Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis.

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Successful treatment of infantile hepatitis B with lamivudine: A case report.

BACKGROUND: How to treat infantile hepatitis B virus (HBV) infection remains a controversial issue. The nucleoside analogue lamivudine (LAM) has been approved to treat children (2 to 17 years old) with chronic hepatitis B. Here, we aimed to investigate the benefit of LAM treatment in infantile hepatitis B. CASE SUMMARY: A 4-mo-old infant born to a hepatitis B surface antigen (HBsAg)-positive woman was found to be infected by HBV during a health checkup. Liver chemistry and HBV seromarker tests showed alanine aminotransferase of 106 U/L, HBsAg of 685.2 cut-off index, hepatitis B "e" antigen of 1454.0 cut-off index, and HBV DNA of > 1.0 × 109 IU/mL. LAM treatment (20 mg/d) was initiated, and after 19 mo, serum HBsAg was entirely cleared and hepatitis B surface antibody was present. The patient received LAM treatment for 2 years in total and has been followed for 3 years. During this period, serum hepatitis B surface antibody has been persistently positive, and serum HBV DNA was undetectable. CONCLUSION: Early treatment of infantile hepatitis B with LAM could be safe and effective.

Analysis of the UGT1A1 Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution.

OBJECTIVE: The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the UGT1A1 genotypes in hyperbilirubinemia patients from southeastern China. METHODS: We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3-76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the UGT1A1 gene by direct sequencing. RESULTS: For patients with Gilbert syndrome, 85% (47/55) harbored pathogenic variants of UGT1A1⁎60. Both UGT1A1⁎28 and UGT1A1⁎81 were detected in the promoter region of UGT1A1. Additionally, 83% (20/24) of patients with Gilbert syndrome heterozygous for UGT1A1⁎60 had an association with heterozygous variation of UGT1A1⁎28 or UGT1A1⁎81, while 91% (21/23) of Gilbert syndrome patients homozygous for UGT1A1⁎60 had biallelic variations of UGT1A1⁎28 and UGT1A1⁎81. We detected 213 UGT1A1 allelic variants, including six novel variations, with the most frequent allele being the UGT1A1⁎60, followed by UGT1A1⁎28 and UGT1A1⁎6. All of the patients showed multiple sites of variants in UGT1A1; however, variation number was not associated with bilirubin levels (P>0.05). CONCLUSIONS: The spectrum of UGT1A1 variants in southeastern Chinese patients was distinct from other ethnic populations. Our findings broaden the knowledge concerning traits associated with UGT1A1 variants and help profile genotype-phenotype correlations in hyperbilirubinemia patients.

Baseline HBsAg predicts response to pegylated interferon-α2b in HBeAg-positive chronic hepatitis B patients.

AIM: To evaluate the predictive effect of baseline hepatitis B surface antigen (HBsAg) on response to pegylated interferon (PEG-IFN)-α2b in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS: This retrospective analysis compared the treatment efficacy of PEG-IFN-α2b alone in 55 HBeAg-positive CHB patients with different baseline HBsAg levels. Serum HBV DNA load was measured at baseline, and at 12, 24 and 48 wk of therapy. Virological response was defined as HBV DNA < 1000 IU/mL. Serum HBsAg titers were quantitatively assayed at baseline, and at 12 and 24 wk. RESULTS: Eighteen patients had baseline HBsAg > 20 000 IU/mL, 26 patients had 1500-20000 IU/mL, and 11 patients had < 1500 IU/mL. Three (16.7%), 11 (42.3%) and seven (63.6%) patients in each group achieved a virological response at week 48, with a significant difference between groups with baseline HBsAg levels > 20000 or < 20000 IU/mL (P = 0.02). Thirteen patients had an HBsAg decline > 0.5 log10 and 30 patients < 0.5 log10 at week 12; and 6 (46.2%) and 10 (33.3%) in each group achieved virological response at week 48, with no significant difference between the two groups (P = 0.502). Eighteen patients had an HBsAg decline > 1.0 log10 and 30 patients < 1.0 log10 at week 24, and 8 (44.4%) and 11 (36.7%) achieved a virological response at week 48, with no significant difference between the two groups (P = 0.762). None of the 16 patients with HBsAg > 20000 IU/mL at week 24 achieved a virological response at week 48. CONCLUSION: Baseline HBsAg level in combination with HBV DNA may become an effective predictor for guiding optimal therapy with PEG-IFN-α2b against HBeAg-positive CHB.

