Hepatitis C Virus Infection in Pregnancy: An Update.

Parenteral transmission is the major route of hepatitis C virus transmission in adults; however, vertical transmission is most common in children. There are several factors that have been shown to be associated with vertical transmission of hepatitis C virus, including hepatitis C virus RNA, human immunodeficiency virus coinfection, and peripheral blood mononuclear cell infection. As there is no effective vaccine to prevent hepatitis C virus infection, and there are no human data describing the safety of the new direct acting antiviral agents in pregnancy, the only preventive strategy for vertical transmission is to treat the hepatitis C virus infection before becoming pregnant. Direct acting antiviral agents are interferon-free, and many are also ribavirin-free. Based on animal studies, sofosbuvir plus ledipasvir may be the best safety profile during pregnancy for now; however, it is too early to recommend treating hepatitis C virus-infected pregnant women with these direct acting antiviral agents currently.

Macrophage Activation Marker Soluble CD163 Is a Dynamic Marker of Liver Fibrogenesis in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Background: Coinfection with human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV)-related liver fibrosis. Macrophages are triggered during both viral infections and are critical in liver inflammation/fibrogenesis. Liver fibrosis strongly associates with serum soluble CD163 (sCD163, a macrophage activation marker); comprehensive evaluation in HIV/HCV coinfection is lacking. Methods: We retrospectively analyzed sCD163 (enzyme-linked immunosorbent assay) and hepatic CD163 (immunofluorescent CD163/CD68 costaining) in patients infected with HIV/HCV, HCV, or HIV, pre- and post-antiviral therapy. Results: sCD163 was significantly higher in HIV/HCV compared to either monoinfection, and decreased following successful antiviral therapy, although did not fully normalize. In HIV/HCV, sCD163 was associated with necroinflammation, Ishak fibrosis scores, and noninvasive fibrosis scores. We observed a novel trend whereby sCD163 levels progressively increase with increasing Ishak fibrosis score, peaking at stage 4, above which levels plateaued. Periportal CD163+ macrophage frequency was also higher with increasing fibrosis score. When stratified by fibrosis stage, sCD163 levels were higher in HIV/HCV than HCV but only in individuals with mild to moderate fibrosis. Conclusions: In HIV/HCV, increasing sCD163 levels accompanied periportal CD163+ macrophage enrichment in mild to moderate fibrosis, but not in established cirrhosis, suggesting that sCD163 is a dynamic biomarker of fibrogenesis rather than accumulated fibrosis. Our findings implicate HIV-related macrophage activation in accelerated fibrosis progression in HIV/HCV coinfection.

Mean platelet volume could be possible biomarker in early diagnosis and monitoring of gastric cancer.

Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related deaths worldwide. The early diagnosis of gastric cancer is fundamental in decreasing the mortality rates. It has been shown that MPV level is a sign of inflammation in hepatocellular carcinoma and pancreatic adenocarcinoma. The aim of this study is to examine whether MPV would be a useful inflammatory marker for differentiating gastric cancer patients from healthy controls. Thirty-one gastric cancer patients and 31 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. MPV level was significantly higher in pre-operative gastric cancer patients compared to healthy subjects (8.31 fL vs. 7.85; p: 0.007). ROC analysis suggested 8.25 fL as the cut-off value for MPV (AUC: 0.717, sensitivity: 61%, specificity: 81%). Surgical tumor resection resulted in a significant decrease in MPV level (8.31 fL vs. 7.55 fL; p: 0.001). No significant difference was found in MPV level between the post-operative group and control subjects. We did not find statistically significant difference between MPV and TNM stages. In conclusion, changes in MPV values may be used as an easily available biomarker for monitoring the healthy patients for GC risk and may prompt physicians to make an early diagnosis of GC.

