scholarly journals Decrease in Chitinase 3-Like Protein 1 Levels Reflects Improvement in Liver Fibrosis after HCV Eradication

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Qian Kang ◽  
Jianhong Chen ◽  
Hao Luo ◽  
Ning Tan ◽  
Hui Gao ◽  
...  

Aim. The success of direct-acting antivirals (DAAs) against hepatitis C virus is a major breakthrough in hepatology. Previous studies have shown that chitinase 3-like protein 1 (CHI3L1) was a marker for staging of liver fibrosis caused by HCV. In this investigation, we used CHI3L1 as a surrogate marker to compare dynamic hepatic fibrosis variations following the elimination of HCV among cases receiving sofosbuvir (SOF)-based regimens and pegylated interferon/ribavirin (PR) treatments. Methods. The study enrolled 105 patients, including 46 SOF-based regimens treated patients, 34 PR-experienced patients, and 25 untreated patients. Serum samples and clinical data were obtained at the baseline, the end of treatment, and at weeks 24 and 48 after treatments. Results. First, we found that serum level of CHI3L1 correlated moderately but significantly with LSM (r=0.615, P<0.001) at the baseline, and diagnosed liver cirrhosis at baseline with high accuracy (AUC=0.939) by ROC analysis. So we explored CHI3L1 as a sensitive biomarker to monitor the regression of liver fibrosis after HCV eradication. We found that the serum CHI3L1 level of CHC cases receiving SOF-based regimen treatments was markedly reduced immediately after treatment compared with that at the baseline (123.79 (118.55) vs. 118.20 (103.68), P=0.001). For cases undergoing PR treatment, the serum CHI3L1 decreased significantly at week 24 posttreatment compared with that at the baseline (69.98 (51.44) vs 89.15 (110.59), P=0.016). For the untreated cirrhotic patients, CHI3L1 levels increased at week 96 follow-up compared with that at the baseline (194.73 (172.46) vs. 89.50 (242.97), P=0.048), reflecting continued worsening of liver fibrosis. Conclusion. CHI3L1 is suggested to be the sensitive marker to monitor fibrosis variations in weeks during treatments and after achieving SVR. It has the potential to allow the identification of early treatment failure for a timely switch to alternative treatment and to allow monitoring progression of fibrosis as a risk factor for liver cirrhosis.

Author(s):  
Rehab Badawi ◽  
Shaimaa Soliman ◽  
Lobna Aboali ◽  
Mahmoud Elkadeem ◽  
Asem Elfert ◽  
...  

Background & Aims: This study aimed to assess the changes in platelet counts of patients with liver cirrhosis due to chronic HCV, who achieved sustained virological response (SVR) after taking direct acting antivirals (DAAs) in a large cohort study in Egypt. Methods: This multicenter observational retrospective study was carried out on 2500 chronic hepatitis C virus (HCV) infected patients who achieved (SVR) after treatment with direct acting antiviral drugs (DAA). HCV infection was confirmed by positive PCR for HCV RNA infection. SVR was defined as a negative PCR test for HCV-RNA 12 weeks after completion of DAA therapy. Platelets count was measured before therapy, during therapy, at the end of treatment, and 12 weeks after the end of the treatment. Results: There were 2186 patients enrolled in the study; 1866 (85.4%) were treatment naïve. There were 1006 (46%) males and 1180 (54%) females. Mean age was 50.82± 11.66 years, 2142 (98 %.0) patients achieved SVR, 2118 (96.9%) patients had Child -Pugh class A cirrhosis, and 68 (3.1%) had Child -Pugh class B liver cirrhosis. A significant increase of the platelets count was detected at the end of treatment in comparison to the pretreatment levels (P<0.001), and after achieving SVR (P <0.001) when compared to the pretreatment values. Conclusion: Improvement of platelets count occurs after HCV therapy with DAAS in patients with liver cirrhosis. These results suggested that HCV eradication may have a role in improvement of platelet count.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3414
Author(s):  
Hye Won Lee ◽  
Dai Hoon Han ◽  
Hye Jung Shin ◽  
Jae Seung Lee ◽  
Seung Up Kim ◽  
...  

By pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it remains controversial whether there is any difference in prognosis depending on regimens—PegIFN or DAAs. We compared the probabilities of hepatocellular carcinoma (HCC) development between patients achieving an SVR by PegIFN/ribavirin (PegIFN group, n = 603) and DAAs (DAAs group, n = 479). The DAAs group was significantly older and had a higher proportion of cirrhosis than the PegIFN group. Before adjustment, the DAAs group had a higher HCC incidence than the PegIFN group (p < 0.001). However, by multivariate analyses, the DAAs (vs. PegIFN) group was not associated with HCC risk (adjusted hazard ratio 0.968, 95% confidence interval 0.380–2.468; p = 0.946). Old age, male, higher body mass index, cirrhosis, and lower platelet count were associated with increased HCC risk (all p < 0.05). After propensity score matching (PSM), a similar HCC risk between the two groups was observed (p = 0.372). We also compared HCC incidences according to sofosbuvir (SOF)-based and SOF-free DAAs, showing a similar risk in both groups before adjustment (p = 0.478) and after PSM (p = 0.855). In conclusion, post-SVR HCC risks were comparable according to treatment regimens; PegIFN- vs. DAA-based regimens and SOF-based vs. SOF-free DAA regimens. Further studies with a longer follow-up period are required.


2020 ◽  
pp. 1-2
Author(s):  
Revathy Marimuthu Shanmugam ◽  
Vinay C ◽  
Sathya Gopalasamy ◽  
Chitra Shanmugam

BACKGROUND: Many noninvasive surrogate marker for Portal hypertension or for the presence or grade of esophageal varices were studied..Splenomegaly along with splenic congestion secondary to splenic hyperdynamic circulation is seen secondary to Portal hypertension in cirrhotic patients that can be quantified by elastography. AIM:The aim of this study was to investigate whether spleen stiffness, assessed by TE, useful tool for grading chronic liver diseases and to compare its performance in predicting the presence and size of esophageal varices in liver cirrhosis patients. METHODOLOGY:86 patients with cirrhosis and 80 controls underwent transient elastography of liver and spleen for the assessment of liver stiffness (LSM) and spleen stiffness (SSM) . Upper GI endoscopy done in all Cirrhotic patients. RESULTS: Spleen stiffness showed higher values in liver cirrhosis patients as compared with controls: 58.2 kpa vs14.8 kpa (P < 0.0001) and also found to be significantly higher in cirrhotic patients compared with varices and those without varices (69.01 vs 42.05 kpa, P < 0.0001). Liver stiffness was also found to be higher in cirrhotic patients with varices when compared to patients without varices (38.5vs 21.2 kpa). Using both liver and spleen stiffness measurement we can predicted the presence of esophageal varices correctly. CONCLUSION: Spleen stiffness can be assessed using transient elastography, higher value correlated well with liver cirrhosis and presence of esophageal varices although it couldn’t correlate with grade of Esophageal Varix. Combined assessment of spleen and liver stiffness had better prediction of presence of Esophageal Varix.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Danielle Cristiane Baldo ◽  
Alessandra Dellavance ◽  
Maria Lucia Gomes Ferraz ◽  
Luis Eduardo C. Andrade

Abstract Background Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years. Methods 327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50–7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (ɣGT) and ELF score were measured by automated methods. Results Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.45% and 8.86% per year; respectively), anti-PDC-E2 avidity (3.02% and 4.94%/year) and ELF score (3.24% and 2.71%/year). IIF-AMA and ɣGT increased in BN/AMA+ (6.59% and 2.36%) and decreased in PBC (− 4.89%/year and − 3.88%/year). In BN/AMA+ individuals there was positive correlation of ELF with IIF-AMA titer (r = 0.465; p < 0.001) and with anti-PDC-E2 levels (r = 0.239; p < 0.001). Expansion of autoantibody targets along time occurred in 39% BN/AMA+ and 49% PBC patients. The frequency of BN/AMA+ with high probability of having established PBC increased from 7 to 14%. Conclusions BN/AMA+ individuals present an orchestrated increase in ELF score and humoral autoimmune response over time, indicating an opportunity for early therapeutic intervention and prevention in autoimmunity.


