[A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19].

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). METHODS: We prospectively enrolled 30 treatment-naïve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1：1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). RESULTS: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1,9) days in HCQ group, which is comparable to that in the control group [2 (1,4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0,2) day after hospitalization, which was also comparable to that in the control group [1 (0,3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). CONCLUSIONS: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.

Combination of sorafenib and gadolinium chloride (GdCl3) attenuates dimethylnitrosamine(DMN)-induced liver fibrosis in rats.

BACKGROUND/AIMS: Liver sinusoidal endothelial cells (SECs), hepatic stellate cells (HSCs) and Kupffer cells (KCs) are involved in the development of liver fibrosis and represent a potential therapeutic target. The therapeutic effects on liver fibrosis of sorafenib, a multiple tyrosine kinase inhibitor, and gadolinium chloride (GdCl3), which depletes KCs, were evaluated in rats. METHODS: Liver fibrosis was induced in rats with dimethylnitrosamine, and the effects of sorafenib and/or GdCl3 in these rats were monitored. Interactions among ECs, HSCs and KCs were assessed by laser confocal microscopy. RESULTS: The combination of sorafenib and GdCl3, but not each agent alone, attenuated liver fibrosis and significantly reduced liver function and hydroxyproline (Hyp). Sorafenib significantly inhibited the expression of angiogenesis-associated cell markers and cytokines, including CD31, von Willebrand factor (vWF), and vascular endothelial growth factor, whereas GdCl3 suppressed macrophage-related cell markers and cytokines, including CD68, tumor necrosis factor-α, interleukin-1ß, and CCL2. Laser confocal microscopy showed that sorafenib inhibited vWF expression and GdCl3 reduced CD68 staining. Sorafenib plus GdCl3 suppressed the interactions of HSCs, ECs and KCs. CONCLUSION: Sorafenib plus GdCl3 can suppress collagen accumulation, suggesting that this combination may be a potential therapeutic strategy in the treatment of liver fibrosis.

Upregulation of heat shock proteins (HSPA12A, HSP90B1, HSPA4, HSPA5 and HSPA6) in tumour tissues is associated with poor outcomes from HBV-related early-stage hepatocellular carcinoma.

BACKGROUND: Heat shock proteins (HSPs) are overexpressed in human hepatocellular carcinoma (HCC) tissue and correlate with aggressiveness and prognosis of HCC. METHODS: Using the GSE14520 microarray expression profile from Gene Expression Omnibus, we compared HSP gene expression between tumour and non-tumour tissues and correlated this with outcomes in HCC patients. RESULTS: We analysed 220 hepatitis B virus (HBV)-related HCC patients and 25 HSPs in this study. With the exception of HSPA4L, HSPA12A and HSPB8, members of the HSP family, including HSPH1, HSPBP1, HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4, HSPA5, HSPA8, HSPA9, HSPAA1, HSPAB1, HSPA14, HSPB11, HSPA13, HSP90B1 and HSPBAP1, were all overexpressed in tumour tissues (all P < 0.001). In contrast, HSPB6, HSPB7, HSPA6, HSPB2 and HSPB3 were upregulated in non-tumour tissues (all P < 0.001). Multivariate analysis showed that cirrhosis (HR = 5.282, 95% CI = 1.294-21.555, P = 0.02), Barcelona Clinic liver cancer (BCLC) staging (HR = 2.151, 95% CI = 1.682-2.750, P < 0.001), HSPA12A (HR = 1.042, 95% CI = 1.003-1.082, P = 0.033) and HSP90B1 (HR = 1.001, 95% CI = 1.000-1.001, P = 0.011) were negatively associated with survival of HBV-related HCC patients. Furthermore, advanced BCLC staging (HR = 1.797, 95% CI = 1.439-2.244, P < 0.001) was also associated with earlier recurrence of HCC. The high expression of HSPA4 (HR = 1.002, 95% CI = 1.000-1.004, P = 0.019), HSPA5 (HR = 1.0, 95% CI = 1.0-1.0, P = 0.046) and HSPA6 (HR = 1.008, 95% CI = 1.001-1.015, P = 0.021) was similarly associated with HCC recurrence. CONCLUSIONS: The expression of most HSPs was higher in tumour tissues than in non-tumour tissues. High BCLC staging scores, advanced cirrhosis and the overexpression of HSPA12A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of HSPA4, HSPA5 and HSPA6 might be associated with earlier recurrence of HCC.

