Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis.

BACKGROUND AND AIM: Existing data are controversial regarding the incidence of hepatitis C (HCV)-related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4). METHODS: Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined. RESULTS: The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×103/mL, and high AFP were independent risk factors of developing HCC. CONCLUSION: Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.

Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID-19: A randomized controlled trial.

Only a few treatments are approved for coronavirus disease-2019 (COVID-19) infections, with continuous debate about their clinical impact. Repurposing antiviral treatments might prove the fastest way to identify effective therapy. This trial aimed to evaluate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or ravidasvir (RDV) added to standard care (SOC) for patients with moderate and severe COVID-19 infection. Multicentre parallel randomized controlled open-label trial. One hundred and twenty eligible patients with moderate and severe COVID-19 infection were randomized to one of the study arms. Ten days of treatment with SOF plus DCV or RDV in addition to the standard of care compared to SOC. Follow up in 7 days. Sum of the counted symptoms at 7 and 10 days, mean change in oxygen saturation level, viral negativity, and rate of intensive care unit (ICU) admission. Compared to SOC, the SOF-DCV group experienced a significantly lower sum of the counted symptoms (fever, headache, generalized aches, or respiratory distress) combined with no evidence of deterioration (ICU admission and mechanical ventilation) on Days 7 and 10 of treatment. Oxygen saturation also significantly improved among the SOF-DCV group compared to SOC starting from Day 4. The study also showed positive trends regarding the efficacy of SOF-DCV with a lower incidence of mortality. On the other hand, adding SOF-RDV to SOC did not show significant improvements in endpoints. The results support the efficacy and safety of SOF-DCV as an add-on to SOC for the treatment of moderate to severe COVID-19 infections.

Sudomotor Changes in Hepatitis C Virus Infection with or without Diabetes Mellitus: A Pilot Study in Egyptian Patients.

Hepatitis C virus (HCV) infection can affect the neurological system, and neuropathy is one of these manifestations. Hepatitis C virus infection is associated with diabetes mellitus (DM) type II, and diabetic patients are at higher risk of acquiring HCV infection. Sweat function has been proposed to assess early autonomic neuropathy. This study aimed to evaluate small fiber neuropathy in asymptomatic HCV-related cirrhotic patients with or without DM through sweat function assessment by Sudoscan test. Three groups were involved: 47 healthy controls, 48 HCV-related cirrhotic patients without DM (group 1), and 49 HCV-related cirrhotic patients with DM type II (group 2). All participants were subjected to liver panel tests, renal function tests, cell blood counts, HbA1c, and abdominal ultrasound. Sweat function was assessed in all patients and controls by measuring hand and feet electrochemical skin conductance (ESC, microSiemens [µS]) using Sudoscan. Peripheral neuropathy was detected in none of the controls, 39% of group 1 patients, and 62% of group 2 patients (P < 0.0001). The mean feet ESC (FESC) was 88.3 ± 6.8 µS in controls, 67.2 ± 19.2 µS in group 1, and 57.9 ± 19.4 µS in group 2 (P < 0.0001). A significant correlation was observed between FESC and bilirubin, albumin, creatinine, international normalized ratio, transaminases, and splenic size. Electrochemical skin conductance measurement is a valuable, noninvasive method for early detection of small fiber neuropathy in asymptomatic HCV-related cirrhosis, with or without DM.

Impact of new direct-acting antiviral drugs on hepatitis C virus-related decompensated liver cirrhosis.

BACKGROUND: The benefits of treatment of hepatitis C virus with direct-acting antiviral drugs in patients with decompensated liver cirrhosis (DLC) are still unclear. AIM: To evaluate the degree of improvement in hepatic decompensation events and quality of life (QOL) in treated patients with DLC. PATIENTS AND METHODS: One hundred and fifty patients with hepatitis C virus-related DLC were included; 75 of these patients received treatment (group I) [sofosbuvir (SOF) with either daclatasvir or ledipasvir for 24 weeks without ribavirin (RBV) or for 12 weeks with RBV] and 75 patients did not receive treatment as a comparable group (group II). Patients who achieved a sustained virological response at 12 weeks were assessed in terms of decompensation events, model for end-stage liver disease score, Child-Turcotte-Pugh score, biochemical changes, and QOL (applied on Mcguill QOL questionnaire) before starting treatment and 6 months after end of treatment, and were compared with untreated patients. RESULTS: Forty-two (56%) patients received SOF/daclatasvir for 24 weeks without RBV and 19 (25.3%) patients received SOF/ledipasvir for 24 weeks without RBV. The model for end-stage liver disease score improved in treated patients (mean change -1.73), but worsened in untreated patients (mean change +11.8) before and after 6 months. Also, the Child-Turcotte-Pugh score improved significantly (P<0.001). Serum albumin, prothrombin time, bilirubin, α-fetoprotein, and alanine aminotransferase improved in treated patients (P<0.001). Health-related QOL improved in treated patients (mean change +17.65) and worsened in untreated ones (mean change -18.68; P<0.001). CONCLUSION: Treated patients with DLC showed an improvement in liver tests and health-related QOL. Longer durations of follow-up for decompensation events are needed.