M30 does not predict the severity of hepatosteatosis, whereas adiponectin level declined with increase of ALT and the severity of hepatic steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging problem all over the world. Because NAFLD and polycystic ovary syndrome (PCOS) are both closely related with insulin resistance, it would be necessary to determine the rate of presence of NAFLD in PCOS patients. So, this study aimed to investigate the utility of M30 in PCOS patients for the diagnosis of hepatic injury. METHODS: Eighty patients with PCOS were included in the study. Ultrasonographic examination for the presence of hepatic steatosis, M30 serum level for determining the severity of ongoing apoptotic cell death in liver, and BARD index for defining the hepatic injury were performed during the study. 25-OH vitamin D and adiponectin level in sera were studied using ELISA (Enzyme-Linked ImmunoSorbent Assay). RESULTS: M30 and vitamin D levels did not change significantly with the severity of hepatic steatosis. On the other hand, M30 levels showed a positive correlation with ALT and AST levels, and M30 level suddenly increased with the presence of hepatic steatosis from 159.7 to 170 U/l, however stabilized with the increasing severity of hepatic setatosis. Adiponectin levels decreased with the increasing severity of hepatic steatosis and significantly varied between ALT greater than 40 U/l and less than 40 U/l. CONCLUSIONS: M30 level in serum increased with the appearance of hepatic steatosis and had a positive correlation with a noninvasive hepatic injury test, BARD (BMI, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio [AAR], diabetes mellitus [DM]) index. Adiponectin level decreased with the increasing ALT level and severity of hepatic steatosis.

Through-the-Scope Suturing for Late-Onset Fistula Closure in the Setting of Bariatric Surgery.

Anastomotic leaks related to bariatric surgeries are uncommon but are related to increased morbidity and mortality. With the recent advances in intraluminal endoscopic interventions, there are some alternative options to close the leak via over-the-scope-clips/suturing or through-the-scope-clips/suturing or covered stent placement. Herein, we aimed to discuss the efficiency and the role of the through-the-scope suturing technique (X-Tack-160-H, Apollo Endosurgery, Austin, Texas, United States) in two different cases who presented with anastomotic leaks following bariatric surgery.

Fetuin-A mRNA expression is elevated in NASH compared with NAFL patients.

Fetuin-A is a pro-inflammatory protein expressed by hepatocytes. Its course in morbidly obese patients with NAFLD (non-alcoholic fatty liver disease) following weight loss by BAS (bariatric surgery) has not been fully elucidated yet. In the present study, we prospectively examined the effects of weight loss on various metabolic factors at 4 weeks and 6 months after surgery. Blood and liver tissues were retrieved from 108 morbidly obese NAFLD patients before/during BAS, and 50 of these individuals met the criteria for NASH (non-alcoholic steatohepatitis). Fetuin-A expression was measured by qPCR (quantitative real-time PCR), Western blotting and immunohistochemistry. Hepatocyte apoptosis was quantified via M30 (caspase-cleaved cytokeratin-18 fragments). Plasma concentrations of adiponectin and fetuin-A were determined by ELISA. Serum-derived parameters were additionally taken at 4 weeks and 6 months post-operatively. In addition, primary human hepatocytes were treated with NEFA (non-esterified fatty acid) to investigate changes in fetuin-A. BMI (body mass index) decreased significantly from 53.0±1.1 to 36.4±1.9 kg/m2 in the NAFL group and from 53.3±1.1 to 37.6±1.2 kg/m2 in the NASH group (P<0.0001) at 6 months post-surgery. This was associated with diminishing M30 and M65 (total cytokeratin-18) levels over 6 months after surgery. Adiponectin levels increased continuously in NASH patients, whereas NAFL patients plateaued at 4 weeks post-operatively. Hepatic fetuin-A mRNA and protein expression was elevated before surgery-induced weight loss. However, plasma concentrations of fetuin-A increased signficantly in NASH patients 4 weeks post-operatively. Treatment of hepatocytes with NEFA led to up-regulation of fetuin-A expression. BAS probably has a beneficial effect on NAFLD, as indicated by reduced hepatocyte apoptosis and improved adipokine profiles. In addition, fetuin-A expression is more prominent in NASH.

