Incidence Of Cirrhosis Research Articles

Hepatocellular Carcinoma Extrahepatic Metastasis in Relation to Tumor Size and Alkaline Phosphatase Levels

Background: Hepatocellular carcinoma (HCC) is known to metastasize. However, there are few reports on patients with metastasis at the time of HCC diagnosis. Aims: To evaluate the incidence and characteristics of extrahepatic metastasis patients presenting at baseline with noncurable, advanced HCC. Results: The total HCC cohort was initially dichotomized into 2 subcohorts, with (n = 214) and without (n = 719) extrahepatic metastasis (‘metastasis'), and patient baseline characteristics were compared. The main findings for patients with metastasis (22.9% of total cohort) compared with other, nonmetastatic patients were: more advanced tumors, as judged by larger tumor diameters, more tumor multifocality and percent with portal vein thrombosis, higher blood α-fetoprotein and des γ-carboxy prothrombin levels and alkaline phosphatase (ALKP), but not bilirubin levels, and a lower incidence of cirrhosis. There was a strong correlation between increases in tumor size and percent of patients with metastasis. A subset of patients with larger tumors was identified with low blood ALKP levels and better survival. Survival in the total metastasis cohort was lower than in the non-metastasis cohort, as expected, but only in patients with smaller tumors. In patients with larger tumors, survival with or without metastasis was similar and poor. Conclusions: There was a lower incidence of cirrhosis in HCC patients with metastasis, and they had larger and more aggressive primary tumors. Patients with smaller, but not larger, tumors and metastasis had worse prognosis than patients without metastasis. A distinct subset of metastatic patients was identified that had better prognosis and low ALKP levels.

Metabonomics: the future of personalized healthcare in liver intensive care?

Metabonomics involves the use of high-resolution analytical platforms to characterize the low-molecular-mass metabolic composition of biofluids and tissues. The resulting complex metabolic phenotype data are modelled using multivariate statistical approaches to identify systems levels panels of metabolites that discriminate between phenotypes (metabotypes), providing mechanistic insight and candidate biomarkers. With the increasing incidence of liver cirrhosis nationally, the pressures on NHS liver units is set to intensify, with mortality rates in these patients remaining high. This article describes a personalized medicine approach to stratify patients' mortality risk using metabolic phenotyping. This could aid doctors in clinical decision-making for patient transplant candidacy and critical care management to improve current survival rates.

Relationship of hepatic fibrosis, cirrhosis, and mortality with cholecystectomy in patients with hepatitis C virus infection.

Studies have suggested that cholecystectomy is a risk factor for nonalcoholic fatty liver disease, but it is not known whether cholecystectomy is a risk factor for the progression of other chronic liver diseases such as hepatitis C virus (HCV) infection. The aim of this study was to assess whether cholecystectomy is associated with an increase in fibrosis, cirrhosis, and cirrhosis-related complications in patients with chronic HCV infection. Among a total of 3989 HCV-positive patients at the VA North Texas Health Care System, we retrospectively reviewed the records of 88 patients who had undergone cholecystectomy between 1998 and 2013, followed up for a median of 4.9 years. We compared the outcomes of these patients with those of two age-matched, race-matched, and sex-matched cohorts: a cohort consisting of 129 HCV-positive patients without gallbladder disease (GBD) and a second cohort consisting of 178 HCV-positive patients with GBD who had not undergone cholecystectomy. Demographics, presence of metabolic syndrome, alcohol use, laboratory data, and clinical progression of liver disease were compared at study entry and 5 years later. Controlling for multiple factors associated with increase in liver fibrosis, analyses confirmed that a there was an increase in the proportion of patients who developed cirrhosis [odds ratio (OR)=3.24, 95% confidence interval (CI) 1.57-6.68, P=0.001] and ascites (OR=3.01, 95% CI 1.14-7.97, P=0.026) as well as in the incidence of death (OR=6.29, 95% CI 2.13-18.59, P=0.001) 5 years after cohort entry among HCV-positive patients with cholecystectomy compared with HCV-positive controls. The HCV-positive patient group with previous cholecystectomy showed an increased incidence of cirrhosis (OR=2.43, 95% CI 1.34-4.41, P=0.004), hepatocellular carcinoma (OR=2.85, 95% CI 1.11-7.36, P=0.030), and death (OR=3.31, 95% CI 1.50-7.28, P=0.003) 5 years after cohort entry compared with HCV-positive controls with GBD who had not undergone cholecystectomy. Cholecystectomy among HCV-positive patients is associated an increased incidence of fibrosis, cirrhosis, and its complications (ascites, hepatocellular carcinoma, and death) compared with HCV-positive controls and HCV-positive patients with GBD who have not undergone cholecystectomy.

