HBV HCV Research Articles

S2592 Donor Derived HSV Hepatitis in a Kidney Transplant Patient

INTRODUCTION: It is estimated that worldwide 66% of the population is infected with herpes simplex virus type 1 (HSV-1). Despite its commonality, liver manifestations are particularly infrequent, and in most cases can lead to fulminant liver disease. In especially rare cases the infection has been reported as being donor-derived after a solid organ transplant leading to HSV hepatitis as shown in this case. CASE DESCRIPTION/METHODS: Forty-three-year-old male with end-stage renal disease presented 10 days after undergoing a deceased donor kidney transplant with a fever of 102.4ºF and diarrhea over 3 days. Initial labs show a WBC of 13 × 10^3 uL, INR of 1.9, total bilirubin 1.2 mg/dL, alkaline phosphatase 127 IU/L, alanine aminotransferase (ALT) > 5000 IU/L, aspartate aminotransferase (AST) 6,788 IU/L. He previously had no known liver disease. Empiric antibiotics were started with cefepime and vancomycin and with suspicion for HSV hepatitis, acyclovir 750mg every 8 hours. In the pre-transplant workup 6 months prior, the HSV 1 and 2 PCR, Hepatitis A, B and C panel were all negative. His medication list included levofloxacin, allopurinol and atorvastatin. Immunosuppression was tacrolimus 4mg twice daily, mycophenolic acid 1 gm twice daily and prednisone 20mg twice daily. The liver enzymes peaked at ALT > 5000 IU/L and AST > 10,000 IU/L and INR of 3.2 after 24 hours. He had no signs of encephalopathy and/or metabolic acidosis and repeat serology Hepatitis A, B, C were negative. Viral loads for HBV DNA, HCV RNA, EBV and CMV were all undetectable. HSV 1 PCR serum was not detected however HSV 2 PCR serum was > 1.0 × 10^8 copies/ mL. Later, a trans-jugular liver biopsy confirmed the diagnosis showing sub-massive hepatic necrosis with HSV. Necrosis involved 60-70% of hepatocytes and immunostain for HSV was strongly positive in necrotic areas. After 11 days of treatment with acyclovir 750mg every 8 hours his labs improved with an INR of 1.2, ALT 325 IU/L, AST 46 IU/L. HSV 2 PCR viral load trended down to 70,070 copies/mL. He remained asymptomatic and was eventually discharged home. DISCUSSION: Although rare, HSV hepatitis is a life threatening disease that we see in 75% of cases lead to liver transplantation or death. Early identification and treatment is particularly important since serology is unreliable and cutaneous lesions only occur in about 30% of cases. Without therapy one report shows in donor derived disease transmission mortality is 100%. In this clinical scenario with high suspicion, treatment can never be delayed.Figure 1.: This graph shows 8 days prior to presentation normal LFTs. Upon admission LFTs are elevated and is the day treatment began. Over time we see the gradual improvement while on treatment.

Expression of hepatic stellate cell activation-related genes in HBV-, HCV-, and nonalcoholic fatty liver disease-associated fibrosis.

Liver fibrosis is a manifestation of chronic liver injury. It leads to hepatic dysfunction and is a critical element in the pathogenesis of cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cells (HSC) plays a central role in liver fibrogenesis of different etiologies. To elucidate the molecular mechanism of this phenomenon, it is important to analyze the changes in gene expression that accompany the HSC activation process. In this study, we isolated quiescent and activated HSCs from control mice and mice with CCl4-induced liver fibrosis, respectively, and performed RNA sequencing to compare the differences in gene expression patterns between the two types of HSCs. We also reanalyzed public gene expression data for fibrotic liver tissues isolated from patients with HBV infection, HCV infection, and nonalcoholic fatty liver disease to investigate the gene expression changes during liver fibrosis of these three etiologies. We detected 146 upregulated and 18 downregulated genes in activated HSCs, which were implicated in liver fibrosis as well. Among the overlapping genes, seven transcription factor-encoding genes, ARID5B, GATA6, MITF, PBX1, PLAGL1, SOX4, and SOX9, were upregulated, while one, RXRA, was downregulated. These genes were suggested to play a critical role in HSC activation, and subsequently, in the promotion of liver fibrosis. We undertook the RNA sequencing of quiescent and activated HSCs and analyzed the expression profiles of genes associated with HSC activation in liver fibrotic tissues from different liver diseases, and also aimed to elucidate the changes in gene expression patterns associated with HSC activation and liver fibrosis.

