Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals?

Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.

Genotype-specific versus pangenotypic regimens in patients infected with hepatitis C virus genotype 1b in real-world settings.

Introduction: The introduction of direct-acting antivirals (DAAs) has provided us with hope to eliminate hepatitis C virus (HCV) infection as a significant public health problem in the coming years. Objective: Our study aimed to compare the effectiveness and safety of genotype-specific and pangenotypic regimens in genotype 1b­infected patients treated in real-world settings. Patients and methods: Patients were selected from 990 HCV-infected individuals treated with DAAs in the Department of Infectious Diseases in Kielce, Poland, who had the therapy initiated between July 1, 2015 and December 31, 2020. Results: A total of 795 genotype 1b­infected patients with a median age of 51 years, female predominance (55%), and a 21.1% rate of cirrhosis were included in the analysis. A total of 69.9% of patients were treated with genotype-specific regimens. Those patients were significantly older, more often were treatment experienced, and had advanced liver fibrosis and cirrhosis compared with patients assigned to pangenotypic regimens. An overall sustained virologic response rate of 97.9% in the intention-to-treat (ITT) analysis and 99% after excluding nonvirologic nonresponders was achieved, with no significant difference between patients in the 2 treatment arms. Significantly higher proportions of men (P = 0.001) and DAA-experienced patients (P = 0.049) were documented among virologic nonresponders. Conclusions: We confirmed very high effectiveness and a good safety profile of both genotype-specific and pangenotypic regimens used in patients with genotype 1b HCV infection, and we found no differences between these 2 generations of medications. Male sex and previous treatment with DAAs were identified as negative predictors for therapy effectiveness.

Impact of Kidney Failure on the Severity of COVID-19.

BACKGROUND: Patients with kidney failure are at an increased risk of progression to a severe form of coronavirus disease 2019 (COVID-19) with high mortality. The current analysis was aimed to assess the impact of renal failure on the severity of COVID-19 and identify the risk factors of the fatal outcome in this population. METHODS: The analysis included patients from the SARSTer database, a national real-world study evaluating treatment for COVID-19 in 30 Polish centers. Data were completed retrospectively and submitted online. RESULTS: A total of 2322 patients were included in the analysis. Kidney failure was diagnosed in 455 individuals (19.65%), of whom 373 presented moderate stage and 82 patients, including 14 dialysis individuals, presented severe renal failure. Patients with kidney failure were significantly older and demonstrated a more severe course of COVID-19. The age, baseline SpO2, the ordinal scale of 4 and 5, neutrophil and platelet count, estimated glomerular filtration rate, and C-reactive protein concentration as well as malignancy and arterial hypertension were the independent predictors of 28-day mortality in logistic regression analysis. CONCLUSIONS: Underlying kidney disease in patients with COVID-19 is among the leading factors associated with a higher risk of severe clinical presentation and increased mortality rate.

Severe intrahepatic cholestasis and liver failure after stanozolol usage - case report and review of the literature.

Stanozolol is a 17α-alkylated synthetic anabolic steroid used illegally by bodybuilders. We present a 19-year-old man who was taking 50 mg of stanozolol intramuscularly, every other day for 2 months, to improve muscle mass. On admission, his bilirubin concentration was 44.34 mg/dl. The serum levels of liver enzymes were normal, with only alanine aminotransferase being slightly elevated. Liver biopsy revealed toxic hepatitis of minor grade with periportal fibrosis and intrahepatic cholestasis. Medical treatment of the patient was conservative. Despite the therapy the patient's general condition deteriorated - bilirubin level increased to 56.64 mg/dl, and INR rose to 1.7. Then we decided to administer low doses of hydrocortisone. As a result of the treatment, bilirubin concentration was 14.61 mg/dl after 2 weeks. Finally all hepatic enzymes returned to normal values 5 months after stanozolol was discontinued. This treatment appears to be safe and leads to a more rapid reduction of bilirubin.