Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Prevalence, Risk Factors, and Impact of Bacterial or Fungal Infections in Acute Liver Failure Patients from India.

BACKGROUND: We evaluated the prevalence, risk factors, and impact of bacterial/fungal infections in acute liver failure (ALF) patients. METHODS: We analyzed clinical, biochemical, and microbiological data of ALF patients with and without bacterial/fungal infections admitted at an institute over the last 5 years. RESULTS: We enrolled 143 patients, 50% males, median age 25 years, with acute viral hepatitis (32.2%), drug-induced injury (18.2%), and tropical illness (14%) as aetiologies of ALF. 110 patients (76.9%) developed bacterial/fungal infections [Bacterial infection: MDR: 70%, PDR: 7%, ESBL: 40%, CRE: 30%, CRAB: 26.6%, MDR-EF: 13.3% and fungal infection: 19 (17.3%)]. On univariable analysis, SIRS (33.6% vs.3%), ICU admission (78.2% vs. 45.5%), mechanical ventilation (88.2% vs. 51.5%), inotropes (39.1% vs. 6.1%), invasive catheters (91.8% vs. 39.4%), and prolonged catheterization (6 days vs. 0 days) were significant risk factors for infections (p < 0.05, each). In contrast, SIRS and catheterization independently predicted infection on multivariable regression. Organ failures [3 (2-4) vs. 1 (0-2)], grade-III-IV HE (67.3% vs. 33.3%), circulatory failure (39.1% vs. 6.1%), coagulopathy (INR > 2.5: 58.2% vs. 33.3%), renal injury (28.2% vs. 6.1%) (p < 0.05), MELD (32.9 ± 8.2 vs. 26.7 ± 8.3) and CPIS [3(2-4) vs. 2(0-2)] were higher in infected vs. non-infected patients (p < 0.001). 30-day survival was significantly lower in infected vs. non-infected patients (17.3% vs. 75.8%, p < 0.001), while no patient survived with fungal infections. Refractory septic shock was the commonest cause of mortality in patients. CONCLUSIONS: Infections due to MDR organisms are high, fungal infections are fatal, and refractory septic shock is the dominant reason for mortality, implying bacterial and fungal infections as the major killer in ALF patients.

Effect of glucocorticoids on the development of COVID-19-associated pulmonary aspergillosis: A meta-analysis of 21 studies and 5174 patients.

COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment.

Efficacy, Tolerability, and Compliance of Direct Acting Antivirals in Patients with HIV and Hepatitis C Coinfection: A Real-Life Experience.

Effective management of HIV and hepatitis C virus (HCV) coinfection warrants special emphasis on interactions between direct acting antivirals (DAAs) and antiretroviral therapy (ART) along with maintenance of treatment compliance. All HIV-HCV coinfected adult patients (2015-2020) were included in this real-life retrospective study. Prevalence of coinfection, proportion of coinfected patients treated, compliance rate, sustained virological response at week 12 (SVR12) after the end of therapy, and adverse events were assessed. Among 4578 HIV patients, 232 (5.1%) had HCV coinfection. Ninety-two (39.7%) were intravenous drug users. One hundred twenty-eight (55.1%) patients presented to the liver clinic. Seventy-six (32.8%) patients [mean age: 36.6 ± 10.4 years; 65 (85.5%) males; mean CD4 count: 396 ± 246 cells/mL] completed DAA therapy, whereas 52 (22.4%) patients defaulted and 75 (32.3%) were lost to follow-up. Sixty-seven (82.2%) patients had chronic hepatitis and 9 (11.8%) had compensated cirrhosis. Median (range) HCV-RNA was 5.9 × 106 IU/mL (2.4 × 105-9.9 × 105). Among 15 (19.5%) treatment experienced patients, 14 were pegylated interferon experienced and one was NS5A-inhibitor experienced. ART regimens comprised a combination of tenofovir (T), lamivudine (L), efavirenz (E), nevirapine (N), and/or zidovudine (Z) at dosage and modifications as applicable [TLE: 63 (82.9%), ZLN:11 (14.5%), and ZLE: 2 (2.6%)]. Overall, 74 (97.4%) out of 76 patients who completed DAA therapy achieved SVR12. Adverse events were minor and well-tolerated. HIV-HCV-coinfected patients demonstrate excellent SVR12 and tolerability with available DAAs, with no major adverse events.