Expression of apoptosis- and vitamin D pathway-related genes in hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and therapeutic options are scarce. As they might represent future targets for cancer therapy, the expression of apoptosis-related genes in HCC is of particular interest. In this pilot study, we further examined apoptosis-related genes in human HCC and also focused on vitamin D signaling as this might be a regulator of HCC cell apoptosis. METHODS: We employed tumor tissue and serum samples from 62 HCC patients as well as 62 healthy controls for these studies. Tissue and serum specimens were analyzed by quantitative RT-PCR, immunohistochemistry and ELISA. RESULTS: In HCC patients the apoptosis marker M30 was found to be elevated and several pro-apoptotic (TRAIL, FasL and FasR) as well as anti-apoptotic genes (Mcl-1 and Bcl-2) were simultaneously upregulated in tumor tissue and especially tumor-surrounding tissue as compared to healthy control livers. Moreover, vitamin D serum levels were decreased in HCC patients whereas vitamin D receptor mRNA expression was increased in tumor tissue and tumor-surrounding tissue as compared to healthy livers. CONCLUSIONS: In human HCC, M30 serum levels are elevated indicating an increased cell turnover. Modulation of the vitamin D pathway might be a supportive, pro-apoptotic HCC therapy.

Adding pineapple juice to a polyethylene glycol-based bowel cleansing regime improved the quality of colon cleaning.

BACKGROUND/AIMS: An unsuccessful colonoscopy procedure is often related to inadequate bowel cleansing. It is difficult for patients to finish the whole 4 liters of polyethylene glycol-electrolyte lavage (PEG-EL) because of its salty taste and the large quantity. Pineapple juice has been shown to be an effective agent in the dissolution of undigested food in the stomach. This study assessed the effectiveness of both 2 and 4 liters of PEG-EL in precolonoscopic bowel cleansing and the quality of colonoscopic cleaning by adding 1 liter of pineapple juice to a reduced-volume PEG-based regime. METHODS: The patients were chosen from those undergoing a colonoscopic procedure. A total of 126 patients were randomized into 3 groups receiving 3 different PEG-EL (Golytely®) regimes, i.e. 4 liters of PEG-EL (group 1, n = 44), 2 liters of PEG-EL (group 2, n = 39) or 2 liters of PEG-EL with 1 liter of pineapple juice (Dimes® 100%; group 3, n = 43). RESULTS: Both the 4- and 2-liter PEG-EL regimes resulted in similar bowel cleansing scores in all parts of the colonic segments. However, adding 1 liter of pineapple juice to the reduced-volume PEG-EL regime improved the quality of the cleansing on the right side of the colon and in the transverse colon. Adequate bowel cleansing was achieved in 68.1% of the patients in group 1, 63.9% in group 2 and 80% in group 3 (the lowest score in one of the segments). On the other hand, the tolerability of the regimes was similar in all 3 groups (p = 0.509). CONCLUSIONS: Reduced PEG-EL (2 rather than 4 liters) may be sufficient for precolonoscopic bowel cleansing in the Turkish population. Administration of pineapple juice in the reduced-dose preparation regime may improve the quality of the bowel cleaning.

Direct medical costs associated with rheumatoid arthritis in Turkey: analysis from National Claims Database.

