Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil.

BACKGROUND: Hepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs). AIM: To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil. METHODS: This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a P value of < 0.05 was considered significant. RESULTS: The mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, P = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, P = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, P = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060-1.233, P = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, P = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, P = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, P = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence. CONCLUSION: Treatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.

Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study.

OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.

Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study

OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.

Multiple hepatic metastases of cardiac angiosarcoma

The differential diagnosis of hepatic focal lesions is challenging because the etiology can be inflammatory, infectious, and even neoplastic. A rare cause of metastatic liver nodules is cardiac angiosarcoma. We report a case of this tumor, which was diagnosed only after autopsy. A 26-year-old Caucasian man was admitted for progressive dyspnea and cough over the past 3 weeks. Physical examination showed only hypophonetic heart sounds. Laboratory analysis demonstrated anemia and elevated inflammatory markers, despite normal biochemical parameters and liver function. Transthoracic echocardiography revealed massive pericardial effusion. Abdomen computed tomography (CT) showed multiple hepatic nodules, the largest of which measured 3 cm, but the percutaneous biopsy revealed only lobular necrosis and perisinusoidal fibrosis without granulomas or neoplastic cells. During hospitalization, the patient had fever and night sweats with weight loss, and empiric treatment for extrapulmonary tuberculosis associated with corticosteroids was initiated. The outpatient follow-up revealed complete improvement of the pericardial effusion, but maintenance of the liver lesions. After 2 months of hospital discharge, the patient was readmitted with hemorrhagic shock due to bleeding liver lesions, which were evidenced by CT. Embolization of the right hepatic artery was performed, but the patient soon died. The autopsy revealed a primary cardiac angiosarcoma with multiple hepatic metastases, rupture of the Glisson's capsule and laceration of the liver. The case shows how important and difficult the diagnosis of focal liver lesions is, since it may result in an unexpected fatal outcome.

Multiple hepatic metastases of cardiac angiosarcoma.

The differential diagnosis of hepatic focal lesions is challenging because the etiology can be inflammatory, infectious, and even neoplastic. A rare cause of metastatic liver nodules is cardiac angiosarcoma. We report a case of this tumor, which was diagnosed only after autopsy. A 26-year-old Caucasian man was admitted for progressive dyspnea and cough over the past 3 weeks. Physical examination showed only hypophonetic heart sounds. Laboratory analysis demonstrated anemia and elevated inflammatory markers, despite normal biochemical parameters and liver function. Transthoracic echocardiography revealed massive pericardial effusion. Abdomen computed tomography (CT) showed multiple hepatic nodules, the largest of which measured 3 cm, but the percutaneous biopsy revealed only lobular necrosis and perisinusoidal fibrosis without granulomas or neoplastic cells. During hospitalization, the patient had fever and night sweats with weight loss, and empiric treatment for extrapulmonary tuberculosis associated with corticosteroids was initiated. The outpatient follow-up revealed complete improvement of the pericardial effusion, but maintenance of the liver lesions. After 2 months of hospital discharge, the patient was readmitted with hemorrhagic shock due to bleeding liver lesions, which were evidenced by CT. Embolization of the right hepatic artery was performed, but the patient soon died. The autopsy revealed a primary cardiac angiosarcoma with multiple hepatic metastases, rupture of the Glisson's capsule and laceration of the liver. The case shows how important and difficult the diagnosis of focal liver lesions is, since it may result in an unexpected fatal outcome.