[Objective]To explore the epidemiology and clinical characteristics of kala-azar patients in Kashgar region,so as to improve the diagnosis and treatment.[Methods]A retrospective analysis was conducted on the clinical data of 71 kala-azar patients admitted to the First People's Hospital of Kashgar Region between January 2013 and December 2023.[Results]Among the 71 patients,the majority were aged 0-5 years(52.11%,37/71),with a male-to-female ratio of 0.92:1.Most cases occurred in winter and spring.Common clinical manifestations included fever,fatigue,decreased appetite,splenomegaly and hepatomegaly.Laboratory investigations mainly found pancytopenia,reversed albumin-to-globulin ratio,elevated transaminases,and increased C-reactive protein and procalcitonin.The positive rates of anti-rK39 antibody detection and bone marrow microscopy were 100%(23/23)and 91.38%(53/58),respectively.Metagenomics next-generation sequencing(mNGS)of liver tissue identified Leishmania donovani in one case.The common complications were infectious toxic hepatitis 49.30%(35/71),myocarditis 29.56%(21/71),and bronchopneumonia 23.94%(17/71).[Conclusions]Potential kala-azar should be taken into consideration for patients from the endemic areas with long-term irregular fever accompanied by splenomegaly,hemocytopenia,and reversed albumin-to-globulin ratio.Bone marrow smear microscopy and anti-rK39 antibody detection are recommended for the diagnosis,and mNGS provides a novel diagnostic solution.

Background and aims:Early and accurate diagnosis of the coexistence of Wilson's disease(WD)and chronic hepatitis B(CHB)presents a significant challenge for clinicians.The objective of this study was to retrospectively analyse the characteristics of such patients to improve clinical practice and provide a reference for clinical management.Methods:From January 2011 to December 2022,35 patients with concurrent CHB and WD(CHB+WD group)were identified.A total of 127 patients with CHB(CHB group)and 168 patients with WD(WD group)were included in the control group between January 2016 and December 2021.Propensity score matching(PSM)was performed to balance the baseline values between groups.The Kaplan-Meier(K-M)survival analysis and log-rank test were performed to compare the prognoses.Results:In the cohort of 35 patients with concurrent CHB and WD,74.3％of patients(26 patients)faced a substantial delay of up to 10 years(range:0-40 years)in WD diagnosis following their CHB diagnosis.Twenty-three(65.7％)patients had cirrhosis at the time of WD diagnosis,and 26(74.3％)patients experienced liver failure.The levels of serum copper and uric acid were lower in patients in the CHB+WD group than in those in the CHB group.Patients in the CHB+WD group presented higher alanine transaminase and total bile acid levels compared to those in the WD group.K-M survival analysis indicated that patients with CHB and WD had poorer outcomes than those with CHB alone;however,the outcomes were similar to those of individuals with WD alone.The optimal cut-point of serum ceruloplasmin(CP)in identifying WD in CHB patients was 0.10 g/L before PSM and after PSM.Conclusions:The present study emphasizes the importance of clinicians being vigilant for concurrent CHB and WD diagnoses,as delays in WD diagnosis may adversely affect patient outcomes.CHB patients with serum CP below 0.10 g/L are highly recommended to screen for WD.

[Objective]To explore the epidemiology and clinical characteristics of kala-azar patients in Kashgar region,so as to improve the diagnosis and treatment.[Methods]A retrospective analysis was conducted on the clinical data of 71 kala-azar patients admitted to the First People's Hospital of Kashgar Region between January 2013 and December 2023.[Results]Among the 71 patients,the majority were aged 0-5 years(52.11%,37/71),with a male-to-female ratio of 0.92:1.Most cases occurred in winter and spring.Common clinical manifestations included fever,fatigue,decreased appetite,splenomegaly and hepatomegaly.Laboratory investigations mainly found pancytopenia,reversed albumin-to-globulin ratio,elevated transaminases,and increased C-reactive protein and procalcitonin.The positive rates of anti-rK39 antibody detection and bone marrow microscopy were 100%(23/23)and 91.38%(53/58),respectively.Metagenomics next-generation sequencing(mNGS)of liver tissue identified Leishmania donovani in one case.The common complications were infectious toxic hepatitis 49.30%(35/71),myocarditis 29.56%(21/71),and bronchopneumonia 23.94%(17/71).[Conclusions]Potential kala-azar should be taken into consideration for patients from the endemic areas with long-term irregular fever accompanied by splenomegaly,hemocytopenia,and reversed albumin-to-globulin ratio.Bone marrow smear microscopy and anti-rK39 antibody detection are recommended for the diagnosis,and mNGS provides a novel diagnostic solution.

[Objective]To explore the clinical characteristics of neurobrucellosis in Kashi,Xinjiang Uygur Autono-mous Region,thus improve the diagnosis and treatment.[Methods]A retrospective analysis was conducted on the clinical data of 18 cases of neurobrucellosis who were admitted to the First People's Hospital of Kashi Prefecture between Decem-ber 2019 and January 2024.[Results]The study included 9 males and 9 females,with a median age of 36 years(range:17-54.5).A clear epidemiological history was found in all the 18 brucllosis patients,12 of whom presented with meningo-encephalitis,5 meningitis,and 1 encephalitis.Two comorbided with spinal meningitis,2 osteoarthritis and 1 epididymitis.Most frequently reported clinical symptoms were headache,fever and fatigue.The prevalence rates of brucellosis by rose bengal plate agglutination test(RBPT)and serum agglutination test(SAT)were 11/12 and 8/9,respectively.Two of 10 patients had positive blood cultures,four of 16 had positive cerebrospinal fluid(CSF)cultures and five of five were detect-ed to be positive by next-generation sequencing(NGS)for pathogens in CSF.CSF showed exudative changes and elevated number of leukocytes,with predominance of single nucleated cells.All patients were treated with the combined use of two to four from the drugs like doxycycline,rifampicin,ceftriaxone,cefixime,minocycline,levofloxacin and sulfanilamide.Most patients had a favorable prognosis.[Conclusions]Neurobrucellosis should be considered in all patients with central nervous system manifestations from endemic areas.If there are exudative changes in CSF,differential diagnoses can be made by serological testing,blood culture,CSF culture and NGS.NGS could significantly increase the accuracy for neuro-brucellosis diagnosis.