Paeoniflorin regulates macrophage activation in dimethylnitrosamine-induced liver fibrosis in rats.

BACKGROUND: Macrophages in other organs (e.g. kidneys, lungs, and spleen, et. al) have rarely been reported in the development of liver fibrosis. Therefore, it is important to investigate macrophage activation in the main organs in liver fibrosis. We investigated the potential antifibrogenic effects of paeoniflorin (PF) in a dimethylnitrosamine (DMN)-induced rat model with special focus on inhibiting macrophage activation in the main organs. METHODS: Rat hepatic fibrosis was induced by treatment with DMN three times weekly over a 4-week period. DMN rats were treated with water, PF, or gadolinium chloride (GdCl3) from the beginning of the 3rd week. The expression of CD68, marker of macrophage, was investigated using immunohistochemical, real-time PCR, and western blot analysis. RESULTS: Hepatic hydroxyproline content markedly decreased and histopathology improved in the DMN-PF rats. Expression of desmin and collagen 1 decreased notably in DMN-PF liver. CD68 expression in the liver, spleen and kidney increased markedly after 2 weeks but decreased in DMN-water rats. PF and GdCl3 decreased CD68 expression in the liver and spleen and there was no effect on kidney. CD68 expression in the lung increased gradually during the course of DMN-induced liver fibrosis, and PF inhibited CD68 expression in the lung significantly while GdCl3 increased CD68 markedly. Expression of tumor necrosis factor (TNF-α) was decreased significantly by GdCl3 in the liver, as revealed by real-time PCR analysis. However, GdCl3 could not decrease TNF-α level in the serum by enzyme linked immunosorbent assay (ELISA). CONCLUSIONS: Macrophage activation was disrupted in the liver, spleen, lung and kidney during development of DMN-induced liver fibrosis. PF administration attenuated DMN-induced liver fibrosis at least in part by regulating macrophage disruption in the main organs.

Risk factors for myocardial injury at admission of 325 patients with coronavirus disease 2019 in Shanghai, China.

OBJECTIVE: Myocardial injury leads to higher mortality in COVID-19, but the causes and risk factors are variable. We evaluated the potential risk factors for myocardial injury in COVID-19 patients to improve treatment strategies and reduce mortality. METHODS: This retrospective analysis enrolled 325 COVID-19 patients in Shanghai, China. RESULTS: The median age in our cohort was 51 [range 15-88] years, 26 (8%) were critically ill, and 177 patients (19.7%) had myocardial injury. The myocardial injury group comprised older, more critically ill patients with hypertension, other comorbidities, history of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, lower peripheral blood lymphocyte count and higher D-dimer levels. Binary logistic regression analysis identified only age was an independent risk factor for myocardial injury (odds ratio 1.019; 95% confidence interval 1.003-1.036; age increase by 1 year = myocardial injury risk increase by 1.9%). CONCLUSIONS: Older age was associated with a higher incidence of myocardial injury for COVID-19 patients.

Measles virus infection in adults induces production of IL-10 and is associated with increased CD4+ CD25+ regulatory T cells.

Despite steady progress in elimination of measles virus globally, measles infection still causes 500,000 annual deaths, mostly in developing countries where endemic measles strains still circulate. Many adults are infected every year in China, with symptoms more severe than those observed in children. In this study, we have used blood samples from adult measles patients in Shanghai and age-matched healthy controls to gain an understanding of the immune status of adult measles patients. IFN-alpha mRNA was reduced in patient PBMC compared with healthy controls. In contrast, gene expression and plasma production of IL-2, IL-10, and IFN-gamma were elevated in patient blood. A similar cytokine profile was observed at early times when cultured PBMC were infected with a clinical isolate of measles virus. In contrast to previous studies in pediatric patients, we did not find a reduction in total CD4(+) and CD8(+) T cells in patient PBMC. Interestingly, we found that CD4(+)CD25(+)CD127(low) regulatory T cells were significantly increased in patient PBMC compared with controls. Using intracellular cytokine staining we also show that the measles virus induces IL-10-producing CD14(+) and CD4(+)CD25(+) cells in PBMC. Our results show that adult measles patients in the acute phase of the disease have a mixed Th1/Th2 type response, accompanied with severe immunosuppression of both innate and adaptive responses including suppression of type I IFN. Both regulatory T cells and plasma IL-10 may contribute to the immunosuppression.

