90 research outputs found
Risk of hepatocellular carcinoma, liver-related complications, and death in persons living with chronic hepatitis B and D
Chronic hepatitis B virus (HBV) infection affects 257 million individuals and is a leading
cause of liver-related morbidity and mortality. Hepatitis D virus (HDV) is a satellite virus,
that needs HBV for packing and propagation, hence infecting only individuals with HBV
infection. It is estimated that around 9-19 million individuals are living with chronic
hepatitis Delta (CHD), hence it is the least common among viral hepatides. CHD
demonstrates a severe course of liver disease than CHB. The treatment options are still
limited, and approved therapies are at a high price. This thesis aims to characterize the
natural course of HBV and HDV infection in a low-endemic setting, predictors of disease
progression, and the effect of therapy on the disease course.
In Study I, we identified 337 patients with positive anti-HDV antibody from 11 infectious
disease clinics in Sweden assembling a nationwide cohort. During a mean follow-up of 6.5
years, HDV RNA replication was significantly associated with a composite outcome of any
liver-related decompensation, HCC, and liver transplantation. The response to IFN therapy
was suboptimal; 18.8% had a virological response defined as negative or more than 2 log
decline of HDV RNA level and a more benign disease course was seen in virological
responders compared to non-responders. HDV RNA replication was independently
associated with liver decompensation events, undergoing liver transplantation, and a
trend toward higher HCC risk.
In Study II, we conducted a systematic review and meta-analysis of published peerreviewed
cohort studies examining the risk of HCC in patients with HBV/HDV infection
compared to peers with HBV mono-infection. The pooled relative risk was 2.12 (95%
confidence interval CI 1.14-3.95), with a particularly higher risk in patients with
HIV/HBV/HDV co-infection and substantial heterogeneity between studies.
In Study III, we present the HDV cascade of care during three decades at Karolinska
University Hospital (KUH) as a secondary care referral facility in the Southern Stockholm
region. In 4095 patients with positive HBsAg, (90.4%, n=3703) have undergone an anti-
HDV test. Anti-HDV positive was prevalent in (83.7%, n=310) and (65.2%, n=202) patients
who had HDV RNA replication. Older age, cirrhosis, and getting a late anti-HDV diagnosis
were independently associated with any prevalent liver outcome. Despite the high
screening rate reaching 95%, 8% of persons meeting the criteria of the American
Association for the Study of the Liver (AASLD) as “high-risk” of infection did not receive
any screening test and 28% of persons with cirrhosis received a remote screening test
(after two years). Persons with concurrent HIV and HBV infection were less likely to
receive a screening test.
In Study IV, we analyze a nationwide cohort of African-born Swedish residents with CHB
without cirrhosis (n=3865), followed for a mean of 12 years from the date of HBV diagnosis
in Sweden to the incidence of HCC. The cohort was compared to individuals without HBV
in 1 to ≤3 on age, sex, and county of residence to persons from the same area of birth
(n=8,488) and in 1 to ≤ 10 on age, sex, and county of residence with a cohort from the
general population (n=39,278). African-born men with CHB were significantly younger at
HCC development compared to women and peers from comparator cohorts. The costeffectiveness
surveillance threshold at 0.2% was exceeded at age 54 years
(IR=0.20/100PYs, 95%CI 0.10-0.40) in men and at age 59 years (IR=0.21/100 PYs, 95%CI
0.10-0.45) in women, while at 20-40 years in the presence of concomitant HDV and HCV
co-infection in men. The probability of HCC was more pronounced at younger ages in
men compared to women. African-born men with CHB had 10.6 times higher risk to
develop HCC compared to African-born peers without HBV and a 35.3 times higher risk
than the general population. The study provides absolute and relative estimates of HCC
development in a nationwide large cohort of African-born first-generation persons with
CHB, without cirrhosis at baseline living in a different environmental setting.
To conclude, HDV RNA replication, older age, and cirrhosis in patients with anti-HDV
positive are independent predictors of progressive liver disease and need for liver
transplantation. Lack of response to IFN therapy might be associated with a worse disease
outcome. Based on our pooled analyses, HDV infection is associated with two-times
higher risk to develop HCC, compared to HBV mono-infection with a higher risk in persons
with triple HIV/HBV/HDV infection. Nine out of 10 patients with CHB received an anti-HDV
test at KUH. Delayed HDV diagnosis was independently associated together with older
age and cirrhosis with a liver-related outcome. Liver cirrhosis is a fertile ground for cancer
development, but some people with CHB can develop cancer without cirrhosis. Costeffectiveness
analysis to surveil persons with CHB without cirrhosis identified a threshold
of 2 per 1000 persons per year to conduct a semi-annual ultrasound examination.
Nevertheless, the age to start liver cancer surveillance, in persons of African origin is
different across guidelines due to few studies examining this risk in this population for a
long time. It is unclear if the current 0.2% cost-effectiveness threshold for HCC
surveillance in persons without cirrhosis might miss a population of younger patients with
co-morbidities who are at increased risk to develop HCC. Our research highlights the
need for cost-effectiveness studies in contemporary cohorts of persons living with CHB
particularly in African-born men given the substantial number of HCCs occurring at
younger ages in this population
A Review of HDV Infection
Hepatitis D is the most severe viral hepatitis. Hepatitis D virus (HDV) has a very small RNA genome with unique biological properties. It requires for infection the presence of hepatitis B virus (HBV) and is transmitted parenterally, mainly by superinfection of HBsAg carriers who then develop chronic hepatitis D. HDV has been brought under control in high-income countries by the implementation of HBV vaccination, and the clinical pattern has changed to a chronic hepatitis D seen in ageing patients with advanced fibrotic disease; the disease remains a major health concern in developing countries of Africa and Asia. Every HBsAg-positive subject should be tested for HDV serum markers by reflex testing, independently of clinical status. Vaccination against HBV provides the best prophylaxis against hepatitis D. The only therapy available so far has been the poorly performing Interferon alfa; however, several new and promising therapeutic approaches are under study
Towards elimination of Hepatitis C in Vietnam
Vietnam has a high burden of viral hepatitis. This thesis strives to advance its elimination, addressing important gaps in the literature that I hope will contribute to treatment guidelines and health policy, both in Vietnam and internationally.