High Prevalence of Hormonal Changes and Hepatic Osteodystrophy in Frail Patients with Cirrhosis-An Observational Study.

Background/Aim: Hormonal changes and hepatic osteodystrophy are less often studied complications of cirrhosis. This study describes the variance in hormones and osteodystrophy between Frail and Not frail patients with cirrhosis. Methods: 116 outpatients with cirrhosis were prospectively enrolled in this study. Frailty assessment was done using Liver Frailty Index (LFI). Sociodemographic assessment, anthropometry, nutritional assessment, hormone profile, and dual-energy X-ray absorptiometry scan were done in all patients. Results: 116 patients, predominantly males (100 (86.2%) with mean age of 50.16 years (95% CI, 48.43-51.89) were included. Malnutrition was more common in Frail group as compared to Not frail group. Subjective global assessment (SGA) class-B patients were significantly more in Frail group (37 (74%) vs 3 (4.5%), P = 0.001). The prevalence of lower parathyroid hormone (PTH) (14 (28%) vs 2 (3%)), testosterone (33 (66%) vs 15 (22.7%)), vitamin D3 (44 (88%) vs 39 (59.1%)), and cortisol (37 (74%) vs 37 (56.1) levels was higher in Frail group (P < 0.05). The number of patients diagnosed with osteodystrophy (34 (68%) vs 21 (31.8%), P = 0.001) was significantly higher in Frail group. The marker of osteoclastic activity, ß-cross laps, was significantly elevated in the Frail group both in males (736 (655-818) vs 380 (329-432), P = 0.001) and (females 619 (479-758) vs 313 (83-543), P = 0.02). Bone mineral density (BMD) at lumbar spine (LS) and neck of femur (NF) had significant correlation with LFI (ρ = 0.60, P = 0.001 for LS and ρ = 0.59, P = 0.001 for NF), serum testosterone (ρ = 0.58, P = 0.001 for LS and ρ = 0.53, P = 0.001 for NF), ß-cross laps (ρ = 0.38, P = 0.001for LS and ρ = 0.35, P = 0.000 for NF), vitamin D3 (ρ = 0.23, P = 0.04 for LS and ρ = 0.25, P = 0.01 for NF), PTH (ρ = 0.52, P = 0.001 for LS and ρ = 0.48. P = 0.001 for NF), and cortisol (ρ = 0.50, P = 0.001 for LS and ρ = 0.45, P = 0.001 for NF) levels. Conclusion: This is the first study that highlights the high prevalence of hormonal changes and hepatic osteodystrophy in frail patients with cirrhosis and opens a new dimension for research and target of therapy in this field.

New insights into development and mortality of COVID-19-associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.

Health-Related Quality of Life Among Liver Disorder Patients in Northern India.

Objective: The present study aims to determine the health-related quality of life (HRQoL) among liver disorder patients being treated in tertiary care hospital in north India and exploration of factors affecting HRQoL. Methodology: The HRQoL was assessed among 230 patients visiting either the outpatient department (OPD) or those admitted in high dependency unit (HDU) or liver intensive care unit (ICU) using direct measuring tools such as Euro QoL five-dimension questionnaire (EQ-5D) and EQ visual analog scale. Multivariate regression was used to explore the factors influencing HRQoL. Results: Mean EQ-5D scores among chronic hepatitis and compensated cirrhosis patients were 0.639 ± 0.062 and 0.562 ± 0.048, respectively. Among those who were admitted in the ICU or HDU, mean EQ-5D score was 0.295 ± 0.031. At discharge, this score improved significantly to 0.445 ± 0.055 (P < 0.001). The multivariate results implied that HRQoL was significantly better among patients with lower literacy level (P = 0.018) and those treated in OPD settings (P < 0.001). Conclusion: HRQoL is impaired among patients suffering from liver disorders specifically those admitted in ICU. Further, there is a need to generate more evidence to explore the impact of determinants and treatment-associated costs on the HRQoL.

The Spectrum of Invasive Fungal Sinusitis in COVID-19 Patients: Experience from a Tertiary Care Referral Center in Northern India.