A phase Ib/II, open-label study of tivozanib in combination with durvalumab in subjects with untreated advanced hepatocellular carcinoma.

e16599 Background: VEGFR TKIs and checkpoint inhibitors are current standards of care in HCC as single agents, however treatment options are limited, and significant unmet need remains. A recent ph3 study combining bevacizumab (VEGF-A Mab) with a PDL1 inhibitor have shown promising improvements in OS demonstrating that a combination of VEGF and PDL1 inhibition can improve patient outcomes over single agent treatment. Tivozanib (T, a potent and selective VEGFR 1, 2 & 3 TKI) and durvlaumab (D, a PD-L1 antibody) have both demonstrated single agent activity in HCC and have been combined safely with other therapies to enhance patient outcomes in other tumor types. It is hypothesized that more complete inhibition of the VEGF pathway by tivozanib compared to bevacizumab combined with PDL1 inhibition may further enhance patient outcomes. The ph1 portion of this study combines T with D to establish the recommended phase 2 dose (RP2D) and provide preliminary safety and efficacy data. Methods: Major eligibility criteria are adults with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, creatinine clearance > 40 ml/min. Major exclusion criteria are co-infection with HBV and either HDV or HCV and significant organ dysfunction. Six patients with untreated advanced HCC will be treated with the combination of T 1 mg orally for 21 days followed by 7 days off treatment and D 1500 mg intravenously every 28 days. A DLT is generally defined as the occurrence of any Grade ≥3 immune or non-immune AE in Cycle 1 that is at least possibly related to the investigational regimen other than any grade of vitiligo or alopecia or Grade 3 controllable hypertension. If two or more patients have a DLT then the dose of tivozanib will be reduced to 1 mg every other day without interruption for the second cohort. In the Phase 2 portion of the study an additional 30 patients will be treated at the RP2D. The primary objective is to establish the RP2D and the safety and tolerability for this combination in patients with advanced HCC. Secondary objectives are to assess the objective response rate, progression free survival, and overall survival in this population. Patients will be treated until progression of disease, unacceptable side effects, or death. Outcome measures will be adverse events per CTCAE v.5 and cross-sectional imaging performed every 8 weeks. Results: Phase 1 safety and efficacy findings for this novel combination will be reported at the meeting. Conclusions: Phase 1 safety and efficacy findings for this novel combination will be reported at the meeting. Clinical trial information: NCT03970616 .

The mutation profiles of HBV or HCV infected hepatocellular carcinoma patients underlie the varied responses to second-line immunotherapy.

e16629 Background: HBV and HCV infections facilitate the development of hepatocellular carcinoma (HCC) via different mechanisms, given that the DNA sequence of HBV but not HCV can integrate into the host genome. However, it remains unclear that whether the altered genomic landscape of HCC patients caused by HBV or HCV infection may result in different responses to treatments. Methods: The MSK panel sequencing results and treatment data of 127 HCC patients were downloaded from the TCGA database (MSK, Clin Cancer Res 2018). Profiles of HBV positive and HCV positive patients were extracted. Based on the treatment received, those patients were classified to sorafenib treated groups and sorafenib + immunotherapy (IT) groups. The progression-free survival (PFS, months) and overall survival (OS, months) were compared, and the mutational profiles of patients were analyzed. Results: Among patients who received sorafenib treatment alone, the mean PFS of HBV positive patients (n = 12, 4.9 ±1.1) is similar to that of the HCV positive patients (n = 21, 5.1±1.8). However, the mean OS of HBV positive patients (n = 12, 18.3 ±6.6) was longer than the mean OS of HCV positive patients (n = 21, 10.0 ±1.9). Among the patients who received immunotherapy following sorafenib treatment, the mean IT PFS of HBV positive patients was (n = 5, 4.4 ±1.8), which was longer than the mean IT PFS of HCV positive patients (n = 5, 2.5 ±0.5). Consistently, the mean IT OS of HBV positive patients (n = 5, 10.9 ±4.4) was longer than the mean IO PFS of HCV positive patients (n = 5, 4.6 ±1.0). Overall it seems that the HBV positive patients responded better to second-line immunotherapy, despite the fact that these comparisons did not reach statistical difference due to the limited sample size. By comparing the MSK panel sequencing results, mutations exclusive to the HBV or HCV infected groups were identified. Enrichment analysis showed that 7/35 mutations exclusively found in the HBV positive group are responsible for lymphocyte activation (p < 0.00001), which may underlie the better IT treatment outcome. Among the mutations restricted to the HCV infected group, 9/50 were involved in histone modification, 7/50 were involved in Hepatitis B pathways (p < 0.0001), suggesting that HCV infection may interfere with diverse molecular processes. Conclusions: HBV and HCV infected HCC patients may respond differently to second-line immunotherapy. This difference is perhaps related to the altered genetic landscape of the patients resulted from virus infections by HBV or HCV.

Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma.

BackgroundGut microbiota (GM) of patients with liver cancer is disordered, and syet no study reported the GM distribution of liver cirrhosis‐induced HCC (LC‐HCC) and nonliver cirrhosis‐induced HCC (NLC‐HCC). In this study, we aimed to characterize gut dysbiosis of LC‐HCC and NLC‐HCC to elucidate the role of GM in the pathogenesis of HCC.MethodsA consecutive series of fecal samples of patients with hepatitis (24 patients), liver cirrhosis (24 patients), HCC (75 patients: 35 infected by HBV, 25 infected by HCV, and 15 with alcoholic liver disease), and healthy controls (20 patients) were obtained and sequenced on the Illumina Hiseq platform. The HCC group contains 52 LC‐HCC and 23 NLC‐HCC. Bioinformatic analysis of the intestinal microbiota was performed with QIIME and MicrobiomeAnalyst.ResultsAlpha‐diversity analysis showed that fecal microbial diversity was significantly decreased in the LC group, and there were significant differences in 3 phyla and 27 genera in the LC group vs the other groups (the healthy, hepatitis, and HCC groups). Beta‐diversity analysis showed that there were large differences between LC and the others. Gut microbial diversity was significantly increased from LC to HCC. Characterizing the fecal microbiota of LC‐HCC and NLC‐HCC, we found that microbial diversity was increased from LC to LC‐HCC rather than NLC‐HCC. Thirteen genera were discovered to be associated with the tumor size of HCC. Three biomarkers (Enterococcus, Limnobacter, and Phyllobacterium) could be used for precision diagnosis. We also found that HBV infection, HCV infection, or ALD (alcoholic liver disease) was not associated with intestinal microbial dysbiosis in HCC.ConclusionOur results suggest that GM disorders are more common in patients with LC‐HCC. The butyrate‐producing genera were decreased, while genera producing‐lipopolysaccharide (LPS) were increased in LC‐HCC patients. Further studies of GM disorders may achieve early diagnosis and new therapeutic approaches for HCC patients.

The Effect of Chronic Viral Hepatitis on Serum Ferritin Level in Thalassemia Patients

