The Interrelation Between Hypothyroidism and Non-alcoholic Fatty Liver Disease, a Cross-sectional Study.

Background: Thyroid hormones play an important role in the regulation of diverse metabolic processes and might play a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, their association remains controversial. Therefore, our aim is to clarify whether overt or subclinical hypothyroidism was associated with NAFLD. Methods: This cross-sectional study included 60 participants with a new diagnosis of hypothyroidism and 30 age- and gender-matched healthy participants with thyroid-stimulating hormone (TSH) level <4.5 mIU/L. Anthropometric measurements, laboratory parameters, plasma fibroblast growth factor 21 (FGF21), and hepatic steatosis diagnosed via controlled attenuation parameter (CAP) using transient elastography between the hypothyroid groups and control group were analyzed. Results: Participants with hypothyroidism displayed significantly higher serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total cholestrol, triglycerides, low-density lipoprotein cholesterol, TSH, hemoglobin A1c, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) but significantly lower serum albumin, high-density lipoprotein cholesterol, and free thyroxine levels than the control group (P = <0.001). The CAP values were significantly higher in participants with overt and subclinical hypothyroidism than the control group (P = <0.001). The only significant independent predictors of steatosis in our study were free T4, body mass index, and HOMA-IR after using multivariate logistic regression. The mean serum FGF21 levels were increased in hypothyroid participants with hepatic steatosis than those without hepatic steatosis (126.9 ± 272.6) pg/ml vs. (106.8 ± 138.7) pg/ml, P = 0.8). Receiver operating characteristic (ROC) curve showed that FGF21 was not a significant marker for hepatic steatosis in hypothyroid participants (area under curve (AUC) = 0.44, P = 0.54). Conclusion: Individuals with subclinical or overt hypothyroidism were more likely to have NAFLD than those with normal thyroid function. Serum FGF21 levels were increased in hypothyroid individuals and its role as a marker of hepatic steatosis in hypothyroid individuals needs further assessment.

Serial changes in renal indices in chronic HCV patients with and without HIV co-infection receiving sofosbuvir and tenofovir-based therapies.

BACKGROUND: Sofosbuvir (SOF) is authorized for hepatitis C virus (HCV) patients. The nephrotoxicity of SOF on HCV mono-infected and HCV-human immunodeficiency virus (HIV) individuals receiving antiretroviral therapy (ART) remains controversial. METHODS: A prospective study including 159 HCV mono-infected and 124 HCV-HIV individuals (47 were ART naïve and 77 were tenofovir [TDF]-based ART) who presented with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2 at baseline and were treated with SOF-daclatasvir for 12 weeks. The eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation over the study period. RESULTS: HCV patients had a progressive decline in median levels of eGFR compared with HCV-HIV patients who were ART naïve and those receiving TDF-based ART during and after discontinuing SOF-DAC treatment (96, 109 and 114 at baseline vs 94, 117 and 108 at the end of treatment [EOT]) vs 95, 114 and 115 ml/min/1.73 m2 at 12 weeks after treatment [SVR12], respectively). Moreover, the rate of eGFR stage worsening was more pronounced in HCV mono-infected compared with HCV-HIV individuals who were ART naïve and those receiving TDF-based ART (21.4% vs 8.5% and 14.3% at EOT; 21.4% vs 2.1% and 6.5% at SVR12, respectively). Multivariable regression analysis showed that baseline variables were not independent predictors of eGFR stage worsening either at EOT or SVR12. CONCLUSIONS: Because the changes in eGFR were minimal and not of clinical significance, and TDF was not associated with an increase in renal dysfunction, SOF-based direct-acting antivirals could be safely used in HCV mono-infected and HCV-HIV individuals, even in those on TDF-based ART.

Incidence of hepatitis C virus infection among people living with HIV: An Egyptian cohort study.

