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Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.

BACKGROUND: The goal of treating chronic hepatitis B (CHB) is to achieve functional cure. We aimed to evaluate the efficacy of the combination of nucleoside (acid) analogues (NAs) and pegylated interferon (Peg-IFN) on the functional cure of CHB patients at the EOT and at the EOF. METHOD: PubMed, Embase, and Web of Science were searched systematically up to March 15, 2025. Sixteen RCTs on CHB patients receiving combination or monotherapy were included. RESULT: Compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 14.05, 95% CI 6.13-32.20) and HBsAg seroconversion rate (RR: 12.82, 95% CI 5.08-32.33) at the EOT. Moreover, compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 7.70, 95% CI 4.24-13.98), HBsAg seroconversion rate (RR: 11.93, 95% CI 5.14-27.67) at the EOF. However, compared with Peg-IFN monotherapy, the combination therapy group did not show any improvement in HBsAg clearance rate, HBsAg seroconversion rate, and the rate of qHBsAg decrease > 1 log10 IU/mL at the EOT and the EOF. Moreover, in terms of safety, the Peg-IFN monotherapy group showed more ALT flares (ALT > 5 × ULN) during the treatment process. CONCLUSION: Compared with NAs therapy, Peg-IFN combined with NAs therapy significantly improves functional cure rate. However, combination therapy shows no additional advantage over Peg-IFN monotherapy in achieving functional cure. The Peg-IFN monotherapy group has a higher incidence of ALT flares than the combination therapy group.

Humans

Prognosis of acute myocardial infarction complicated by complete heart block (the Worcester Heart Attack Study).

As part of a community-based study of patients hospitalized with acute myocardial infarction (AMI) in the Worcester, Massachusetts, metropolitan area, changes over time in the incidence rates of complete heart block (CHB) complicating AMI, and the prognostic impact of CHB on the in-hospital and long-term survival of these patients were examined. In all, 4,762 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area during 1975, 1978, 1981, 1984, 1986 and 1988 constituted the study sample. The incidence rates of CHB complicating AMI remained relatively stable at 5.8% over the 13-year (1975 to 1988) period studied. The incidence rates of CHB were approximately twice as high in patients with inferior/posterior wall AMI (7.7%) as in those with anterior wall AMI (3.9%). Use of a multivariate regression analysis to control for factors affecting the incidence rates of CHB revealed that patients were at highest risk for developing CHB during the latter 2 study years (1986 and 1988). Patients with AMI developing CHB had higher in-hospital case fatality rates than did those without CHB overall, as well as during each of the 6 periods studied. The in-hospital survival associated with CHB did not improve over time. After use of a multivariate regression analysis to control for additional prognostic factors, the independent effect of CHB on in-hospital prognosis remained (adjusted risk of dying = 2.10; 95% confidence intervals = 1.37, 3.21). Patients with inferior wall AMI complicated by CHB were at significantly increased risk of dying during hospitalization compared with those without CHB (adjusted risk of dying = 2.71; 95% confidence intervals = 1.60, 4.59).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Intrahepatic Exhausted Antiviral Immunity in an Immunocompetent Mouse Model of Chronic Hepatitis B.

BACKGROUND & AIMS: Targeting exhausted immune systems would be a promising therapeutic strategy to achieve a functional cure for HBV infection in patients with chronic hepatitis B (CHB). However, animal models recapitulating the immunokinetics of CHB are very limited. We aimed to develop an immunocompetent mouse model of CHB for intrahepatic immune profiling. METHODS: CHB mice were created by intrahepatic delivery of the Sleeping Beauty transposon vector tandemly expressing the hepatitis B virus (HBV) genome and fumarylacetoacetate hydrolase (FAH) cDNA into C57BL/6J congenic FAH knockout mice via hydrodynamic tail vein injection. We profiled the viral and intrahepatic immune kinetics in CHB mice with or without treatment with recombinant IFNα or the hepatotropic Toll-like receptor 7 agonist SA-5 using single-cell RNA-seq. RESULTS: CHB mice exhibited sustained HBV viremia and persistent hepatitis. They showed intrahepatic expansion of exhausted CD8+ T (Tex) cells, the frequency of which was positively associated with viral load. Recruited macrophages increased in number but impaired inflammatory responses in the liver. The cytotoxicity of mature natural killer (NK) cells also increased in CHB mice. IFNα and SA-5 treatment both resulted in viral suppression with mild hepatic flares in CHB mice. Although both treatments activated NK cells, SA-5 had the capacity to revitalize the impaired function of Tex cells and liver-recruited macrophages. CONCLUSIONS: Our novel CHB mouse model recapitulated the intrahepatic exhausted antiviral immunity in patients with CHB, which might be able to be reinvigorated by a hepatotropic TLR7 agonist.

