrate 480 mg/day plus metronidazole 750 mg/day and tetracycline 1000 mg/day from day 1 to day 14. Patients were evaluated endoscopically and clinically at the end of treatment. Patients with healed ulcers were followed up for 1 year after cessation of the treatment. Endoscopy was performed at 3 and 12 months. RESULTS: Ulcer healing occurred in 100% (21/21) of patients on triple therapy and 70.5% (12/17) of those treated with omeprazole alone (P = 0.0123). The relapse rate at the 3rd month was 11.7% (2/17) in the triple therapy group and 60% (6/10) in the omeprazole group (P = 0.0248). Of the patients followed to study endpoint (relapse or endoscopy at 12 months) three of 12 (25%) receiving triple therapy, compared to six of eight (75%) receiving omeprazole, relapsed (P = 0.0648). CONCLUSION: These results show that triple therapy is more effective than omeprazole in the treatment of refractory duodenal ulcers and reduces the rate of ulcer relapse.

The effect of endothelin-1 on vena jugularis thrombus model in rabbits.

Endothelins (ET) are the most important vasoconstrictors known, and administration results in contraction of vascular strips in man and experimental animals in vitro. We examined the effects of ET-1 on thrombus formation in rabbits. We used vasoconstrictor and thrombus forming agents and we selected an animal model, the vena jugularis thrombus model. In addition, intravascular endothelium was examined ultrastructurally. The ET-1 level is known to be high in patients with hypertension; if these patients also have atherosclerosis, then intravascular thrombus formation may increase. In the vena jugularis thrombus model, thromboplastin and ET-1 act synergistically to increase intravascular thrombus formation. On injection of ET-1 dose dependent vasoconstriction was shown in the vessel wall. Although similar maximal contraction is achieved, a decrease in vessel diameter is associated with increased potency of ET-1 and thromboplastin. The results suggest that ET-1 may regulate vascular tone through constriction of vessels.

Cerebral echinococcosis multilocularis. Case report.

Cerebral occurrence of Echinococcus multilocularis is very rare and there is no widely accepted therapeutical method. In this report we present a case with an intracranial mass lesion and a palpable hepatic mass, which appeared to be due to Echinococcus multilocularis in the histopathological examination.

Effect of diltiazem on renal function in patients with liver cirrhosis.

Calcium channel blockers have strong vasodilator, natriuretic and diuretic actions in normal and hypertensive subjects. The aim of this study was to evaluate the effect of diltiazem on renal function, renin-angiotensin-aldosterone axis (RAA) and atrial natriuretic factor (ANF) in patients with liver cirrhosis. Seven patients (3 females and 4 males) with a mean age of 56.3 +/- 11.1 years (36-68) entered the trial. All of the patients had HBV (6 cases) or HCV (1 case) related Child A (3 cases) or Child B (4 cases) liver cirrhosis proven by liver biopsy. Patients were given placebo for 15 days followed by p.o. diltiazem 30 mg t.i.d. for 15 days. Urinary volume, natriuresis, creatinine clearance, plasma renin activity (PRA), ANF and aldosterone (ALD) levels were determined after the washout period and during the first and second weeks of drug treatment. Urinary volume increased by 25-170% in 5 cases but this difference did not reach statistical significance. Slight increases in natriuresis occurred in some cases on the 3rd day of the trial but the overall results were not statistically significant (191.50 +/- 26.85 vs 204.07 +/- 39.83 mmol/l). Diltiazem induced no significant changes in PRA, ALD and ANF levels or creatinine clearance during the first or second weeks of the trial. There was a significant drop in the pulse rate on the first or second weeks of the treatment (p less than 0.01 and p less than 0.05, respectively). No significant changes were noted on mean arterial pressure (MAP).(ABSTRACT TRUNCATED AT 250 WORDS)

Safety of alcohol after viral hepatitis.

To test the validity of the generally held belief that moderate consumption of alcohol during convalescence from acute viral hepatitis adversely affects outcome, 87 adults recovering from acute viral hepatitis (hepatitis A in 36, hepatitis B in 34, hepatitis non-A, non-B in 17) were studied. Criteria for entry to the study attempted to ensure that no patient was a chronic hepatitis B carrier. Patients were randomised either to a moderate alcohol intake, or to continued complete abstention. Drinkers consumed 26 g alcohol daily (mean) and none remained abstinent. At 3 months all patients were well, with normal liver function tests. There were no significant differences between the two groups at anytime. The findings suggest that moderate alcohol intake during convalescence from acute viral hepatitis does not seem to be harmful.

The effect of chronic guanfacine administration on high plasma vasopressin levels in essential hypertension.

In the past several years, investigators have given evidence that vasopressin (VP), in addition to its antidiuretic function, may play an important role in cardiovascular regulation through other mechanisms. An increased plasma VP level has been reported in some patients with mild-to-moderate essential hypertension (EH). Additionally, yohimbine, a selective alpha 2-adrenoceptor antagonist, has been shown to increase the plasma VP level and blood pressure (BP) in man. The present study was performed to evaluate the effects of chronically administered guanfacine, a centrally acting alpha 2-adrenoceptor agonist, on high plasma VP levels in patients with mild-to-moderate EH in whom no other causes responsible for elevated plasma VP levels were present. The relations among VP, BP and renin-angiotensin-aldosterone system were also investigated. Eleven patients (8 women and 3 men aged 62 +/- 3 years) with untreated and uncomplicated EH were included in the study after a 2-week placebo period and kept on a diet containing 120 mmol sodium and 80 mmol potassium daily. In all patients treated once daily with 1 mg of guanfacine for 4 weeks, the drug-induced changes in plasma levels of VP and aldosterone (ALD), plasma renin activity (PRA), plasma osmolality, BP and heart rate were determined. A marked reduction in plasma VP levels (p less than 0.001) was observed and this was accompanied by a significant fall in mean arterial blood pressure (p less than 0.001). No significant changes in heart rate, plasma osmolality, PRA and plasma ALD levels were found. The results suggest that guanfacine might suppress VP secretion via alpha 2-adrenoceptors without significantly affecting renin-angiotensin-aldosterone system.(ABSTRACT TRUNCATED AT 250 WORDS)