Long-term effect of mass chemotherapy of Schistosoma mansoni on infection rate and diagnosis accuracy.

OBJECTIVES: To assess the performance of microscopic stool examination, which is used widely for the diagnosis and assessment of infection rates of Schistosoma mansoni in Egypt, for the evaluation of chemotherapy efficacy after a decade of regular mass treatment. METHODS: A total of 651 individuals from Lower Egypt (55 children and 596 adults) were examined for S. mansoni ova by microscopic stool examination (MSE) alone (n=166; 111 adults and 55 children), rectal biopsy (RB) alone (n=32 adults), or both MSE and RB (n=453 adults). RESULTS: Infection detection rates were significantly lower in the MSE alone group (9%; 15/166) compared to the RB alone group (40.6%; 13/32) and to the RB+MSE group (37.7%; 171/453). Out of all positive cases in the MSE+RB group, only 23/171 patients (13.5%) were positive by stool examination, of whom 21 were also positive by RB, in contrast to 169/171 patients (86.5%) positive by RB in the same group. It was noted that adding MSE to RB did not increase the prevalence compared to RB alone: 37.3% in the MSE+RB group vs. 40.6% in the RB only group. Using the summation of both MSE and RB tests as the gold standard, the sensitivity of MSE was significantly lower than that of RB: 13.5% vs. 98.8%. CONCLUSIONS: The implementation of mass treatment programmes has resulted in a new era of light infection, for which conventional parasitological methods for the diagnosis and monitoring of infection can miss many patients.

Hepcidin mRNA level as a parameter of disease progression in chronic hepatitis C and hepatocellular carcinoma.

BACKGROUND: Hepcidin, a key regulator of iron metabolism, is synthesized by the liver. Hepcidin binds to the iron exporter ferroportin to regulate the release of iron into plasma from macrophages, hepatocytes, and enterocytes. AIM: To study hepcidin expression in liver tissue of patients with hepatocellular carcinoma (HCC), chronic hepatitis C (CHC) and normal human liver biopsies and to compare its level with serum and liver iron indices. PATIENTS AND METHODS: Liver biopsies from 66 patients (36 HCC and 30 CHC) were analysed as well as normal human liver biopsies obtained from 20 healthy liver transplant donors as a control group. Liver function tests, AFP, hepatitis markers, HCV-RNA levels, hemoglobin concentration and serum iron parameters were analyzed. Hepcidin mRNA was quantified in all liver biopsies of patients and controls by real-time PCR. Liver iron concentration (LIC) was evaluated and hepatic iron index (HII) was calculated by dividing LIC in mmol/gm dry weight by the patient's age. RESULTS: The mean level for hepcidin mRNA in HCC, CHC and healthy controls were 2351±505, 5735±2403 and 16308±2194 copies/ml, respectively; with significant decrease in cancerous (HCC) than non-cancerous (CHC) and control liver tissues. The level was significantly lower in patients with multiple tumour masses. Hepcidin mRNA had a significant positive correlation with synthetic function of the liver (serum albumin and prothrombin concentration) and haemoglobin. In contrast, hepcidin mRNA was negatively correlated with parameters of iron stores as (serum ferritin and HII) and grade of liver fibrosis in both patient groups. CONCLUSION: The expression of hepcidin mRNA is decreased in liver tissues of CHC patients and more suppressed in the liver tissues of patients with HCC, suggesting that hepcidin expression appears to be appropriately responsive to iron status and disease progression in cirrhosis and hepatocarcinogenesis. KEY WORDS: HCC - Hepcidin - mRNA - Real-time PCR.