Animals

The relative risk of spontaneous complete atrioventricular block in elderly patients with impaired intra-ventricular conduction.

We reviewed 144 consecutive patients with symptomatic high grade atrioventricular block. Cases due to congenital heart disease, acute myocardial infarction, cardiac surgery or digitalis toxicity were excluded. Of the remaining, we chose 71 patients in whom atrioventricular conduction was observed either intermittently during complete heart block (CHB) or in electrocardiograms taken within two years prior to documentation of CHB. The mean age was 69 years, with the peak incidence in the seventh decade in 43 men and eight decade in 28 women. Bundle branch block (BBB) was present in 76% of patients as follows: 47% had right BBB (20% with normal QRS axis, 20% with left axis deviation and 7% with right axis deviation), 17% had left BBB (11% with normal QRS axis and 6% with left axis deviation) and 12% had either alternating BBB, right BBB with alternating axis deviation or atypical BBB. "Trifascicular block" patterns accounted for 21% of the total group of CHB. We also studied the prevalence of various patterns of BBB in a group of 2000 random hospital patients of comparable age and sex exclusive of those with acute myocardial infarction and heart surgery. The risk of CHB for the various patterns of BBB was calculated relative to normal intraventricular conduction. All patterns of BBB carried a considerably increased relative risk of CHB, (P smaller than .01). The relative risk was highest for RBBB with left axis deviation and lowest for LBBB with normal or left axis deviation. In the men, 74% had QRS patterns of "bifascicular" or "trifascicular" block during atrioventricular conduction. By contrast, 71% women had atrioventricular beats showing either no BBB or right BBB with normal QRS axis. QRS pattern during CHB was unchanged from that during atrioventricular conduction in 52% if cases (rabge 38%-76% with different QRS patterns) suggesting idiojunctional pacemaker. CHB in these cases was thought to be due probably to coexistent disease in the AV node or His bundle. Although the concept of uni-, bi- and trifascicular block patterns has been useful in identifying patients at greater risk of CHB, the predictability of the electrocardiogram has obvious limitations, particularly in women.

Aged

Hemodynamic changes during ventricular pacing in patients with complete heart block and aortic and mitral valvular heart disease.

Increasing the heart rate to near normal in patients with complete heart block (CHB) and slow ventricular rates may lead to greater improvement in ventricular function than when the heart rate is increased from normal to more rapid heart rates. Improvement in ventricular function is usually manifested by a decrease in left ventricular end-diastolic pressure (LVEDP) and volume and by an increase in contractility. In patients with both CHB and valvular heart disease improvement in ventricular function during pacing may be modified by the nature of the valvular disease. Hemodynamic data from six patients with both valvular heart disease and CHB were compared with those from ten patients with CHB and normal cardiac valves. Hemodynamic studies were performed at slow or idioventricular rates and again after increasing the heart rate to more nearly normal levels by ventricular pacing. When obstruction to left ventricular inflow (mitral stenosis) co-existed with CHB, increasing the heart rate resulted in a reduction of an elevated LVEDP to normal. This resulted in only a small increase in left atrial pressure in spite of a striking increase in the mean left atrial-ventricular gradient. When obstruction to left ventricular outflow prevailed (aortic stenosis), improvement in cardiac function was manifested mainly by a decrease in LVEDP and was accompanied by a decrease in left ventricular stroke work. When a large regurgitant volume (aortic insufficiency) was added to a ventricle which has enlarged subsequent to CHB, there was striking elevation in ventricular filling pressures which returned to more nearly normal levels when the heart rate was increased. This was accompanied by a reduction in regurgitant stroke volume in the patient in whom it was measured. Thus, an increase in heart rate may be especially beneficial to those patients with CHB who also have valvular lesions which contribute to an increase in LVEDP and end-diastolic volume. Careful hemodynamic evaluation is helpful in determining appropriate therapy in these patients.