Background: Egypt used to have one of the highest hepatitis C virus (HCV) infection prevalence rates worldwide, with an estimated HCV prevalence of around 4.5% to 6.7%. Objectives: To determine the HCV infection incidence rate amid Egyptian patients living with HIV. Method: A total of 460 HIV-positive patients were recruited in a retrospective cohort study from Imbaba Fever Hospital, Cairo, between January 2016 and March 2019. The patients had a negative baseline and at least one other HCV antibody test. Hepatitis C virus antibody testing was done by antibody sandwich third-generation enzyme-linked immunosorbent assay. The hepatitis C virus infection incidence rate among HIV-infected patients was calculated using the person-time incidence rate. Results: Two hundred and eighteen patients were finally included: 146 (31.7%) patients were excluded for having a positive baseline HCV Ab result and 96 patients were excluded for not having a follow-up HCV Ab test. Eighteen patients had HCV seroconversion (8.3%), achieving an incidence rate of 4.06 cases per 100 person-years (95% confidence interval: 3.87-4.24). Injection drug use (IDU) was the commonest risk factor among seroconverters, with an HCV incidence rate of 7.08 cases per 100 person-years. Injection drug use history was reported in 83.3% of the seroconverters and in only 47.2% of non-seroconverters; P = 0.005. Conclusion: Egyptian HIV-infected patients show a high incidence rate of HCV infection especially among those who have a history of IDU. Accordingly, attention should be paid for prevention, screening and timely treatment of HCV in patients infected with HIV. What this study adds: The demonstration of a high HCV infection incidence rate among HIV-infected patients and shows the need for screening and prevention in this population.

Prevalence and clinical characteristics of patients with metabolic dysfunction-associated fatty liver disease with hepatitis C virus infection-a population-based study.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) was proposed in 2020 to identify fatty liver disease associated with metabolic risks. Metabolic abnormalities with hepatitis C virus (HCV) and MAFLD frequently co-exist. However, data on the co-existence are still lacking. AIM: To explore the prevalence and characteristics of metabolic profiles among a large cohort of patients with HCV infection between 2007 and 2020 based on new diagnostic criteria METHODS: We recruited 288,222 patients with chronic HCV infection with demographic data, laboratory parameters, and ultrasound from a web-based registry of the National Committee for Control of Viral Hepatitis in Egypt from 2007 to 2020. RESULTS: Among the participants, 41.9% (95% CI: 41.69-42.05) met diagnostic criteria for MAFLD, with a significant increase in the period 2014-2020 compared to 2007-2013 (43.3% vs. 19%, respectively). Participants with MAFLD had a high prevalence of obesity, diabetes mellitus and hypertension. The prevalences increased significantly over time (obesity: 66.7% vs. 76.9%, p < 0.01; diabetes mellitus: 14.6% vs. 31.5%, p < 0.01; hypertension: 0.9% vs. 7.6%, p < 0.01; prediabetes: 28.8% vs. 25.9%, p < 0.01) for the periods 2007-2013 and 2014-2020, respectively. The percentage of advanced fibrosis by fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) was significantly higher in participants with MAFLD during 2014-2020 than during 2007-2013 (FIB-4; 18.4% vs. 8% and NFS; 17.1% vs. 7%). CONCLUSION: MAFLD is highly prevalent in patients with HCV infection and has risen over time. This rising prevalence parallels the alarming rise in obesity, diabetes mellitus and hypertension. Early detection of metabolic dysfunction in patients with HCV infection is recommended to prevent MAFLD progression.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulins using chemiluminescence immunoassay and its correlation with neutralizing antibodies.

