Hepatitis B is mostly a chronic, progressive disease that, if not treated promptly and effectively, can slowly progress to cirrhosis, liver failure, or hepatocellular carcinoma. Therefore, antiviral therapy, i.e., a "complete therapy" strategy, should be started as long as the virus is positive. Immediate antiviral treatment is not recommended for infected patients who are only in the immune-tolerant phase, mainly because of the milder conditions and poor antiviral therapy efficacy, according to antiviral indications in China's Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version). The relevant issues of why hepatitis B virus infection in the immune-tolerant phase is the last mile of "complete therapy," with an emphasis on the disease’s characteristics and antiviral treatment strategies, are discussed here.

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.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Fibrosis ; Liver Diseases/drug therapy* ; Treatment Outcome ; Liver Cirrhosis/drug therapy*

Timely and effective antiviral therapy can prevent or delay the progression of the disease to cirrhosis, liver failure, or hepatocellular carcinoma in patients with chronic hepatitis B. Antiviral therapy indications are constantly expanding, and eventually it will be manageable to treat viral positives based on the new understanding of the disease progression and the changes in the definition of abnormal values in liver function tests.

Objective:To prospectively explore the treatment strategies for clinical difficulties in patients with hyperviremia HBeAg-positive chronic hepatitis B with incomplete response to first-line nucleos(t)ide analogues (NAs).Methods:Patients with hyperviremia HBeAg-positive chronic hepatitis B were treated with first-line NAs, including entecavir, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) for 48 weeks or more. Tenofovir amibufenamide (TMF) or TAF therapy was changed when HBV DNA remained positive and then divided into a TMF group and a TAF group. Clinical efficacy of treatment was evaluated at 24 and 48 weeks, including HBV DNA undetectable rates and virological and serological responses in both patient groups.Results:In the TMF group and the TAF groups, 30 and 26 cases completed 24-week follow-up, while 18 and 12 cases completed 48-week follow-up. There were no statistically significant differences in baseline HBV DNA, HBsAg, and HBeAg levels between the two groups before switching to TMF/TAF therapy ( P > 0.05). At 24 weeks of treatment, 19 (19/30, 63.33%) cases in the TMF group had HBV DNA negative conversion, while 14 (14/26, 53.85%) cases in the TAF group had HBV DNA negative conversion ( P > 0.05). Among the patients who completed 48 weeks of follow-up, 15 (15/18, 83.33%) cases in the TMF group and 7 (7/12, 58.33%) cases in the TAF group had negative HBV DNA tests ( P > 0.05). The changes in HBsAg and HBeAg levels between the two groups of patients at 24 and 48 weeks of treatment were not statistically significant compared to baseline ( P > 0.05). Conclusion:TMF is effective in treating patients with hyperviremia HBeAg-positive CHB with an incomplete response to first-line NAs treatment, but there is no significant difference compared to TAF.

Objective:To identify 3 the disease-causing genes and mutations of Leber congenital amaurosis (LCA), and to study the correlation of phenotype and genotype.Methods:A retrospective study. Four LCA patients and seven family members who were diagnosed by eye examination in Ning Xia Eye Hospital of People's Hospital of Ningxia Hui Autonomous Region from January to December 2021 were included in the study. Four patients were from 3 unrelated families. Detailed collection of medical history and family history were received. Related ophthalmologic examination were collected and genomic DNA was extracted from peripheral blood. Whole-exome sequencing method was used for genetic diagnosis. The identified variant was confirmed with Sanger sequencing. Potential pathogenic mutation was analyzed using software and conserved domain analysis and performed co-separated analysis between the family member and the proband.Results:Of the 4 patients, 1 patient was males and 3 patients were females; the age was from 4 to 18 years. Nystagmus were seen in 3 cases, finger pressing eyes and night blindness was seen in 1 cases; electroretinogram showed 4 cases of extinction or near extinction. The foveal reflection was visible in all eyes, and there was no obvious abnormality in the peripheral retina. One eye had strong reflection signal with raised ellipsoid in macular area; two eyes had weak reflection signal faintly visible between retinal layers; 1 eye had increased blood vessel branches, peripheral retinal non-perfusion area with capillary leakage; annular strong autofluorescence in macular area 4 eyes. No obvious abnormality was found in the phenotypes of family members. Genetic testing showed that the proband of pedigree 1 (Ⅱ-1) was found a homozygous missense mutation in c.640A>T (p.C214S) (M1) of PRPH2 gene. The proband of pedigree 2 (Ⅱ-2) was found compound heterozygous mutation in c.1256G>A(p.R419Q) (M2) and c.1A>C (p.M1L) (M3) of TULP1 gene. The proband 3 (Ⅱ-1) and her sister (Ⅱ-2) were both found compound heterozygous mutation in c.1943T>C (p.L648P) (M4) and c.380C>T (p.P127L) (M5) of GUCY2D gene. The parents and sister (Ⅱ-1) of the proband in family 2 and the parents of the proband in family 3 were all carriers of the corresponding heterozygous variant. M1, M3, M4, M5 were novel mutations and unreported. The genotype and disease phenotype were co-segregated within the family. According to the analysis of pedigree and genetic testing results, all 3 families were autosomal recessive inheritance. The amino acid conservation analysis found that M1, M2, M3, M4, and M5 were highly conserved among species. The results of bioinformatics analysis were all pathogenic variants. Conclusions:PRPH2 gene M1, TULP1 gene M3, and GUCY2D gene M4, M5 were novel mutations and not been reported in the literature and database. This research expanded the gene mutation spectrum of LCA. The patients with LCA have available characterristics, including onset age, varying ocular fundus and severe visual impairment.

