Efficacy of elbasvir/grazoprevir in treatment of genotype 1 chronic hepatitis C: A real-world study / 临床肝胆病杂志

ObjectiveTo investigate the efficacy and safety of elbasvir/grazoprevir in patients with genotype 1 hepatitis C in the real world. MethodsA total of 35 patients with hepatitis C who received elbasvir/grazoprevir treatment in Guangzhou Eighth People’s Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine, and Guangdong General Hospital from August 2018 to March 2019 were enrolled, treated for 12 weeks, and then followed up for 12 weeks after drug withdrawal. The patients were observed in terms of sustained virologic response at week 12 after drug withdrawal (SVR12), biochemical response, and incidence rate of adverse events during treatment and follow-up. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups, and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the risk factors for virologic response in patients with hepatitis C. ResultsAmong the 35 patients with HCV infection, 97.1% (34/35) had genotype 1b HCV and 2.9% (1/35) had genotype 1a HCV; of all patients, 28 (80%) were non-cirrhotic patients with chronic hepatitis C and 7 (20%) had compensated liver cirrhosis. At the end of treatment, the virologic response rate of 100% (28/28) and SVR12 was 94.74% (18/19). In addition, age, sex, baseline HCV RNA load, previous treatment history, presence or absence of liver cirrhosis, renal function, and presence or absence of other diseases did not affect the treatment outcome (all P＞0.05). There were significant changes in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and albumin from baseline to the end of 12-week treatment (Z=-7.131, -6.797, -3.060, and -2.875, all P＜0.05). No patient experienced drug withdrawal during treatment. ConclusionThis study confirms that elbasvir/grazoprevir has good efficacy and safety in the treatment of hepatitis C in domestic real-world studies.

Real-world study of paritaprevir/ritonavir-ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China / 中华肝脏病杂志

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.

A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.@*Methods@#Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.@*Results@#132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.@*Conclusion@#Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Research advances in the diagnosis and treatment of acute-on-chronic liver failure with infection / 临床肝胆病杂志

Acute-on-chronic liver failure (ACLF) is a severe syndrome of liver diseases commonly seen in clinical practice and can lead to severe disorders and decompensation of liver synthesis, metabolism, detoxification, and biotransformation, as well as multiple organ failure and an extremely high short-term mortality rate. Infection can induce or aggravate the condition of ACLF and is an independent influencing factor for patient prognosis. This article describes the mechanism and characteristics of ACLF with infection, summarizes the common types and clinical features of infection, reviews the recommended anti-infective regimens, and emphasizes the importance of early prophylactic treatment. ACLF patients with infection tend to have critical conditions, and early diagnosis and empirical anti-infective treatment is the key to successful treatment.

PBMCs microRNA-122 level correlates with virological responses to pegylated interferon alpha therapy in patients with hepatitis C genotype 1b / 中华实验和临床病毒学杂志

Objective@#To clarify the predictive power of PBMCs miR-122, as well as other clinical factors, for response to IFNα therapy in chronic HCV infected patients.@*Methods@#A total of 40 patients chronically infected with HCV genotype 1b were enrolled. All the patients received pegylated interferon alpha (PEG-IFN α) in combination with ribavirin for 48 weeks. To perform the analyses, the patients were compared in terms of achieving sustained virological response (SVR) or not (NSVR) at 24th week after antiviral treatment.@*Results@#SVR rate was 72.5% (29/40) and NSVR rate was 27.5% (11/40). SVR group experienced significantly lower HCV viral load, total bilirubin (TBIL), alpha fetal protein (AFP), fibroscan and laminin (LN) compared with NSVR group before treatment (P<0.05). PBMCs miR-122 expression level was also lower in SVR group than that in SNVR group, although the difference was not statistically significant (P>0.05). and there was no significant change of miR-122 level from baseline to the last available measurement between SVR group and NSVR group. However, no significant association was found between baseline PBMCs miR-122 and HCV viral load, body mass index (BMI), alanine transaminase (ALT), aspartate transaminase (AST), degree of liver fibrosis, respectively.@*Conclusions@#Our result suggest that PBMCs miR-122 level is not an efficient biomarker to predict response to IFN alpha therapy in chronic HCV patients. However, baseline HCV viral load, TBIL, AFP and fibroscan may serve as predictive factors.