2019 ◽  
Vol 9 (1) ◽  
pp. 95 ◽  
Author(s):  
Yukihisa Yuri ◽  
Hiroki Nishikawa ◽  
Hirayuki Enomoto ◽  
Kazunori Yoh ◽  
Yoshinori Iwata ◽  
...  

We aimed to clarify the relationship between sustained virological response (SVR) and gastroesophageal varices (GEVs) progression among hepatitis C virus (HCV)-related liver cirrhosis (LC) patients treated with interferon (IFN)-based therapies (n = 18) and direct-acting antiviral (DAA)-based therapies (n = 37), and LC patients with no SVR (n = 71) who had already developed GEVs. Factors influencing GEVs progression were also examined. During the follow-up period, GEVs progression was observed in 50 patients (39.7%). The 3-year cumulative GEVs progression rates in the DAA-SVR group, the IFN-SVR group, and the non-SVR group were 32.27%, 5.88%, and 33.76%, respectively (overall p value = 0.0108). Multivariate analysis revealed that sex (p = 0.0430), esophageal varices (EVs) F2 or more (p < 0.0001), and DAA-SVR (p = 0.0126, IFN-SVR as a reference) and non-SVR (p = 0.0012, IFN-SVR as a reference) were independent predictors for GEVs progression. The proportion of GEVs progression in patients with no or F1 EVs was significantly lower than that in patients with F2 or F3 EVs (33.9% (38/112) vs. 85.7% (12/14), p = 0.0003). In conclusion, IFN-based therapies can have a favorable impact for preventing GEVs progression in HCV-related LC patients with GEVs. Clinicians should be aware of a point of no return where SVR is no longer capable of avoiding GEVs progression.


2008 ◽  
Vol 54 (11) ◽  
pp. 1840-1843 ◽  
Author(s):  
Anna Lempiäinen ◽  
Ulf-Håkan Stenman ◽  
Carl Blomqvist ◽  
Kristina Hotakainen

Abstract Background: We studied whether measurement of the free β subunit of human chorionic gonadotropin (hCGβ) in serum offers additional diagnostic information compared to determination of intact hCG alone in testicular cancer. Methods: We determined hCG and hCGβ with ultrasensitive assays in 94 serum samples obtained preoperatively, 22 samples obtained during relapse, and 3687 samples obtained during routine follow-up of 351 patients with testicular tumors. Results: In preoperative samples, isolated increases of hCGβ were seen in 40% of the samples from seminoma patients (n = 42) and in 8% of those from patients with nonseminomatous testicular cancer (NSGCT) (n = 51). Both markers were increased in 12% of the seminoma and 71% of the NSGCT patients and were within reference intervals in 43% of the seminoma and 20% of the NSGCT patients. Specific determination of hCGβ increased the frequency of marker-positive seminomas from 17% to 57% and of marker-positive relapses from 32% to 59% (n = 22). Theoretically, about 40% of marker-positive seminomas and relapses would have been missed with an assay measuring hCG and hCGβ together. Preoperative hCG and hCGβ concentrations correlated with stage, tumor histology, and disease-related mortality. Additionally, hCGβ correlated with tumor size. Conclusions: hCGβ is a diagnostically sensitive marker for testicular cancer. In patients with seminomatous testicular cancer, hCGβ is superior to hCG, and in some NSGCT patients it provides additional information.


2021 ◽  
Author(s):  
Maria Giovanna Quaranta ◽  
Luigina Ferrigno ◽  
Xhimi Tata ◽  
Franca D'Angelo ◽  
Carmine Coppola ◽  
...  