BACKGROUND: Neutralizing antibodies (NAbs) against SARS-CoV-2 infection have a pivotal role in protective immune response; however, their measurement requires specialized facilities. We evaluated the degree of correlation between NAbs and anti-SARS-CoV-2 IgG/total Ig antibodies detected by chemiluminescent immunoassay in asymptomatic and previously symptomatic SARS-CoV-2 patients. METHODS: A total of 1241 participants (previously symptomatic patients and asymptomatic individuals), who were screened for SARS-CoV-2 infection by RT-PCR or serology, were enrolled in our study. Sera were analyzed for the presence of anti-spike-1(S1)-SARS-CoV-2 IgG/total Ig antibodies, using Ortho Clinical Diagnostics, USA. A signal/cut-off value (S/CO) ≥ 1 was considered reactive. NAbs were measured in 103 random samples from groups using microneutralization assay, with titer ≥ 1:10 being considered positive. RESULTS: Asymptomatic (n = 229) and 261 previously symptomatic individuals with positive serology and negative RT-PCR were finally included. Significant higher anti-S1-IgG titers were seen in asymptomatic individuals (P < 0.0001). Conversely, anti-S1-total Ig titers were significantly higher in previously symptomatic (P < 0.0001). NAbs were detected in both groups, however, higher titers were seen in previously symptomatic patients. There is a correlation between NAbs and both IgG/total anti-S1-SARS-CoV-2 antibodies (r = 0.47, P < 0.0001 and r = 0.49, P < 0.0001, respectively). IgG and total Ig could predict a neutralization titer of ≥ 1:160 at S/CO >4.44 and >65 with AUC 0.69 and 0.67, respectively. CONCLUSION: Asymptomatic SARS-CoV-2 infection can produce comparable antibodies response to previously symptomatic individuals, however higher neutralization activity was seen in the previously symptomatic. Anti-S1-SARS-CoV-2 IgG/total Ig antibodies showed a correlation with neutralization activity and can be used to estimate the presence of protective immunity.

Highly Sensitive Serum miRNA Panel for the Diagnosis of Hepatocellular Carcinoma in Egyptian Patients with HCV-Related HCC.

OBJECTIVE: This study aimed at exploring the potential role of a panel of serum micro-RNA (miRNA) markers in liver fibrosis and hepatocellular carcinoma (HCC) diagnosis in patients with chronic hepatitis C virus (HCV) infection. METHODS: The study included 157 chronic HCV patients and 62 HCC patients who presented to the Cairo University Center for Hepatic Fibrosis, Endemic Medicine Department, from 2015 to 2017. Relevant clinical and laboratory data were collected and sera were subjected to miRNA expression profiling. Eleven miRNA markers were studied and receiver operating characteristic curves were constructed to investigate the best cutoff values of the miRNAs that showed altered expression in HCC compared to HCV-associated advanced fibrosis. RESULTS: miRNA expression profiling revealed 5 miRNAs (miR-124, miR-141, miR-205, miR-208a, miR-499a) were significantly upregulated and 2 miRNAs were significantly downregulated (miR-103a, miR-15a) in HCC compared to advanced fibrosis patients. No significant difference was observed in miRNA expression between advanced fibrosis and early hepatic fibrosis apart from a significant downregulation of miR-155-5p in advanced fibrosis. CONCLUSION: Serum miRNAs could serve as potential diagnostic tools for the diagnosis of HCC.

Metabolic-associated fatty liver disease and autoimmune hepatitis: an overlooked interaction.

INTRODUCTION: Metabolic-associated fatty liver disease (MAFLD) is the most common liver disease globally, and affects about a quarter of the general population. Autoimmune hepatitis (AIH) is a severe (sometimes fatal) liver disease that affects children and adults, with a rising prevalence. Thus, not surprisingly, both conditions can frequently coexist, with potential synergistic impact on the course of the disease and response to therapy of both entities. AREAS COVERED: In this work, the authors aimed to provide a narrative updated review on this interaction, diagnosis, and management of MAFLD/AIH and the current challenges. EXPERT OPINION: Clarifying the nature of the complex interaction between the two diseases was hampered by a myriad of factors, particularly the previous diagnosis of exclusion for fatty liver disease associated with metabolic dysfunction. The recent redefinition of fatty liver disease that led to the development of positive diagnostic criteria for MAFLD has the premise to help in circumventing some of these challenges.

Prevalence of SARS-CoV-2 infection and dynamics of antibodies response among previously undiagnosed healthcare workers in a university hospital: A prospective cohort study.