Objective:To understand the diagnostic value of tuberculosis (TB) pathogenic detection methods (TPDM) in pathological tissue for TB.Methods:A retrospective study was conducted with 190 pathological specimens from different tissues suspected with TB from Third People′s Hospital of Shenzhen during May 2016 and May 2019. Specimens were divided into four groups according to histomorphology: group one, necrotizing granulomatous inflammation (109 cases); group two, non-necrotic granulomatous inflammation (20 cases); group three, non-granulomatous inflammation (45 cases); group four, non-tuberculous lesions (16 cases). The positive rates of each TPDM among specimens from four groups were compared. The positive rates of all TPDM for specimens from group one were compared. Meanwhile, the influence of antituberculosis treatment course on the TPDM was analyzed. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:The positive rates of Ziehl-Neelsen acid-fast staining among the four groups were 17.4%(19/109), 5.0%(1/20), 4.4%(2/45) and 0(0/16), respectively. The positive rates of Mycobacterium tuberculosis (MTB) complex culture were 32.0%(32/100), 4/19, 4.8%(2/42) and 0(0/16), respectively. The positive rates of Mycobacterium tuberculosis/rifampin resistance real-time quantitative nucleic acid amplification detection system (Xpert MTB/RIF) were 74.3%(81/109), 15.0%(3/20), 13.3%(6/45) and 0(0/16), respectively. The positive rates of fluorescent quantitative polymerase chain reaction (FQ-PCR) were 63.0%(58/92), 0(0/15), 2.6%(1/38) and 0(0/10), respectively. The positive rates of simultaneous amplification and testing (SAT) were 32.4%(24/74), 0(0/10), 0(0/15) and 0(0/10), respectively. The differences of each TPDM among four groups were all statistically significant (all P<0.05). The positive rate of Xpert MTB/RIF in group one specimens was significantly higher than those of acid-fast staining, MTB culture and SAT ( χ2=71.016, 37.162 and 35.679, respectively, all P<0.01), while the difference was not statistically significant when compared with FQ-PCR ( χ2=2.517, P=0.112). The positive rate of combined TPDM (85.3%(93/109)) was significantly higher than Xpert MTB/RIF(74.3%(81/109)) ( χ2=4.100, P=0.043). The positive rates of acid-fast staining group 1A (anti-tuberculosis treatment course was less than one month) and group 1B (anti-tuberculosis treatment course was longer than one month) were 14.3%(7/49) and 20.0% (12/60), respectively ( χ2=0.612, P=0.434); those of MTB culture were 48.9% (22/45) and 18.2% (10/55), respectively ( χ2=10.721, P=0.001); those of Xpert MTB/RIF were 69.4%(34/49) and 78.3%(47/60), respectively ( χ2=1.131, P=0.287); those of FQ-PCR were 55.0%(22/40) and 69.2%(36/52), respectively ( χ2=1.965, P=0.161); those of SAT were 43.3%(13/30) and 25.0%(11/44), respectively ( χ2=2.736, P=0.098). Conclusions:The results of TPDM correlate closely with the typical histomorphological features of tuberculosis. Xpert MTB/RIF possesses significantly higher sensitivity than any other single TPDM, and is not attenuated by early anti-tuberculosis treatment. Combined TPDM could significantly improve the sensitivity of TB pathogenic detection, which is suggested to be applied when the tissue specimen is sufficient.

Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(1TT)and modified 1TT(mITT)populations were used in the analysis. Results:One hundred forty patients were included,among whom 90.0％(126/140)were newly diag-nosed,9.3％(13/140)had compensated cirrhosis,92.9％(130/140)received 12 weeks of treatment,and 7.1％(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4％(108/112),and at the end of treatment was 100％(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4％)patients,and none were considered to be drug-related.Sixty-six(47.1％)patients did not return to receive the HCV RNA test at 12 weeks post-treatment. Conclusions:The rate of SVR12 was consistent with Phase Ⅲ clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.

Copper is an important trace element in the human body, and copper deficiency or overload can lead to a series of body dysfunctions. This review focuses on hepatolenticular degeneration and related diseases of abnormal copper metabolism. Hepatolenticular degeneration has various clinical phenotypes, and related diseases, such as cholestatic liver disease, hereditary ceruloplasmin deficiency, and congenital abnormal glycosylation, may bring confusion to the clinical diagnosis of hepatolenticular degeneration. With reference to the latest research advances and experience in the diagnosis and treatment of hepatolenticular degeneration, this article discusses the pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism from the perspective of liver diseases.

Objective: To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients. Methods: A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data. Results: 80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment. Conclusion In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.

The clinical phenotype of genetic liver disease is significantly different. Although the incidence of disease is low, because of the wide spectrum of diseases, the overall affected population is not rare. Therefore, clinical concern is a matter of alarm. Additionally, these diseases rarity in clinical practice has covered the recognition, causing increased problem of clinical misdiagnosis. In accordance with the problems encountered in clinical practice of our hospital, we explore the clinical diagnosis of genetic liver disease.

OBJECTIVETo evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).

METHODSA total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.

RESULTSOver the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.

CONCLUSIONFor CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; therapeutic use ; Retrospective Studies ; Tenofovir ; Young Adult