Background: Serum ferritin is widely used as a marker of iron overload in thalassemia patients. However, the ferritin level is affected by active infections or inflammation. The association between viral hepatitis and serum ferritin level in thalassemia patients is still unclear. This study aimed to determine the effect of chronic viral hepatitis on serum ferritin level in thalassemia patients. Methods: This was a cross-sectional study in thalassemia patients aged ≥15 years-old at Chiang Mai University hospital. We expected that thalassemic patients in our clinic have a mean serum ferritin of 767 ng/mL with a standard deviation of 210 ng/mL. As a result, we have to enroll a total of 28 patients to demonstrate 30% difference of mean serum ferritin when the power was set at 80% with alpha level of 0.05. Information on chronic viral hepatitis, mean serum ferritin and liver iron concentration (LIC) as measured by T2* MRI were collected. Chronic viral hepatitis status was confirmed by either HBV DNA or HCV RNA testing. Patients were categorized to hepatitis and non-hepatitis group. Serum ferritin levels were compared between two groups. LIC measurement was used as a gold standard for iron overload. Subgroup analysis was performed according to iron overload and transfusion requirement status. Categorical and continuous variables were compared using the Chi-squared test and T-test, respectively. The correlation between viral loads and mean serum ferritin levels was analyzed by Pearson's correlation. Result: Of 32 thalassemia patients (25 non-transfusion dependent [NTDT] and 7 transfusion dependents [TDT]), 13 patients had chronic viral hepatitis (7 with hepatitis B and 6 with hepatitis C infections). The LIC between hepatitis and non-hepatitis groups were not significantly different (7.28 [SD 4.7] vs 9.08 [SD 5.2] mg Fe/g, p=0.19). In the higher LIC group (≥ 5 mg Fe/g), the mean serum ferritin level was higher in the hepatitis group than non-hepatitis group (1,776 [SD 488] vs 967 [SD 860] ng/mL, p=0.03). For the lower LIC group (<5 mg Fe/g), the mean ferritin levels were not significantly different between the hepatitis and non-hepatitis groups (646 [SD 224] vs 459 [SD 205] ng/mL, p=0.22). The correlation between the viral load and mean ferritin level in NTDT group showed a significant linear correlation with R=0.7 (p=0.04). Conclusions: We observe a higher serum ferritin level among thalassemia patients who concurrently have chronic viral hepatitis. Chronic viral hepatitis is a possible cause of a falsely high ferritin level in these patient population. Furthermore, the viral load is positively correlated with serum ferritin level. Disclosures No relevant conflicts of interest to declare.

Detecting Liver Fibrosis by Recent Reliable Biomarkers in Viral Hepatitis Patients

Abstract Objectives By far, chronic viral hepatitis and its complications have been considered a fatal health public issue. Liver biopsy has a pivotal role to distinguish patients who need proper care and regular screening. The correlation between alternative biomarkers and liver fibrosis has been studied by current research to avoid histopathology techniques. Methods Several biomarkers such as COLL-IV, COMP, and hyaluronic acid besides scoring systems (FIB-4, APRI, NAFLD, and SHASTA) were measured and calculated in 143 infected cases with HCV and HBV. Also, the same parameters were determined in 75 healthy persons as controls. The Metavir system was used to classify infected cases from F0 to F4. Alternative marker levels were determined by using the ELISA technique. HBV DNA and HCV RNA were quantified by implementing the RT-PCR assay. Noninvasive markers were approved by comparison with the mentioned scoring indexes. Results Our research has indicated that hyaluronic acid, COMP, Coll-IV, and scoring indexes of fibrosis discriminate fibrosis cases from the nonfibrosis group. The studied biomarkers have high sensitivity from 77.05% to 96.72% and accuracy from 89.71% to 97.79% as well as their cutoff, which approved the aim of this study. Thereafter, the studied markers’ reports assisted in differentiating primary stages F1+F2 from late levels F3+F4 of fibrosis. Conclusions According to reports of the current study, serum markers including HA and CO-IV have performed better than biopsy in excluding advanced fibrosis from mild fibrosis patients comfortably as well as differentiating fibrosis patients from healthy individuals, while the COMP test has low accuracy and needs further research. Scoring systems alone are likely not sufficiently sensitive to rule out significant disease. Hence, gathering serological markers and scoring indexes are being perfected to determine all stages of fibrosis definitely. However, further research is needed to prove reliable noninvasive markers of liver fibrosis.

Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort.

To evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017. In total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of ≥2.5× upper limit of normal (ULN) for patients with normal baseline values or ≥2.5× baseline for patients with higher baseline values. One hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25-0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02-0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission. In our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections.

Prevalence of hepatitis B and hepatitis C among diabetes mellitus type 2 individuals.

