Normal Alanine Aminotransferase Research Articles

Anemia and its association with glycemia and transaminitis in patients with type 2 diabetes mellitus: A cross-sectional pilot study

ABSTRACT Background and Aims: Anemia impairs glucose homeostasis, affects glycemic control, and predisposes to complications in diabetics. It correlates with oxidative stress and increases the risk of developing microvascular and macrovascular complications. However, it is an underrecognized comorbidity in diabetics. This study was conducted to assess the prevalence of anemia in diabetic patients and compare the metabolic profiles of anemic and non-anemic diabetics. Methods: This is a cross-sectional study, conducted among type 2 diabetes (T2DM) patients, at the outpatient clinic. Patients with chronic kidney disease (CKD), known hematological disorders, and chronic inflammatory disorders were excluded. Results: Of the 97 patients, 37 (38.14%) were found to be anemic (hemoglobin (Hb): male <13 g/dl, female <12 g/dl). The mean values of fasting blood sugar (FBS) in low and normal mean corpuscular volume (MCV) patients were 265.9 ± 43.7 mg/dl and 157.2 ± 7.2 mg/dl, respectively (P = 0.0026), and those of postprandial blood sugar (PPBS) were 370.3 ± 58.4 mg/dl and 226.3 ± 10.1 mg/dl, respectively (P = 0.0015). It was found that 6 (22.2%) of 27 patients with raised alanine aminotransferase (ALT) had anemia against 27 (45.8%) of 59 patients with normal ALT (P = 0.03). The mean Hb levels in patients with raised and normal ALT were 13.31 ± 2.3 gm% and 12.2 ± 2.0 gm% (P = 0.03), respectively. Conclusions: Blood sugar may have a direct relationship with MCV in T2DM patients. Hb tends to relate to hepatic enzymes likely due to altered dietary patterns in anemics. Further larger studies on the effect of iron supplementation and dietary habits on glycemic control and hepatic steatosis are warranted.

Unmet needs in autoimmune hepatitis: Results of the prospective multicentre European Reference Network Registry (R-LIVER).

The European Reference Network on Hepatological Diseases (ERN RARE-LIVER) launched the prospective, multicentre, quality-controlled R-LIVER registry on rare liver diseases. The aim of this study was to assess the presentation and outcome of autoimmune hepatitis (AIH) after 1 year of treatment. Data were prospectively collected at the time of diagnosis and after 6 and 12 months follow-up. Complete biochemical response (CBR) was defined as normalization of alanine aminotransferase (ALT) and immunoglobulin G (IgG) serum levels. A total of 231 patients from six European centres were included in the analysis. After 6 months of treatment 50% (106/212), and after 12 months 63% (131/210) of patients reached CBR with only 27% (56/211) achieving a steroid-free CBR within the first year. Overall, 16 different treatment regimens were administered. Change of treatment, mostly due to intolerance, occurred in 30.4% within the first 6 months. In multivariate analysis, younger age at diagnosis (odds ratio [OR] = 1.03 [95% confidence interval (CI) 1.01-1.05]; p = .007), severe fibrosis (OR .38 [95% .16-.89], p = .026) and change of treatment within the first 6 months (OR .40 [95% CI .2-.86]; p = .018) were associated with a lesser chance of ALT normalization at 12 months follow-up. The landscape of AIH treatment in Europe is highly heterogeneous, even between expert centres. The results from this first European multicentre prospective registry reveal several unmet needs, highlighted by the overall low rates of CBR and the frequent failure to withdraw corticosteroids.

Melatonin mitigated methotrexate-induced hepatotoxicity through interrelated biological processes.

Hepatotoxicity associated with methotrexate (MTX) is mainly due to disruption of redox balance and development of oxidative injury to hepatocytes. Melatonin (MLT) is a potent antioxidant and regulates wide range of biological functions, processes and utilized as adjuvant for number of medical applications. The current study investigated the mitigating effect of MLT on the MTX-induced hepatotoxicity. Adult male rats received MLT (25mg/kg, orally) for seven days flowed by single injection of MTX (20mg/kg, ip) then treat with MLT continued for additional 7days. The present result showed MLT treatment mitigated histopathological changes in the liver that associated with normalization of ALT and AST activity as well as bilirubin, albumin and alfa-fetoprotein levels in serum of MLT + MTX-treated rat to comparable control level. MLT treatment significantly reduced MDA content and myeloperoxidase activity while enhanced the activity of superoxide dismutase, catalase and glutathione content in the liver indicating the empowerment of the antioxidant status. Amelioration of MLT-induced oxidative stress resulted in a reduction in the inflammatory response due to antioxidant restoration and inhibited apoptosis indicated by downregulation of caspase-3 expression. The replenishment of antioxidant content powers the defense system of the hepatocytes. As a result, apoptosis is reduced which might be due to the ability of MLT protect DNA integrity thus maintaining hepatocyte functions and structure. Consequently, liver histology was protected. In summary, MLT modulates liver function and structure by orchestrating linked processes, including redox balance, inflammatory response, suppression of caspase-3, and DNA damage.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase (ALT) serum levels increase because of hepatocellular damage. Metabolic dysfunction-associated fatty liver disease (MAFLD), which identifies steatotic liver disease (SLD) associated with ≥ 2 metabolic abnormalities, has prominent sexual differences. The Metabolic Syndrome defines a cluster comprising abdominal obesity, altered glucose metabolism, dyslipidemia, and hypertension. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and age independently predict ALT levels among blood donors. Over the last few decades, the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges. With this backset, Chen et al have recently published a study which has two main findings. First, > 80% of individuals with MAFLD had normal ALT levels. Second, there was a linear increasing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD. This study has biologically credible findings. However, it inaccurately considered sex differences in the MAFLD arena. Therefore, future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase

BackgroundThe association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA.MethodsSix hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis.ResultsThe median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis.ConclusionLower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

Circulating metabolites are associated with persistent elevations of ALT in patients with chronic hepatitis B with complete viral suppression.

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

Association between BMI Change, Transaminases, and Other Metabolic Parameters in Children with Nonalcoholic Fatty Liver Disease.

Weight loss and lifestyle interventions are the mainstay of treatment in pediatric NAFLD. There are gaps in the literature on the objective improvement in BMI to meaningfully impact NAFLD in children. To determine the decrease in BMI associated with a significant decline in ALT and other metabolic parameters. Retrospective chart review of pediatric patients with the diagnosis of NAFLD. Data were collected at the baseline and 6 and 12 months. A linear regression model was used to assess the percent change in BMI predictive of change in ALT and other metabolic parameters. 281 charts were included. 71% of patients who had up to a 2.5% loss in BMI at 6 months had a decrease in ALT of up to 10 U/L compared to 43% patients who did not have a decrease in BMI up to 2.5% loss at the same time period (P=0.01). The linear regression model showed that 6-month and 12-month percent changes in BMI are predictive of 6-month and 12-month ALT changes (P=0.01 and 0.02), respectively. ALT normalization was achieved on 12% of patients with a ≥2.5% decrease in BMI at 6 months compared to 1% of patients that had no decrease of ≥2.5% decrease in BMI at 6 months (P=0.01). The mean BMI Z-score decline was 0.18 (P=0.001) in the group with a ≥2.5% decrease in BMI at 6 months. BMI loss of up to 2.5% and the mean BMI Z-score 0.18 are associated with a significant decrease in ALT of up to 10 U/L. BMI percent change at 6 months and 12 months is predictive of changes in ALT. These results should help guide providers in clinical practice set objective goals for the management of children with NAFLD resulting from obesity.

Idiopathic Immune Mediated Haemolytic Anaemia (IMHA) in a 2.5-Month-old Puppy: A Case Report

Background: A 2.5-month-old puppy was presented to the Veterinary Clinical Complex of the College of Veterinary Sciences and AH, Jalukie, Nagaland with a complaint of emesis for one week, inappetence, icterus of the lower abdominal area and other visible mucous membrane. Detailed clinical history was collected and clinical examination was conducted. Methods: 4 ml blood peripheral blood was collected from the cephalic vein in the Lev-Lock blood clot activator vacutainer to harvest serum for biochemical analysis. Another 2 ml of whole blood was also collected in Lev-Lock K3 EDTA vacutainer for complete blood count, blood smear examination for blood parasites, morphological changes in the RBC and IDEXX SNAP 4Dx Plus test kit was also used for diagnosis of the blood parasites test. Result: Peripheral blood smear examination and IDEXX SNAP 4Dx Plus test were found to be negative for blood parasites, but spherocytosis could be observed in the blood smears. A complete blood count (CBC) examination revealed severe anaemia of macrocytic normochromic type, neutrophilic leucocytosis and thrombocytopenia. Serum biochemistry revealed a decrease in blood urea nitrogen (BUN) and creatinine with normal alanine transaminase (ALT). Treatment with whole blood transfusion, corticosteroid and other supportive therapy was successful in this case. Based on the clinical presentation, laboratory findings and its response to the treatment with prednisolone, it was diagnosed as an idiopathic immune-mediated haemolytic anaemia (IMHA) with an extravascular mechanism of haemolysis. A follow-up review after 1 year and 4 months post-treatment reported that the dog was still alive and healthy.

