Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial.

PURPOSE: Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year. METHODS: Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year. RESULTS: Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence. CONCLUSION: Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

Occult hepatitis C virus infection in hemodialysis patients who achieved a sustained virological response to directly acting antiviral drugs: is it a concern?

PURPOSE: Hepatitis C virus infection is a major health problem in hemodialysis patients. Occult HCV infection is defined as the presence of HCV-RNA in hepatocytes or peripheral blood mononuclear cells without the detection of HCV-RNA in the serum. We aimed to evaluate the prevalence and predictors of occult HCV infection among hemodialysis patients after treatment with direct-acting antiviral agents. METHODS: This research is a cross-sectional study that included 60 HCV patients maintained on regular HD patients who achieved 24 weeks of sustained virological response after treatment with direct-acting antiviral agents. Real-time PCR was performed to detect HCV-RNA in peripheral blood mononuclear cells. RESULTS: HCV-RNA was detected in peripheral blood mononuclear cells of three patients (5%). Occult HCV infection cases were treated by Interferon/ribavirin before direct-acting antiviral agents and two of them had raised pre-treatment alanine aminotransferase levels. Logistic regression analyses revealed that high pre-treatment viral load and raised pre-treatment alanine aminotransferase were associated with an increased risk of occult HCV infection with p value of 0.041 and 0.029, respectively. CONCLUSIONS: Occult HCV infection in hemodialysis patients who achieved sustained virological response after treatment with direct-acting antiviral agents may occur, and this may necessitate dual testing for HCV in both serum and peripheral blood mononuclear cells to ensure viral clearance. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT04719338.

Association of serum 25-hydroxyvitamin D3 levels and insulin resistance with viral load and degree of liver fibrosis in Egyptian chronic HBV patients: a case-control study.

Aim of the study: To assess serum 25-hydroxyvitamin D3 level and insulin resistance (IR) in hepatitis B virus (HBV) patients compared with controls and to evaluate the correlation with HBV viral load, severity of liver disease and degree of liver fibrosis. Material and methods: A case-control study. Sixty HBV patients and 60 controls were enrolled. Chemiluminescence was used to determine 25-hydroxyvitamin D3 levels. Insulin resistance was evaluated using the homeostasis model assessment method. Polymerase chain reaction was used to quantify HBV viral loads. Severity of liver disease was assessed by Child-Pugh scores. Transient elastography was used to evaluate the degree of liver fibrosis. Results: 25-Hydroxyvitamin D3 deficiency is more prevalent among HBV patients compared to controls. 25-Hydroxyvitamin D3 levels declined considerably as viral load rose (p < 0.001). 25-Hydroxyvitamin D3 level declined as liver fibrosis progressed (34.0 ±0.0 ng/ml in F1 vs. 12.67 ±8.0 ng/ml in F4) and the severity of the disease increased (22.75 ±6.36 ng/ml in Child A vs. 5.50 ±0.58 ng/ml in Child C). Insulin resistance is more prevalent among HBV patients compared to controls and it appeared to deteriorate progressively with boosting of the viral load, degree of fibrosis and severity of liver disease (p < 0.001). Conclusions: HBV patients had significantly lower 25-hydroxyvitamin D3 levels compared to healthy individuals and HBV infection is associated with IR. 25-Hydroxyvitamin D3 deficiency and IR were associated with HBV viral loads, severity of liver disease, and degree of liver fibrosis.

Evaluation of adrenal function in hemodynamically stable patients with liver cirrhosis.

Aim of the study: To estimate the prevalence of adrenal insufficiency (AI) in hemodynamically stable cirrhotic patients and to evaluate the potential association with patients' clinical characteristics, cirrhosis etiology and liver disease severity. Material and methods: The cross-sectional study included 132 stable liver cirrhosis patients. Severity of liver disease was graded using the Child-Pugh classification and Model for End-stage Liver Disease (MELD) score. The adrenal function was evaluated by measuring basal and peak cortisol after 60 minutes following the short Synacthen test (SST). Differences in terms of demographic data, clinical information and liver disease severity were compared between cirrhotic patients with and without AI. Results: Out of 132 cirrhotic patients, 86 patients had evidence of AI based on the peak serum cortisol value while the prevalence was lower (67 patients out of 132) when basal cortisol level was taken as the basis. A total of 82 patients were classified as Child-Pugh class C, with an average MELD score of 20 ±7.1. Most patients with AI had Child-Pugh class C. Patients with AI had a higher prevalence of ascites, gastrointestinal hemorrhage, and hepatic encephalopathy, a higher MELD score and a lower serum sodium level compared to patients with normal adrenal function. AI was not related to the etiology of cirrhosis but was related to the severity of liver disease and the degree of hyponatremia. Conclusions: Adrenal insufficiency is common among hemodynamically stable patients with cirrhosis. It is related to the severity of liver disease and the degree of hyponatremia.

Serum Ghrelin Concentration in Patients With Primary Biliary Cirrhosis (PBC).