This study aimed to determine the patient demographics, risk factors, which include comorbidities, medications used to treat COVID-19, and presenting symptoms and signs, and the management outcome of COVID-19-associated invasive fungal sinusitis. A retrospective, propensity score-matched, comparative study was conducted at a tertiary care center, involving 124 patients with invasive fungal sinusitis admitted between April 2021 and September 2021, suffering from or having a history of COVID-19 infection. Among the 124 patients, 87 were male, and 37 were female. A total of 72.6% of patients received steroids, while 73.4% received antibiotics, and 55.6% received oxygen during COVID-19 management. The most common comorbidities were diabetes mellitus (83.9%) and hypertension (30.6%). A total of 92.2% had mucor, 16.9% had aspergillus, 12.9% had both, and one patient had hyalohyphomycosis on fungal smear and culture. The comparative study showed the significant role of serum ferritin, glycemic control, steroid use, and duration in COVID-19-associated invasive fungal disease (p < 0.001). Headache and facial pain (68, 54.8%) were the most common symptoms. The most involved sinonasal site was the maxillary sinus (90, 72.6%). The overall survival rate at the three-month follow-up was 79.9%. COVID-19-related aggressive inflammatory response, uncontrolled glycemic level, and rampant use of steroids are the most important predisposing factors in developing COVID-19-associated invasive fungal sinusitis.

Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure.

BACKGROUND: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. METHODS: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. RESULTS: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 µmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III-IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients. CONCLUSIONS: HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.

Comparative accuracy of prognostic models for short-term mortality in acute-on-chronic liver failure patients: CAP-ACLF.

BACKGROUND: Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients. METHODS: Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-R2, relative prediction errors, and odds ratios. RESULTS: Thirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p < 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, R2 0.609 and lower prediction errors by 10-50%. Day-7 NACSELD-ACLF-binary was the simple model (minimum AIC/BIC 12/17) with the highest odds (8.859) and sensitivity (100%) but with a lower PPV (70%) for mortality. Patients with day-7 AARC score > 12 had the lowest 30-day survival (5.7%). CONCLUSIONS: APASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score > 12 may be used as a futility criterion in APASL-ACLF patients.

Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy.

Hepatic encephalopathy (HE) is a frequent and serious complication of both chronic liver disease and acute liver failure. HE manifests as a wide spectrum of neuropsychiatric abnormalities, from subclinical changes (mild cognitive impairment) to marked disorientation, confusion and coma. The clinical and economic burden of HE is considerable, and it contributes greatly to impaired quality of life, morbidity and mortality. This review will critically discuss the latest classification of HE, as well as the pathogenesis and pathophysiological pathways underlying the neurological decline in patients with end-stage liver disease. In addition, management strategies, diagnostic approaches, currently available therapeutic options and novel treatment strategies are discussed.

Incidence and Risk Factors for Hepatitis C Virus and Hepatitis B Virus Seroconversion in End-Stage Renal Failure Patients on Maintenance Hemodialysis.

BACKGROUND: Renal replacement therapy in the form of either dialysis or transplantation is the only option for end-stage renal disease (ESRD). Blood-borne infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are of special concern in these patients because of their high incidence. Although there are sufficient data from the developed world, there is scarcity of data from developing countries such as India. METHODS: All newly diagnosed ESRD patients initiated on hemodialysis after attending the Department of Nephrology, PGIMER, Chandigarh between January 2015 and October 2015 were included in the study. All the subjects were initially screened for HCV and HBV serology status and subsequent HCV and HBV status on follow-up at the end of 6 months and evaluated by standardized precoded questionnaires and biochemical examinations. Univariate and multivariate analyses were done to identify the risk factors for seroconversion. RESULTS: A total of 196 patients were recruited for the study after confirming seronegative status. At the end of 6 months, 61 patients lost to follow-up. Anti-HCV antibody had shown moderate association to HCV RNA testing at the end of 6 months by kappa test. Out of 135, 16.3% seroconverted to HCV RNA positive and 0.7% patient became hepatitis B surface antigen positive. Isolation of dialysis machine and nursing staff was associated with lower seroconversion. CONCLUSION: In a real-life scenario, HCV seroconversion is observed in 15% of the patients initiated on hemodialysis. Isolation of both dialysis machine and personnel was associated with lower seroconversion.