[The studies on clinical value of AFP-L3 detected by microspincolum method for judgment of treatment response in patients with HCC undergoing TACE].

OBJECTIVE: To explore the clinical value of Lens culinaris agglutinin-reactive alpha-fetoprotein detected by microspincolum method for judgment of treatment response in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization. METHODS: Twenty eight patients with HCC undergoing TACE follow-up in hospital were recruited. AFP and AFP-L3 were measured in all the patients before and after TACE, and correlations were analyzed between AFP-L3% and response to treatment. RESULTS: Among the twenty eight patients with HCC undergoing TACE, 8 out 11 case in AFP-L3% descent group had well treatment response, 5 out 17 case in AFP-L3% elevated group had well treatment response(Chi2 = 4. 858, P < 0. 05). CONCLUSIONS: The detection of AFP-L3 by microspincolum method is useful to judgment of treatment response in patients with HCC undergoing TACE.

[Indigenous and imported low molecular weight heparin in the treatment of chronic hepatitis B and cirrhosis with hepatitis B virus: a prospective randomized controlled clinical study].

OBJECTIVE: To evaluate the effect of indigenous and imported low molecular weight heparin (LMWH) in the treatment of chronic hepatitis and hepatic cirrhosis aiming at seeking a safe and effective anti-fibrosis therapy. METHODS: A prospective randomized controlled clinical study of the treatment of patients with chronic hepatitis B using indigenous and imported LMWH was performed. Seventy-five patients were randomly divided into three groups: conventional treatment group (n=15), conventional treatment plus imported LMWH treatment group (n=30) and conventional treatment plus indigenous LMWH treatment group (n=30). The clinical parameters and treatment results in three groups were compared. RESULTS: Three weeks after treatment, Child-Pugh scores in LMWH treatment groups were significantly lower than that in conventional treatment group (all P<0.05), hepatic function, serum PIII P and type IV collagen levels and portal vein blood flow velocity were much better (all P<0.05), levels of serum prealbumin were significantly elevated (all P<0.05). There were no significant differences between two groups with LMWH treatment. Subcutaneous hemorrhage, incidence of hematoma was lower (10.0% vs. 33.3%, P<0.05), area of ecchymosis was smaller [(0.004 2+/-0.012 7) cm(2) vs. (0.01 64+/-0.027 8) cm(2), P<0.05], and pain was released (8.3% vs. 81.0%, P<0.05) in conventional treatment plus indigenous LMWH treatment group than in conventional treatment plus imported LMWH treatment group. CONCLUSION: LMWH in combination with conventional treatment for patients with cirrhosis of liver, significantly improves the outcome, indigenous LMWH calcium is a safe and effective anti-fibrosis drug as imported LMWH, also the price is lower and pain is less intense during injection than the latter.

Association between TRAIL expression on peripheral blood lymphocytes and liver damage in chronic hepatitis B.

AIM: To explore a novel mechanism for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), upregulation of CD4(+) and CD8(+) T lymphocytes participating in the patho-physiological process of chronic hepatitis B (CHB). METHODS: The levels of serum soluble TRAIL (sTRAIL), serum IFN-gamma and membrane-bound TRAIL expression on peripheral leucocytes from 58 CHB patients were examined by ELISA and flow cytometry respectively. The levels of TRAIL were compared with the baseline levels of 17 healthy controls, and correlation analysis was performed between ALT, TBIL, PT, morphological change in hepatic tissues, and serum IFN-gamma. RESULTS: The results showed that TRAIL levels on membranes of CD4(+), CD8(+) T cells in CHB patients were much higher than those in healthy controls (P<0.001), and were correlated with serum TBIL (r = 0.354, P = 0.008 for CD4(+) and r = 0.522, P = 0.000 for CD8(+), respectively), ALT (r = 0.393, P = 0.003 for CD8(+)), PT (r = 0.385, P = 0.004 for CD8(+)) and serum IFN-gamma level (r = 0.302, P = 0.011 for CD4(+) and r = 0.307, P = 0.009 for CD8(+)). On the contrary to membrane-bound TRAIL expression, serum level of sTRAIL was not correlated with that of TBIL and PT, though it was higher than that of the normal population and was positively correlated with serum HBeAg expression (r = 0.695, P = 0.001). CONCLUSION: The expression level of TRAIL on the membrane of lymphocytes was upregulated and associated with the liver injury in CHB patients. These findings suggest that upregulation of TRAIL expression may be induced by virus antigen and inflammatory cytokine IFN-gamma.

[Involvement of TRAIL up-regulation of CD4+, CD8+ T cells in liver injury in chronic hepatitis B].

OBJECTIVE: To describe a novel mechanism for TRAIL up-regulation of CD4+, CD8+ T cells to participate in the pathophysiological process in patients with chronic hepatitis B (CHB). METHODS: The serum levels of soluble TRAIL (sTRAIL), IFN-gamma and membrane bound TRAIL expression on peripheral leucocytes from 58 CHB patients were examined by ELISA and flow cytometry respectively. The levels of TRAIL were compared with the baseline levels of 15 healthy controls, and correlation analysis were performed between ALT, TBil and PT, morphological change in hepatic tissues. RESULTS: The results showed that TRAIL levels on membranes of CD4+, CD8+ T cells in CHB patients were much higher than the healthy controls (P < 0.001), which of CD4+ T cells positively correlated with serum TBil (r=0.354, P = 0.008), Serum IFN-gamma level (r=0.302, P = 0.011) and which of CD8+ T cells positively correlated with serum TBil (r=0.522, P = 0.000), ALT (r=0.393, P = 0.003), PT (r=0.385, P = 0.004), serum IFN-gamma level (r=0.307, P = 0.009). The serum levels of soluble TRAIL only correlated with serum HBeAg expression (r=0.695, P = 0.001). CONCLUSION: These findings suggest that the expression of TRAIL on the membranes of lymphocytes was up-regulated, which may take part in the immunopathogenesis in CHB patients. TRAIL expression can be induced either by virus-specific protein expression or by inflammation cytokine IFN-gamma

[Modulation and implications in pathogenesis of interferon gamma receptor 1 in patients with chronic hepatitis B].

OBJECTIVE: To study the possible differences in the interferon gamma receptor (IFN-gamma R1) response among a variety of clinical types in patients with chronic hepatitis B (CHB) and implications in pathogenesis. METHODS: The serum level of IFN-gamma and the expression level of IFN-gamma R1 in peripheral leucocytes, from 53 CHB patients, were examined by ELISA and flow cytometry respectively, which were compared with the baseline levels of 15 healthy controls and were performed correlation analysis with alanine aminotransferase (ALT), total bilirubin (TBil) in serum and morphological change in hepatic tissues. RESULTS: The results showed that the level of IFN-gamma R1 (28.89% 11.77%) expressed on the membranes of lymphocytes in CHB patients, which correlated with liver inflammation (r=0.621, P<0.01) and serum TBil level (r=0.575, P<0.01), was much higher than that (9.23% 1.30%) of the healthy controls (Z=3.988, P<0.05), and no obvious difference on the membranes of leucocytes. The serum levels of IFN-gamma in patients with cirrhosis and severe hepatitis were higher than those of healthy controls. And the two was no difference from each other, but the standard deviation in each group was relatively large. CONCLUSION: These findings suggest that the IFN-gamma signal transduction pathway is modulated through up-regulating the expression of IFN-gamma R1 on the membranes of lymphocytes, which takes part in the immuno-pathogenesis in CHB patients.