RESUMO
BACKGROUND: In cirrhosis, activation of renin-angiotensin-aldosterone system leads to sodium and water retention causing ascites. Dapagliflozin, a sodium glucose linked transporter-2 inhibitor, induces natriuresis in patients with heart failure. A similar natriuretic effect may improve ascites in patients with cirrhosis. In this pilot study, we evaluated the safety and efficacy of dapagliflozin in patients with cirrhosis and recurrent ascites. METHODS: Forty patients with recurrent ascites and cirrhosis were randomized to 1:1 in a double blinded fashion to receive either dapagliflozin (10 mg/day) with standard medical therapy (Group A) or placebo with standard medical therapy (Group B). The primary outcome was control of ascites at 6 months. Secondary outcomes were urine output, 24-h urinary sodium, Child Turcotte Pugh (CTP), model for end-stage liver disease (MELD) scores, survival at 6 months, incidence of acute kidney injury (AKI) and infections. RESULTS: The 2 groups were comparable at baseline. Control of ascites at 6 months was significantly better in group A than that in Group B (p = 0.04). Change in urinary sodium was significantly higher in Group A (p < 0.001]. However, there was no difference in change in urine output, CTP or MELD scores and survival (65% vs 72.2%, p = 0.75) between the groups at 6 months. Incidence of AKI (50% vs 15%, p = 0.04) and infections (55% vs 20%, p = 0.04) were significantly higher in Group A. CONCLUSION: Significantly better control of ascites and higher natriuresis are observed with dapagliflozin. However, it does not improve disease severity scores or survival, and is associated with increased AKI and infections (NCT05014594).
RESUMO
Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART.