Addressing barriers to the prevention, diagnosis and treatment of hepatitis B and C in the face of persisting fiscal constraints in Europe: report from a high level conference.

In the WHO-EURO region, around 28 million people are currently living with chronic viral hepatitis, and 120,000 people die every year because of it. Lack of awareness and understanding combined with the social stigma and discrimination exacerbate barriers related to access to prevention, diagnosis and treatment services for those most in need. In addition, the persisting economic crisis has impacted on public health spending, thus posing challenges on the sustainable investment in promotion, primary and secondary prevention, diagnosis and treatment of viral hepatitis across European countries. The Hepatitis B and C Public Policy Association in cooperation with the Hellenic Center for Disease Prevention and Control together with 10 partner organizations discussed at the Athens High Level Meeting held in June 2014 recent policy developments, persisting and emerging challenges related to the prevention and management of viral hepatitis and the need for a de minimis framework of urgent priorities for action, reflected in a Call to Action (Appendix S1). The discussion confirmed that persisting barriers do not allow the full realisation of the public health potential of diagnosing and preventing hepatitis B and C, treating hepatitis B and curing hepatitis C. Such barriers are related to (a) lack of evidence-based knowledge of hepatitis B and C, (b) limited access to prevention, diagnosis and treatment services with poor patient pathways, (c) declining resources and (d) the presence of social stigma and discrimination. The discussion also confirmed the emerging importance of fiscal constraints on the ability of policymakers to adequately address viral hepatitis challenges, particularly through increasing coverage of newer therapies. In Europe, it is critical that public policy bodies urgently agree on a conceptual framework for addressing the existing and emerging barriers to managing viral hepatitis. Such a framework would ensure all health systems share a common understanding of definitions and indicators and look to integrate their responses to manage policy spillovers in the most cost-effective manner, while forging wide partnerships to sustainably and successfully address viral hepatitis.

Characteristics of chronic hepatitis B patients who underwent liver biopsies.

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT) but most studies performed biopsies on selected patients only. The aims of this study were to determine the rate of liver biopsy, characteristics of patients who underwent a biopsy and factors associated with significant liver disease in a cohort of such patients. Records of patients with chronic hepatitis B during a 10-year period were reviewed. Significant liver disease was defined as Knodell HAI ≥ 7 and/or Ishak fibrosis ≥ 3. Of 743 patients, 55.7% were Asian, 56.4% were men, and the mean age was 43.1 years. One hundred and ninety-three (26%) had undergone a biopsy. Biopsied patients were more likely to be men, HBeAg positive, and had lower platelet and higher alkaline phosphatase, bilirubin, ALT and hepatitis B virus (HBV) DNA. Significant liver disease was observed in 20% of patients who had normal ALT at presentation, 14% of those with normal ALT at the time of biopsy and in none of the patients with persistently normal ALT. Patients with normal ALT who were biopsied had higher HBV DNA and higher ALT than those not biopsied. Multivariate analysis showed that low albumin at the time of biopsy and HBV DNA >5 log(10) copies/mL were predictors of significant liver disease. Significant liver disease is rare in patients with chronic HBV and persistently normal ALT and liver histology of chronic HBV infected patients with normal ALT cannot be generalized to other patients with normal ALT that were not biopsied.

Impact of virologic breakthrough and HBIG regimen on hepatitis B recurrence after liver transplantation.

The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre-OLT and HBIG regimens post-OLT. Data from the NIH HBV-OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1-81) post-OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log(10) copies/mL, 74% were receiving antiviral therapy. Twenty-five patients experienced virologic breakthrough before OLT. Post-OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high-dose, IV low-dose, intramuscular low-dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre-OLT as long as rescue therapy is administered pre- and post-OLT.

Fibrinogen storage disease without hypofibrinogenemia associated with estrogen therapy.

BACKGROUND: Cytoplasmic inclusion bodies within hepatocytes may have different etiologies, including the Endoplasmic Reticulum Storage Diseases (ERSDs). ERSD is a pathological condition characterized by abnormal accumulation of proteins destined for secretion in the endoplasmic reticulum of hepatocytes; it may be congenital (primary) or acquired (secondary). Fibrinogen storage disease is a form of ERSD. CASE PRESENTATION: We present a case of fibrinogen storage disease secondary to estrogen replacement therapy. Its causal relationship to the drug is shown by histological, immunohistochemical and ultrastructural studies of paired liver biopsies obtained during and after the drug therapy. CONCLUSION: The liver biopsies of patients with idiopathic liver enzyme abnormalities should be carefully evaluated for cytoplasmic inclusion bodies and, although rare, fibrinogen deposits.

Detection of Candida albicans by culture, serology and PCR in clinical specimens from patients with ulcerative colitis: re-evaluation of an old hypothesis with a new perspective.

The relationship between inflammatory bowel disease and microorganisms was evaluated. The presence of Candida albicans-specific IgM and IgG antibodies in serum samples and the presence of C. albicans in stool and colonal mucosa samples of the patients did not exhibit any significant difference between 21 patients in active stage and 15 patients in remission of ulcerative colitis (UC) (compared with 19 control patients). The invasion of yeast cells to the colonal mucosa was demonstrated by detecting C. albicans DNA using specific PCon1, PCon2, and PspA2 primers in PCR assay. Eighteen of 36 patients (50%) were found to be DNA positive while in 19 controls only 4 (21%) were found to be positive. The presence of DNA in the association of the positive serological reactivity is suggested as an important diagnostic marker of UC.