Assessment of the Performance of Non-invasive Criteria for the Evaluation of Clinically Significant Portal Hypertension in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Assessment of clinically significant portal hypertension (CSPH) non-invasively using a combination of liver stiffness measurement (LSM) and platelet counts is proposed as an alternative to hepatic venous pressure gradient (HVPG) estimation. Utility of these criteria in compensated advanced chronic liver disease (cACLD) patients of different etiologies including nonalcoholic steatohepatitis (NASH) with BMI  >  30 kg/m2 was studied in a large cohort. METHODS: Consecutive patients of cACLD with available anthropometric and laboratory details, LSM, and HVPG were included in a retrospective analysis. A LSM of ≥ 25 kPa alone and LSM ≤ 15 kPa plus platelets ≥ 150 × 109/L were evaluated as non-invasive rule-in and rule-out criteria for CSPH, respectively. The NASH-ANTICPATE model (composite of BMI, platelets, and LSM) was evaluated in patients with obese NASH. RESULTS: Patients with cACLD (n = 626) (mean age: 50.8 ± 12.4 years, 74.2% males) with alcohol (ALD, 30.3%), NASH (26.4%), hepatitis C (HCV, 16.6%), hepatitis B (HBV,10.2%) etiology were included. The prevalence of CSPH was  >  80% across all etiologies except in HBV (62.5%) and in obese non-NASH (71-72%). The rule-in criteria had a PPV  >  90% for all etiologies except in HBV (80.8%). The rule-out criteria had a negative predictive value (NPV) of 65%, 53%, and 40% in ALD, HCV, and NASH, respectively. The NASH-ANTCIPATE model had specificity of 100% and NPV of 33% to detect CSPH in obese NASH (n = 62). CONCLUSIONS: LSM ≥ 25 kPa predicted CSPH in most etiologies except HBV. A significant proportion of patients have CSPH despite satisfying the rule-out criteria. The NASH-ANTICIPATE model is specific but fails to exclude CSPH in nearly two-third patients with obesity and NASH. There is a need for precise disease-specific non-invasive models for detecting CSPH.

Liver stiffness assessment as an alternative to hepatic venous pressure gradient for predicting rebleed after acute variceal bleed: A proof-of-concept study.

BACKGROUND AND AIM: Hepatic venous pressure gradient (HVPG), although an important determinant in predicting rebleeding after an episode of acute variceal bleed (AVB), is seldom utilized in clinical practice. We aimed to study the role of liver stiffness measurement (LSM) after variceal bleeding as a potential noninvasive predictor of rebleed. METHODS: This was a post hoc analysis of clinical trial of patients undergoing HVPG (postbleed HVPG) and LSM (postbleed LSM) assessment within 3-5 days of index AVB. HVPG response was assessed after 4 weeks of pharmacotherapy. Comparative assessment of long-term rebleeding rates stratified using postbleed LSM, postbleed HVPG, and HVPG response was performed. Decision curve analysis (DCA) was conducted to identify the most appropriate tool for routine use. RESULTS: Long-term clinical and HVPG response data were available for 48 patients post-AVB, of whom 45 patients had valid postbleed LSM. Rebleeding occurred in 13 (28%) patients over a median follow-up of 4 years with no early rebleeds. Postbleed LSM >30 kPa and baseline HVPG >15 mm Hg were optimal cutoffs for identifying patients at high risk of rebleeding. Time-dependent receiver operating characteristic curves and competing risk analysis accounting for death showed similar discriminative values for all three stratification tools. At usual risk thresholds, HVPG response had maximum benefit on DCA followed by postbleed LSM. On DCA, 50-60 additional HVPGs were required to detect one additional patient at high risk of rebleed. CONCLUSION: Liver stiffness measurement during AVB can potentially be used as an alternative to portal pressure indices in decompensated cirrhosis to identify those at high risk of late-onset rebleed.

Body mass index-based controlled attenuation parameter cut-offs for assessment of hepatic steatosis in non-alcoholic fatty liver disease.