Metabolic syndrome and female gender, but not methotrexate, are the important associations of significant liver fibrosis in patients with moderate-to-severe psoriasis as detected by transient elastography.

BACKGROUND: Many international guidelines on psoriasis management have emphasized upon the need to identify risk factors for liver fibrosis and that the risk may be increased after a certain total cumulative dose of methotrexate. METHODS: Consecutive patients with moderate-to-severe psoriasis were assessed for liver fibrosis using transient elastography and noninvasive scores. Based on the presence of significant liver fibrosis, the Odds ratio associated with various factors was calculated using logistic regression analysis. Receiver operating characteristic curves were calculated to find maximal cutoff values of noninvasive tests to detect fibrosis. RESULTS: In this cross-sectional study, 134 patients completed the study. Significant fibrosis (liver stiffness measurement ≥7, corresponding to F2 fibrosis or higher) was seen in 33 (24.6%) patients. Neither methotrexate exposure nor total cumulative dose of ≥1.5 was associated with significant fibrosis. Female sex (P = 0.024) and the presence of metabolic syndrome (P = 0.034) were the two variables associated with significant liver fibrosis. On logistic regression analysis, the odds ratio for the female gender and metabolic syndrome was estimated to be 2.51 (95% confidence interval - 1.09-5.81) and 2.33 (95% confidence interval - 1.03-5.27), respectively. Aspartate transaminase to platelet ratio index, nonalcoholic fatty liver disease score and the fibrosis-4 index had low sensitivity in comparison to transient elastography. LIMITATIONS: These included small sample size, small number of patients with a total cumulative methotrexate dose of >3-4.5 g, and lack of control group consisting of healthy persons. Another is the absence of liver biopsies considered as the gold standard in the diagnosis of liver fibrosis. CONCLUSIONS: Metabolic syndrome and female sex are associated with the development of significant liver fibrosis in patients with psoriasis. Methotrexate exposure does not seem to be significantly associated with significant liver fibrosis.

The Spectrum of Gastrointestinal Symptoms in Patients With Coronavirus Disease-19: Predictors, Relationship With Disease Severity, and Outcome.

INTRODUCTION: We prospectively studied the frequency, spectrum, and predictors of gastrointestinal (GI) symptoms among patients with coronavirus disease-19 (COVID-19) and the relationship between GI symptoms and the severity and outcome. METHODS: Consecutive patients with COVID-19, diagnosed in a university hospital referral laboratory in northern India, were evaluated for clinical manifestations including GI symptoms, their predictors, and the relationship between the presence of these symptoms, disease severity, and outcome on univariate and multivariate analyses. RESULTS: Of 16,317 subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in their oropharyngeal and nasopharyngeal swabs during April-May 2020, 252 (1.5%) were positive. Of them, 208 (82.5%) were asymptomatic; of the 44 symptomatic patients, 18 (40.9%) had non-GI symptoms, 15 (34.1%) had a combination of GI and non-GI symptoms, and 11 (25.0%) had GI symptoms only. Thirty-three had mild-to-moderate disease, 8 severe, and 5 critical. Five patients (1.98%) died. On multivariate analysis, the factors associated with the presence of GI symptoms included the absence of contact history and presence of non-GI symptoms and comorbid illnesses. Patients with GI synptoms more often had severe, critical illness and fatal outcome than those without GI symptoms. DISCUSSION: Eighty-two percent of patients with COVID-19 were asymptomatic, and 10.3% had GI symptoms; severe and fatal disease occurred only in 5% and 2%, respectively. The presence of GI symptoms was associated with a severe illness and fatal outcome on multivariate analysis. Independent predictors of GI symptoms included the absence of contact history, presence of non-GI symptoms, and comorbid illnesses.(Equation is included in full-text article.).

Cost-Effectiveness of Therapeutic Use of Safety-Engineered Syringes in Healthcare Facilities in India.