BACKGROUND: Healthcare workers (HCWs) are a presumed high-risk population for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Identifying factors associated with seroprevalence can help establish better practices in healthcare settings. In this study, we evaluate prevalence of SARS-CoV-2 infection among previously undiagnosed HCWs and describe profiling of antibody responses against SARS-CoV-2, including neutralizing antibodies (NAbs). METHODS: We analyzed a cohort of 386 HCWs in a university hospital in Egypt and 725 volunteers not affiliated to any healthcare facility (non-healthcare workers - NHCWs). Participants provided a nasopharyngeal swab and serum samples for SARS-CoV-2 nucleic acid and SARS-CoV-2-specific antibodies, respectively. HCWs who tested positive by either test were sequentially monitored. RESULTS: At baseline, point prevalence of viral carriage was 11.4% in HCWs (n = 44/386) and 11.9% in NHCWs (86/725). The cumulative prevalence of SARS-CoV-2 infection among HCWs considering all studies was 25.6%, which was statistically lower than in NHCWs (41.0%). Prevalence was greatest among janitorial staff (45.9%) and the most affected departments were gastroenterology (31.1%), and emergency medicine (30.0%). Prior anosmia, fever or headache were associated with higher odds of positivity for SARS-CoV-2 infection. Regarding serial antibody measurements, RT-PCR-positive HCWs displayed IgG detection rates of 29.5%, 70% and 60% at visit 1, visit 2 and visit 3, respectively with slow decline of median IgG antibody titers, whereas, corresponding detection rates for total Ig antibodies were 50%, 90.3%, and 88.9%, respectively with increasing median titers. NAbs measured at each time point were positively correlated with total Ig levels, whereas IgG levels were positively correlated with NAbs at visit 1 and visit 3. CONCLUSION: Our results demonstrate lower cumulative prevalence of SARS-CoV-2 infection in HCWs than general population and suggest that asymptomatic HCWs exhibit considerable IgG and total Ig antibodies response as well as NAbs for up to 120 days, with positive correlation in between.

Is Serum-Ascites Vitamin D Gradient a Valid Marker for Diagnosing Spontaneous Bacterial Peritonitis in Patients with Cirrhotic Ascites?

OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is considered the paradigmatic model of infection in patients with liver cirrhosis. Therefore, there is a need for an accurate and rapid method for SBP diagnosis. The aim of this study was to evaluate the validity of serum-ascites 25-hydroxyvitamin D (25-OH vitamin D) gradient (SADG) as a marker for diagnosing SBP in patients with cirrhotic ascites. METHODS: We conducted a cross-sectional analytic study of 88 patients with portal hypertensive ascites resulting from liver cirrhosis of any etiology. The demographic, clinical, and laboratory characteristics of the patients were recorded. The level of 25-OH vitamin D in serum and ascitic fluid was measured using high-performance liquid chromatography autoanalyzer. The SADG was calculated with the formula: 25-OH vitamin D in serum - 25-OH vitamin D in ascites. RESULTS: Vitamin D deficiency was detected in 89.8% of the studied patients. The SADG values ranged between 0 and 69.2 ng/mL, with a median value of 5.58 ng/mL. It was significantly lower in patients with SBP than in those without SBP (P = .004). The area under the curve for SADG in exclusion of SBP was 0.67 at a cutoff value of ≥5.57 ng/mL. CONCLUSION: We found that SADG may be a valid marker of SBP in patients with cirrhotic ascites.

Improvement of platelet in thrombocytopenic HCV patients after treatment with direct-acting antiviral agents and its relation to outcome.

Little is known about evolution of platelet count after treatment with direct-acting antiviral agents (DAAs). The study aimed to evaluate the changes in platelet count after treatment with DAAs among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis. A total of 915 chronic HCV patients with advanced fibrosis and cirrhosis who were treated with different DAAs-based regimens were retrospectively enrolled in final analysis. Included patients were those with thrombocytopenia (TCP). Platelet count was recorded at baseline, end of treatment (EOT) and 24-weeks after EOT (SVR24). Changes in platelet count and its relation to SVR were analyzed. The overall SVR24 rate was 98.8%. The platelet count showed statistically significant improvement from baseline to EOT (107 (84-127) × 103/mm3 vs. 120 (87-153) × 103/mm3(P = <0.0001) but remained unchanged thereafter to SVR24. Among responders, the platelet count significantly increased at SVR24 compared to baseline (P = <0.0001) but in relapsers, there was improvement in platelet count that didn't reach statistical significance (P = 0.9). Logistic regression analysis showed that higher Child-Pugh score and more advanced fibrosis at baseline were significant predictors of decreasing of platelet count and development of severe TCP at SVR24. Among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis, the platelet count improved after treatment with DAAs regardless to treatment response.