Aged

Prognosis of patients with complete heart block or arrhythmic syncope who were not treated with artificial pacemakers. A long-term follow-up study of 101 patients.

This paper reports the results of a retrospective study carried out with special reference to the survival rate in a series of 101 selected cases including patients with complete heart block (CHB) combined or not combined with Adams-Stokes attacks and patients with arrhythmic syncope without ECG evidence of CHB. All these patients were treated in our Department during 1958-68, none being artificially paced. Twenty-seven patients were alive at the end of the follow-up, i,e 6-15 years after admission to this Department on account of syncopal episodes or CHB. The survival rate--higher in females than males--was lower in the cases of CHB combined with Adams-Stokes attacks than in the cases of asymptomatic CHB. This applied also to the instances in which a complicating disease such as ischaemic heart disease (IHD), hypertension, diabetes, digitalis intoxication or cardiac enlargement coexisted. The survival rate in the 68 cases of CHB was higher at one year (68%) as well as at 5 years (37%) than that reported by other investigators. When assessing the survival rate in cases treated with artificial pacemakers, it is important to study the individual case histories with special reference to a previous or coexisting condition such as IHD, hypertension, diabetes or the presence of cardiac enlargement. The present results support the view that the indications for treatment with artificial pacing should be wide, albeit that the prognosis in this series was more favourable than might have been anticipated from observations by others.

Adams-Stokes Syndrome

[The course and outcome of chronic hepatitis B in children].

Overall 98 children aged 1 to 14 years suffering from chronic hepatitis B (CHB) were followed up clinically for 1 to 6 years. CHB was diagnosed on the basis of the clinical and laboratory data. In the majority of the children, the diagnosis was verified by the results of a histological study of liver biopsy specimens. Chronic active hepatitis (CAH), was revealed in 27 children, chronic persistent hepatitis (CPH) in 31. CHB was marked by the presence of HBe-antigenemia in 89 patients (90.8%). The studies have demonstrated that CHB associated with HBe-antigenemia runs its course with insignificant clinical manifestations and enzymic exacerbations without jaundice. In the presence of persistent HBs-antigenemia, the natural course of CHB (in CAH and CPH) is characterized by seroconversion (from HBeAg to anti-HBe) with a simultaneous decrease and normalization of aminotransferase activity and a reduction of the pathological process activity in the liver (transformation of CAH to CPH). Seroconversion and clinico-biochemical amelioration supervene at different observation periods (after 1-6 years) and do not depend on the initial activity of hepatitis. As the observation period increases, the rate of anti-HBe appearance in the blood rises, amounting to 90% with the observation period exceeding 5 years. The conclusion is made that CHB patients do not need active drug therapy but require long and permanent observation.

Adolescent

Prognosis of right bundle branch block and left anterior hemiblock after intracardiac repair of tetralogy of Fallot.

One hundred and forty-one survivors of intracardiac repair of tetralogy of Fallot (TOF), operated on between 1958 and 1972, were studied in order to document the incidence of right bundle branch block and left anterior hemiblock (RBBB and LAH) and to definite the late prognosis. RBBB and LAH occurred in 31 patients (22 per cent), all of whom have had complete follow-up. Transient complete heart block (CHB) occurred postoperatively in 2 patients; there were no other significant arrhythmias. Two late deaths have occurred, neither from arrhythmia (one from progressive congestive heart failure, and the other from attempted reclosure of a ventricular septal defect). The remainder of the patients are well an average of 76 months postoperatively (range, 144 to 12 months). The absence of late-onset CHB or sudden death in this series contrasts with the relatively high incidence of these events in some studies of RBBB and LAH after intracardiac repair of TOF. However, in those reports a history of transient postoperative CHB (indicative of trifascicular disease in this setting) can be found in 75 per cent of those who developed late-onset CHB or died suddenly. We conclude that the occurrence of RBBB and LAH after intracardiac repair of TOF does not of itself carry a bad late prognosis. The critical factor in a bad late prognosis in patients with ECG evidence of RBBB and LAH may be with ECG evidence of RBBB and LAH may be the history of transient postoperative CHB.

Adolescent