Correlation of alanine aminotransferase levels and a histological diagnosis of steatohepatitis with ultrasound-diagnosed metabolic-associated fatty liver disease in patients from a centre in Nigeria

BackgroundMetabolic-associated fatty liver disease (MAFLD) is defined as the occurrence of hepatic fat accumulation in patients with negligible alcohol consumption or any other cause of hepatic steatosis. This study aimed to correlate the ultrasound-based diagnosis of MAFLD with the histological diagnosis of nonalcoholic steatohepatitis (NASH) and alanine aminotransferase (ALT) levels in patients with MAFLD.MethodsThis was a hospital-based cross-sectional study of 71 patients with MAFLD diagnosed by ultrasound. Percutaneous liver biopsy was performed for histological evidence of NASH in all patients, regardless of liver function test (LFT) values, provided that they had no contraindications. Liver histology was graded using the NASH Clinical Research Network MAFLD Activity Score. The data obtained were entered into SPSS version 21 and analysed using descriptive and inferential statistics. The significance level was set at < 0.05.ResultsA total of 71 patients (26 males and 45 females) with MAFLD were included. Thirty-nine (76.5%) patients with MAFLD and normal ALT levels had NASH, while 14 (82.4%) had elevated ALT levels. There was no statistically significant difference in the histological grade of NASH between patients with normal and elevated ALT levels. A weak correlation was found between the severity of steatosis on ultrasound scan and NASH incidence (p = 0.026). The sensitivity and specificity of ALT levels for predicting NASH according to the area under the receiver operating characteristics (AUROC 0.590) at an ALT cut-off value of 27.5 IU/L were 55.8% and 64.7%, respectively.ConclusionNASH can occur in patients with MAFLD, irrespective of alanine transaminase (ALT) levels, and ultrasound grading of the severity of steatosis cannot accurately predict NASH. Liver biopsy remains the investigation of choice.

Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial

Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24. In this ongoing, open-label, randomized phase 3 study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/mL from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA. Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independent of virologic response. Adverse events (AEs) were mostly mild, with no serious AEs related to BLV. Virologic and biochemical responses were maintained and/or increased with longer-term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96. In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2-mg and 10-mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96. NCT03852719.

A Comparison of Alanine Aminotransferase Normalization between Pemafibrate and Bezafibrate in Patients with Nonalcoholic Fatty Liver Disease.

Objective Pemafibrate is a recently developed selective peroxisome proliferator-activated receptor alpha modulator that can improve alanine aminotransferase (ALT) levels in patients with nonalcoholic fatty liver disease (NAFLD). However, the effectiveness of ALT normalization with pemafibrate and bezafibrate, a traditional fibrate, has not been compared. Methods In this retrospective study, we compared the effects of pemafibrate and bezafibrate on ALT normalization in patients with NAFLD. The primary endpoint was the ALT normalization rate at 12 months after administration. Patients Twenty and 14 patients with NAFLD receiving pemafibrate and bezafibrate, respectively, were included in this retrospective analysis. All patients had elevated ALT levels and dyslipidemia at entry. Results The ALT normalization rates at 3, 6, and 12 months were 40%, 55%, and 60% for pemafibrate and 14.3%, 28.6%, and 14.3% for bezafibrate, respectively. The ALT normalization rate at 12 months was significantly higher in patients treated with pemafibrate than in those treated with bezafibrate (p=0.01). Pemafibrate, when compared with bezafibrate, was shown to be a significant factor for ALT normalization in a multivariable analysis with an adjusted odds ratio (95% confidence interval) of 13.8 (1.6-115, p=0.01). Conclusion Pemafibrate is effective in ALT normalization in patients with NAFLD and may be used as a treatment for NAFLD.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA<20IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. This study included 309 patients with a median age of 59years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6months after switching (74.8%-83.5%; P=0.008). Adjusted eGFR significantly improved at 6months (+5.55±10.52mL/min/1.73m2; P<0.001) and 12months (+6.02±10.70mL/min/1.73m2; P<0.001) after switching. In the subgroup of patients with renal impairment (eGFR<60mL/min/1.73m2), significant improvement in renal function was observed at 6months (+0.6±10.5mL/min/1.73m2; P<0.001) and 12months (+1.0±10.7mL/min/1.73m2; P<0.001) after switching to TAF. In patients with osteoporosis (n=182), switching to TAF resulted in significant improvement in spine and hip BMD at 12months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Naif Kronik Hepatit B Tedavisinde Tenofovir Alafenamid: Tek Merkezli Retrospektif Çalışma

Kronik hepatit B (KHB), dünya çapında yaklaşık 257 milyon insanı etkileyen önemli bir küresel sağlık sorunudur. Tenofovir alafenamid (TAF), kronik hepatit B tedavisinde kullanılan yeni ve etkili bir antiviral ilaç olmakla birlikte tedaviye naif hastalarda TAF etkinliğine ilişkin gerçek dünya verileri sınırlıdır. Bu çalışmanın amacı, tedaviye naif KHB hastalarında TAF'ın etkinliğini değerlendirmektir. Virolojik yanıt ve alanin aminotransferaz (ALT) normalizasyonu ile ilişkili faktörler de çalışmada analiz edilmiştir. Çalışmaya Ocak 2021-Aralık 2022 tarihleri arasında TAF başlanan 41 tedavi naif KHB hastası dahil edilmiştir. Demografik, klinik ve laboratuvar verileri başlangıçta ve 48. haftada toplanmıştır. Birincil sonlanım noktaları tam virolojik yanıt (TVY) ve 48. haftada ALT normalizasyonu idi. 48. haftada ALT ve hepatit B virüsü-deoksiribonükleik asit (HBV DNA) düzeyleri istatiksel açıdan anlamlı olacak şekilde azalmıştır (her ikisi de p

HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA

ABSTRACT Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients.