Is urinary ß2-microglobulin a reliable marker for assessment of renal tubular dysfunction in chronic hepatitis B patients receiving tenofovir therapy?

BACKGROUND AND AIM: Urinary ß2-microglobulin (ß2-M) is a marker for renal tubular dysfunction. The current study aimed to assess urinary ß2-M as a reliable marker for early prediction of tenofovir disoproxil fumarate (TDF)-related nephrotoxicity among hepatitis B virus (HBV) patients. METHODS: Forty-two HBV patients who were a candidate for TDF therapy or have recently started it (for less than 6 months) were enrolled and subjected to demographic, clinical, laboratory assessment, abdominal ultrasound and transient elastography. The glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Also, urinary ß2-M was measured by the ELISA method within 6 months after the introduction of TDF treatment and 6 months later. RESULTS: Mean age was 41.8 (9.55) years, 27 were males and 59.5% of patients have elevated urinary ß2-M after 6 months follow-up of TDF therapy. Urinary ß2-M was 0.07 ± 0.07 µg/ml at baseline and insignificantly increased up to 0.09 ± 0.08 µg/ml after 6 months follow-up. Despite the insignificant increase in serum creatinine from 0.85 ± 0.23 mg/dl at baseline to 0.9 ± 0.21 mg/dl after 6 months and the insignificant decrease in eGFR from 126.2 ± 39.72 ml/min at baseline and 117.64 ± 42.23 ml/min at 6 months follow-up. No correlation was found between the changes in urinary ß2-M and the changes in other renal function indices at baseline and 6 months follow-up. CONCLUSIONS: Short-term TDF therapy is associated with nonsignificant changes either in eGFR or urinary ß2-M; these changes are not clinically relevant that indicates disease progression. Therefore, the suitability of urinary ß2-M as a screening tool for tenofovir induced tubular dysfunction should be further.

Impact of sustained virological response on metabolic disorders in diabetic chronic hepatitis C virus patients after treatment with generic sofosbuvir and daclatasvir.

OBJECTIVES: To evaluate the effect of generic sofosbuvir and daclatasvir (SOF/DCV) treatment on the glycemic state and insulin resistance as well as lipid profiles of those who achieved sustained virological response (SVR) in diabetic chronic hepatitis C virus (CHC) patients. METHODS: We retrospectively reviewed 114 CHC patients with evidence of type 2 diabetes that were treated with generic SOF/DCV between May 2016 and August 2017. Baseline demographic and laboratory data were recorded. At 12-week post end of therapy (SVR12), glycemic state and insulin resistance as well as lipid profiles were re-evaluated and compared with baseline. RESULTS: A total of 98 diabetic CHC patients were finally included and were responders. A significant decline in the glycemic state as well as Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P ≤ 0.0001) was observed, but HOMA-S showed a statistically significant increase (P ≤ 0.0001) at SVR12 in comparison to baseline values. Also, a significant increase in serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels was observed at SVR12 compared to baseline, but serum triglycerides levels showed a significant decrease. Logistic regression showed that the higher baseline HOMA-IR was a significant predictive variable of a decrease ≥20% of HOMA-IR, while higher baseline HOMA-IR and baseline triglycerides emerged as the only significant predictors of the Δ increase LDL-C level at SVR12. CONCLUSION: SOF/DCV-based therapy led to an improvement of glycemic state associated with a global worsening of lipid profile. Further studies are strongly warranted to evaluate the cardiovascular balance between amelioration of insulin resistance and negative changes of the lipid profile.

Renal profile of chronic hepatitis C patients with sofosbuvir-based therapy.

