Direct-Acting Antivirals in the Treatment of Hepatitis C Virus (HCV)/Human Immunodeficiency Virus (HIV) Co-infected Patients: Real-Life Experience From Nepal.

Background Direct-acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C patients. However, the real-life data regarding its use in a human immunodeficiency virus (HIV) co-infection from a developing country is lacking. We aimed to see the efficacy of DAA in hepatitis C virus (HCV)/HIV co-infected populations. Methods In this prospective, observational, intention-to-treat study from Nepal, treatment-naïve patients undergoing treatment for chronic HCV in HIV co-infected individuals with DAA were studied. Patients on nevirapine were switched to efavirenz or atazanavir. Patients received sofosbuvir/ledipasvir or sofosbuvir/daclatasvir with or without ribavirine. Sustained virological response (SVR) at week 12, adverse events, and treatment compliance were evaluated. Treatment efficacy was compared between cirrhotic and non-cirrhotic patients. Results Of 218 patients presenting with an anti-HCV report, 181 (83%) had detectable HCV RNA. Eighty-five (85; 47%) patients were having ART at presentation. Three patients could not complete treatment due to gall stone pancreatitis and 82 completed treatment. Twenty-nine (29; 35%) were cirrhotic at presentation. Fifty-one (51; 62%) patients were genotype 3, 27 (33%) were genotype 1, three (4%) were mixed 1a/3, and one (1%) was 6. Seventy-four (74; 90%) had SVR12. Non-cirrhotics had 96% SVR compared to 79% in cirrhotics. SVR in genotype 3 was 88% while it was 93% in genotype 1. Conclusions Real-life experience showed that the DAAs are equally effective in HCV HIV co-infected patients. In non-cirrhotic patients, the result is comparable to mono-infected patients. Genotype 3 co-infected are also difficult-to-treat patients. DAA treatment is well-tolerated in HCV/HIV co-infected patients, and there was no dropout during treatment.

Estimation of Liver Fat by FibroScan in Patients With Nonalcoholic Fatty Liver Disease.

Background Assessment of nonalcoholic fatty liver disease (NAFLD) includes estimation of liver fat (steatosis). Controlled attenuation parameter (CAP) value obtained by FibroScan® (Echosens, Paris, France) is an alternative to liver biopsy for diagnosing and estimating steatosis (S). This study aimed to estimate the liver fat by CAP in NAFLD patients. Methods An observational cross-sectional study was conducted at the Liver Unit of Bir Hospital, from January 2021 to May 2021 after ethical clearance from the Institutional Review Board of the National Academy of Medical Sciences. A convenient sampling method was used. Data were analyzed with descriptive and inferential statistics involving bivariate and multivariate analysis. Results A total of 127 NAFLD patients were enrolled. The mean (±SD) CAP value was 271.53 (±50.69) dB/m. Total cholesterol, triglyceride, and body mass index (BMI) correlated positively (p<0.05) while systolic blood pressure correlated negatively with CAP value (p=0.031). On multivariate analysis, patients with BMI ≥25 kg/m2 were found 3.7 times more likely to have CAP ≥291 dB/m (S3, severe steatosis) than those with BMI <25 kg/m2 (p=0.048, 95% CI 1.01, 13.50). The mean (±SD) CAP values were 276.19 (±49.93) and 246.60 (±48.50) dB/m among those with BMI ≥25 kg/m2 and <25 kg/m2, respectively (p=0.016, using independent t-test). CAP steatosis grading correlated positively with both the ultrasound grading (p<0.001) and fibrosis grading by liver stiffness measurement (p=0.004).  Conclusion In this observational cross-sectional study of NAFLD patients, the mean (±SD) CAP value was 271.53 (±50.69) dB/m, which corresponds to moderate steatosis (S2). Obese NAFLD patients with ≥25 kg/m2 were 3.7 times more likely to have severe steatosis (S3) than nonobese NAFLD patients with BMI <25 kg/m2.

The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease.

