Bhaskar Thakur

Acute on chronic liver failure because of acute hepatic insults: Etiologies, course, extrahepatic organ failure and predictors of mortality.

Acute on chronic liver failure (ACLF) because of precipitating factors (variceal bleed/infections) identifies cirrhotics at risk for high short‐term mortality. Information on ACLF because of acute hepatic insults is lacking. The aim of the study was to evaluate acute hepatic insults in ACLF and their effect on the course and outcome.

Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score

Results of endovascular interventions in hepatic venous outflow tract obstruction (HVOTO) have been reported from limited studies. Treatment outcomes and prognostic scores need further validation.

Demographic profile, host, disease & viral predictive factors of response in patients with chronic hepatitis C virus infection at a tertiary care hospital in north India

Background & objectives: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The response to treatment in real life stetting is unclear. The objectives of this study were to evaluate the demographic profile and assess the virological response and predictors of response in CHC patients. Methods: Consecutive patients with CHC were included in this study. Detailed clinical history, risk factors, and predictive factors of response were noted. Patients were treated with peginterferon α2b (1.5 µg/kg/wk) and RBV (12 mg/kg/day) for 6 to 18 months based on response. Results: A total of 211 patients were included in the analysis, mean age 40.6±12.3 yr, 144 (68%) were males and 71 (34%) had compensated cirrhosis. Commonest risk factor for acquiring CHC was previous transfusion and surgery (51%). Genotype 3 (72%) was most common followed by genotype 1 (23%). Overall sustained virologic response (SVR) was 64 per cent [95% CI 57.1%-70.4%]. The SVR was 66.5 per cent [95% CI 58.34-73.89%] for genotype 3 and 61.2 per cent [95% CI 46.23 to 74.80%] for genotype 1. Non-cirrhotics had better SVR rates compared to cirrhotics (76 vs 41%, P<0.001). On multivariate analysis, BMI ≥23 kg/m2, HOMA-IR ≥2, compliance (≤80%), and fibrosis >2 were predictors of low SVR. Interpretation & conclusions: Genotype 3 was the commonest HCV genotype. The commonest source of infection was previous transfusion and surgery. SVR rates for genotypes 3 were better than genotype 1 patients. Predictors of non-response were high BMI, insulin resistance, significant fibrosis and inadequate compliance.

Severity and Outcome of Acute-on-chronic Liver Failure is Dependent on the Etiology of Acute Hepatic Insults: Analysis of 368 Patients

Background: Acute-on-chronic liver failure (ACLF) may be precipitated by various hepatic insults. The present study evaluated the outcomes of ACLF with different acute insults. Patients and Methods: A total of 368 ACLF patients were included. Data collected included etiologies of acute hepatic insult and underlying chronic liver disease, and organ failure. Model for end-stage liver disease (MELD), chronic liver failure consortium (CLIF)-C ACLF, and acute physiology and chronic health evaluation (APACHE) II scores were calculated. Predictors of survival were assessed by the Cox proportional hazard model. Results: The most frequent acute insult was active alcohol consumption [150 (40.8%) patients], followed by hepatitis B virus (HBV) [71 (19.3%) patients], hepatitis E virus (HEV) superinfection [45 (12.2%) patients], autoimmune hepatitis flare [17 (4.6%) patients], antituberculosis drugs [16 (4.3%) patients], and hepatitis A virus superinfection [2 (0.5%) patients]; 67 (18.2%) cases were cryptogenic. Alcohol-ACLF and cryptogenic-ACLF were more severe. Median CLIF-C, MELD, and APACHE II scores in alcohol-ACLF and cryptogenic-ACLF were significantly higher than those in HBV-ACLF and HEV-ACLF (CLIF-C: 47.1, 47.4 vs. 42.9, 42.0, P=0.002; MELD: 29, 29.9 vs. 28.9, 25.2, P=0.02; APACHE II: 16.5, 18.0 vs. 12, 14, P<0.001, respectively). Frequencies of kidney and brain failures were also higher in alcohol/cryptogenic-ACLF than in HBV/HEV-ACLF (kidney failure: 35.3%/34.3% vs. 23.9%/11.1%, P=0.009; brain failure: 26.0%/22.4% vs. 15.5%/4.4%, P=0.01, respectively). Mortality in the alcohol-ACLF group was the highest (64.0%), followed by that in the cryptogenic-ACLF (62.7%), HBV-ACLF (45.1%), and HEV-ACLF (17.8%) groups (P<0.001). In multivariable analysis, alcohol-ACLF had significantly higher mortality compared with HEV-ACLF (hazard ratio, 3.06; 95% confidence interval, 1.10-8.49, P=0.03). Conclusions: Alcohol/cryptogenic-ACLF had more severe phenotypic presentation, more incidence of organ failures, and higher mortality compared with HEV/HBV-ACLF. Alcohol-ACLF had the highest mortality, whereas HEV-ACLF had the best survival.

Mechanism of Increased Intestinal Permeability in Acute Pancreatitis: Alteration in Tight Junction Proteins.