After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase. All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed. The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: -1.5%, (95% CI: -6.4 to -3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, -2.85 mL/min vs. -3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF. The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.

Clinical outcomes of cessation of nucleoside/nucleotide analogues in Chinese patients with HBeAg-negative chronic hepatitis B

Background and aimsCessation of nucleoside/nucleotide analogue (Nuc) therapy in patients with HBeAg-negative chronic hepatitis B (CHB) remains controversial. MethodsIn this prospective, single-center cohort study, we recruited 45 patients with HBeAg-negative CHB from The Fifth Medical Center of Chinese People's Liberation Army General Hospital in mainland China. Patients were classified into a Nuc cessation group (n = 27) and Nuc continuation group (n = 18) and followed-up for 36 months. Nuc were stopped after being inactive for at least 4 years (normal alanine aminotransferase (ALT), undetectable hepatitis B virus (HBV) DNA), with liver fibrosis ≤ Stage1 (S1) and inflammation ≤ Grade (G1). ResultsWithin 3 years of follow-up, 51.9% patients with Nuc cessation had virological relapse and 14.8% had ALT elevation, while all patients with Nuc continuation had undetectable HBV DNA and normal ALT. The rate of HBsAg loss after Nuc cessation was 22.2% compared with no seroconversion in patients with Nuc continuation. The hepatitis flare rate was 11.1% and there were no cases of hepatic decompensation after Nuc cessation. End of treatment (EOT) HBsAg, HBV RNA, and decline in HBV core-related antigen (HBcrAg) rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation. ConclusionThis study showed favorable HBsAg loss and low hepatitis flare rates after Nuc cessation. EOT HBsAg, HBV RNA, and decline in HBcrAg rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.

Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage

BackgroundThe timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years.MethodsA retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system.ResultsThe liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels.ConclusionsA considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.

The efficacy of antiviral treatment in chronic hepatitis B patients with hepatic steatosis

Background & aimsWith a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. MethodsCHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. ResultsIn total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245–0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. ConclusionsAmong CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Immunological Remission as a Basis for Dose Reduction of Immunosuppressors in Autoimmune Hepatitis: Results of Monocenter Surveillance Study

Aim of the study: evaluate the role of normalization of humoral immunity to address dose reduction or discontinuation of immunosuppressors in patients with autoimmune hepatitis (AIH).Patients and methods. The data of 47 patients with AIH who received immunosuppressive therapy from April 2001 to August 2023 were analyzed: 10 men (21 %), 37 women (79 %); the average age was 37 (17–66) years. The follow-up period was 10–180 months. Type 1 AIH was diagnosed in 37 patients, type 2 AIH — in 7 patients, seronegative AIH — in 3 patients. The diagnosis was established according to the IAIHG point system. To confirm the diagnosis, a liver biopsy was performed in 17 patients, a histological picture of AIH was detected in all of them. The most used combination was prednisolone and azathioprine — in 25 patients (53.2 %), as well as methylprednisolone and azathioprine — in 8 patients (17 %).Results. In some patients, when the immunosuppressive therapy decreased below the recommended dose, a relapse of the disease developed (Group 1), and in others, remission persisted (Group 2). The concentration of гамма-globulins in patients of Group 1 was 22.5 mg%, in Group 2 — 17.95 mg% (p = 0.00055). IgG level after achieving remission in Group 1 was 1709.7 mg/dL, in Group 2 — 1381.7 mg/dL (p = 0.000001). The terms of ALT normalization in Group 1 were 2.14 months, in Group 2 — 1.47 months (p = 0.037); AST normalization in Group 1 made 2.22 months, in Group 2 — 1.48 months (p = 0.026).Conclusions. Normalization of humoral immunity, as well as rapid normalization of ALT and AST can be considered as markers of maintaining AIH remission when immunosuppressor doses are reduced below standard doses, and in individual patients — the possibility of immunosuppressive therapy withdrawal. This will reduce the risk of adverse events and increase adherence to the therapy. We propose introducing the term “immunological remission” into the clinical lexicon, which, along with biochemical and histological remission, acts as a predictor of persistent remission of AIH.