Background and objective The prevalence of non-alcoholic fatty liver disease (NAFLD) is 60% in patients with type 2 diabetes mellitus (T2DM). NAFLD can lead to non-alcoholic steatohepatitis (NASH), both of which are the leading causes of cirrhosis. This study was undertaken to evaluate whether empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, reduces liver fat content in these patients after therapy. Methods After enrolling patients of T2DM with NAFLD, they were administered empagliflozin 10 mg once daily orally for six months without modifying existing oral hypoglycemic agents (OHA) if any. All demographic data were collected, and anthropometric measurements, as well as laboratory investigations, were performed, and controlled attenuation parameter (CAP) and liver stiffness (LS) were measured using FibroScan® (Echosens, Paris, France) at baseline, and six months of therapy. The adverse effects related to therapy were also taken into account. Results There was a significant decrease in mean CAP value from 282.07 ± 47.29 dB/m to 263.07 ± 49.93 dB/m and LS from 5.89 ± 4.23 kPa to 5.04 ± 1.49 kPa along with a significant decrease in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) among the patients. Compared to the baseline, there was a significant reduction in post-treatment weight, body mass index (BMI), and blood pressure (BP). The most commonly observed adverse effects of the therapy were urinary tract infection (UTI) (17.8%), nasopharyngitis (11.9%), and hypoglycemia (10.71%). Conclusion A reduction in hepatic fat content was seen in our prospective study cohort after six months of empagliflozin therapy. Empagliflozin also led to beneficial effects such as weight loss and reduction in transaminases and GGT. Given the absence of significant side effects of the therapy, empagliflozin could be used as an effective treatment modality for T2DM patients with NAFLD, which are two conditions commonly seen in combination.

Prevalence of Acute Kidney Injury in Patients with Liver Cirrhosis.

INTRODUCTION: Acute kidney injury is a common and life-threatening event in patients with liver cirrhosis occurring in approximately 20-50% of hospitalized patients of liver cirrhosis. Pre-renal acute kidney injury, the hepatorenal syndrome type of acute kidney injury and acute tubular necrosis represent the common causes. The aim of this study was to study the profile of acute kidney injury in patients with liver cirrhosis. METHODS: Consecutive patients of liver cirrhosis admitted in Liver unit of Bir Hospital were studied to see the presence of acute kidney injury in this hospital based descriptive cross-sectional study. Clinical and laboratory parameters along with various clinical outcome were compared between different groups categorized by the severity of liver disease and renal dysfunction. RESULTS: Out of 302 liver cirrhosis patients, 56 (18.5%) had acute kidney injury among which 23 (46%) were found to have pre-renal acute kidney injury, 15 (30%) with hepatorenal syndrome- acute kidney injury and 12 (24%) with intrinsic renal disease. Patients with higher stages of acute kidney injury had longer duration of hospital stay and hepatorenal syndrome-acute kidney injury was seen in patients with higher grade of ascites and with hyponatremia. CONCLUSIONS: Acute kidney injury is a common occurrence in patients with advanced liver cirrhosis with pre-renal acute kidney injury being the commonest cause. Median hospital stay is directly affected by the severity of acute kidney injury and hepatorenal syndrome-acute kidney injury was seen in patients with higher grade of ascites and hyponatremia. Early identification of patients at high risk for acute kidney injury may help to reduce mortality and contain costs.

Hepatitis C (HCV) therapy for HCV mono-infected and HIV-HCV co-infected individuals living in Nepal.

BACKGROUND: Despite direct-acting antivirals (DAA), aims to "eradicate" viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR. CONCLUSIONS/SIGNIFICANCE: Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient's profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.

Cardiac Dysfunction in Patients with Liver Cirrhosis.