Abstract Background: The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA in the multicenter PITER cohort.Methods: Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in PITER, who achieved a sustained virological response (SVR12) and with an available follow-up after DAA treatment, were analysed. Liver function was prospectively evaluated as changes in Child-Pugh (C-P) class during patient’s follow-up after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication.Results: We evaluated 1350 successfully DAA treated patients with cirrhosis, of whom 1242 HCV monoinfected (median follow-up of 24.7, range 6.8-47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up of 27.1, range 6-44.6 months after viral eradication). Despite the significant younger age (p<0.001), coinfected patients had higher liver disease severity in terms of C-P class score (p<0.001). Following HCV eradication, C-P class improved in 17/20 coinfected (85%) and in 53/82 (64.6%) monoinfected patients with a pre-treatment C-P class B or C (p>0.05). C-P class worsened in 3/56 coinfected (5.3%) and in 84/1024 (8.2%) monoinfected patients with pre-treatment C-P class A or B (p>0.05). Factors independently associated with C-P class deterioration were male sex (HR=2.01; 95% CI=1.19-3.40), platelet count <100,000/µl (HR=1.88; 95% CI 1.17-3.03) and higher pretreatment INR value (HR=2.34; 95% CI 1.47-3.71). Following viral eradication, in 7 of 15 coinfected (47%) and in 61 of 133 (45.6%) monoinfected patients with previous history of decompensation a new decompensating event occurred. An incident decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients. Conclusions: Improvement of liver function is observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication does not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 356-356
Author(s):  
Fabian Finkelmeier ◽  
Georg Dultz ◽  
Bernd Kronenberger ◽  
Kai Henrik Peiffer ◽  
Franziska Krauss ◽  
...  

356 Background: The aim of the study was to evaluate the risk of HCC development after treatment with direct-acting antivirals (DAA) and to compare hepatocellular carcinoma (HCC) occurrence to patients treated with interferon (IFN)-based therapies. Methods: We analyzed a large cohort with chronic HCV patients for the onset of new hepatocellular carcinoma after DAA treatment. A historic interferon treated cohort was investigated for comparison. Results: 819 patients were included in the DAA group, 269 (32.8%) had established cirrhosis. Median follow up was 263 days (0-1001). 25 patients (3.1%) were diagnosed with de novo HCC within the observation time. All of these patients had established cirrhosis. Patients with new HCC were mostly male, older, treatment experienced, had a lower SVR12 rate and higher levels of liver inflammation markers. Investigation of the subcohort of 269 cirrhotic patients yielded a HCC rate of 9.3% during the follow-up of approximately one year. Non-SVR12 was an independent risk factor for de novo HCC (OR 4.983, 1.39-17.88, 0.014). Most HCCs were diagnosed in early stage BCLC A. In the historical cohort of 351 IFN treated patients the rate of de novo HCC was 5.4% overall and 11.8% in patients with already established cirrhosis (n = 68). In the multivariate analysis failed SVR (OR 5.386, 1.155-25.108, p = 0.032) remained an independent risk factor for de novo HCC. In a combined analysis of all patients (DAA and IFN treated) in a multivariate approach male gender, failed SVR and cirrhosis were independent factors for HCC development. Conclusions: DAA treatment in cirrhotic patients does not seem to reduce the risk of HCC development in the short term. HCC rates were not different between DAA-treated patients and those who received interferon. Achievement of SVR seems to be the most important aim to prevent HCC development.


2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Geng-lin Zhang ◽  
You-ming Chen ◽  
Ting Zhang ◽  
Qing-xian Cai ◽  
Xiao-hong Zhang ◽  
...  

Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, −1.33 versus 0.86,P<0.001). The albumin levels and platelet counts significantly increased during the follow-up period after SVR (44.27±4.09versus42.63±4.37,P=0.037and173.89±87.36versus160.11±77.97,P=0.047). These data indicated that HCV-related cirrhotic patients with SVR after PegIFN + RBV may have a favorable clinical course and improvements in laboratory data. Moreover, HCC should be monitored.


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