BACKGROUND: Globally, 16 billion injections are administered each year of which 95% are for curative care. India contributes 25-30% of the global injection load. Over 63% of these injections are reportedly unsafe or deemed unnecessary. OBJECTIVES: To assess the incremental cost per quality-adjusted life-year (QALY) gained with the introduction of safety-engineered syringes (SES) as compared to disposable syringes for therapeutic care in India. METHODS: A decision tree was used to compute the volume of needle-stick injuries (NSIs) and reuse episodes among healthcare professionals and the patient population. Subsequently, three separate Markov models were used to compute lifetime costs and QALYs for individuals infected with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Three SES were evaluated-reuse prevention syringe (RUP), sharp injury prevention (SIP) syringe, and syringes with features of both RUP and SIP. A lifetime study horizon starting from a base year of 2017 was considered appropriate to cover all costs and consequences comprehensively. A systematic review was undertaken to assess the SES effects in terms of reduction in NSIs and reuse episodes. These were then modelled in terms of reduction in transmission of blood-borne infections, life-years and QALYs gained. Future costs and consequences were discounted at the rate of 3%. Incremental cost per QALY gained was computed to assess the cost-effectiveness. A probabilistic sensitivity analysis was undertaken to account for parameter uncertainties. RESULTS: The introduction of RUP, SIP and RUP + SIP syringes in India is estimated to incur an incremental cost of Indian National Rupee (INR) 61,028 (US$939), INR 7,768,215 (US$119,511) and INR 196,135 (US$3017) per QALY gained, respectively. A total of 96,296 HBV, 44,082 HCV and 5632 HIV deaths are estimated to be averted due to RUP in 20 years. RUP has an 84% probability to be cost-effective at a threshold of per capita gross domestic product (GDP). The RUP syringe can become cost saving at a unit price of INR 1.9. Similarly, SIP and RUP + SIP syringes can be cost-effective at a unit price of less than INR 1.2 and INR 5.9, respectively. CONCLUSION: RUP syringes are estimated to be cost-effective in the Indian context. SIP and RUP + SIP syringes are not cost-effective at the current unit prices. Efforts should be made to bring down the price of SES to improve its cost-effectiveness.

Real-world cost-effectiveness of pan-genotypic Sofosbuvir-Velpatasvir combination versus genotype dependent directly acting anti-viral drugs for treatment of hepatitis C patients in the universal coverage scheme of Punjab state in India.

BACKGROUND: We undertook this study to assess the incremental cost per quality adjusted life year (QALY) gained with the use of pan-genotypic sofosbuvir (SOF) + velpatasvir (VEL) for HCV patients, as compared to the current treatment regimen under the universal free treatment scheme in Punjab state. METHODOLOGY: A Markov model depicting natural history of HCV was developed to simulate the progression of disease. Three scenarios were compared: I (Current Regimen)-use of SOF + daclatasvir (DCV) for non-cirrhotic patients and ledipasvir (LDV) or DCV with SOF ± ribavirin (RBV) according to the genotype for cirrhotic patients; II-use of SOF + DCV for non-cirrhotic patients and use of SOF+VEL for compensated cirrhotic patients (with RBV in decompensated cirrhosis patients) and III-use of SOF+VEL for both non-cirrhotic and compensated cirrhotic patients (with RBV in decompensated cirrhosis patients). The lifetime costs, life-years and QALYs were assessed for each scenario, using a societal perspective. All the future costs and health outcomes were discounted at an annual rate of 3%. Finally, the incremental cost per QALY gained was computed for each of scenario II and III, as compared to scenario I and for scenario III as compared to II. In addition, we evaluated the lifetime costs and QALYs among HCV patients for each of scenario I, II and III against the counterfactual of 'no universal free treatment scheme' scenario which involves patients purchasing care in routine setting of from public and private sector. RESULTS: Each of the scenarios I, II and III dominate over the no universal free treatment scheme scenario, i.e. have greater QALYs and lesser costs. The use of SOF+VEL only for cirrhotic patients (scenario II) increases QALYs by 0.28 (0.03 to 0.71) per person, and decreases the cost by ₹ 5,946 (₹ 1,198 to ₹ 14,174) per patient, when compared to scenario I. Compared to scenario I, scenario III leads to an increase in QALYs by 0.44 (0.14 to 1.01) per person, and is cost-neutral. While the mean cost difference between scenario III and I is-₹ 2,676 per patient, it ranges from a cost saving of ₹ 14,835 to incurring an extra cost of ₹ 3,456 per patient. For scenario III as compared II, QALYs increase by 0.16 (0.03 to 0.36) per person as well as costs by ₹ 3,086 per patient which ranges from a cost saving of ₹ 1,264 to incurring an extra cost of ₹ 6,344. Shift to scenario II and III increases the program budget by 5.5% and 60% respectively. CONCLUSION: Overall, the use of SOF+VEL is highly recommended for the treatment of HCV infection. In comparison to the current practice (scenario I), scenario II is a dominant option. Scenario III is cost-effective as compared to scenario II at a threshold of one-time GDP per capita. If budget is an important constraint, velpatasvir should be given to HCV infected cirrhotic patients. However, if no budget constraint, universal use of velpatasvir for HCV treatment is recommended.