A clinical study of antiviral therapy for patients with compensated hepatitis C cirrhosis / 中华肝脏病杂志

Objective@#To investigate the effect of antiviral therapy on the progression of liver cirrhosis and related predictive factors through a retrospective analysis of patients with compensated hepatitis C cirrhosis.@*Methods@#The patients with compensated hepatitis C cirrhosis who were treated in our hospital from 2004 to 2015 were divided into sustained virologic response (SVR) group, non-SVR (NSVR) group, and untreated group. The baseline features of patients with or without liver cirrhosis were compared to identify the predictive factors for the progression of liver cirrhosis. The changes in platelet count, spleen sizes, Model for End-Stage Liver Disease (MELD) score, Sequential Organ Failure Assessment (SOFA) score, and Child-Turotte-Pugh (CTP) score were analyzed, and the incidence rate of liver cancer was compared between groups. A one-way analysis of variance, the Kruskal-wallis H test, the two-independent-sample t test, the chi-square test, and a multivariate logistic regression analysis were used for data analysis based on data type.@*Results@#A total of 89 patients with compensated liver cirrhosis were enrolled, among whom 42 received the antiviral treatment with interferon and ribavirin (30 were treated with pegylated interferon-α and 12 were treated with ordinary interferon) and 47 did not receive any antiviral therapy. Among the patients who received the antiviral treatment with interferon and ribavirin, 20 achieved SVR and 22 did not achieve SVR. Compared with baseline values, platelet count in the SVR group and the NSVR group was increased by (44.93 ± 32.66)×109/L and (9.73 ± 28.83)×109/L, respectively, and platelet count in the untreated group was reduced by (19.76 ± 54.5)×109/L; the three groups had a significant change in platelet count (F = 14.731, P < 0.001). Spleen size was reduced by 0.91 ± 1.09 cm in the SVR group and increased by 0.20±0.84 cm and 1.11 ± 1.69 cm in the NSVR group and the untreated group, respectively; the three groups had a significant change in spleen size (F = 14.943, P < 0.001). The three groups had no significant changes in MELD, SOFA, and CTP scores (P > 0.05). One patient (5.00%) in the SVR group, 5 (22.73%) in the NSVR group, and 6 (12.77%) in the untreated group progressed to liver cancer (χ 2 = 13.787, P = 0.001). The univariate analysis showed that SVR, HCV RNA, total bilirubin, and albumin were predictive factors for disease progression, and the multiple logistic regression analysis demonstrated that SVR and total bilirubin were predictive factors for disease progression.@*Conclusion@#Interferon combined with ribavirin has a marked clinical effect in the treatment of compensated hepatitis C cirrhosis with good short- and long-term efficacy.

Clinical characteristics of patients with HBsAg(+) versus HBsAg(-)/HBcAb(+) primary hepatic carcinoma treated by hepatectomy: a comparative analysis / 临床肝胆病杂志