Traditional Chinese Medicine Formulation Therapy in the Treatment of Coronavirus Disease 2019 (COVID-19).

This study aimed to investigate the efficacy of Traditional Chinese Medicine (TCM) decoction with different intervention timepoints in the treatment of coronavirus disease 2019 (COVID-19) patients. We retrospectively collected the medical records and evaluated the outcomes of COVID-19 patients that received TCM decoction treatment at different timepoints. A total of 234 COVID-19 patients were included in this study. Patients who received TCM decoction therapy within 3 days or 7 days after admission could achieve shorter hospitalization days and disease periods compared to those who received TCM decoction [Formula: see text] 7 days after admission (all [Formula: see text]). Patients who received TCM decoction therapy within 3 days had significantly fewer days to negative SARS-CoV-2 from nasopharyngeal/oral swab and days to negative SARS-CoV-2 from urine/stool/blood samples compared to those received TCM decoction [Formula: see text] days after admission (all [Formula: see text]). Patients who received TCM decoction therapy on the 3rd to 7th day after admission had a faster achievement of negative SARS-CoV-2 from urine/stool/blood samples compared to those who received TCM decoction [Formula: see text] days after admission ([Formula: see text]). Logistic models revealed that more days from TCM decoction to admission [Formula: see text] days might be a risk factor for long hospitalization days, disease period, and slower negative-conversion of SARS-CoV-2 (all [Formula: see text]). Conclusively, our results suggest that TCM decoction therapy should be considered at the early stage of COVID-19 patients.

Predictors for imaging progression on chest CT from coronavirus disease 2019 (COVID-19) patients.

OBJECTIVE: This study aimed to investigate the potential parameters associated with imaging progression on chest CT from coronavirus disease 19 (COVID-19) patients. RESULTS: The average age of 273 COVID-19 patients enrolled with imaging progression were older than those without imaging progression (p = 0.006). The white blood cells, platelets, neutrophils and acid glycoprotein were all decreased in imaging progression patients (all p < 0.05), and monocytes were increased (p = 0.025). The parameters including homocysteine, urea, creatinine and serum cystatin C were significantly higher in imaging progression patients (all p < 0.05), while eGFR decreased (p < 0.001). Monocyte-lymphocyte ratio (MLR) was significantly higher in imaging progression patients compared to that in imaging progression-free ones (p < 0.001). Logistic models revealed that age, MLR, homocysteine and period from onset to admission were factors for predicting imaging progression on chest CT at first week from COVID-19 patients (all p < 0.05). CONCLUSION: Age, MLR, homocysteine and period from onset to admission could predict imaging progression on chest CT from COVID-19 patients. METHODS: The primary outcome was imaging progression on chest CT. Baseline parameters were collected at the first day of admission. Imaging manifestations on chest CT were followed-up at (6±1) days.

Clinical progression of patients with COVID-19 in Shanghai, China.

BACKGROUND: Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. METHODS: In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. RESULTS: Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. CONCLUSIONS: The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

Antiviral Activity and Safety of Darunavir/Cobicistat for the Treatment of COVID-19.