PURPOSE: The impact of SOF-based therapy on renal functions is quite controversial in clinical practice. Therefore, we aimed to evaluate the serial changes of renal indices during SOF-based therapy in CHC patients with normal kidney function or mild renal impairment. METHODS: We retrospectively reviewed all CHC patients who received different SOF-based regimens from January 2015 until December 2017, and presented with a baseline eGFR ≥ 30 ml/min/1.73m2. Patients who didn't achieve SVR, with missing creatinine or eGFR data, and patients with eGFR less than 30 ml/min/1.73m2 at baseline were excluded. eGFR was calculated for each time of evaluation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: A total of 1004 patients were finally included. The mean serum creatinine and eGFR levels varied between 0.84 mg/dl and 106.53 ml/min/1.73m2 for baseline and 0.87 mg/dl and 104.24 ml/min/1.73m2 for SVR12, respectively. The maximum increase of creatinine was 3.69 mg/dl and the maximum decrease of eGFR level was 83.30 ml/min/1.73m2 during treatment. Moreover, 74.4% of treated patients stayed in the same eGFR category, 14.3% progressed to a higher eGFR category, and 11.3% had an improvement eGFR category at EOT and continued to SVR12. Age > 65 years, baseline eGFR, and ribavirin-containing regimens were independent risk factors of eGFR decline during and after SOF-based treatment. CONCLUSION: SOF-based therapies seem to be safe in CHC patients with baseline normal or slightly impaired renal function.

Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography.

BACKGROUND: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. OBJECTIVES: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. METHODS: Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. RESULTS: By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = -.529, P < .001), liver volume (r = -.298, P = .034) and liver stiffness (r = -.652, P < .001). CONCLUSIONS: Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.

Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection.

BACKGROUND: Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients. METHODS: A single-centre, prospective study including HIV/HCV-GT 4-coinfected patients who were treated with sofosbuvir and daclatasvir (SOF/DCV) was conducted for 12 wk. Sustained virological response (SVR) at week 12 post-treatment (SVR12), adverse events (AEs) and changes in liver stiffness measurement (LSM) at SVR12 in comparison with baseline were evaluated. RESULTS: SVR12 was achieved in 46 of 50 patients (92%). No significant difference in SVR12 was noticed among patients who received antiretroviral therapy (ART) regimens compared with those who did not receive ART regimens or between those with insignificant fibrosis (

Serum Serotonin as a Potential Diagnostic Marker for Hepatocellular Carcinoma.

To assess the potential role of serum serotonin level in hepatocellular carcinoma (HCC) diagnosis. A case-control study that involved 100 Egyptian adults. Subjects were divided into 4 groups: Group I: 21 patients with late-stage HCC on top of liver cirrhosis, Group II: 28 patients with early-stage HCC on top of liver cirrhosis, Group III: 26 patients with cirrhosis with no evidence of HCC, and Group IV: 25 healthy age- and sex-matched subjects were as a control group. Serum serotonin level was determined in all recruited subjects using high-performance liquid chromatography-fluorescent detection method. Alpha-fetoprotein had a statistically significant elevation in group I with a median of 1300 ng/L (195-2544 ng/L) compared to groups II and III (P ≤ 0.01). Regarding serum serotonin level, it had a statistically significant elevation in group II with a median of 275 ng/µL (204.7-400 ng/µL) compared to groups I, III, and IV with median of 33 ng/µL (30-50 ng/µL), 50 ng/µL (30-60 ng/µL), and 102 (85-150 ng/µL), respectively (P = 0.001). Receiver operating characteristic curve showed that serum serotonin at cutoff value of 108 ng/µL had a sensitivity of 100% and specificity of 92.3% in discriminating early-stage HCC from cirrhosis. Serum serotonin level is a rapid, sensitive, noninvasive diagnostic biomarker for the detection of early-stage HCC.

Liver stiffness measurements and FIB-4 are predictors of response to sofosbuvir-based treatment regimens in 7256 chronic HCV patients.