BACKGROUND AND AIM: In patients with liver disease, etiology and body mass index (BMI) affects controlled attenuation parameter (CAP) assessment using FibroScan. We aimed to assess the performance characteristics of CAP for hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) stratified into obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. METHODS: In this prospective study, 219 consecutive adult NAFLD patients, with an available FibroScan value (liver stiffness measurement-[LSM] and CAP) and liver biopsy, were included. Receiver operating characteristic curves were used for assessment of the CAP cut-off values predicting different stages of hepatic steatosis. RESULTS: The mean ± standard deviation age of patients was 39.7 ± 10.5 years, 116 (53%) were males, and median (interquartile range) BMI was 31.8 (25.7-43.8) kg/m2. One hundred (45.7%) and 119 (54.3%) patients were non-obese and obese, respectively. The median values of CAP and LSM were significantly higher among obese patients as compared with the non-obese ones: 333 (304-368) vs. 320 (296-345) dB/m, p = 0.002 and 8.3 (6.1-11.4) vs. 6.6 (5.7-10.3) kPa, p = 0.012, respectively. Among non-obese NAFLD, optimal CAP cut-off values for steatosis (S) ≥ S1, ≥ S2, and ≥ S3 were 275 dB/m, 319 dB/m, and 337 dB/m, respectively. The corresponding CAP values among obese patients were higher as 285 dB/m, 340 dB/m, and 355 dB/m, respectively. BMI independently predicted CAP on multivariate analysis. The discordance of 2-grades between CAP and biopsy measured steatosis was seen in 13% in non-obese and 19.3% in obese NAFLD. CAP overestimated steatosis more often than underestimating it, with a higher proportion in obese NAFLD. CONCLUSION: In patients with NAFLD, interpretation of CAP requires consideration of BMI.

Economic and social impact of out-of-pocket expenditure on households of patients attending public hospitals.

BACKGROUND: We aimed to generate evidence on the social and economic impact of out-of-pocket expenses incurred by households on illness. METHODS: We did a hospital-based cross-sectional study including a convenience sample of 374 inpatients and outpatients. RESULTS: The median illness expenditure was the same (₹62 500) for inpatients and outpatients. Of all respondents, 51.3% among the rural and 65.5% among the urban patients were employed before illness, but after illness only 24.4% among the rural and 23.4% among the urban patients remained in employment. The proportion of rural households of different socioeconomic categories that experienced decrease in expenditure on food, education and health, and those who had to sell land or cattle, and the education of whose children suffered was statistically significant. The proportion of indebted families in different socioeconomic classes was also statistically significant among both rural and urban patients. The lowest socioeconomic strata depended mostly upon the financial support of their friends to tide over the financial crisis of an illness. CONCLUSION: Our study shows that out-of-pocket expenses on healthcare are a burden not only for the poor but also the middle classes.

Errors of inclusion and exclusion in income-based provisioning of public healthcare: Problems associated with below poverty line cards.

This study examined the effect of out-of-pocket expenditure of patients on their illness and other household changes impacting on their well-being, and assessed the socioeconomic status and below poverty line (BPL) card status among patients at the All India Institute of Medical Sciences, New Delhi. We did a hospital-based cross-sectional study of 374 inpatients and outpatients. Among the 374 study subjects, more than 69% of poor did not possess a BPL card. On the other hand, 5.5% of the above poverty line patients among the respondents possessed a BPL card. Of those having BPL cards, 84.4% belonged either to the lower middle, upper lower and lower socioeconomic status categories. Our data suggest that the inaccuracies in providing BPL cards limit access of the genuine poor to healthcare. In the light of national-level surveys on accessing healthcare and out-of-pocket expenditure by patients there is a case against 'targeting' in the delivery of public health services and user charges have an adverse impact on access to healthcare by the poor.

Translation and validation of the Hindi version of chronic liver disease questionnaire (CLDQ) for the assessment of health related quality of life in patient with chronic liver disease in India.

Background: Chronic liver disease questionnaire (CLDQ) is an established disease specific tool to assess the health related quality of life (HRQOL) in patients with CLD irrespective of the etiology and severity. The objective of the study was to develop the Hindi language version of CLDQ and to assess the validity of the Hindi CLDQ. Methods: CLDQ was adapted into Hindi language by following a standard method of forward and back-translation by two bilingual translators, revision by expert panel and formulation of a consensual version followed by pilot testing and appropriate modifications before final administration. Hindi CLDQ along with short form 36 (SF-36) were administered in 494 patients with chronic liver disease (CLD) and 103 healthy controls (HC). To assess reproducibility, Hindi CLDQ was re-administered in a subsample of 20 patients. Internal consistency was assessed by Cronbach's alpha coefficient. Structural validity was assessed by exploratory factor analysis and construct validity was assessed with help of correlation of SF-36 scores and CLDQ pattern across disease severity groups. Results: The Cronbach's alpha coefficient was 0.93 and intra class coefficient correlation was 0.88 for the average CLDQ score, suggestive of good reliability. An inverse relationship of the average CLDQ score with the disease severity (CLDQ score of Child A vs. B vs. C = 5.2±1.10 vs. 4.73±1.24 vs. 4.15±1.19 respectively; p<0.001) and good correlation with SF-36 scores (average CLDQ score with PCS & MCS; r=0.63 & 0.55; p<0.001) was suggestive of good validity of Hindi CLDQ. The factor analysis identified 6 domains accounting for 62% of variability. The derived cut-off of 6 for the average CLDQ had the AUC of 0.826 with a sensitivity of 76.7. Conclusion: Hindi version of CLDQ is found to be a reliable and a valid tool comparable to the original English version. The HRQOL of patients with CLD is lower than healthy controls and HRQOL decreases with increase in disease severity.