This study aimed to estimate and identify determinants of direct medical costs associated with rheumatoid arthritis (RA) in Turkey using nationwide real-world data. Using the Turkish National Health Insurance Database (2009-2011), RA patients (ages 18-99) were identified using International Classification of Disease Tenth Revision Clinical Modification (ICD-10-CM) codes. Patients were required to have two RA diagnoses at least 60 days apart and were grouped as prevalent and incident cases. The date of the first RA claim was identified for each patient and designated as the index date. Total healthcare costs were examined over the 12-month period following the index date. Descriptive and multivariate analyses are provided. Generalized linear models were used to calculate expected annual costs for incident and prevalent RA patients after controlling for age, gender, region, comorbid conditions and medication. A total of 2,613 patients met all inclusion criteria (693 incident; 1,920 prevalent patients). Prevalent patients were older, less likely to reside in the Marmara region, had higher comorbidity index scores and were more likely to use non-steroidal anti-inflammatory drugs, biologics and disease-modifying anti-rheumatic drugs relative to incident patients. Average direct annual costs were 2,000 [(1,750, 2,247) 95 % CI] for incident cases and 2,385 [(2,224, 2,545) 95 % CI] for prevalent cases, most due to pharmacy costs (73 % for incident cases, 60 % for prevalent cases). For incident and prevalent cases, a significant portion of inpatient and outpatient costs were due to physician costs (31 % for incident cases, 40 % for prevalent cases). Although the costs were not significantly different in terms of age or region, prior comorbid conditions and medication use significantly affected the cost estimation. RA total annual costs were found to be lower in Turkey, relative to estimates in Europe. The significant portion of the annual costs was due to pharmaceutical expenditures. Comparative effectiveness analysis may be useful to decrease RA-related pharmacy costs.

Risk factors for intensive care unit acquired nasal colonization of MRSA and its impact on MRSA infection.

OBJECTIVE: We aimed to determine the risk factors of methicillin-resistant Staphylococcus aureus (MRSA) colonization, and the impact of colonization on MRSA infection to evaluate the necessity of MRSA survey program in intensive care units (ICUs) in Turkey. METHODS: The patients hospitalized in medical and neurosurgical ICUs longer than 24 hr were included into the study. To determine anterior nares MRSA colonization, swabs were taken from each patient in the first 48 hr, and followed by once a week till discharge from ICUs. RESULTS: During the one-year follow-up period, the number of the hospitalized patients who spent more than 24 hr in ICUs was 195 of 372 and 85 of 619 in medical and neurosurgical ICUs, respectively. Totally, 23 out of 280 patients (14 from medical ICU, 9 from neurosurgical ICU) were colonized with MRSA, and 11 out of 23 colonized patients were accepted as ICU-acquired infection. The duration of ICU hospitalization in patients with ICU-acquired MRSA colonization was found to be longer than the noncolonized patients (18 days vs. 8 days, P value < 0.001). The presence of gastrostomy and femoral catheter were determined as risk factors for ICU-acquired MRSA colonization. The percentages of MRSA infection in patients with and without MRSA colonized were 8.6% and 1.1%, respectively (P value: 0.009). CONCLUSION: The presence of gastrostomy and femoral catheter, and the duration of ICU hospitalization were found to be related with ICU-acquired MRSA colonization. Also, MRSA nares colonization increased the rates of both MRSA infection and ICU hospitalization.

Is there an association between the measurement of qualitative HBsAg and virologic response in chronic HBV infection?

BACKGROUND: In the follow up of chronic hepatitis B infection (HBV), a significant correlation between quantitative HBsAg titer measurement and HBV DNA level, and moreover with intrahepatic covalently closed circular DNA was already shown. However, besides their impact on long-term follow up, they are really expensive methods, and not available widespread. We aimed to investigate the utility of qualitative measurement of HBsAg titer in prediction of virologic response at the end of the first year of anti-viral treatment in chronic HBV infection. MATERIAL AND METHODS: A total of 70 patients receiving anti-viral therapies for chronic HBV infection were included into the study. The patients were evaluated according to Hbe Ag status and response to treatment. The determinations used in the study (biochemical, virologic responses, primary non-response) were accepted as it was described in AASLD. RESULTS: Qualitative HBsAg titer increased significantly in both HBeAg positive and negative patients (p values 0.002 and < 0.000). Increasing of HBsAg titer in first three months is more dramatic in responder group, however the difference was disappeared at the sixth and twelve moths on follow up. Similarly, a fast increasing in anti-HBe titer in HBeAg negative chronic HBV patients was related with higher response at the end of first year therapy. However, the changings at the 12th month of anti-viral treatment were similar in both responder and non-responder groups. CONCLUSION: In conclusion, the fast increase in qualitative measurement of HBsAg titer seemed to be a predictor of higher anti-viral medication success in chronic HBV patients. However, this meaningful increasing was disappeared on the follow up, particularly after the six months examination.