A Histo-Pathological Study of Liver in 118 Cases of Cirrhosis

The day has not arrived when predictive value of liver disease can be given like many laboratory tests. Autopsy studies provide us with useful baseline data to start a step towards achieving good morphological accuracy. The present study compromised of 118 cases of cirrhosis detected from the period January 2008 to December 2013. 3960 autopsies done during this period were scrutinized and 824 cases had liver pathology. Out of the 824 cases 118 had cirrhosis as the liver pathology, which makes incidence of cirrhosis at autopsy as 14.3% of all liver pathology, which shows a decreasing incidence of cirrhosis which may be due decrease in autopsy rate over the years, the reasons for the continuing decline are complex and include attitudes toward autopsies of hospital administrative staff, medical staff, and family members and also because of increase in diagnosis by liver biopsy and introduction of antifibrotic therapy.

Epitope Mapping of a Long Peptide Candidate for Diagnosis of Hepatitis C - Evaluation of the Antigenicity by the Multiple Antigen Blot Assay (MABA)

Epitope Mapping of a Long Peptide Candidate for Diagnosis of Hepatitis C - Evaluation of the Antigenicity by the Multiple Antigen Blot Assay (MABA) Hepatitis C is a worldwide public health problem by its high prevalence and relevance and the impact in the high incidence of liver cirrhosis and liver cancer. Previous studies identified the peptide IMT-286 (40 mer), located in the core of the virus as a possible candidate to be used in the diagnosis of Hepatitis C by ELISA. The synthesis of long peptides in addition to its higher cost may be limited by undesirable reactions (cycling, deletions, etc.) that impede the synthesis. Therefore, we decided to reduce its size by selecting the potential epitopes of this sequence, whether corresponded to continuous or discontinuous primary sequences. For this, different peptide sequences were synthesized and evaluated for their antigenicity (SPOT mapping) by the pep scan strategy. Two peptides of Core antigen showed the highest sensitivities, peptide IMT-1700 (26 mer), located in the central region, presented a 59.09% recognition by sera from infected patients by the Multiple Antigen Blot Assay (MABA), while the IMT-286 (40 mer) peptide showed a recognition of 70.45 % The alkaline phosphatase conjugate showed a better sensitivity than the peroxidase conjugate with Luminol® as a substrate by MABA.

How Far we are towards Eradication of HBV Infection

Hepatitis B virus (HBV) infection is a major health problem with an important biological and a significant socio-economic impact all over the world. There is a high pressure to come up with a new and more efficient strategy against HBV infection, especially after the recent success of HCV treatment. Preventing HBV infection through vaccine is currently the most efficient way to decrease HBV-related cirrhosis and liver cancer incidence, as well as the best way to suppress the HBV reservoir. The vaccine is safe and efficient in 80-95% of cases. One of its most important roles is to reduce materno-fetal transmission, by giving the first dose of vaccine in the first 24 hours after birth. Transmission of HBV infection early in life is still frequent, especially in countries with high endemicity. Successful HBV clearance by the host is immune-mediated, with a complex combined innate and adaptive cellular and humoral immune response. Different factors, such as the quantity and the sequence of HBV epitope during processing by dendritic cells and presenting by different HLA molecules or the polymorphism of T cell receptors (TOL) are part of a complex network which influences the final response. A new potential therapeutic strategy is to restore T-cell antiviral function and to improve innate and adaptive immune response by immunotherapeutic manipulation. It appears that HBV eradication is far from being completed in the next decades, and a new strategy against HBV infection must be considered.

Biomarker panels and regression of fibrosis in chronic viral hepatitis.