Objectives: To assess the role of baseline liver stiffness (LS) by Transient elastography (TE) and FIB-4 in the prediction of virological response to sofosbuvir - based regimens in chronic HCV patients.Methods: A retrospective, multicenter study including 7256 chronic HCV patients who received different sofosbuvir-based regimens. Baseline demographic and laboratory data were recorded. TE was performed with FIB-4 calculation at baseline.Results: Sustained virological response at week 12 post-treatment (SVR12) was 91.4%. Pretreatment TE values and FIB-4 were significantly lower among sustained responders (17.8 ± 11.5 kPa, 2.66 ± 1.98, respectively) versus relapsers (24.5 ± 13.9 kPa, 4.02 ± 3.3, respectively). Best cutoff levels for LS by TE and FIB-4 score for prediction of failure to treatment response were 16.7 kPa and 2.4, respectively. Among different treatment protocol, patients with FIB-4 > 2.4, TE values >16.7 kPa are more prone to treatment failure except when using SOF/SIM treatment regimens.Conclusion: Baseline LS by TE and FIB-4 score may be useful for predicting treatment outcome in the new era of DAAs and could be integrated into pretreatment assessment of chronic HCV patients for better optimization of patient management.

DAAs therapy associated with improved hepatic fibrosis in HCV-GT4 patients co-infected with HIV.

Background: The present work aimed at evaluation of the potential dynamic changes in hepatic fibrosis following treatment of chronic HCV using DAAs in patients coinfected with HIV. Patients and methods: In total, 50 HCV/HIV coinfected patients [age; 34.68 ± 10.38 years, 82% men] were included. For all included patients, liver stiffness measured using transient elastography as well as serum liver fibrosis scores; [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were calculated at baseline and at 12 and 24-weeks following 12 weeks therapy of HCV with once daily sofosbuvir 400 mg plus daclatasvir 60 mg. Results: Most of the included patients (70%, n = 35) were on anti-retroviral therapy. SVR24 was achieved by 93.48% of the patients. There was significant serial improvement in baseline liver stiffness measurement (LSM), FIB-4 and APRI among responders; [LSM: baseline, 7.05 ± 4.84 kPa vs. 5.66 ± 2.63 kPa at SVR24, p < 0.001], [FIB-4: baseline, 1.24 ± 1.08 vs. 0.93 ± 0.64 at SVR24, p 0.001) and (APRI: baseline, 0.725 ± 0.66 vs. 0.36 ± 0.19at SVR24, p 0.001) respectively. Conclusion: Treatment of HCV patients coinfected with HIV using DAAs is associated with a rapid significant regression in hepatic fibrosis, as evaluated by FibroScan, FIB-4, and APRI scores.

Clinical impact of serum α-fetoprotein and its relation on changes in liver fibrosis in hepatitis C virus patients receiving direct-acting antivirals.

BACKGROUND: α-Fetoprotein (AFP) is used widely as a serological marker for hepatocellular carcinoma. However, the AFP value is elevated in chronic hepatitis C virus (HCV) patients without hepatocellular carcinoma. Yet, data on the impact of direct-acting antiviral agents (DAAs) therapy on AFP levels after viral eradication are still lacking. AIM: The aim of this study was to elucidate the changes in the serum AFP level in chronic hepatitis C patients treated with DAA-based therapy and their relation to response and liver fibrosis parameters. PATIENTS AND METHODS: A total of 456 chronic HCV patients who received different DAAs-based treatment regimens were enrolled. Laboratory data including serum AFP, transient elastography values, and fibrosis scores were recorded at baseline and sustained virological response at 24 weeks after treatment (SVR24). The outcome was the changes in the AFP level from baseline to SVR24 and its relation to changes in liver fibrosis parameters at SVR24 using Spearman's rank correlation test. RESULTS: Overall, 96.9% of enrolled patients were responders. A statistically significant improvement in serum transaminases, albumin, transient elastography values, and fibrosis scores at SVR24 was reported. The AFP level was significantly decreased from a median (interquartile range) of 6 (3.2-10.8) ng/ml before DAAs to 4 (2.3-6) ng/ml at SVR24 (P < 0.0001). Only 22.6% of patients showed an increase in the AFP level after treatment. On multivariate analysis, the only independent baseline variable associated with an increase in the AFP level after treatment was baseline AFP (odds ratio: 0.95, 95% confidence interval: 0.91-0.99, P = 0.02). There is a significant correlation between changes in AFP and liver fibrosis parameters at SVR24. CONCLUSION: DAAs-based regimens are a highly efficient antiviral therapy for chronic hepatitis C patients that resulted in improvements in the serum AFP level.