Durability and on-treatment predictors of recompensation in entecavir-treated patients with hepatitis B and decompensated cirrhosis.

Background & Aims: Hepatic recompensation may be achieved in patients with decompensated cirrhosis due to chronic hepatitis B (CHB) upon effective suppression of viral replication by nucleos(t)ide analogues (NAs). However, the optimal timing and predictors of recompensation and the subsequent clinical course of patients with CHB with vs. without recompensation are not well-defined. Methods: This study was a retrospective extension of a multi-centre prospective cohort, focusing on patients with CHB and decompensated cirrhosis treated with entecavir. We followed patients beyond treatment week 120 until a second decompensation event or June 2023. We identified the optimal timing and predictors of recompensation by week 120, evaluated durability of recompensation in patients fulfilling recompensation criteria by week 120 and examined late recompensation in those who did not fulfil it by week 120. Results: At treatment week 24, serum albumin ≥34 g/L predicted recompensation by week 120. The Brec-PAS model offered good predictive ability for recompensation by week 120. Of the 283 patients who finished 120 weeks of therapy, 175 were followed beyond week 120 (median follow-up: 240 weeks). Among the 106 patients achieving recompensation by week 120, 92 (86.8%) maintained recompensation for another 120 (72-168) weeks. Among the 69 patients without recompensation by week 120, 40.6% attained late recompensation during the subsequent 120 (72-168) weeks. Additionally, hepatocellular carcinoma incidence was lower in the recompensated group (5.0% vs. 16.13%, p = 0.002). Conclusions: A serum albumin ≥34 g/L at treatment week 24 predicted recompensation by week 120. Recompensation achieved by week 120 of NA treatment is maintained in >80% of patients in the long term. Some patients may achieve recompensation only after >120 weeks of NA treatment. The incidence of hepatocellular carcinoma was reduced but not completely abolished after recompensation. Impact and implications: Our research provides a meaningful contribution to understanding the long-term prognosis of recompensation in patients with chronic hepatitis B and decompensated cirrhosis, as well as to evaluating the predictive value of serum albumin levels, offering a comprehensive view of clinical outcomes after recompensation. The significance of early biomarkers in guiding therapeutic decisions is highlighted, shedding light on the continued benefits and possible risks after recompensation. This enhances the capability for more precise prognostic evaluations and informed therapeutic strategies. For healthcare providers, these insights afford a detailed perspective on patient monitoring and intervention planning, underscoring the need for ongoing assessment past the initial recompensation phase.

Validation of Baveno VII criteria for recompensation in entecavir-treated patients with hepatitis B-related decompensated cirrhosis.

BACKGROUND & AIMS: Antiviral therapy improves the clinical outcomes of patients with chronic hepatitis B (CHB), including those with cirrhosis. In the present study, we validated the Baveno VII definition of recompensation and explored the criteria for stable improvement of liver function tests in entecavir-treated patients with CHB-related decompensated cirrhosis. METHODS: In this multicentre prospective study, patients with decompensated (ascites) CHB-related cirrhosis were enrolled and treated with entecavir for 120 weeks. Patients were followed up for clinical events, viral and biochemical tests, and ultrasonography every 6 months. The recompensation rate per Baveno VII criteria was calculated. Multivariate regression models were used to identify the predictors of recompensation. Finally, the criteria for stable improvement of liver function tests were explored. RESULTS: Of the 320 recruited patients, 283 completed the 120-week study, with 261/283 (92.2%) achieving HBV DNA levels <20 IU/ml and 171/283 (60.4%) achieving resolution of ascites, encephalopathy, and absence of recurrent variceal bleeding for at least 12 months. We identified model for end-stage liver disease <10 and/or liver function tests within Child-Pugh Class A (albumin >35 g/L, international normalised ratio <1.50 and total bilirubin <34 µmol/L) as the criteria for stable improvement of liver function tests. Accordingly, 56.2% (159/283) of patients fulfilled the Baveno VII definition of recompensation with a stable improvement of liver function tests defined by the current study. CONCLUSIONS: Our study defined the criteria for a stable improvement of liver function tests required by the Baveno VII definition of recompensation in patients with CHB-related decompensated cirrhosis on antiviral therapy. The criteria derived from this multicentre prospective study warrant further validation in patients with cirrhosis of other aetiologies. LAY SUMMARY: Decompensation of cirrhosis marks the point at which the liver is no longer able to function normally (and symptoms become apparent). Recently the idea of recompensation was proposed for individuals who may experience an improvement in liver function if the underlying cause of their liver disease is addressed (e.g. antivirals for viral cirrhosis). Herein, we show that over 50% of patients with hepatitis B-related decompensated cirrhosis treated with antivirals could recompensate and we propose laboratory criteria which could be used to define recompensation.

Evaluation of an antigen assay for diagnosing acute and chronic hepatitis E genotype 4 infection.

