Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants.

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. METHODS: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. RESULTS: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83-0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94-0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. CONCLUSIONS: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.

Frequency, characteristics and impact of multiple consecutive nosocomial infections in patients with decompensated liver cirrhosis and ascites.

BACKGROUND: Nosocomial infections are a particular threat for patients with liver cirrhosis. It is not uncommon that individuals develop even several consecutive infections during a single hospital stay. We aimed to investigate the impact and characteristics of multiple, consecutive nosocomial infections. METHODS: A total of 514 consecutive patients with liver cirrhosis and ascites were included and followed up for 28 days for nosocomial infection, death or liver transplantation (LTx). Laboratory values were assessed at the time of hospitalization as well as at the onset of each new infectious episode. RESULTS: 58% (n = 298) of the patients developed at least one nosocomial infection and in 23% (n = 119) even multiple infections were documented during a single hospital stay. Consecutive infections usually occurred shortly after the previous episode. Spontaneous bacterial peritonitis (SBP) was the most common infection. However, the proportion of SBP declined from 43% at the first to only 31% at the third nosocomial infection (p = 0.096). In contrast, the likelihood for other, less common types of infection such as blood stream infections increased. Third nosocomial infections were also more likely to be linked to the detection of fungal pathogens (21% vs. 52%; p = 0.001). Each additional infectious episode had a dramatic detrimental impact on LTx-free survival that was independent from the stage of liver disease (adjusted-HR: 6.76, p = 0.002 for first nosocomial infection; adjusted-HR: 14.69, p<0.001 for second nosocomial infection; adjusted-HR: 24.95, p<0.001 for third nosocomial infection). CONCLUSION: In patients with decompensated liver cirrhosis LTx-free survival significantly decreases with every consecutive infectious episode. Development of prevention strategies is urgently required.