Thanks to non-invasive blood diagnosis panels of liver lesions such as FibroMax and liver elastography (transient and real-time), the entire perception of the disease has been transformed in such a way that the patient will get within 20 minutes the exact status of the illness, prognostic information and predictability of treatment response. Predetermined cutoffs of biomarkers of fibrosis and activity are used to rank the severity of liver disease from low-risk status to cirrhosis (F4.1 – not decompensated, F4.2 – varices only and F4.3 – decompensated), and to follow-up fibrosis dynamics. Despite the efficient drugs with high rates of viral cure (SVR) in HCV chronically infected patients (CHC), and suppression in HBV chronic carriers (CHB) that lead to the improvement of long-term prognosis of patients, the non-invasive evaluation of fibrosis remains important for staging fibrosis and even cirrhosis severity and is still an independent negative predictor for the response rates to treatments. CHC patients with cirrhosis had lower response rates to second and even third generation interferon-free (DAA) containing therapy (JAMA 2014). Sensitive biomarkers such as FibroTest are extremely useful in cured HCV patients for tracking the remaining risk of hepatocellular carcinoma (HCC) estimated to be about 5% at 10 years after SVR, patients that are supposed to not regress fibrosis. The presence of two or more metabolic factors is a strong risk predictor of non-regression of fibrosis after SVR (J Hepatol 2014). Fibrosis progression rates are higher in HIV-HCV coinfected than in non-HIV patients, in both SVR and not treated; SVR was associated with a slower regression of fibrosis and a worrisome remaining risk of HCC, higher than in HCV monoinfected patients (J Hepatol 2014). In CHB patients, despite effective virus suppression under NUC, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC at 10 years. Almost all (93%) HBV carriers that developed HCC being under efficient viral suppression had fibrosis progression during repeated evaluation using FibroTest (J Hepatol 2014). Clinicians have to continue to estimate fibrosis dynamics despite viral cure (CHC) or viral control (CHB) as fibrosis can continue to progress in more than 10% of patients. Noninvasive biomarkers demonstrated to be efficient for the screening of steatohepatitis and fibrosis in metabolic–risk subjects (i.e., diabetics, hyperlipemics, overweight) (APT 2014). Notably, an Italian screening in the GP having ultrasound steatosis identified as high as 13% prevalence of presumed severe fibrosis using FibroMax panel (Ann Hepatol 2013). In the era when liver germs are endangered, it sounds good that the metabolic factor-oriented screening strategy (SS) seems the most sensitive selective for liver diseases, better than the alcohol-oriented and the standard HCV/HBV-oriented strategy (BMC Gastroenterology 2010).

Clinical characteristics of 4132 patients with alcoholic liver disease

To study the clinical characteristics of patients with alcoholic liver disease (ALD). The records of the 302 Hospital of People's Liberation Army (Beijing, China) were searched to identify patients diagnosed with liver disease for retrospective analysis of ALD. Measurement data was summarized as mean +/- standard deviation and intergroup comparisons were made using ANOVA; count data was assessed using the chi-square test. Among the total 4132 ALD cases, 97.68% were male and 2.32% were female; ages ranged from 18 to 95 years-old,with the average age being 48.11+/-10.58 years and the range of 40 to 60 years-old being the most frequently represented.Considering all patients with liver disease from 2003 to 2012,ALD cases increased over time (from 2.00% in 2003 to 5.05% in 2012). The overall ALD cases were represented by alcoholic cirrhosis (70.35%), alcoholic hepatitis (19.26%), alcoholic fatty liver (6.29%), and alcoholic liver failure (4.09%). Among the ALD patients between 40 and 60 years of age, 73.81% had cirrhosis,compared to 50.42% of ALD patients less than 40 years-old (P less than 0.001). Comparison of ALD cases in 5-year increments showed increasing trends in rates of alcoholic cirrhosis and alcoholic hepatic failure;moreover, there was an increasing annual trend in the percentage of alcoholic liver failure cases among the total cases of liver failure in our hospital. From 2003 to 2012,our hospital admissions increased for patients with alcoholic liver disease, and the patients were primarily in the age range of 40-60 years-old. In general, incidences of alcoholic liver failure and cirrhosis increased in recent years, and cirrhosis has been common among the elderly patients with ALD.