LOXL-2 and TNC-C are markers of liver fibrogenesis in HCV/HIV-, HIV- and HCV-infected patients.

Background: Lysil oxidase like enzyme-2 (LOXL-2) and TNC-C play important roles in organ fibrosis. We assessed circulating LOXL-2 and TNC-C levels and their relationship to fibrosis severity in HIV- and/or HCV-infected individuals. Methods: Healthy controls (n = 22), HIV mono- (n = 15), HCV mono- (n = 52) and HCV/HIV-co-infected (n = 92) subjects were included. Results: LOXL-2 and TNC-C levels were significantly higher in HCV mono- and HCV/HIV-co-infected individuals with F0 compared to healthy controls. In addition, in HCV/HIV-co-infected individuals, LOXL-2 levels were higher in intermediate fibrosis compared to no/mild fibrosis. Conclusion: In HCV/HIV-co-infected study participants, both LOXL-2 and TNC-C were significantly higher in intermediate fibrosis compared to no/mild fibrosis, but did not further increase with advanced fibrosis. Furthermore, both markers were elevated among HCV/HIV-positive individuals with mild/no fibrosis.

Mean platelet volume as a fibrosis marker in patients with chronic hepatitis B.

INTRODUCTION: Many noninvasive tests have been studied for the diagnosis and determining the liver fibrosis score (LFS). In this study, we aimed to research the correlation of mean platelet volume (MPV) and stage of liver fibrosis in patients with chronic hepatitis B (CHB). PATIENTS AND METHODS: Fifty-nine patients with CHB were enrolled retrospectively into the study. Age-sex matched 25 healthy subjects were used as control group. The following data were obtained from computerized patient registry database: HBV-DNA level, hepatitis B e-antigen seropositivity, liver enzymes and function tests, white blood cell count, platelet count, hemoglobin, histological activity index, LFS, and MPV. Patients were divided into two groups: patients without significant fibrosis (F0, F1, or F2) (Group 1) and patients with advanced fibrosis (F3, F4) (Group 2). RESULTS: A statistically significant increase in MPV was seen in patients with CHB compared with healthy controls (8.49±0.84 fl vs.7.65±0.42 fl, P<0.001). Receiver operating characteristic curve analysis suggested that the optimum MPV level cut-off points for CHB was 8.0 fl, with sensitivity, specificity, PPV, and NPV of 68, 76, 86, and 50%, respectively. MPV levels were significantly higher in Group 2 (8.91±0.94 fl, P: 0.009) compared with Group 1 (8.32±0.74 fl). ROC curve analysis suggested that the optimum MPV level cut-off points for Group 2 was 8.45 fl, with sensitivity, specificity, positive and negative predictive value of 77, 59, 45, and 85%, respectively. Multivariable logistic regression model, which consisted of HAI, ALT, HBV-DNA, platelet count, and MPV, was performed. We showed that MPV was independently associated with advanced fibrosis (P: 0.031). CONCLUSION: We suggest that MPV might help in the assessment of fibrosis in CHB. It should not be considered a stand-alone test for this use owing to nonspecificity with other diseases.

Cutoff level to detect heterozygous alpha 1 antitrypsin deficiency in Turkish population.