Diabetes mellitus type 2 (DM2) patients have higher risk to be infected with parenterally transmitted viruses, like hepatitis B or C virus. This study aims to determine HBV and HCV infection prevalence in DM2 patients from Northeast and Southeast Brazil. A total of 537 DM2 patients were included, 194 (36.12%) males and 343 (63.87%) females, with mean age of 57.13±11.49 years. HBV and HCV markers were determined using serological and molecular analysis, and risk factors were evaluated in a subgroup from Southeast (n = 84). Two HBV acute (HBsAg+/anti-HBc -) and one HBV chronic case (HBsAg+/anti-HBc+) were found. Six individuals (1.1%) were isolated anti-HBc, 37 (6.9%) had HBV infection resolved (anti-HBc+/anti-HBs+), 40 (7.4%) were considered HBV vaccinated (anti-HBc-/anti-HBs+). Thirteen patients (2.42%) had anti-HCV and 7 of them were HCV RNA+. In the subgroup, anti-HBc positivity was associated to age and anti-HCV positivity was associated to age, time of diabetes diagnosis, total bilirubin, indirect bilirubin, alkaline phosphatase at bivariate analysis, but none of them was statistically significant at multivariate analysis. As conclusion, low prevalence of HBV and high prevalence HCV was found in DM2 patients.

Evaluation of hepatitis B virus and Hepatitis C virus frequency in hemodialysis patients

Aim: This study aimed to investigate the prevalence of the hepatitis B virus and hepatitis C virus in patients undergoing hemodialysis in Karabuk city.Material and Methods: For patients presented to the Karabuk University Training and Research Hospital for hemodialysis between January 2016 and December 2018, HBsAg, anti-HBs, and anti-HCV assays were conducted using the chemiluminescence method and HBV DNA, HCV RNA and HCV genotyping tests were conducted using real-time polymerase chain reaction. The data was retrospectively evaluated.Results: Of 345 patients undergoing hemodialysis, 211 (61.2%) were male and 134 (38.8%) were female. The mean age of the patients was 62 (15–96) years. Moreover, 0.9% (n = 3) of patients were HBsAg positive and 4.3% (n = 15) were anti-HCV positive. Three patients with HBsAg positivity were also HBV DNA positive. Of the 15 patients who were anti-HCV positive, 12 were also HCV RNA positive. Of these, eight patients had the HCV genotype 1b and four patients had the genotype 4. Anti-HBs seropositivity was detected in 65.8% of patients. The highest Anti-HBs seropositivity rate was observed in patients aged 40 years (76%) and the difference between age groups was statistically significant (p = 0.002). Conclusion: In our study, the prevalence of HBsAg seropositivity in patients undergoing hemodialysis (0.9%) was lower than that reported by the Turkish Society of Nephrology (2.65%). This difference may arise from the high anti-HBs seropositivity rate. Conversely, the prevalence of anti-HCV seropositivity (4.3%) was similar to the mean prevalence in Turkey (4.2%). Infection prevention measures against viral hepatitis should be strictly implemented, especially in hemodialysis units.

Evaluation of 2015-2016 MOTAKK HBV DNA and HCV RNA external quality assessment national program results

MOTAKK, as a national external quality control program has been launched to evaluate the molecular detection of viral infections including HBV DNA and HCV RNA in molecular microbiology diagnostic laboratories in Turkey. This program is prepared in compliance with ISO 17043:2010 (Conformity assessment general requirements for proficiency testing) standards, and aims to take the place of external quality control programs from abroad, contributing to standardization and accuracy of molecular diagnostic tests in our country. The aim of this study was to evaluate 2015 and 2016 results of the MOTAKK External Quality Control Program for HBV DNA and HCV RNA viral load . The calls were announced on the web page of MOTAKK (www.motakk.org). The quality control samples were sent to participating laboratories in 2015 and 2016. Main stocks were prepared from patients with chronic hepatitis B and C who had viral load detection with reference methods according to WHO reference materials for viral load studies to improve quality control sera. From these main stocks, samples with different viral loads were prepared from dilutions of plasma with HBV, HCV, HAV, HIV, Parvovirus B19 and CMV negative serologic markers. Quality control samples were sent to the participating laboratories along with the negative samples in the cold chain. The laboratories accomplished the related tests within 2-3 weeks and entered their results on the MOTAKK web page. These results were analysed according to ISO 13528 (Statistical methods for use in proficiency testing by interlaboratory comparison) and scoring reports were created by a software developed by MOTAKK and sent to participating labs. Each laboratory evaluated their own results in comparison with the other laboratory results, reassessed the tests via observing the distance from the mean result and the reference values. The number of laboratories participating in the HBV DNA and HCV RNA external quality control program was 70-73 in 2015-2016. Participants were able to comply with the program tools, registering, entering results and receiving the results reports without problem. In HBV panel, 72.6-89.1% and 84.7-90.3% of the participant laboratories were in 1 standard deviation (SD) in 2015-2016, respectively. In HCV panel, 70.8-89.1% and 84.7-90.3% of the participant laboratories were in 1 SD in 2015-2016, respectively. A national external quality control program for HBV DNA and HCV RNA in Turkey has been prepared for the first time with this project and implemented successfully. All the data provided in the MOTAKK external quality control program final report, compensate all the data provided by the quality control program final reports from abroad; additionally, the report allows comparison of used technologies and commercial products.