ObjectiveTo explore the differences in clinical characteristics between patients with HBsAg(+) and HBsAg(-)/HBcAb(+) primary hepatic carcinoma (PHC) treated by hepatectomy. MethodsForty-three HBsAg(+) and 18 HBsAg(-)/HBcAb(+) patients who underwent liver resection against PHC from October 2009 to November 2014 in Guangzhou 8th People′s Hospital were selected for the study. The clinical data of the subjects, including sex, age, histological differentiation, intravascular tumor thrombi, and hepatic cirrhosis, were compared, using t test for continuous data, chi-square test for categorical data, and Mann-Whitney U test for non-parametric data. ResultsNo significant differences existed between patients with HBsAg(+) and HBsAg(-)/HBcAb(+) PHC in terms of the age of onset (50.77±12.93 years vs 54.28±9.89 years, t=-1.031, P＞0.05), the incidence of cholangiocarcinoma (2.3% vs 167%, χ2=2.24, P＞0.05), the incidence of hepatic cirrhosis (62.8% vs 44.4%, χ2=1.746, P＞0.05), alpha-fetoprotein level (3638±7869 ng/ml vs 3577±9628 ng/ml, t=0.026, P＞0.05), histological differentiation (Z=-1.085, P＞0.05), and the rate of intravascular tumor thrombi (34.9% vs 22.2%, χ2=0.949, P＞0.05). ConclusionThere are no significant differences in the age of onset and progression of disease between patients with HBsAg(+) and HBsAg(-)/HBcAb(+) PHC treated by hepatectomy. However, given the possibility of occult hepatitis B virus infection, it is necessary to monitor hepatic carcinoma even post HBsAg seroconversion

The correlation between APOBEC3G mRNA in peripheral blood mononuclear cells and serum hepatitis C viral RNA level / 中华传染病杂志

Objective To study the relationship between APOBEC3G mRNA level in peripheral blood mononuclear cells (PBMC) and serum hepatitis C viral RNA level in patients with chronic hepatitis C infection. Methods TaqMan real-time fluorescence relative quantitative polymerase chain reaction (RT-PCR) was used to quantify APOBEC3G mRNA levels in PBMC from 49 patients with chronic hepatitis C (CHC) and 31 healthy subjects. The relationship between APOBEC3G mRNA level and hepatitis C virus (HCV) viral load was analyzed. SPSS11. 0 statistics software was used for t test and regression analysis. Results APOBEC3G mRNA level in CHC patients [(1.5×10-5±1.9×10-5 ) copy/mL] was significantly lower than that [( 5. 2 × 10-5 ± 5. 5 × 10-5 ) copy/mL] in the healthy control subjects (t=-3.005, P＜0.01). While APOBEC3G mRNA level was not related with HCV viral loads (r=-0.082, P＞0.05). Conclusion HCV has an inhibitive effect on APOBEC3G expression, whereas APOBEC3G doesn't affect HCV replication directly in vivo.

Analysis of clinical laboratory diagnosis in 484 Dengue fever patients / 中华检验医学杂志

Objective To analyze the characteristics of laboratory test resuits of dengue fever(DF)patients in Guangzhou area.Methods Routine tests were performed in the patients admission to hospital. Serology examination was performed in the patients in acute phase or recovery phase.The clinieal symptoms and teatures were analyzed and positive numbers and positivity ratios were calculated.Results The clinical symptoms of the dengue fever were typieal,with the features of fever,headache,myalgia and rash.The leukopenia rate was 76.0%,and the thromboeytopenia rate was 62.6%.The levels of ALT increased in 56.7%patients,and the levels of AST increased in 84.0%patients.Hypopotassemia was found in 46.1%patients.Dengue virus antibody IgM(DF-IgM)was detected positive from the first day to the 16th day of the onset,and the positive rate was 85.9% on the 8th day.Virus loads were positive by fluorescence real-time PCR in seven acute serum samples(within 3 days of the onset)of 51 cases whose DE-IgM were negative all the time, and the results was 105 -106 copies/ml(＜103 copies/ml means negative).Conclusions Clinical manifestations of this DF epidemic were typical including fever,headache,myalgia and skin rash.Most of the patients had decreased leukocyte and thrombocyte obviously.Liver damage was common but kidney damage was seldom.Halt of the patients got hypopotassemia.DF-IgM appeared in very early and persisted for a long time.The detection of DF-IgM within 7 days of the onset was helpful for diagnosis as early as possible.Viral load detected by real-time PCR could be another indicator of early pathogen diagnosis which provides complementation for antibody detection.