Bacterial infections in alcoholic and nonalcoholic liver cirrhosis

Longitudinal, population-based data on the occurrence, localization, and severity of bacterial infections over time in patients with alcoholic compared with nonalcoholic cirrhosis are limited. All patients with incident cirrhosis diagnosed in 2001-2010 (area of 600,000 inhabitants) were retrospectively identified. All bacterial infections resulting in or occurring during an inpatient hospital episode during this period were registered. The etiology of cirrhosis (alcoholic vs. nonalcoholic), infection localization, and outcome as well as bacterial resistance patterns were analyzed. Patients were followed until death, transplant, or the end of 2011. In all, 633 cirrhotics (363 alcoholic, 270 nonalcoholic) experienced a total of 398 infections (2276 patient-years). Among patients diagnosed with cirrhosis each year from 2001 to 2010, increasing trends were noted in the occurrence of infection (from 13 to 27%, P<0.001) and infection-related in-hospital mortality (from 2 to 7%, P=0.05), the latter mainly in the alcoholic group. Although alcoholic etiology was related to the occurrence of more frequent infection (Kaplan-Meier, P<0.001), this relationship was not significant after adjustment for confounders in Cox regression analysis (P=0.056). Resistance to piperacilin-tazobactam and carbapenems was more common in infections occurring in alcoholic versus nonalcoholic cirrhosis (13 vs. 5%, P=0.057 and 12 vs. 2%, P=0.009). Alcoholic etiology predicted pneumonia and infections caused by Gram-positive bacteria in multivariate analysis (P<0.05 for both). In a population-based cirrhotic cohort, bacterial infections increased over time, which, in the case of alcoholic cirrhosis, was associated with pneumonia and bacterial resistance to antibiotics. However, alcoholic etiology was not related indepedently to the occurrence of bacterial infections.

Trends in Burden of Cirrhosis and Hepatocellular Carcinoma by Underlying Liver Disease in US Veterans, 2001–2013

Cirrhosis and hepatocellular carcinoma (HCC) are predicted to increase in the United States but the accuracy of prior forecasts and the contributions from various liver disease etiologies remain unclear. We aimed to determine the burden of cirrhosis and HCC according to underlying cause from 2001 to2013. We developed a national retrospective cohort of Veterans Affairs (VA) patients with the diagnosis of cirrhosis (n= 129,998) or HCC (n=21,326) from 2001 to 2013. We used laboratory results, International Classification of Diseases, ninth edition (ICD-9) codes, and body mass index to identify underlying etiologies. In 2013, VA provided care to 5,720,614 individuals, of whom 60,553 (1.06%) had cirrhosis and 7,670 (0.13%) had HCC. Hepatitis C virus (HCV) was present in an increasing proportion of cirrhosis and HCC between 2001 and 2013, reaching 48% of cirrhosis cases and deaths and 67% of HCC cases and deaths by 2013. Cirrhosis prevalence nearly doubled from 2001 to 2013 (664 to 1058 per 100,000 enrollees), driven by HCV and nonalcoholic fatty liver disease (NAFLD). Cirrhosis incidence ranged from 159 to 193 per 100,000 patient-years. Deaths in patients with cirrhosis increased from 83 to 126 per 100,000 patient-years, largely driven by HCV. HCC incidence was 2.5-fold increased from 17 to 45 per 100,000 patient-years. HCC mortality tripled from 13 to 37 per 100,000 patient-years, driven overwhelmingly by HCV, with much smaller contributions from NAFLD and alcoholic liver disease. Cirrhosis prevalence and mortality and HCC incidence and mortality increased from 2001 to 2013, driven by HCV, with a smaller contribution from NAFLD. If current trends continue, cirrhosis prevalence will peak in 2021. Health care systems will need to accommodate rising numbers of patients with cirrhosis and HCC.

Long-term follow-up for incident cirrhosis among pediatric cancer survivors with hepatitis C virus infection