PREVALENCE OF HEPATITIS B AND HEPATITIS C VIRUS INFECTIONS AT PREMARITAL SCREENING PROGRAM IN DUHOK, IRAQ

Background: Viral hepatitis causes increasing mortality worldwide despite all the efforts to control this health problem. Premarital screening program provides an opportunity to detect and manage hepatitis B and hepatitis C viruses. Determination of a carrier status during premarital testing will create awareness between the couples and lead to the protection of the prospective spouse by early vaccination or treatment. The objective of this study is to determine the prevalence of hepatitis B and hepatitis C virus infections among premarital couples in Duhok, Iraq. Subject and Methods: This cross-sectional study was conducted from August 2016 to April 2017 in the clinic and laboratory of the premarital screening program within the preventive health affairs in Duhok-Iraq. The sample size was 2000 persons (1000 males and 1000 females). All persons were tested for HBs Ag, total anti-HBc, and anti-HCV. Results: The age ranged from 14 years to 75 years with a mean of 25.1 years (95% CI = 24.8-25.4 years). The prevalence of HBV infection was 1.1% (N=22), isolated anti-HBc as 3.1% (N=62) and HCV seropositivity was 0.2% (N=4).The factors associated with HBV and HCV were being a health professional (P <0.001), having a history of trauma (P =0.003) and having a family history of HBV or HCV (P<0.001). Conclusions: The prevalence of HBV infection, isolated anti-HBc, and HCV seropositivity is low among the premarital people. Including total anti-HBc in the current premarital screening program will detected anti-HBc which helps in the efforts to control and manage HBV.

Commentary: A review of risk of hepatitis B and C transmission through biting or spitting.

A draft UK Parliamentary Bill sought to criminalize assaults on emergency workers through biting and spitting. This seemed to be based on a fear of bloodborne virus transmission. We undertook a literature search to clarify the risk of hepatitis infection from such exposures. We identified 245 possible papers and then reduced these to those relevant to HBV and HCV transmission through biting or spitting and the scientific plausibility. Nine papers were identified, reporting 16 possible cases of HBV (15 bites, 1 spitting) and 2 of HCV transmission (both bites). Only 3 HBV transmissions by bites and 1 by spitting and both HCV transmissions were felt to be plausible. Although both HBV DNA and HCV RNA can be found in the saliva of infected patients, it seems unlikely that there is enough to transmit infection unless there is blood contamination. In conclusion, the risk of acquiring HCV through spitting is negligible and is very low for HBV. The risk is also low for acquiring HBV and HCV through biting, especially if no blood is apparent in the saliva.

CDKN2A promoter methylation and hepatocellular carcinoma risk: A meta-analysis

Lots of studies have explored cyclin-dependent kinase inhibitor 2A (CDKN2A) promoter methylation in hepatocellular carcinoma (HCC), but the established results were controversial. Hence, we conducted the meta-analysis to comprehensively investigate the association between CDKN2A promoter methylation and HCC risk. A comprehensive search was implemented through searching PubMed, Web of Science and Embase. Associations of CDKN2A promoter methylation with HCC risk, clinicopathological features, and CDKN2A expression were assessed by the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Subgroup analyses and meta-regression were served for exploring the potential sources of heterogeneity. A total of 59 articles including 3067 cases and 2951 controls were incorporated in this meta-analysis. Overall, we observed a high CDKN2A promoter methylation rate (58.18%) in HCC and a significant association between the methylation and HCC risk (OR, 7.07; 95% CI, 5.67-8.80). Furthermore, CDKN2A promoter methylation was robustly associated with decreased mRNA (OR, 13.89; 95% CI, 5.44-35.45) and protein (OR, 48.19; 95% CI, 5.56-417.29). In addition, we found the methylation was related with HBV infection (OR, 3.31; 95% CI, 1.47-7.47), HCV infection (OR, 2.76; 95% CI, 1.80-4.23), cirrhosis status (OR, 1.57; 95% CI, 1.01-2.44) and older age (OR, 1.83; 95% CI, 1.14-2.94). Our results indicated that CDKN2A promoter methylation was associated with an enhancive HCC risk and played a crucial role in the process of HCC with a potential value to being a triage marker for HCC.