BACKGROUND: We aimed to evaluate the antiviral activity and safety of darunavir/cobicistat (DRV/c) in treating COVID-19 patients. METHODS: In this single-center, randomized, and open-label trial, mild patients with polymerase chain reaction (PCR)-confirmed COVID-19 were enrolled in Shanghai, China. Participants were randomized to receive DRV/c for 5 days on the top of interferon alpha 2b inhaling or interferon alpha 2b inhaling alone. The primary end point was the virological clearance rate of oropharyngeal swabs at day 7 after randomization in the intention-to-treat population (clinicaltrials.gov: NCT04252274). RESULTS: From January 30, 2020, to February 6, 2020, a total of 30 patients were enrolled, of whom 18 (60%) were male, aged 47.2 ±â€…2.8 years; 63.3% (19/30) of the participants had fever, and 46.7% (14/30) had cough at enrollment. The participants were randomized (range) at 4 (2-5) days after onset of symptoms. The proportion of negative PCR results at day 7 was 46.7% (7/15) and 60.0% (9/15) in the DRV/c and control groups (P = .72), respectively. The viral clearance rate at day 3 was 20% (3/15) in both study groups, while the number increased to 26.7% (4/15) in the DRV/c group and remained 20% (3/15) in the control group at day 5. Fourteen days after randomization, 1 participant in the DRV/c group progressed to critical illness and discontinued DRV/c, while all the patients in the control group were stable (P = 1.0). The frequencies of adverse events in the 2 groups were comparable. CONCLUSIONS: Five days of DRV/c did not increase the proportion of negative conversion vs standard of care alone, although it was well tolerated.

Epidemiology and clinical course of COVID-19 in Shanghai, China.

Background: Novel coronavirus pneumonia (COVID-19) is prevalent around the world. We aimed to describe epidemiological features and clinical course in Shanghai. Methods: We retrospectively analysed 325 cases admitted at Shanghai Public Health Clinical Center, between January 20 and February 29, 2020. Results: 47.4% (154/325) had visited Wuhan within 2 weeks of illness onset. 57.2% occurred in 67 clusters; 40% were situated within 53 family clusters. 83.7% developed fever during the disease course. Median times from onset to first medical care, hospitalization and negative detection of nucleic acid by nasopharyngeal swab were 1, 4 and 8 days. Patients with mild disease using glucocorticoid tended to have longer viral shedding in blood and feces. At admission, 69.8% presented with lymphopenia and 38.8% had elevated D-dimers. Pneumonia was identified in 97.5% (314/322) of cases by chest CT scan. Severe-critical patients were 8% with a median time from onset to critical disease of 10.5 days. Half required oxygen therapy and 7.1% high-flow nasal oxygen. The case fatality rate was 0.92% with median time from onset to death of 16 days. Conclusion: COVID-19 cases in Shanghai were imported. Rapid identification, and effective control measures helped to contain the outbreak and prevent community transmission.

Add-On Therapy with Traditional Chinese Medicine Improves Outcomes and Reduces Adverse Events in Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Traditional Chinese medicine (TCM) therapy for hepatocellular carcinoma remains controversial. This study aimed to evaluate the efficacy and safety of TCM regimens in HCC treatment. METHODS: Randomized controlled trials (RCTs) up to June 1, 2016, of the TCM treatment for hepatocellular carcinoma were systematically identified in PubMed, CNKI, Ovid, Embase, Web of Science, Wanfang, VIP, CBM, AMED, and Cochrane Library databases. RESULTS: A total of 1010 and 931 patients in 20 RCTs were randomly treated with add-on TCM therapy and conventional therapy, respectively. The additional use of TCM significantly improved six-month, one-year, two-year, and three-year overall survival rates in HCC cases (RR = 1.3, P = 0.01; RR = 1.38, P = 0.0008; RR = 1.44, P < 0.0001; RR = 1.31, P = 0.02, resp.). Add-on TCM therapy significantly increased PR rate and total response rate (tRR) and reduced PD rate compared to those in control group (34.4% versus 26.3%, RR = 1.30, P = 0.002; 41.6% versus 31.0%, RR = 1.30, P < 0.0001; and 16.6% versus 26.5%, RR = 0.64, P < 0.0001, resp.). Additionally, TCM combination therapy significantly increased the quality of life (QOL) improvement rate and reduced adverse events including leukopenia, thrombocytopenia, anemia or erythropenia, liver injury, and gastrointestinal discomfort in HCC patients (all P < 0.05). CONCLUSION: Add-on therapy with TCM could improve overall survival, increase clinical tumor responses, lead to better QOL, and reduce adverse events in hepatocellular carcinoma.