BackgroundPediatric cancer patients who received blood transfusions were potentially exposed to hepatitis C virus (HCV) prior to second-generation HCV screening of blood products in 1992. Limited evidence is available about long-term incident cirrhosis in this population. ObjectivesWe aimed to estimate the overall and sex-specific incidence of cirrhosis among HCV-seropositive survivors of pediatric cancer. Study designWe identified 113HCV-seropositive pediatric cancer patients treated at St. Jude Children’s Research Hospital between 1962 and 1997, who survived ≥5 years post-diagnosis, and were followed through 2014. Our outcome was cirrhosis determined by liver biopsy or diagnostic imaging. We used a competing-risk framework to estimate the overall and sex-specific cumulative incidence and 95% confidence limits (CL) of cirrhosis at 10-year follow-up intervals. ResultsThe median duration of follow-up was 30 years (interquartile range=28–36) post-cancer diagnosis. Cumulative incidence of cirrhosis increased at each 10-year interval from 0% after 10 years to 13% after 40 years (Ptrend<0.001). The median age at diagnosis of cirrhosis was 30 years (interquartile range=24–38). We observed a linear trend in incidence for males (Ptrend<0.001), with a cumulative incidence of 18% (95% CL: 6.1%, 34%) after 40 years. The cumulative incidence for females was 6.5% (95% CL: 0.42%, 26%) after 40 years, but we did not observe a linear trend (Ptrend=0.99). ConclusionOur results suggest that the incidence of cirrhosis is similar between HCV-seropositive pediatric cancer survivors and the general population given similar duration of follow-up, but survivors may be diagnosed with cirrhosis at an earlier age.

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia.

BackgroundThe prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.MethodsAn age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.ResultsIn the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.ConclusionsThe HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.

Risk of liver cirrhosis in patients with tuberculosis: a nationwide cohort study.

Most of the previous reports found cirrhosis patients with a high risk of subsequent tuberculosis (TB). However, data about the risk of developing liver cirrhosis in TB patients are limited. As a hepatitis endemic area, the risk of liver cirrhosis in patients with TB should be elucidated in Taiwan. We conducted the study using Taiwan's National Health Insurance Research Database. Patients with TB (n=9339) were identified as the TB cohort and matched with a control (n=37356). Each study participant was followed until diagnosis of liver cirrhosis, loss of follow-up, death, withdrawal from the insurance or until 31 December 2011. A cumulative incidence of liver cirrhosis in the TB cohort had a significantly higher risk for liver cirrhosis compared with the control (log-rank test, P<0·001). The overall incidence of liver cirrhosis was significantly higher in the TB group than in controls [3·83 vs. 2·02 per 1000 person-year; crude hazard ratio (HR)=1·88; 95% confidence interval (CI)=1·59-2·23]. After controlling for age, gender and comorbidities, the risk was 1·79-fold (95% CI=1·50-2·14) higher in the TB group than in the controls. Analysis by Cox proportional hazard regression revealed that TB increased the risk of cirrhosis in patients with either hepatitis B (adjusted HR=1·91; 95% CI=1·05-3·47) or hepatitis C (adjusted HR=2·56; 95% CI=1·37-4·78). An increased incidence of liver cirrhosis was observed among TB patients in Taiwan.

PWE-090 Does my patient–s normal liver biopsy mean they won't develop liver disease?

Introduction Liver biopsy remains a commonly used investigation amongst patients with abnormal liver biochemistry and normal serology, both in the diagnosis and staging of liver disease. Although commonly considered the “gold standard” it typically samples approximately 1/50,000thof the total liver mass and as such diffuse liver disease could plausibly be missed.1It is associated with complications of pain and bleeding and has a small but appreciable mortality (0.01–0.17%).2We report follow up data from a Nottinghamshire cohort of patients with abnormal liver biochemistry and normally reported liver biopsy between 1992–2001. We aim to assess whether a normal liver biopsy in the context of abnormal liver biochemistry is protective against development of and death from chronic liver disease. Method Patients with a normally reported liver biopsy and abnormal liver chemistry from Nottingham University Hospitals between 1992–2001 were identified from retrospective scrutiny of local Histopathology databases. Patient notes and computer records as of 1stJanuary 2015 were analysed to assess mortality, cause of death (where applicable), and development of cirrhosis. Office of National Statistics (ONS) UK population data was used to provide a comparable “control” group. Results 171 patients were identified. 32 (18.7%) were known to have died by 1stJan 2015. Of those who had died, 2 (6.5%) had hepatocellular carcinoma secondary to cirrhosis recorded as cause of death. This figure is significantly higher than the 1.53% of deaths attributed to liver disease in the UK population in 2010.3We intend to report on the incidence of cirrhosis in the remainder of the cohort as compared to a matched control population. Conclusion Our data suggest that a normal liver biopsy in the presence of abnormal liver biochemistry does not protect against future death from complications of chronic liver disease. We question whether alternative non-invasive markers of fibrosis could potentially have comparable or superior value in predicting development of cirrhosis and death from liver disease in this patient group. Disclosure of interest None Declared. References Guido M, Rugge M. Liver biopsy sampling in chronic viral hepatitis. Semin Liver Dis. 2004;24(1):89–97 Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. BSG. See comment in PubMed Commons below Gut. 1999;45(Suppl 4):IV1–IV11 Office of National Statistics – Mortality statistics – England and Wales, 2010