Seroprevalence and risk factors of hepatitis B and C virus infections in female workers of Lao garment factories.

The prevalence of hepatitis B and C virus infections may be higher in vulnerable populations or in individuals likely to be exposed through risk behaviors such as female garment factory workers in Lao People’s Democratic Republic. A cross-sectional study was performed on 400 female garment workers in Vientiane Capital. Women were tested for hepatitis B virus surface antigen and antibodies against hepatitis B core, surface antigen and hepatitis C virus using commercial Enzyme-linked immuno-absorbent assays. Participants completed a standardized questionnaire about potential risk factors for both infections. Sixteen women (4±1.9%) were HBsAg carriers, 187 (47%) had anti-HBc, 116 (29%) anti-HBs and 7 (1.8±1.3%) anti-HCV antibodies. Three factors were significantly associated with the presence of anti-HBc (indicating previous exposure to HBV): (i) residence in dormitories, (ii) more than one sexual partner, (iii) history of abortion. Despite a high risk of exposure, the prevalence of anti HBV and anti HCV infection markers in this sample of female workers was not higher than in the Lao general population. Our data suggest that exposure to HBV happens later during life and was significantly associated with sexual risk behavior. Thus, this study highlights the vulnerability of these women who were mostly young, uneducated, unvaccinated, of rural origin and were not aware of the risk of infections. An occupational health program targeting the female factory workers should be implemented in Lao PDR.

An important role of SREBP-1 in HBV and HCV co-replication inhibition by PTEN

HBV HCV co-infection leads to more severe liver diseases including liver cancer than mono-infections. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor, inhibits sterol regulatory element binding protein-1 (SREBP-1). In this study, we characterized the effect of the PTEN – SREBP-1 pathway on HBV HCV co-replication in a cellular model. We found that HBV and HCV can co-replicate in Huh-7 cells with no interference. Overexpression of PTEN inhibits, whereas PTEN knockdown enhances, HBV replication as well as HBV and HCV co-replication. Knocking down SREBP-1 decreases HBV replication in an HBx-dependent manner. SREBP-1 knockdown also decreases HCV replication. PTEN knockdown is concomitant with increased nuclear SREBP-1 levels. PTEN and SREBP-1 double knockdown results in intermediate levels of HBV and HCV replication in mono- and co-replication scenarios. Taken together, we demonstrated, for the first time, that the PTEN – SREBP-1 pathway can regulate HBV HCV co-replication.

Prevalence and risk factors for HBV and HCV in prisoners in Iran: a national bio‐behavioural surveillance survey in 2015

To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Cross-sectional study of 6200 Iranian prisoners in 2015. Data were collected through questionnaires and interviews. HBV infection and HCV exposure status of the participants was determined by HBsAg and HCV antibodies blood tests using enzyme-linked immunosorbent assay (ELISA). Data were analysed in STATA-12. Prevalence of HCV exposure was 9.48% (95% CI: 8.73-10.27), and prevalence of HBV was 2.48% (95% CI: 2.07-2.89) in the general prison population. In multivariate analysis, the most important risk factor for HBV was a history of drug use in lifetime (adjusted odds ratio, AOR: 1.8, 95% CI: 1.17-3.02). The main risk factors for HCV exposure were a history of drug use in lifetime (AOR: 4.08, CI: 2.56-6.27), age over 30 (AOR: 2.68, CI: 2.01-3.56), and having tattoos (AOR=1.67, CI: 1.35-2.07). Although vaccination is used to control HBV among prisoners, prevalence of HCV exposure is alarming in the prison population of Iran, especially among people who inject drugs. Eliminating viral hepatitis in Iran by 2030 requires a national commitment and rapid measures for targeting this high-risk group. Given the increased efficiency of HCV treatment in recent years, prisons provide an opportunity to access patients for treatment.