Naturally occurring basal core promoter A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma: a meta-analysis.

Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis.

Elevated serum gamma-glutamyltransferase predicts advanced histological liver damage in chronic hepatitis B.

Recently, several studies have demonstrated that serum gamma-glutamyltransferase (GGT) is associated with some diseases, such as chronic hepatitis B (CHB). This study investigates the association between GGT levels and liver pathological grading in patients with CHB. 300 patients with CHB who underwent liver biopsy were enrolled. Histological assessment was based on the Scheuer scoring system. Univariate and multivariate analyses were performed to evaluate the independent predicting factors for the presence of liver pathological grade in patients with CHB. In patients with CHB, the mean GGT level was 44.14±3.69 (U/L) in low activity group and 114.87±15.75 (U/L) in the high activity group (p<0.001). Also, there was significant difference between the low and high fibrosis group with regard to GGT levels [45.32±4.64 (U/L) vs. 90.41±11.06 (U/L), p<0.001, respectively]. The variables that were significant in the univariate analysis were evaluated in multivariate logistic regression analysis, and GGT was an independent predicting factor of necroinflammation and fibrosis (OR=1.007, 95%CI: 1.001-1.014, p=0.030; OR=1.009, 95%CI: 1.003-1.014, p=0.003, respectively). Results of this study suggest that GGT is a new non-invasive marker that can be used to predict advanced histological liver damage.

Moxibustion for Diarrhea-Predominant Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background. The complementary and alternative medicines in treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) are controversial. Methods. We searched PubMed, Ovid Embase, Web of Science, Cochrane Library databases, CNKI, Wanfang Database, CBM, VIP, and AMED for randomized controlled trials (RCTs) of moxibustion compared with pharmacological medications in patients with IBS-D. A meta-analysis was performed using both fixed and random-effects models based on heterogeneity across studies. Results. In total, 568 patients in 7 randomized controlled trials were randomly treated with moxibustion and pharmacological medications. The improvement of global IBS-D symptoms and overall scores was significant (P = 0.0001 and P < 0.0001, resp.) in patients treated by moxibustion only compared to pharmacological medications. The specific IBS-D symptoms of abdominal pain, abdominal distension, abnormal stool, and defecation frequency were alleviated in patients treated by moxibustion compared to pharmacological medications, but no significance was found except for abdominal distension and defecation frequency (P = 0.03 and P = 0.02, resp.). There were no serious adverse events related to moxibustion. Conclusions. Moxibustion appears to be effective in treating IBS-D compared with pharmacological medications. However, further large, rigorously designed trials are warranted due to insufficient methodological rigor in the included trials.

HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus.

OBJECTIVE: This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival. METHODS: We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376. RESULTS: Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797-0.983, and P = 0.023) and disease-free survival time (HR = 0.913, 95% CI = 0.835-0.998, and P = 0.045). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01-1.137, and P = 0.022 and HR = 2.4, 95% CI = 1.092-5.273, and P = 0.029, resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rank P = 0.616). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008-1.29, and P = 0.037). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523-0.803, and P < 0.001). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277-1.646, and P < 0.001 and OR = 1.613, 95% CI = 1.1-2.365, and P = 0.014, resp.). CONCLUSIONS: Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes.

Elevation of serum GGT and LDH levels, together with higher BCLC staging are associated with poor overall survival from hepatocellular carcinoma: a retrospective analysis.

Serum biomarkers predicting prognosis have not been adequately explored in HCC patients. The aim of this study was to investigate prognostic significance of parameters of liver function, tumor markers, and other clinicopathological features in HCC patients. Medical records of HCC patients were retrospectively extracted and overall survival was evaluated with the Kaplan-Meier method. Significant difference was estimated with the Log rank method. Univariate and multivariate analyses were used for the study of significance of prognostic factor. A total of 273 HCC patients were included in this analysis. According to the Cox regression analysis and Kaplan-Meier event analysis, GGT and LDH levels of liver function tests were significantly associated with HCC overall survival. Elevated serum CEA level was a risk factor related to poor HCC overall survival. And advanced BCLC staging contributed to a lower overall survival in HCC patients. HCC could benefit from surgical resection, TACE, and radiotherapy. ROC curves demonstrated that different from CEA, elevated GGT and LDH could accurately predict HCC overall survival. In conclusion, serum GGT and LDH together with higher BCLC staging should be potential predictive factors for HCC overall survival.