OC-018 Obesity and type 2 diabetes are predominant risk factors underlying previously undetected cirrhosis in the general population

<h3>Introduction</h3> Epidemiological studies have attributed the rising cirrhosis incidence and mortality in the UK predominantly to excess alcohol consumption. However, obesity acts synergistically with alcohol to increase the risk of cirrhosis. In addition, asymptomatic liver disease goes undetected; as a result nearly 50% of cirrhotics are diagnosed when presenting with hepatic decompensation. We utilised Transient Elastography (TE) to screen at-risk individuals in the general population, aiming to establish the prevalence of undetected liver cirrhosis and the risk factors underlying these cases. <h3>Method</h3> The study was undertaken in 4 general practices in Nottingham between February 2012 and September 2014. The total adult patient population was 20,868. Patients with pre-defined risk factors for chronic liver disease (hazardous alcohol use as identified by general practitioner (GP), type 2 diabetes and/or persistent ALT rise with negative serology) were identified from the GP electronic records and invited for TE even if liver enzymes were normal. TE was performed by trained nurses at the general practice sites. Liver stiffness of ≥8 kilopascals prompted review by a Consultant Hepatologist and liver cirrhosis was confirmed by established histological, radiological and biochemical methods. <h3>Results</h3> Of 2,022 patients eligible, 919 attended TE; 899 (97.8%) had valid liver stiffness measurements. Elevated liver stiffness was detected in 230 patients (25.6%) and cirrhosis in 26 (2.9%). Liver enzymes were normal in 16/26 (61.5%) of cirrhosis cases. Prior to the study, 23 patients with cirrhosis (aetiologies: alcohol (14), viral hepatitis (5), Non-alcoholic steatohepatitis (1), other (3)) had been identified; a diagnosed cirrhosis prevalence which was not significantly different compared to general population estimates of 76.3 cases per 100,000. Following the study, the prevalence of cirrhosis diagnosis was 49/20,868 (234.8 cases per 100,000 (95% CI 201.3–268.3)) was 3 fold higher than the previous general population estimate. Risk factors for new cirrhosis diagnoses were obesity and/or type 2 diabetes in 16 patients (61.5%), alcohol alone in 3 (11.5%) and both alcohol and obesity and/or diabetes in 7 (26.9%). <h3>Conclusion</h3> Investigating defined risk factors for liver disease using TE in a community setting detects a significant amount of previously unidentified cirrhosis. Cirrhosis prevalence in the general population is at least 3 times recent UK estimates. Obesity and type 2 diabetes are the predominant risk factors underlying previously undetected cirrhosis cases. <h3>Disclosure of interest</h3> None Declared.

Rates of cirrhosis and hepatocellular carcinoma in chronic hepatitis B and the role of surveillance: a 10-year follow-up of 673 patients.

Background and objectivesDevelopment of cirrhosis and hepatocellular carcinoma (HCC) are critical milestones in the natural history of chronic hepatitis B virus (HBV) infection. There are no prospective data on the risk of these critical milestones in HBV patients in Singapore. The efficacy and justification of HCC surveillance is determined by the rate of HCC development. Our study aims to determine the rates of cirrhosis and HCC in HBV patients in Singapore and hence the appropriateness of HCC surveillance.Materials and methodsA total of 673 HBV patients were enrolled between March 2003 and March 2004 and followed up for 10 years with regular surveillance for HCC using α-fetoprotein and abdominal ultrasound.ResultsOverall, 62.6% of the patients were men, mean age 56.4 years. In all, 31% were hepatitis B e antigen-positive and 14.9% had cirrhosis at baseline. Seventy-four patients developed cirrhosis and 42 patients developed HCC after 10 years. The overall 10-year incidence of cirrhosis and HCC was 16.2% (1.6%/year) and 7.8% (0.8%/year), respectively. The overall incidence of HCC in cirrhotics was 29.7% (3.0%/year), highest within a year of diagnosis of cirrhosis (7.9%). The rate of cirrhosis was significantly higher in those aged more than 55 years (P=0.001). Sex and hepatitis B e antigen status did not affect the rate of cirrhosis. Factors with significantly higher overall rates of HCC were age 55 years or more (P=0.001), male sex (P=0.001), and baseline α-fetoprotein of 4.1 µg/l or more (P<0.0001). However, age more than 55 years was not significant in the development of HCC in cirrhotics.ConclusionThe rate of cirrhosis in HBV patients in Singapore is about 1.6% per year. The rate of HCC is about 0.8% per year overall and 3.0% per year in cirrhotics, which justifies HCC surveillance.

Clinical analysis of pulmonary infection in patients with hepatitis B virus-related acute-on-chronic liver failure

Objective To investigate the clinical features of pulmonary infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). Methods A total of 666 hospitalized patients with HBV-ACLF in Department of Liver Disease of Fuzhou Infectious Diseases Hospital were retrospectively analyzed. Data of demographic and clinical parameters (sex, age, presence of liver cirrhosis and diabetes), complications (spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, and upper gastrointestinal hemorrhage), and baseline biochemical parameters were collected from the medical records database. Univariate and multivariate regression analyses were performed to determine the independent risk factors of pulmonary infection in patients with ACLF. Distributions of the pathogenic bacteria were further analyzed. Student t test was used for the means consistent with normal distribution, while non-parametric statistics were used for the data consistent with abnormal distribution. Mann-Whitney U test was used for the data between two groups. Chi square test and Fisher exact probability method were used for comparing the count data. Results A total of 125 out of 666 patients with ACLF developed pulmonary infection. The incidence of pulmonary infection was 18.76% (125/666). Most patients were infected with fungi (54.84%). The incidence rate of pulmonary infection in patients with liver failure over 60 years (41.18%) was significantly higher than that in patients under 60 years (16.91%; χ2=19.136, P<0.01). The incidence of cirrhosis or diabetes in the 125 patients with pulmonary infection was higher than patients with no pulmonary infection. The difference between the two groups was statistically significant (P<0.01). Levels of albumin, cholesterol, alpha-fetoprotein, white blood cell count, hemoglobin, plasma thromboplastin antecedent, international normalized ratio (INR), and serum sodium were all significantly different between the two groups (all P<0.05). The incidence of spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy in patients with pulmonary infection were significantly higher than those without pulmonary infection (P<0.01). Spontaneous bacterial peritonitis, age, albumin, hemoglobin and serum sodium were important factors in the development of the pulmonary infection. And albumin, hemoglobin and serum sodium were protective factors. Conclusions Pulmonary infection, as one of the common and serious complications, significantly affects the prognosis of liver failure patients. Prediction of pulmonary infection in the early stage is essential. Patients with elder age, spontaneous bacterial peritonitis, low albumin level, low serum sodium level and low hemoglobin level should be timely monitored to prevent the development of pulmonary infection. Key words: Hepatitis B virus; Liver failure; Pneumonia; Prognosis; Regression analysis

Su1079 Changes in the Incidence and Prevalence of Cirrhosis in the National Veterans Administration Over a Decade: 2002-2012