Seroprevalence occurrence of viral hepatitis and HIV among hemodialysis patients

Patients with chronic renal failure (CRF) were on maintenance invasive haemodialysis (HD) procedure. This procedure by itself affects immunity of the patients and they become more susceptible to viral infections. We investigate the occurrence of HBV HCV and HIV infections in patients with hemodialysis. A retrospective study of 430 endstage renal failure patients referred to hemodialysis department at AlKindy Teaching Hospital Baghdad, Iraq from January 2015 to January 2017 was conducted. Patients were investigated for HBsAg using enzymelabeled antigen test (ForesightEIAUSA) HCV Abs (IgG) specific immunoglobulin using a HCV enzymelabeled antigen test (ForesightEIAUSA) and anti HIV Abs (IgG) using enzymelabeled antigen test (ForesightEIAUSA). The frequency of HBV infection in the first year was not significant between males (111%) and females (000%)(P = 0295). About HCV also there are no significant differences between males (1263%) and females (931%)(P = 0347). After one year of follow up the frequencies of HBV and HCV were not significant between two sexes. Additionally none of the patients had an HIV infection. This study brings to light that HBV and HCV have the same frequencies in both genders and lower occurrence with time. Furthermore HIV was not detected in those patients.

Serum level of IL-6 in liver cirrhosis patients

Cytokines are polypeptides that have a wide spectrum of inflammatory, metabolic, hematopoietic and immunologic regulatory properties. The liver represents an important site of synthesis and clearance organ for several cytokines. This study aimed to evaluate serum IL-6 in liver cirrhosis with the type of underlying disease, child pugh group and various clinical and laboratory parameter. This cross-sectional study was at Adam Malik General Hospital and Pirngadi General Hospital from July - December 2016. We examine 75 patients with liver cirrhosis. The exclusion criteria were hepatoma, sepsis and renal impairment. There were 28 (37.3%), 8 (10.6%) and 39 (52%) for HBV-positive; HCV-positive and HBV- HCV negative liver cirrhosis patients, respectively were 14 (18.7 %), 15 (20 %) and 46 (61.3%) for Child- Pugh A, B and C respectively. There was no significant difference value of IL-6 between HBV positive, HCV positive, and HBV-HCV negative group (7.7/6.1/10.9). There was no significant difference value of IL-6 between child pugh A, B, and C group (4.2/11.0/7.9).

Role of Plasma Osteopontin Level as a Predictor of Hepatic Fibrosis Regression and Response to Antiviral Treatment in Patients with Chronic HBV or Chronic HCV Infection

Background: Hepatitis B virus and Hepatitis C virus infection is one of the public health problems in Egypt. So we aimed to evaluate the efficacy of serum osteopontin as predictor of hepatic fibrosis regression and virological response in patients with chronic HBV or HCV infection. Methods: This study has been conducted on 74 HBeAg + ve chronic HBV infection, 74 chronic HCV infection and 74 healthy controls. HBV patients treated with Entecavir. HCV patients treated with sofosbuvir, daclatasvir with or without ribavirin. One year post HBeAg seroconversion and 3 months after end of regular antiviral treatment for patients with chronic HBV and chronic HCV infection respectively, hepatic condition was reevaluated. Results: 14.9% of patients with HBV, failed to achieve undetectable HBV DNA or HBeAg seroconversion and 2.7% of patients with HCV infection, failed to achieve SVR. In chronic HBV, pretreatment high serum osteopontin predict failure of virological response and hepatic fibrosis regression at a cutoff > 115.5, with 90.91% sensitivity, 82.54% specificity. Also high degree of liver stiffness predicts failure of hepatic fibrosis regression at a cutoff > 8.7, with 81.8% sensitivity, 73% specificity. Conclusions: In chronic HBV infection low osteopontin predicts good virological response and hepatic fibrosis regression. But it has no role in predicting SVR or hepatic fibrosis regression in chronic HCV infected patients.