Incidental Detection of Urinary Bladder Herniation in 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Mimicking as Metastatic Deposit in the Inguinal Canal.

Although 18F-fluorodeoxyglucose (FDG) is the most extensively used tracer in oncological positron emission tomography/computed tomography (PET/CT) studies, various physiological as well as benign pathological conditions are known to cause false-positive results. This report describes 18F-FDG PET/CT done in an elderly man with primary hepatocellular carcinoma, revealing a metastasis mimicking lesion in the left inguinal canal, which was identified as the herniated portion of the urinary bladder. Though rare, bladder herniation, especially with a narrow neck, can be a pitfall in the evaluation for metastatic disease. The study also highlights the utility of delayed imaging in the evaluation of pelvic pathology.

Detection of Hepatic Encephalopathy on 18F-FDG PET/CT Brain Images in a Patient With Decompensated Liver Cirrhosis.

We present a case of decompensated liver cirrhosis with ascites, which had history of asterixis, impaired balance with swaying gait along with mild irritability since 1 month. F-fluorodeoxyglucose PET/CT (FDG-PET/CT) performed to rule out malignancy did not reveal any abnormal FDG avid lesion suspicious for malignancy but showed hypermetabolism in the bilateral basal ganglia and thalamus with reduced metabolism in cerebral cortices and cerebellum, suggesting hepatic encephalopathy.

Low-Dose Sofosbuvir Is Safe and Effective in Treating Chronic Hepatitis C in Patients with Severe Renal Impairment or End-Stage Renal Disease.

BACKGROUND AND AIMS: There is sparse data on the use of Sofosbuvir based directly acting antiviral (DAA) drug regimens in chronic hepatitis C (CHC) patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2. We evaluated the safety and efficacy of low-dose Sofosbuvir plus full-dose Daclatasvir in CHC patients with CKD. METHODS: Sixty-five CHC patients with CKD with eGFR less than 30 mL/min/1.73 m2 [54 (83%) patients with ESRD on hemodialysis] were included. All patients irrespective of genotype were treated with half-dose Sofosbuvir [200 mg (half tablet of 400 mg)] plus full-dose Daclatasvir (60 mg) given daily for either 12 or 24 weeks given in patients with genotype 3 cirrhosis. The efficacy was assessed by the sustained virological response (SVR12) with negative HCV RNA 12 weeks after the end of treatment (ETR). RESULTS: The median HCV RNA level in 65 patients (Males 40, mean age 42.9 ± 13 years) was 1.65 × 106 (1.2 × 103-1.73 × 108) IU/mL with 42 (64.6%) patients having HCV genotype 1, followed by genotype 3 and 2 in 22 (34%) and 1 (1.4%) patients, respectively. Twenty-one (32%) patients had evidence of cirrhosis, and ten (15.4%) patients were treatment experienced. Sixty-four (98.5%) patients achieved ETR, and 65 (100%) patients attained SVR12. All patients tolerated the DAAs well with none of the patients reporting any serious adverse events. Minor side effects noted were nausea seen in five (7.7%) patients, insomnia and headache in four (6.2%) patients each, and pruritus in one (1.5%) patient. CONCLUSION: Low-dose Sofosbuvir and full-dose Daclatasvir are safe and effective in treating CHC in patients with CKD with eGFR less than 30 mL/min/1.73 m2.