BACKGROUND: The clinical picture in cirrhosis is dominated by the classical complications such as ascites, bleeding varices, portal hypertension and encephalopathy. Cardiac dysfunction in patients with cirrhosis, which contributes significantly to the morbidity and, mortality though prevalent, is less studied and not widely recognized entity since it is largely asymptomatic at rest, with overt heart failure seen mainly during pharmacological stress, transjugular intrahepatic portosystemic shunt, liver transplantation. METHODS: It is a cross sectional study done on patients admitted in wards or attending to outpatient department of Liver unit, Bir Hospital, between May 2015 to May 2016. Diagnosis of cirrhosis was based on clinical examination, lab parameters, ultrasound examination, endoscopy and/or liver biopsy. Cirrhotic patients after assessing the exclusion criteria were recruited for the study. Child Pugh and model for end stage liver disease scores were calculated to assess the liver function. Cardiac function was evaluated by resting pulse, mean arterial pressure, electrocardiography, and 2 dimensional echocardiography. RESULTS: Diastolic dysfunction was seen in 61.9%(48) and was more common in alcoholic group (63.2% Vs 58.6%). Systolic dysfunction was seen in 6.6% of alcoholic patients only. 51.4% had cirrhotic cardiomyopathy according to the criteria (proposed by World congress of gastroenterology in 2005). Prolonged QTc of >0.44 seconds was noted in 79%, mainly in child pugh C, with model for end stage liver disease score >10. CONCLUSIONS: Cardiac dysfunction is prevalent with sizeable number of patients with cirrhosis especially in the form of diastolic dysfunction independent of etiology. QTc prolongation might be an early indicator of cardiac dysfunction and is directly correlated with child pugh and model for end stage liver disease scores.

Prevalence of Hepatitis D Among Patients with Hepatitis B Viral Infection Attending a Tertiary Care Centre of Nepal.

INTRODUCTION: Worldwide there is variation in prevalence of Hepatitis D viral infection. Superinfection and co infection with hepatitis B viral infection is known to occur in 15-20 million people. METHODS: This was a descriptive cross-sectional hospital based study carried out in NAMS, Bir hospital, Kathmandu, Nepal from period of January 2017 to June 2017. Consecutive patients of chronic hepatitis B viral infection of HBsAg positive with more than two-time upper normal limit of ALT were enrolled and tested for HDV IgG. RESULTS: Forty patients were enrolled during study period. Mean age was 30.9±12.2 years. Males were 28 (70%) and females 12 (30%). Most of the patients were asymptomatic for HBV infection 32 (80%). HBeAg negative chronic hepatitis was most commonly present in 31 (77.5%). Family history of Hepatitis B viral infection was seen in 7 (17.5%) and sexual promiscuity in 5 (12.5%) as the mode of acquisition of hepatitis B viral infection. HBcIgM was positive in three patients with mean HBV DNA of 4.97x10(5)±4.5x10(5) IU/ml in HBeAg positive group. HDV IgG was negative in all patients. CONCLUSIONS: Coinfection and superinfection of hepatitis D virus were found to be uncommon at Bir hospital, Nepal.

Significance of Non-Invasive Markers as Predictor of Esophageal Varices in Liver Cirrhosis.

INTRODUCTION: Upper gastro-intestinal endoscopy remains the gold standard for screening for esophageal varices but it has its own limitations. It is an invasive, expensive and uncomfortable procedure and needs clinical expertise. Accordingly, this study was conducted to establish the role of non-invasive markers for prediction of esophageal varices in liver cirrhosis. METHODS: A hospital based descriptive cross-sectional study was carried out in Liver unit of National Academy of Medical Sciences, Bir Hospital, from October 2016 to September 2017. Complete blood count, liver function test, liver ultrasound and upper gastro-intestinal endoscopy were done for all patients to detect esophageal varices and to correlate with different non-invasive markers. RESULTS: Total 191 patients of liver cirrhosis were studied after exclusion. Platelet count of 92082.00±43435.83/mm3 and spleen size of 144.21±10.71 mm was found to be good predictors of presence of EV (P≤0.001). Significant association between Child-Turcotte-Pugh class and presence of varices was observed (P≤0.001). AST/ALT ratio with cutoff value of 1.415 showed sensitivity of 82.4% and specificity of 36.4%. APRI at a cutoff value of 1.3 showed a sensitivity of 83.2% and specificity of 50%. CONCLUSIONS: Platelet count, spleen size and Child-Turcotte-Pugh class are good predictors of presence of esophageal varices in patients with liver cirrhosis. AST/ALT ratio and APRI score are not good substitutes for upper gastro-intestinal endoscopy.