Background and Aims: Intestinal permeability (IP) has been shown to be increased in acute pancreatitis (AP) and is considered to be responsible for development of septic complications. However, the mechanism of increase in IP is not well studied. We studied whether alteration in tight junction proteins (TJP) has any role in altered IP in patients with AP. Materials and Methods: This is a prospective study conducted at a tertiary care referral center. Twenty consecutive moderate and severe AP patients fulfilling the study criteria were included along with 20 controls that underwent gastroduodenoscopy for dyspepsia. IP was measured with lactulose mannitol (LM) ratio and TJP were studied by measuring expression of claudin-2 and claudin-4 in duodenal biopsy samples. Statistical analysis was done with STATA 13.0. Results: IP as depicted by LM ratio was significantly higher in AP patients as compared with controls (4.659±10.4 vs. 0.101±0.297; P<0.001). Claudin-4 expression was reduced in duodenal biopsies in AP patients (P<0.001 for crypt intercellular junction and P=0.007 for crypt cytoplasm). However, LM ratio was not associated with either mortality (P=0.12) or development of infected pancreatic necrosis (P=0.3). Conclusions: IP is increased in AP. Alteration in TJP in the form of reduced claudin-4 expressions could be the possible mechanism for increased IP.

Neoadjuvant chemotherapy regimens in treatment of breast cancer: a systematic review and network meta-analysis protocol

BackgroundNeoadjuvant chemotherapy (NACT), a standard of care for locally advanced breast cancer patients, is widely used for early breast cancer patients also. The varying role of regimens used as NACT needs to be investigated. Despite availability of some randomized controlled trials (RCTs), it is unclear which treatment regimen suits best. Further, there is no study comparing all the three regimens. Accordingly, present study will compare the efficacy of anthracyclines, taxanes, and targeted therapy administered in neoadjuvant setting on the basis of oncological outcomes and functional outcomes.Method/designOnline databases PubMed and Cochrane Register of Controlled Trials will be searched to acquire eligible studies. Further, content of relevant journals, references of relevant articles, and proceedings of major related conference will also be searched. The RCTs comparing any of abovementioned regimen as NACT on breast cancer patients will be eligible. Two reviewers independently and in duplicate will screen the records on the basis of title and abstract and complete full-text review to determine eligibility. Similarly, data extraction and risk of bias assessment will be done by two independent reviewers. The pair-wise meta-analysis as well as network meta-analysis will be conducted to assess the relative efficacy of anthracyclines, taxanes, and targeted therapy regimens.DiscussionThe present systematic review will improve the understanding of the relative efficacies of the three treatment regimens and possibly guide the clinical practices by providing the current best evidence on the efficacy of various regimens of NACT in the management of breast cancer patients.Systematic review registrationPROSPERO (CRD42016027236).

Comparison of Dynamic Changes Among Various Prognostic Scores in Viral Hepatitis-Related Acute Liver Failure

INTRODUCTION AND AIM Multiple prognostic scores are available for acute liver failure (ALF). Our objective was to compare the dynamicity of model for end stage liver disease (MELD), MELD-sodium, acute liver failure early dynamic model (ALFED), chronic liver failure (CLIF)-consortium ACLF score and Kings College Hospital Criteria (KCH) for predicting outcome in ALF. MATERIALS AND METHODS All consecutive patients with ALF at a tertiary care centre in India were included. MELD, MELD-Na, ALFED, CLIF-C ACLF scores and KCH criteria were calculated at admission and day 3 of admission. Area under receiver operator characteristic curves (AUROC) were compared with DeLong method. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and diagnostic accuracy (DA) were reported. RESULTS Of the 115 patients included in the study, 73 (63.5%) died. The discrimination of mortality with baseline values of prognostic scores (MELD, MELD-Na, ALFED, CLIF-C ACLF and KCH) was modest (AUROC: 0.65-0.77). The AUROC increased on day 3 for all scores, except KCH criteria. On day 3 of admission, ALFED score had the highest AUROC 0.95, followed by CLIF-C ACLF 0.88, MELD 0.81, MELD-Na 0.77 and KCH 0.52. The AUROC for ALFED was significantly higher than MELD, MELD-Na and KCH (P < 0.001 for all) and CLIF-C ACLF (P = 0.05). ALFED score ≥ 4 on day 3 had the best sensitivity (87.1%), specificity (89.5%), PPV (93.8%), NPV (79.1%), LR positive (8.3) and DA (87.9%) for predicting mortality. CONCLUSIONS Dynamic assessment of prognostic scores better predicts outcome. ALFED model performs better than MELD, MELD, MELD-Na, CLIF-C ACLF scores and KCH criteria for predicting outcome in viral hepatitis- related ALF.INTRODUCTION AND AIM Multiple prognostic scores are available for acute liver failure (ALF). Our objective was to compare the dynamicity of model for end stage liver disease (MELD), MELD-sodium, acute liver failure early dynamic model (ALFED), chronic liver failure (CLIF)-consortium ACLF score and Kings College Hospital Criteria (KCH) for predicting outcome in ALF. MATERIALS AND METHODS All consecutive patients with ALF at a tertiary care centre in India were included. MELD, MELD-Na, ALFED, CLIF-C ACLF scores and KCH criteria were calculated at admission and day 3 of admission. Area under receiver operator characteristic curves (AUROC) were compared with DeLong method. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and diagnostic accuracy (DA) were reported. RESULTS Of the 115 patients included in the study, 73 (63.5%) died. The discrimination of mortality with baseline values of prognostic scores (MELD, MELD-Na, ALFED, CLIF-C ACLF and KCH) was modest (AUROC: 0.65-0.77). The AUROC increased on day 3 for all scores, except KCH criteria. On day 3 of admission, ALFED score had the highest AUROC 0.95, followed by CLIF-C ACLF 0.88, MELD 0.81, MELD-Na 0.77 and KCH 0.52. The AUROC for ALFED was significantly higher than MELD, MELD-Na and KCH (P < 0.001 for all) and CLIF-C ACLF (P = 0.05). ALFED score > 4 on day 3 had the best sensitivity (87.1%), specificity (89.5%), PPV (93.8%), NPV (79.1%), LR positive (8.3) and DA (87.9%) for predicting mortality. CONCLUSIONS Dynamic assessment of prognostic scores better predicts outcome. ALFED model performs better than MELD, MELD, MELD-Na, CLIF-C ACLF scores and KCH criteria for predicting outcome in viral hepatitis-related ALF.

Comparison of Various Scoring Systems and Biochemical Markers in Predicting the Outcome in Acute Pancreatitis

Objective Early risk assessment is important in acute pancreatitis (AP). The primary objective of this study was to compare various scores and biochemical markers done on the day of admission in predicting the outcome. Methods Demographic, clinical, and laboratory data of patients presenting within 2 weeks of onset were collected. Various scores were calculated and biochemical markers were measured on the day of admission. Optimum cutoffs were identified through receiver operating curve analysis. Multivariate analysis was used to identify predictors of outcome. Results Of 343 patients included, 202 (59%) were male; mean (SD) age was 38.7 (15.5) years. Acute pancreatitis was severe in 170 (49.6%) patients. Twenty-eight percent of the patients developed infected pancreatic necrosis and 18% died. An Acute Physiology and Chronic Health Evaluation (APACHE II) score of at least 7, bedside index for severity of AP (BISAP) of at least 2, systemic inflammatory response syndrome score of at least 3, and C-reactive protein of at least 82 ng/mL predicted severity. Predictors of infected pancreatic necrosis were as follows: PANC 3 score of at least 1, BISAP score of at least 2, and Marshall score of at least 2, whereas C-reactive protein of greater than 98, BISAP score of at least 2, APACHE score of at least 10, and a blood urea nitrogen of at least 17 predicted mortality. Conclusions Both BISAP and APACHE II are comparable in predicting outcome, but BISAP predicted all 3 outcomes with the same cutoff and hence is a robust scoring system.

Etiology and mode of presentation of chronic liver diseases in India: A multi centric study

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

Detection of Mycoplasma pneumoniae and Legionella pneumophila in Patients Having Community-Acquired Pneumonia: A Multicentric Study from New Delhi, India

Atypical pathogens including Mycoplasma pneumoniae and Legionella pneumophila are increasingly recognized as important causes of community-acquired pneumonia (CAP). Mycoplasma pneumoniae accounts for 20-40% of all CAP and L. pneumophila is responsible for 3-15% of cases. The paucity of data from India in this regard prompted us to conduct this prospective multicentric analysis to detect the prevalence of M. pneumoniae and L. pneumophila in our geographical region. A total of 453 patients with symptoms of pneumonia and 90 controls with no history of lower respiratory tract infections were included in the study. A duplex polymerase chain reaction (PCR) targeting 543 bp region of P1 adhesin gene of M. pneumoniae and 375 bp region of macrophage infectivity potentiator (mip) gene of L. pneumophila was standardized for simultaneous detection of these atypical pathogens. Respiratory secretions, blood, and urine samples were collected from each patient and control and were subjected to duplex PCR, culture and serology for M. pneumoniae and L. pneumophila. Urine samples were subjected for detecting L. pneumophila antigen. Among the 453 patients investigated for M. pneumoniae, 52 (11.4%) were positive for IgM antibodies, 17 were positive by culture, and seven tested positive by PCR (P1 gene). Similarly for L. pneumophila, 50 cases (11%) were serologically positive for IgM antibodies, one was positive by PCR (mip gene) and urine antigen detection. A total of eight samples were positive by duplex PCR for M. pneumoniae P1 gene (N = 7) and L. pneumophila mip gene (N = 1). Of the 90 controls, two samples (2.2%) showed IgM positivity, and 15 (16.7%) showed IgG positivity for M. pneumoniae. For L. pneumophila, three samples (3.3%) tested positive for IgM, and 12 (13.3%) tested positive for IgG antibodies. The study findings indicate the presence of M. pneumoniae and L. pneumophila in our geographical region, and a combination of laboratory approaches including PCR, culture, and serology is required for effective detection of these agents.