Overexpression of APOBEC3F in tumor tissues is potentially predictive for poor recurrence-free survival from HBV-related hepatocellular carcinoma.

UNLABELLED: The relationship between members of APOBEC3 in tumor tissues and hepatocellular carcinoma prognosis was not well studied. We compared APOBEC3 expression between tumor and non-tumor tissues based on the expression profile GSE14520 from Gene Expression Omnibus (GEO), and correlated APOBEC3 in tumor tissues with outcomes of HCC patients. APOBEC3B, which was significantly up-regulated in HCC tumor tissues (P < 0.001), was negatively associated with HCC overall survival by Cox regression (HR = 1.005, 95% CI = 1.0-1.009, P = 0.033). However, no significant difference was found of APOBEC3B and HCC overall survival by Kaplan-Meier method. HCC patients with high APOBEC3F expression in tumor tissues more likely coexist with multinodular tumors than those with low APOBEC3F level (26.4% and 13.6%, respectively, P = 0.018). Cox univariate and multivariate regression analyses revealed that APOBEC3F overexpression in tumor tissues was negatively associated with HCC recurrence (HR = 1.132, 95% CI = 1.013-1.265, P = 0.028). Additionally, the higher the APOBEC3F expressed, the greater risk of poor recurrence-free survival for HCC patients (mean survival time high = 32.25 and low = 42.68 months, respectively; log rank P = 0.012) when grouped by lower quartile cut-off of 10.98. CONCLUSIONS: Overexpression of APOBEC3F in tumor tissues is potentially predictive for poor recurrence-free survival from HBV-HCC patients. The role of other APOBEC3 members in HCC development needed further research.

Correlation of APOBEC3 in tumor tissues with clinico-pathological features and survival from hepatocellular carcinoma after curative hepatectomy.

OBJECTIVE: This study aimed to evaluate the relationships between members of APOBEC3 in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and prognosis. METHODS: Using the expression profile GSE36376 from Gene Expression Omnibus (GEO), we compared APOBEC3 expression between tumor and non-tumor tissues, and correlated this with clinico-pathological features and outcomes of HCC patients. RESULTS: A3B, A3D, A3F and A3H were overexpressed in HCC tumor tissues compared to non-tumor tissues (all P≤0.001). Cox regression shown that A3G was negatively associated with overall survival of HCC patients (HR=2.277, 95% CI=1.324-3.915, P=0.033), in contrast, A3C level in tumor tissues might play a positive role in HCC overall survival (HR=0.364, 95% CI=0.182-0.727, P=0.004). Interestingly, A3F contributed to a poor disease-free survival of HCC (HR=3.383, 95% CI=1.249-9.715, P=0.017), while A3H may be a positive factor associated with HCC disease-free survival (HR=0.25, 95% CI=0.098-0.636, P=0.004). Cirrhosis, tumor size and intrahepatic metastasis were associated with HCC poor disease-free survival (HR=1.838, 95% CI=1.308-2.583, P<0.001; HR= 1.095, 95% CI=1.042-1.15, P<0.001 and HR=3.669, 95% CI=2.447-5.5, P<0.001; respectively). Logistic regression analysis indicated that up-regulation of A3F in tumor tissues promoted HCC vascular invasion, intrahepatic metastasis and AFP elevation (all P<0.05). In contrast, A3H might decrease these risks (all P<0.05). CONCLUSIONS: APOBEC3G and APOBEC3F might be risk factors for HCC development and survival, while APOBEC3C and APOBEC3H should play positive roles in HCC aggressiveness and prognosis. Further investigation for APOBEC3 mechanisms are needed in the future.