Response-guided treatment of cirrhotic chronic hepatitis B patients: Multicenter prospective study

AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection:A single-center retrospective observational study in China

Background:Infections still represent the main factors influencing morbidity and mortality following liver transplantation.This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation.Methods:We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital.Clinical manifestations and results of pathogen detection test were used to define infection.We analyzed the prevalence,risk factors and prognosis of patients with infection.Results:The median follow-up was 214 days;the incidence of infection after liver transplantation was 46.7%(n=98)which included pneumonia(43.4%),biliary tract infection(21.9%),peritonitis(21.4%)and bloodstream infection(7.6%).Among the pathogens in pneumonia,the most frequently isolated was Acinetobacter baumanii(23.5%)and Klebsiella pneumoniae(21.2%).Model for end-stage liver disease(MELD)score(OR=1.083,95%CI:1.045–1.123;P<0.001),biliary complication(OR=4.725,95%CI:1.119–19.947;P=0.035)and duration of drainage tube(OR=1.040,95%CI:1.007–1.074;P=0.017)were independent risk factors for posttransplant infection.All-cause mortality was 11.0%(n=23).The prognostic factors for postoperative infection in liver recipients were prior-transplant infection,especially pneumonia within 2 weeks before transplantation.Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection(65.2%vs.90.0%;hazard ratio:4.480;P<0.001).Conclusions:Infection,especially pneumonia within 2 weeks before transplantation,complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.

Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudine-based therapy

AIM: To compare the histological outcome of chronic hepatitis B(CHB) patients treated with entecavir(ETV) or lamivudine(LAM)-based therapy.METHODS: We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis(baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People's Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baselinecharacteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ2 test or Fisher's exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test.RESULTS: Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74%(18/19) of the patients in the ETV arm and 95.65%(22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/m L. The majority of the patients(94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM(P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients(P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients(P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy.CONCLUSION: CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.