INTRODUCTION: The appetite-modulating hormone ghrelin may have a role in the etiology of anorexia which is a serious concern in patients with primary biliary cirrhosis (PBC). This study aims to assess the difference in ghrelin level between cases of PBC and healthy controls matched for age and gender, and to evaluate the level of ghrelin in relation to clinical and laboratory findings among cases. METHODS: Twenty patients with primary biliary cirrhosis and 30 healthy controls matched by gender and age were recruited. The severity of liver disease was determined using the Child-Pugh grading system. Clinical comorbidities such as a history of ascites, gastrointestinal bleeding, and encephalopathy were evaluated. A commercial enzyme-linked immunosorbent assay was used to measure total ghrelin.  Results: PBC cases had a significantly higher average level of ghrelin (2305.3 ± 639.4) pg/mL compared to controls (682 ± 197.3) pg/mL. Furthermore, the minimum reported level in cases was 1258 pg/mL compared to 326 pg/mL in controls, while the maximum level nearly tripled the control's maximum level. In PBC patients, plasma levels of total ghrelin showed a weak positive correlation with age, an inverse correlation with body mass index, and were not associated with gender. The level was significantly higher than those in the controls. Ghrelin was associated with the severity of cirrhosis. Levels of serum ghrelin were higher in patients with associated comorbidities such as a history of ascites, gastrointestinal bleeding, and encephalopathy. CONCLUSIONS: Our study demonstrated elevated serum ghrelin levels in patients with primary biliary cirrhosis. Serum ghrelin was associated with the degree of severity and the presence of related comorbidities. Patients with primary biliary cirrhosis remain anorexic and catabolic despite elevated ghrelin levels, suggesting tissue resistance to this anabolic peptide which could be crucial to understanding anorexia and cachexia in primary biliary cirrhosis.

Evaluation of Serum Levels of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Patients With Colorectal Cancer: A Case-Control Study.

BACKGROUND/AIM: Limited information is available about the relationship between colorectal cancer (CRC) and serum concentration of insulin-like growth factor 1 (IGF1) and insulin-like growth factor-binding protein 3 (IGFBP3). This study aims to compare the serum levels of IGF1and IGFBP3 in colorectal cancer cases and controls and to assess the relationship between their level and the demographic and histopathological characteristics. METHODS: A case-control study in which 50 patients with colorectal cancer and 50 controls matched by gender and age were compared regarding the demographic characteristics and the level of both IGF1 and IGFBP3. The correlation with different clinicopathological features was assessed. RESULTS: Levels of IGF1 were significantly higher while levels of IGFBP3 were significantly lower among cases compared to control. IGF1 was significantly higher among patients with liver metastasis, lymph node (LN) spread, and lymphovenous invasions and did not show significant association with gender, smoking status, family history, or primary site of colorectal cancer. Lower IGFBP3 was significantly high among patients with liver and lymph node metastasis, lymphovenous invasion, and patients with positive family history. This significant negative correlation was also detected between IGFBP3 levels and the size of the tumor. CONCLUSIONS: High IGF1 levels and low concentrations of IGFBP3 are related to colorectal cancer and were significantly associated with liver metastasis, lymph node spread, and lymphovenous invasions. Further research is recommended to investigate if circulating IGF1 and IGFBP3 levels can be used to identify people at high risk of colorectal cancer and to investigate potential lifestyle or pharmaceutical ways to lower IGF1 bioactivity as a risk reduction strategy.

Evaluation of thyroid function and thyroid autoimmune disease in patients with non-alcoholic fatty liver disease.

Aim of the study: Evaluation of thyroid function and thyroid autoimmunity in patients with non-alcoholic fatty liver disease (NAFLD). Material and methods: A case control study. Fifty patients with NAFLD and 50 control subjects matched by gender and age were recruited. Serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured to assess thyroid function. Thyroid autoimmune disease was evaluated by measuring thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibodies (TgAb). The FIB-4 score and the APRI score were calculated to assess the degree of fibrosis. The association between thyroid parameters and NAFLD was explored. Results: About one quarter of patients with NAFLD had hypothyroidism compared to 10% of the control group whilst 6% of NAFLD patients had hyperthyroidism compared to 2% of the controls. NAFLD cases showed substantially higher TSH and lower FT4 compared to controls; meanwhile, levels of fibrosis indices (FIB-4 and APRI score) were significantly higher among hypothyroid patients in both cases and controls. TSH had a positive strong correlation with FIB-4 and APRI score, whereas FT4 had a negative significant correlation with both fibrosis indicators, and this clinical relationship was similar in NAFLD cases and controls. Conclusions: Hypothyroidism is more prevalent among patients with NAFLD compared to controls and high levels of TSH with low FT4 might be a risk factor for NAFLD and may impact the development of liver fibrosis. The role of thyroid autoimmunity in NAFLD needs further assessment. NAFLD patients should be monitored by yearly TSH and FT4 testing.