Pregnancy-related liver disease is a group of severe diseases that usually resulting in worsening clinical outcome in pregnant women and fetuses. Therefore, diagnosis and treatment at early-stage are essential. This paper reviews the early-stage clinical features, pathogenesis, diagnosis and treatment key points of common pregnancy-related liver diseases such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, hemolysis, elevated liver enzymes and low platelet syndrome, and acute fatty liver of pregnancy, in order to help clinicians, improve their understanding of pregnancy-related liver disease.

Objective:To analyze, explore and evaluate the clinical characteristics, abnormal thyroid function and follow-up of anti-hyperthyroidism treatment mode in patients with hyperthyroidism (commonly abbreviated as HT) combined with liver injury.Methods:The clinical data of patients with hyperthyroidism combined with liver injury were retrospectively analyzed, and then patients were divided into treated and untreated group according to whether they received anti-hyperthyroidism treatment before the consultation. Patients’ thyroid and liver function test indicators at the time of treatment were analyzed to determine the main cause of liver injury. The characteristics of liver injury were analyzed in the treatment group. Patients with severe thyroid toxicity and hyperthyroidism combined with liver injury were followed-up with anti-hyperthyroid therapy, mainly low-dose methimazole (MMI) and radioactive iodine therapy to evaluate its efficacy and safety. The comparison between data groups was performed by t-test, rank sum test and χ2 test. Results:Among the 43 cases with hyperthyroidism combined with liver injury, 19 were males and 24 were females, aged 49.0 ± 14.6 years-old; 16 cases (16/43, 37.21%) aged 40 to≤60 years- old, and 15 cases (15/43, 34.88%) aged > 60 years-old. There were 22 untreated cases (untreated group, accounting for 51.16%), and 21 treated cases with anti-hyperthyroidism (treatment group, accounting for 48.84%) at the time of consultation. Thyroid function indicators (FT3, FT4, TSH) and liver function indicators (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase, total bilirubin) of the two groups were compared, and the difference was not statistically significant ( P > 0.05). The order of liver injury from mild to severe in patients with different treatment options were: methimazole (MMI) < propylthiouracil < radioactive iodine

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.

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.

Objective: To analysis the gene mutation spectrum of retinitis pigmentosa (RP) patients in Ningxia Region of China. Methods: Fifty-five pedigrees and 74 sporadic RP patients were included in Ningxia Eye Hospital from January 2015 to December 2016.Two hundred unrelated healthy adults were enrolled as normal controls during the same period.The clinical features of patients and their family members were evaluated by ophthalmic examinations, including visual acuity, best corrected visual acuity, fundus examination, optical coherence tomography, fundus fluorescein angiography, and visual field and electroretinogram.The next generation sequencing, PCR and direct sequencing were used to confirm the pathogenic mutation.This study was approved by Ethic Committee of the Ningxia Eye Hospital (NO.20150107), and informed consent was obtained from each subject. Results: The mutations were detected in 37 RP pedigrees, 8 pedigrees showed autosomal dominant inheritance and 6 pathogenic genes were confirmed, all the autosomal dominant RP (ADRP) patients carried a single heterozygous mutation.Twenty-five pedigrees were autosomal recessive RP (ARRP) and 12 pathogenic genes were confirmed.Among ARRP patients, the mutations rate of USH2A gene was the highest, accounting for 28% (7/25), EYS gene and MYO7A gene accounted for 12% (3/25). Four X-linked RP (XLRP) pedigrees carried the homozygous mutations on RPGR gene.Twenty-five disease-causing genes were detected in 49 sporadic RP patients.The mutation rate of USH2A gene was the highest, accounting for 26.5% (13/49), followed by RP1 gene, accounting for 8.1% (4/49). Conclusions Recessive inheritance is the most common cause of RP.USH2A gene is the main pathogenic gene of RP in Ningxia region of China.