Firstly, to define the hepatitis epidemic in Vietnam, I assimilate all published seroprevalence data since 1990 to estimate pooled prevalence of HBV, HCV and HDV in high and low risk populations. I show that although blood safety has improved, and HDV is largely confined to high-risk populations, a renewed focus on birth dose HBV vaccination and targeted HCV screening and treatment of people who inject drugs, is urgently required to meet elimination targets.
The next chapters address HCV therapy, namely predictive factors for selecting individuals who could be treated for shorter duration, treatment failure in relation to rare HCV subtypes, and the clinical importance of resistance mutations. I describe a prospective clinical trial evaluating the efficacy of shortened sofosbuvir and daclatasvir therapy, based on early virological response: firstly, in genotype 1 or 6-infected individuals with mild disease (chapter 3) and then in genotype 6-infected individuals with advanced liver fibrosis (chapter 4). I show that shortened therapy, with retreatment if needed, can reduce antiviral use while maintaining high cure rates, but that day 2 virologic response alone is not an adequate predictor of cure. I demonstrate that a high frequency of putative NS5A inhibitor resistance mutations in genotype 6 infection does not impact cure rates, negating the need for costly genotyping in Vietnam.
In my final data chapter, I explore an innovative means of decentralising HCV care. In two independent study populations from Vietnam and the UK, I show that an increase in routinely taken alanine transaminase after HCV therapy is a reliable screen for treatment failure that could substantially reduce reliance on nucleic acid testing in remote and resource-limited settings.Open Acces
LABRAD : Vol 34, Issue 1 - January 2009
N-Telopeptide of Type I Collagen (NTx): A Biochemical Tool for Assessing Bone Turnover Automated Blood Grouping Leukocyte Alkaline Phosphatase (LAP Score) Pathology Quiz Synovial Fluid Analysis in Important Joint Diseases Intraductal Papillary Mucinous Tumor (IPMT) of the Pancreas: A Diagnostic Challenge Hepatitis Delta Virus (HDV) Answers to Pathology Quiz Thyroid Autoimmune Diseases and Thyroid Peroxidase (TPO) Antibody Therapeutic Monitoring of Tacrolimus Meeting Report: 32 Annual Conference of Pakistan Association of Pathologists AKU Clinical Laboratory Continuing Medical Education (CME) Seminar in Bahawalpurhttps://ecommons.aku.edu/labrad/1015/thumbnail.jp
New Perspectives on Treatment of Hepatitis B Before and After Liver Transplantation
open5noThe hepatitis B virus (HBV) infects more than 260 million people globally, with increasing incidence, especially in developing countries. Despite antiviral therapies, HBV-related end-stage liver disease remains one of the most important indications for liver transplantation worldwide. Although new available treatments have improved the outcome of patients with both compensated and decompensated liver disease in some specific clinical settings as acute-on-chronic liver failure mortality is still high. Moreover, the incidence of HBV-related hepatocellular carcinoma (HCC) seems to be increasing and represents a major challenge for the transplant team. In the post-transplant setting, combination of anti-HBV immunoglobulins and oral nucleos(t)ides provided significant improvement on graft and patient survival. Furthermore, recent data suggested the possibility of personalized therapeutic algorithms based on pre and post-transplant viral and host risk factors. Finally, liver grafts from HBV core antibody (anti-HBc) positive or hepatitis B surface antigen (HBsAg) donors can be safely used in order to expand the donor pool, considering adequate allocation and tailored prophylaxis after LT. In this review we have focused on the evolution of antiviral therapy for HBV, highlighting useful information to aid the transplant hepatologist in clinical practice.ReviewopenZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, Francesco PaoloZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, FRANCESCO PAOL
Hepatitis B virus infection as a neglected tropical disease
PCM is funded by a Wellcome Trust Intermediate Fellowship Grant (ref 110110/Z/15/Z).Publisher PDFPeer reviewe
Human Immunodeficiency Virus-Hepatitis B Virus (HIV-HBV) Coinfection
The global epidemics of hepatitis B and HIV have led to a new understanding of the complex interactions between these two viruses. Due to similar patterns of contamination, the high prevalence of HBV infection among the 33 million people living with HIV (PLHIV) across the world is about 10%. In highly endemic areas such as sub-Saharan Africa, this prevalence can be as high as 15% and leads us systematically to seek HIV/HBV co-infection. According to WHO, nearly 240 million people are chronically infected with HBV worldwide. Of these, 4 million are co-infected with HIV. Overall, co-infection rates range from 5 to 14% in areas of low prevalence of HBV infection and 5–73% in areas of high prevalence for HBV infection. Studies have revealed the complexity of the infection relationship between HIV and HBV. This complex relationship is thought to be responsible for greater morbidity and mortality of hepatic origin in co-infected patients than in mono-infected individuals. This chapter will highlight the following main points:
Concomitant negative impact of HIV and HBV on their natural histories
Implication of concomitant negative impact on the overall management of HIV-HBV coinfection
Treatment and management
Chronic hepatitis B
No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34785/1/510340622_ftp.pd
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