BACKGROUND: Alpha 1 antitrypsin (AT) deficiency is a hereditary disorder leading to the defective defence system against neutrophil elastasis in lung and accumulation of insoluble heterodimer AT molecules in hepatocytes. Knowledge of the prevalence of AT deficiency in each country is important to organize the public health policy. The aim of this study is to determine the prevalence of AT deficiency in Turkish population and to define the cutoff value of AT level in serum to detect heterozygous AT deficient subjects. MATERIALS AND METHODS: Serum samples from 1,203 healthy blood donors were used, attending the Blood Bank of Hacettepe Medical Faculty. Isoelectric focusing method for determining PIM, PIS, and PIZ alleles and rate immune nephelometry for measuring the level of AT in serum were used. RESULTS: Out of 1,203 healthy blood donors enrolled, 1,164 (%96.8) had normal variant PI MM allelee, 9 (%0.7) PI MZ, 7 (%0.6) PI MS, 6 (%0.5) MF, and 17 (%1.4) PI M? (unidentified variants with existing standards). Most individuals (89.6%) with low AT level (cutoff <100 mg/dl) in serum were positive for PI MM allele. The cutoff value to investigate PI MZ was 100.5 mg/dl, which had PPV and NPV of 5.0 and 99.9%, respectively. AT deficiency is a rare hereditary disorder in asymptomatic healthy Turkish blood donors. Although the cutoff value of 100.5 mg/dl for AT level in serum was able to detect heterozygous AT deficiency in the healthy population, this finding should be conformed to case-control studies.

[Investigation of occult hepatitis B in HIV infected patients]. / HIV Pozitif Olgularda Okült Hepatit B Varliginin Arastirilmasi

Due to their shared transmission route, hepatitis B virus (HBV) or hepatitis C virus (HCV) co-infections can be observed in human immunodeficiency virus (HIV)-infected cases and are associated with more severe clinical courses. The detection of HBV DNA despite HBV surface antigen (HBsAg) seronegativity is defined as occult HBV infections. According to the current seroepidemiological data, Turkey is classified as an intermediate HBV, low HIV endemic region. Occult HBV infections have previously been reported from Turkey but has not been investigated previously in HIV infected cohorts. The aim of this study was to identify occult HBV infections in HIV-infected persons. Twenty-eight HIV-positive cases followed-up at Hacettepe University Hospital, Infectious Diseases Unit were included in the study after informed consent. For the detection of HBsAg, anti-HBs and anti-HCV, commercial ELISA tests (Architect System, Abbott Diagnostics, USA) were employed. Absolute CD4+ and CD8+ T-cell counts were determined via flow cytometry. HIV viral load was calculated via COBAS TaqMan HIV-1 Real-time PCR (Roche Diagnostics, USA) and the presence of HBV DNA was evaluated via COBAS TaqMan HBV Real-time PCR (Roche Diagnostics, USA), in addition to a nested PCR assay targeting HBV S gene. The mean age of the study group was 43.2 (range between 27-65) years, 64.3% (18/28) of them were males and the mean duration of HIV infection was 4.2 (2-11) years. Mean CD4+ ve CD8+ T-cell counts were 414 ± 267 cells/mm3 and 854 ± 293 cells/mm3, respectively. Twenty-six (92.8%) cases were under highly-active anti-retroviral therapy at the time of the study, 88.5% of which included HBV-active drugs (lamivudine or tenofovir). HIV RNA were found negative in 11 (39.3%) patients, of those nine (81.8%) were the cases who treated with HBV-active antiretroviral therapy. HBsAg were negative in all of the 28 patients, while the positivity rates of anti-HBs and anti-HCV were 39.3% (11/28) and 3.6% (1/28), respectively. All samples were negative for HBV DNA via the commercial real-time PCR and in-house nested PCR assays. The absence of occult HBV in the study group may indicate the absence of occult HBV or suppression of viral replication due to the anti-retroviral therapy. In conclusion, further large-scale studies are required to fully understand the impact of occult HBV in HIV-infected patients in Turkey.

Spontaneous HBsAg seroconversion after severe flare of chronic hepatitis B infection.

The results of the acute exacerbations of hepatitis B virus are varied from silent to severe acute hepatitis. HBsAg seroconversion induced by either antiviral drugs or occurred spontaneously, as a targeted end point of HBV infection management is infrequent. The affect of the severe hepatitic flare on HBsAg seroconversion was reported before, however the predictive markers of HBsAg seroconversion are not clear yet. The reasons of the spontaneously HBV re-activations, or its usual results are not known well. We, herein reported a case, with the high serum HBV DNA titer during an acute spontaneously induced severe exacerbation of HBV infection which spontaneously resulted in total HBV recovery.