The challenges of ascites management: An Indian perspective

Abstract

Answer questions and earn CME Content available: Author Interview and Audio Recording Ascites is the most common type of decompensation in liver cirrhosis. Current guidelines recommend the management of ascites with sodium restriction and diuretics. However, this approach fails to account for several factors, including the differing etiologies of liver disease, advanced stages of the disease at presentation, nutritional status, body composition, and genetic factors (predisposition to metabolic syndrome and drug tolerance) that affect the management of ascites in the Indian population. In this review, we discuss the unique factors of ascites management in the Indian population. Malnutrition is highly prevalent in India, with an average body mass index of 22 kg/m2, which is much lower than in other countries. In addition, the prevalence of frailty (reduced muscle mass and function) is higher in India than in other low- and middle-income countries.1 Patients with cirrhosis often present late, and frailty is prevalent in nearly 50% of the patients with decompensated cirrhosis.2, 3 Loop diuretics can further deplete the muscle mass and lead to a vicious cycle of reduced ammonia metabolism, poor nutrition, and increased protein catabolism.4, 5 Aldosterone-antagonist monotherapy is the recommended first-line treatment for ascites. However, given the difficulty of frequent monitoring for adverse effects, we prefer a combination of loop diuretics and aldosterone antagonists. The standard initiating dose is 20 mg of furosemide and 50 mg of spironolactone, titrated according to the patient’s response. A full dose of 160 mg of furosemide and 400 mg of spironolactone is rarely tolerated because of sarcopenia and a higher incidence of diuretic-induced complications, including acute kidney injury (AKI), dyselectrolytemia, and encephalopathy.4, 6 Due to the low protein intake and reduced skeletal mass, the glomerular filtration rate and serum creatinine levels are lower in the South Asian population.7 The incidence of paracentesis-induced circulatory dysfunction (PICD) in patients undergoing large-volume paracentesis (LVP) is slightly higher in the Indian population.8 Indeed, even moderate-volume paracentesis can also precipitate PICD, and a 5-L cutoff for the use of albumin in LVP may not be applicable to Asian cohorts9 (Figure 1). Another frequent issue with Indian patients is the high prevalence of undiagnosed cirrhotic cardiomyopathy or left ventricular diastolic dysfunction (LVDD), which affects 50% to 70% of patients with advanced chronic liver disease in South Asia versus 30% to 40% in Western populations.10 The use of beta-blockers in decompensated cirrhosis is associated with worsening ascites and an increased risk for AKI, especially in patients with reduced mean arterial pressure (MAP).11 Therefore, the tolerated dose of beta-blockers is also lower in Indian patients, resulting in impaired ascites clearance by diuresis. Furthermore, therapy monitoring is inadequate because of the limited understanding of the pathophysiology of LVDD, the difficulties in performing hepatic and cardiac hemodynamic tests, and the lack of surrogate biomarkers for an optimum beta-blockade.10, 11 Cirrhosis-related or drug-induced decrease in MAP can be counteracted using oral midodrine. The cost of midodrine therapy in India is significantly offset because of the easy availability of cost-effective, bioequivalent generic drugs. Patients with refractory ascites, who are without transplant prospects, can be managed for years on domiciliary albumin therapy; however, the cost of albumin therapy precludes its routine use. In addition, alfa-pump is not yet available, and long-term abdominal drains are not recommended outside of hospice care. Therefore, in India, midodrine is the preferred drug for refractory ascites,12 hepatic hydrothorax,13 and prevention of PICD14, 15 because of its excellent safety profile and patient acceptance. Although refractory ascites is a common indication for liver transplantation (LT), access to LT is not equitable in India.16 TIPS is an excellent therapy for refractory ascites. However, the results of TIPS are often suboptimal in the Indian population because of the presence of cirrhotic cardiomyopathy, a higher model for end-stage liver disease score at presentation, sarcopenia, and the difficulty in monitoring shunt patency and function.17 In addition, sarcopenia significantly increases the risk for hepatic encephalopathy.17 These relative contraindications frequently preclude a successful TIPS in our population. The feasible treatment options for ascites management in an Indian setting are described in Table 1. Unrecognized factors in the management of ascites in low- and middle-income countries are the limited access to health care and expert diagnosis, poor public awareness of chronic diseases, malnutrition, and economic and social disparities. Many Asian countries have launched national programs to eliminate chronic hepatitis (B and C) using population-based screening and treatment access, and the provision of free-of-charge generic antiviral drugs for infected patients, in conjunction with improved access to immunization.18 However, there is a lack of public health care policies, transplant registries, and funding to support definitive therapies, including LT in patients with advanced chronic liver disease. Despite these limitations, access to transplantation and expertise has recently improved in South Asia.16, 19 The launch of a universal health insurance policy in India, which provides reimbursement to eligible low-income families, provides some relief for interventions such as TIPS. The common causes of ascites in India are tuberculosis (TB), cirrhosis, Budd-Chiari syndrome, pancreatitis, hypoalbuminemia, and cardiac failure. The incidence of TB is relatively high in South Asian countries.20, 21 Initial ascitic fluid analysis should include adenosine deaminase (ADA) levels and TB nucleic acid testing (when available). It is also essential to exclude TB by ADA and TB nucleic acid testing before labeling refractory ascites in patients with cirrhosis. Patients with tubercular ascites often present with diuretic intolerance, which is one of the indications against portal hypertension–related ascites. Clinical and laboratory features for differentiating between tubercular and portal hypertension–related ascites are described in Table 2. Norfloxacin is the drug of choice for primary and secondary prophylaxis of spontaneous bacterial peritonitis. Fluoroquinolones are second-line anti-TB drugs, and empirical treatment can lead to the development of drug resistance. In contrast, trimethoprim-sulfamethoxazole (TMP-SMX) is a safer alternative. However, it is challenging to monitor cytopenia, and TMP-SMX is prescribed only for patients who can self-monitor for cytopenia. Hence it is necessary to exclude TB before initiating norfloxacin prophylaxis. The management of ascites is challenging in India, despite a significant increase in the acceptability of definitive therapies, including LT, in recent years.19 National health care policies are the need of the hour to provide improved access to treatment options. Although this article is specific to South Asia, with medical tourism and immigration, this article remains relevant for all clinicians who care for Indian/Asian patients. Some recommendations for adequate management of ascites are provided in Table 3. Nothing to report.

Topics & Concepts