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Guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) expanded the indications for antiviral therapy in patients with chronic hepatitis B. The guidelines recommend to initiate antiviral therapy for patients with chronic HBV infection who have a normal alanine aminotransferase (ALT) level, positive HBV DNA, and an age of >30 years. However, for pregnant women aged >30 years, no consensus has been reached on whether to start antiviral therapy immediately. Some experts believe that pregnant women with a normal ALT level are mostly in the immune-tolerant phase, and antiviral therapy tends to have an unsatisfactory therapeutic effect; in addition, medication during pregnancy may affect the safety of mothers and fetuses. Therefore, it is not recommended to start antiviral therapy immediately in early pregnancy even if the pregnant women are aged >30 years. Other experts believe that immune changes of the body during pregnancy may be a special period for HBV immune clearance, and if the patients are aged >30 years, antiviral therapy should be initiated immediately even if the patient has a normal ALT level; pregnant women may get better virologic and even serological response. With a focus on the above issues, this article elaborates on the purpose, treatment timing, and drug withdrawal timing of antiviral therapy during pregnancy.
ABSTRACT
Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.
Subject(s)
Humans , Drugs, Chinese Herbal/therapeutic use , Fibrosis , Liver Diseases/drug therapy , Treatment Outcome , Liver Cirrhosis/drug therapyABSTRACT
The main transmission route of chronic hepatitis B virus infection is mother-to-child transmission of hepatitis B virus and the main cause of combined immune prophylaxis failure in neonates at the end of pregnancy is high viral load. Moreover, oral administration of nucleos(t)ide analogues (NAs) during the second and third trimesters of pregnancy can significantly reduce or even completely block mother-to-child transmission of HBV. This article focuses on the necessity and feasibility of oral NAs antiviral therapy for HBV carrier pregnant woman with high viral load, and the issues commences at the time of medication and viral load thresholds.
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Objective@#To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection.@*Methods@#A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve.@*Results@#Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2–5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log10 IU/ml and (3.95 + 0.40) log10 IU/ml; t = 8.465, P < 0.001).@*Conclusion@#Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.
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Objective@#To explore the difference of liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV) infection, and to investigate the relationship between hepatic pathology and alanine aminotransferase (ALT).@*Methods@#57 patients with chronic HCV infection and 346 patients with chronic HBV infection who were hospitalized at Shengjing Hospital of China Medical University from January 2012 to September 2016 were enrolled. In chronic HBV infection, including 88 cases whose ALT were more than two times of upper limited of normal (ALT≥2×ULN) and 258 cases whose ALT were less than two times of upper limited of normal (ALT < 2×ULN).All the patients were underwent liver biopsy. Chronic HBV infection (ALT≥2×ULN and ALT < 2×ULN) and chronic HCV infection were compared respectively. Statistical analyses were performed using a Univariate χ²-test and Mann–Whitney U test for comparison. Correlations between variables were analyzed using Spearman's rank correlation.@*Results@#In chronic HBV infection group, 169 cases (48.8%) had inflammation grade≥2 (G≥2), 98 cases (28.3%) had fibrosis stage≥2 (S≥2), 81 cases (23.4%) with G≥2 and S≥2.In the ALT < 2×ULN group, there were 109 cases (42.2%) with G≥2, 62 cases (24%) with S≥2, 49 cases (19%) with G≥2 and S≥2. In the ALT≥2×ULN group, 60 cases (68.2%) with G≥2, 35 cases (39.8%) with S≥2, 31 cases (35.2%) with G≥2 and S≥2. The grade of inflammation and fibrosis have significantly different between ALT≥2×ULN group and ALT < 2×ULN group (χ² = 17.66, χ² = 8.06, P < 0.01). In chronic HCV infection group, 47 cases (82.5%) with G≥2, 20 cases (35.1%) with S≥2, 20 cases (35.1%) with G≥2 and S≥2. ALT had no correlation with inflammation and fibrosis (P > 0.05). The grade of inflammation was significantly different between chronic HCV infection and chronic HBV infection whose ALT < 2×ULN (χ² = 30.19, P < 0.01) but the fibrosis have no difference (χ² = 2.96, P > 0.05). Compared with chronic HBV infection whose ALT≥2×ULN, both inflammation and fibrosis had no significantly different (χ² = 3.65, χ² = 0.32, P > 0.05 respectively).@*Conclusion@#In chronic HBV infection whose ALT < 2×ULN, about 30%-40% liver tissue with significant necroinflammation and /or fibrosis. About 80% chronic HCV infection with significant necroinflammation, and the grade of inflammation has no correlation with ALT. The grade of inflammation has significantly different between chronic HCV infection group and chronic HBV infection group whose ALT < 2×ULN.
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<p><b>OBJECTIVE</b>To assess the relationship between nodular goiter and hepatitis C virus infection.</p><p><b>METHODS</b>Ninety-seven cases of early treatment in patients with chronic hepatitis C were collected for analysis.Data on patient age,sex,hepatitis duration and other general information were collected.In addition, data on clinical measures of thyroid function (including T3, t4, tSH) and thyroid autoantibodies (thyroid peroxidase antibody TPO-Ab, thyroglobulin antibody Tg-Ab), as well as findings from thyroid dimensional ultrasonography were collected. One hundred and eleven cases of early treatment in patients with chronic hepatitis B and 106 eases of females 40 years old or older with high risk of nodular goiter were collected for use as controls.The relationship between nodular goiter with thyroid function, thyroid autoantibodies levels,sex,age,and hepatitis C virus infection were statistically analyzed.</p><p><b>RESULTS</b>The prevalence rates of nodular goiter in the chronic hepatitis C group, the chronic hepatitis B group and the more than or equal to 40 year-old women with high risk of nodular goiter were 53.6%,36.9% and 59.4% respectively.The prevalence rates of nodular goiter in the chronic hepatitis C group and the more than or equal to 40 year-old women with high risk of nodular goiter were significantly higber than that in the chronic hepatitis B group (x² values: 5.820 and 10.996, P < 0.05). The average age of patients with chronic hepatitis C combined with nodular goiter was significantly higher than their counterparts without goiter (F=6.408, P < 0.05),and the prevalence rate in the more than or equal to 40 year-old women with high risk of nodular goiter was significantly higher than that of their counterparts who were less than 40 years-old (60.0% vs. 23.5%; x² =7.499, P less than 0.05). The prevalence of nodular goiter in patients with chronic hepatitis C was significantly greater for females than for males (62.1% vs. 41.0%; x 2 =4.152, P < 0.05).The prevalence of nodular goiter in patients with chronic hepatitis C was also significantly higher for females more than or equal to 40 years old than for males (70.2%, 33/47 vs. 45.5%,15/33; x² = 4.952, P < 0.05).The duration of hepatitis, thyroid function and thyroid autoantibodies were similar between the patients in the chronic hepatitis C group with or without nodular goiter.</p><p><b>CONCLUSIONS</b>The patients with chronic hepatitis C had a higher prevalence of nodular goiter,with an average of up to 53.6%, than the patients with chronic hepatitis B,and the women the more than or equal to 40 years old had even higher prevalence, at 70.2%, suggesting that patients with chronic hepatitis C should be routinely examined by thyroid ultrasound. Thyroid function and thyroid autoantibodies were not correlated with prevalence of goiter among the chronic hepatitis C patients.</p>