BACKGROUND AND AIM: Results obtained from different hepatitis E virus (HEV) tests are usually inconsistent. The detection of serum HEV antigen (Ag) has been suggested to be more sensitive for the diagnosis of genotypes 1 and 3 HEV. METHODS: We compared the diagnostic accuracies of serum HEV Ag and HEV RNA by using 202 serum samples from patients suspected acute viral hepatitis. RESULTS: The HEV Ag assay was 100% specific. The lower detected levels of viremia ranged from 102 to 103  copies/mL. The sensitivity of the HEV Ag test was 90.5%. One of the 42 cases was negative for anti-HEV IgM, but HEV Ag was still detectable. The detectable period of HEV Ag was in concordance with the detectable period of HEV RNA. Serum HEV Ag was persistently detected in two cases of chronic hepatitis E, confirmed by the persistent presence of HEV RNA despite being negative for anti-HEV IgM. HEV Ag demonstrated good consistency with positive HEV RNA (k = 0.938, P < 0.001). Receiver operating characteristic analysis of HEV Ag suggested a second cut-off value of >0.095 to predict HEV patients with 95.24% sensitivity and 98.75% specificity, and the area under the curve was 0.9887, which was higher than that of three commercial anti-HEV IgM ELISA tests. CONCLUSIONS: The presence of HEV Ag has good consistency with HEV RNA in both acute and chronic genotype 4 hepatitis E. HEV Ag is a more promising serum marker to identify active genotype 4 HEV infection than anti-HEV IgM and HEV RNA.

Outcome of hepatitis C virus infection in Chinese paid plasma donors: a 12-19-year cohort study.

BACKGROUND AND AIMS: Commercial plasma donation was introduced in China in the 1970s. Cases of non-A, non-B hepatitis (hepatitis C) continued to occur, with multiple outbreaks among plasma donors in Guan county, Hebei province between 1972 and 1990. The outcomes of hepatitis C virus (HCV) infection in these paid plasma donors from six villages of Guan county were followed up for 12-19 years. METHODS: A total of 402 plasma donors with HCV infection were enrolled since anti-HCV-positive in 1991 or 1998. Follow up was maintained until death or the end of the observation period. No antiviral treatment was applied during the period of infection. RESULTS: Follow up was lost in 23 cases. After a 12-19-year follow up, 31 donors died, with the cause of death directly related to liver disease in 15 cases, and an overall mortality of 8.18% (31/379). The incidence of liver cirrhosis was 10.03%, and hepatocellular carcinoma (HCC) was 2.90%. The rate of viral spontaneous clearing was 20.32% (77/379), and 13.69% (23/168) in males and 25.59% (54/211) in females. In May 2010, detections were performed in 348 cases. Abnormality of liver function was related to HCV viremia. Sex and alcohol intake impacted the outcome of HCV infection. There was no correlation between the viral spontaneous clearance with age of infection and genotype. CONCLUSIONS: This area has a high rate of chronicity in HCV infection due to plasma donation. Twenty-five years after virus infection, liver cirrhosis or HCC developed in one-tenth of patients, with an overall mortality of 8.18%.

[Thirteen to fourteen years' follow-up of patients with hepatitis C].

OBJECTIVE: To investigate the clinical outcomes and hepatic histology of patients with hepatitis C. METHODS: Nine patients with hepatitis, 4 males and 5 females, aged 44 +/- 7, who were infected during transfusion or blood donation underwent follow-up for 13 approximately 14 years: liver histological examination by biopsy, ultrasonography, biochemical examination of alanine transaminase (ALT), apartate aminotransferase (AST), and total bilirubin (TBIL), serum anti-HCV by ELISA, and HCV RNA quantification by PCR. RESULTS: ALT were higher than the normal value at every time point and HCV RNA remained positive (3.57 x 10(8) approximately 7.21 x 10(9) copies/L) in all patients. Ultrasonography showed mild and moderate hepatitis (3 and 6 cases respectively). The modified histological activity indices (HAI) were 5.0 approximately 8.5 and the fibrosis scores were 1 approximately 4. The ALT value was higher in the moderate cases than in the mild cases, and higher in those with higher HAI. The viral load was higher in the patients infected by the virus of the genotype 1b than in the patients infected by the virus of the genotype 2. CONCLUSION: The clinical outcomes and hepatic histology of patients with hepatitis C seem not very severe.

[Analysis of prognosis of patients with decompensated liver cirrhosis using the criterion of the Model of End-Stage Liver Disease].

OBJECTIVE: To investigate the relationship between the Model for End-Stage Liver Disease (MELD) with Child-Pugh scoring, and the prognosis of patients with decompensated liver cirrhosis. METHODS: 110 patients with decompensated liver cirrhosis were graded with MELD formula and with Child-Pugh. The death rate was observed within three months. RESULTS: 31 patients died within 3-months. The mortality of patients whose MELD scores were between 10 approximately 19, 20 approximately 29, and > or = 30 was higher than those with MELD < or = 9 (The mortality of those with MELD less than 9, 10 approximately 19, 20 approximately 29, or > or = 30 was 11.76%, 38.18%, 64.71%, 75.00% respectively). The mortality of patients whose MELD scores were > or = 18 was higher than those with MELD < 18 (The mortality of those with MELD < 18, MELD > or = 18 was 26.58%, 58.06% respectively. chi2 = 9.643). The mortality of Child A, B, C was 14.89%, 42.55%, 75% respectively. CONCLUSION: Both MELD and Child-Pugh scores can accurately predict the short-term prognosis of patients with decompensated liver cirrhosis.