Clinical, radiological and functional assessment of pulmonary status in patients with achalasia cardia before and after treatment.

OBJECTIVES: Patients with achalasia have respiratory symptoms due to chronic microaspiration. Achalasia can lead to radiological and functional changes in the lung. We studied the effect of either balloon dilatation or laparoscopic Heller's cardiomyotomy on the reversal of these changes in the lung. METHODS: Thirty patients with achalasia were included in this study. Oesophageal symptoms and pulmonary symptoms were recorded. Pulmonary function tests (PFTs) were done at baseline and at the end of 6 months. High-resolution computed tomography of the chest was performed prior to treatment and repeated 6 months after treatment if found abnormal at the initial evaluation. RESULTS: The mean age of the patients was 30.97 years and mean duration of symptoms was 22.5 months. Fifteen patients (50%) had respiratory symptoms, nocturnal cough being the commonest symptom in 13 (43.3%). Thirteen patients (43.3%) had parenchymal lung changes on high-resolution computed tomography (HRCT). Eight patients (28.5%) had functional abnormalities in the lungs in the form of restrictive airway disease. Nineteen patients opted for Laparoscopic Heller's cardiomyotomy, while 11 patients underwent pneumatic dilatation. Six months after treatment, the respiratory symptoms resolved in all except two patients (13.3%). Four patients (66.6%) with active lung changes at HRCT showed resolution at 6 months. There was improvement in functional parameters on PFT evaluation with normalization of PFT in one patient. CONCLUSIONS: Pulmonary symptoms as well as radiological and functional abnormalities are common in patients with achalasia. Treatment in the form of pneumatic dilatation or Lap cardiomyotomy improves pulmonary symptoms.

Healthcare financing: approaches and trends in India.

Despite the importance of healthcare for the well-being of society, there is little public debate in India on issues relating to it. The 'human capital approach' to finance healthcare largely relies on private investment in health, while the 'human development approach' envisages the State as the guarantorof preventive as well as curative care to achieve universalization of healthcare. The prevailing health indices of India and challenges in the field of public health require a human developmentapproach to healthcare. On the eve of independence, India adopted the human development approach, with the report of the Bhore Committee emphasizing the role of the State in the development and provision of healthcare. However, more recently, successive governments have moved towards the human capital approach. Instead of increasing state spending on health and expanding the public health infrastructure, the government has been relying more and more on the private sector. The public-private partnership has been touted as the new-age panacea for the ills of the Indian healthcare system. This approach has led to a stagnation of public health indices and a decrease in the access of the poor to healthcare.

Boom in clinical research industry: a dangerous trend.

Over the last decade or so India has witnessed a phenomenal growth in the clinical trial industry. The projections forecast a continuing growth of this trend. It has been predicted that by 2011 India will be in charge of 15% of global clinical trials. The enthusiasm for the growth of this industry in India is shared not just by the major pharmaceutical companies and CROs but also equally so by government agencies. The raison d'être for medical research is that it should lead to maximum possible benefit to the largest number of people. Hence, an examination of the extent to which public good is served can act as a measure for objective analysis of this exponential increase in the clinical trial industry. After all it is the health and lives of the people that are at stake. On the face of it, it would seem that all trials testing the safety and efficacy of various molecules, by their very nature work towards public welfare as they are indispensible to the development of any drug including the life-saving ones. An increasing number of clinical trials at all stages in a product's life cycle are funded by the pharmaceutical industry. It would then seem that the industry-sponsored medical research is necessarily furthering the larger objective of human wellbeing. However, the operations of the pharmaceutical industry, the nature of the processes involved and the operative motives are a bit too complex to facilitate this larger objective so simply, just as yet. This warrants a closer look at the various aspects of industry-sponsored clinical research.