BACKGROUND: Cirrhosis is associated with a high morbidity and mortality, and is a risk factor for hepatocellular carcinoma. Yet there is limited information regarding the burden of cirrhosis from population-based studies in the U.S. We aimed to determine the annual incidence and prevalence of cirrhosis as well as time trends in the underlying etiology in a national veterans cohort. METHODS: Using the Veterans Administration Corporate Data Warehouse, we calculated the time trends in the annual incidence and prevalence of overall cirrhosis and decompensated cirrhosis between 2002 and 2012. In addition to the overall trends, we also examined the time trends by subgroups based on the underlying etiology for liver disease. We defined cirrhosis on the basis of previously validated ICD-9 code based algorithms. We used direct standardization method to adjust the time trends for changing age of the cohort (where 2002 VA population used as standard), and used joinpoint regression models to determine the magnitude of these time trends (by calculating average annual percentage change (AAPC)). RESULTS: The age-adjusted incidence rates of cirrhosis per 100 persons slightly increased from 0.22 (95% CI 0.21-0.22) in 2002 to 0.23 in 2012 (95% CI 0.23-0.24). The average annual percentage change (AAPC) in the age-adjusted incidence was 1.76% (p<0.05). The age-adjusted prevalence of cirrhosis per 100 persons increased steeply (AAPC=6.75%) from 0.62 (95% CI 0.61-0.63) in 2002 to 1.27 (95% CI 1.26-1.28) in 2010 and then the rate of increase slowed (AAPC=1.69%) between 2010-2012 to 1.36 (95% CI 1.35-1.37) in 2012. The prevalence of decompensated cirrhosis increased in parallel (0.46 in 2002 to 0.72 in 2012 per 100 persons). There were 68,760 and 41,780 patients with a diagnosis of cirrhosis and decompensated cirrhosis, respectively, who received care in VA facilities in 2012. Figures 1 and 2 shows the trends in overall incidence and prevalence of cirrhosis by etiology. HCV was the leading underlying etiology. In 2002, 47% of prevalent cirrhosis cases had HCV; this proportion increased to 53% in 2012. The proportion of cirrhosis patients with alcohol as the underlying etiology fell slightly from 29.8% in 2002 to 26.1% in 2012, whereas those with HBV remained stable at 0.9% to 1.2%. CONCLUSION: The prevalence of cirrhosis and decompensated cirrhosis has increased significantly over the last decade, and the trend is still upwards. Most patients with cirrhosis have underlying HCV, and successful diffusion of treatment may change the future trajectory of cirrhosis burden. Yet, given the existing and large burden of cirrhosis (and its complications), clinicians and healthcare system need to develop strategies targeted to provide timely and effective care to this high-risk patient population.

Antiviral therapies and prospects for a cure of chronic hepatitis B.

Current therapies of chronic hepatitis B (CHB) remain limited to either pegylated interferon-α (Peg-IFN-α), or one of the five approved nucleoside analog (NA) treatments. Although viral suppression can be achieved in the majority of patients with high-barrier-to-resistance new-generation NAs (i.e., entecavir and tenofovir), HBsAg loss is achieved in only 10% of patients with both classes of drugs after a follow-up of 5 years. Attempts to improve the response by administering two different NAs or a combination of NA and Peg-IFN-α have been unsuccessful. Therefore, there is a renewed interest to investigate a number of steps in the hepatitis B virus (HBV) replication cycle and specific virus-host cell interactions as potential targets for new antivirals. Novel targets and compounds could readily be evaluated using both relevant in vitro and newly developed in vivo models of HBV infection. The addition of one or several new drugs to current regimens should offer the prospect of markedly improving the response to therapy, thus reducing the burden of drug resistance, as well as the incidence of cirrhosis and hepatocellular carcinoma (HCC).

Predictors of mortality among patients with compensated and decompensated liver cirrhosis: the role of bacterial infections and infection-related acute-on-chronic liver failure

Objective. Population-based data on the impact of bacterial infections on the course of compensated and decompensated cirrhosis as well as the occurrence, predictors of infection-related acute-on-chronic liver failure (ACLF) and its fatal outcome are limited. Material and methods. All patients with incident cirrhosis in the period 2001–2010, residing in an area of 600,000 inhabitants, were retrospectively identified. All serious bacterial infections (resulting in or occurring during an inpatient hospital episode) during this period were analyzed. Infection site and acquisition type, comorbid illness (Charlson comorbidity index) and infection severity features were analyzed. Patients were followed up until death, transplant, or the end of 2011. Results. Overall, 398 serious bacterial infections occurred in 241/633 (38%) patients (106/332 diagnosed with compensated and 135/301 with decompensated disease; follow-up time was 2276 patient-years). ACLF occurred in 95/398 (24%) serious infections with an in-hospital mortality of 50%. In logistic regression analysis, the model for end-stage liver disease score, active alcohol misuse and healthcare-associated infections were predictors of infection-related ACLF (p < 0.05 for all). In-hospital mortality in infections with ACLF was related to albumin levels, Charlson comorbidity index >1 and occurrence of one or more organ failures (p > 0.05 for all). In Cox regression analysis, infection-related ACLF was an independent negative predictor of transplant-free survival in decompensated patients (p = 0.049). Conclusions. In a population-based cirrhotic cohort, infection-related ACLF was a negative predictor of survival in decompensated disease. Infection-related ACLF was frequent and related to cirrhosis severity and infection acquisition type, as well as to high inpatient mortality, in particular in patients with significant comorbidity.