Diagnostic accuracy of transient elastography in diagnosing clinically significant portal hypertension in patients with chronic liver disease: a systematic review and meta-analysis.

PURPOSE: Liver stiffness measurement using transient elastography (TE-LSM) is a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for diagnosing clinically significant portal hypertension (CSPH). However, previous studies have yielded conflicting results. We evaluated the correlation between TE-LSM and HVPG and the performance of TE-LSM in diagnosing CSPH (HVPG ≥ 10 mmHg). METHODS: We conducted a systematic review and meta-analysis by searching PubMed and Scopus databases for relevant literature evaluating the clinical usefulness of TE for diagnosing CSPH in patients with chronic liver disease. RESULTS: Twenty-six studies (4337 patients with valid TE and HVPG) met our inclusion criteria. The median correlation coefficient of TE with HVPG was 0.70 (range 0.36-0.86). The weighted mean of optimal cut-off of liver stiffness value for diagnosing CSPH was 22.8 kPa (95% CI 22.7-23.0 kPa). The summary sensitivity and specificity were 79% (95% CI 74-84%) and 88% (95% CI 84-91%), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.91 (95% CI 0.88-0.93) according to the bivariate model. One limitation of the study was significant heterogeneity in the results of summary sensitivity and specificity (I2 83 and 74%, respectively). The heterogeneity could be explained by the variable liver stiffness cut-offs used in studies. The meta-regression plot revealed that as the optimal cut-off increased, the sensitivity decreased, the specificity increased, and vice versa. CONCLUSIONS: Liver stiffness measurement using TE correlates well with HVPG, and a liver stiffness cut-off value of 22.8 kPa shows a high accuracy for diagnosing CSPH. Thus, use of TE should be integrated into clinical practice for noninvasive diagnosis of CSPH.

Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis.

BACKGROUND: Many case series on Corona Virus Disease (COVID-19) have reported gastrointestinal (GI) and hepatic manifestations in a proportion of cases; however, the data is conflicting. The relationship of GI and hepatic involvement with severe clinical course of COVID-19 has also not been explored. OBJECTIVES: The main objectives were to determine the frequency of GI and hepatic manifestations of COVID-19 and to explore their relationship with severe clinical course. METHODS: We searched PubMed for studies published between January 1, 2020, and March 25, 2020, with data on GI and hepatic manifestations in adult patients with COVID-19. These data were compared between patients with severe and good clinical course using the random-effects model and odds ratio (OR) as the effect size. If the heterogeneity among studies was high, sensitivity analysis was performed for each outcome. RESULTS: We included 62 studies (8301 patients) in the systematic review and 26 studies (4676 patients) in the meta-analysis. Diarrhea was the most common GI symptom (9%), followed by nausea/vomiting (5%) and abdominal pain (4%). Transaminases were abnormal in approximately 25%, bilirubin in 9%, prothrombin time (PT) in 7%, and low albumin in 60%. Up to 20% patients developed severe clinical course, and GI and hepatic factors associated with severe clinical course were as follows: diarrhea (OR 2), high aspartate aminotransferase (OR 1.4), high alanine aminotransferase (OR 1.6), high bilirubin (OR 2.4), low albumin (OR 3.4), and high PT (OR 3). CONCLUSIONS: GI and hepatic involvement should be sought in patients with COVID-19 since it portends severe clinical course. The pathogenesis of GI and hepatic involvement needs to be explored in future studies.

COVID-19 in patients with inflammatory bowel disease.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread world over causing morbidity and mortality in affected patients, especially elderly and those with co-morbidities. Inflammatory Bowel Disease (IBD) patients frequently require immunosuppressive therapy and are known to be at risk of opportunistic infections. AREAS COVERED: We hereby review the available literature pertaining to COVID-19 in IBD based on published consensus guidelines, expert opinions, case series, registries and reports. EXPERT OPINION: Preliminary data suggests no increase in incidence of COVID-19 in IBD patients as compared to general population. Morbidity and mortality rates attributable to COVID-19 are also similar in IBD patients as compared to general population. Though exact reason is unknown, some aspects of COVID-19 pathogenesis may explain this paradox. Medications for IBD need to be carefully reviewed during COVID-19 crisis. Steroids may need dose tapering or substitution to avoid complications based on anecdotal evidence. Endoscopic procedures for IBD maybe deferred unless absolutely necessary. General measures recommended for COVID-19 tailored to specific needs of IBD patients maybe the best way to prevent infection. Our understanding of the disease outcomes and optimal management protocols are likely to evolve as we move ahead in this pandemic.

Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-analysis.

Background: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known. Methods: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes. Findings: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35). Interpretation: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission; and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care.

Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis.

BACKGROUND: Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. METHODS: We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. RESULTS: We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37-2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09-3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74-2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%-10.9%) (after adjusting for heterogeneity). CONCLUSIONS: Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.

Role of EUS-FNA for gallbladder mass lesions with biliary obstruction: a large single-center experience.

Background and study aims Although endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) is an established modality for pathological sampling of pancreatic and biliary lesions, limited data are available on the diagnostic value of EUS-FNA for evaluation of gallbladder mass lesions, a common cause of obstructive jaundice. We aimed to evaluate the usefulness of EUS-FNA for diagnosis of gallbladder mass lesions presenting with biliary obstruction. Patients and methods This study was a retrospective analysis of data from patients who had undergone EUS-FNA for gallbladder mass lesions. FNA was performed on either a gallbladder mass, metastatic node or liver lesions. Outcome measures were diagnostic yield of EUS FNA and adverse events. Results From April 2011 to August 2018, 101 patients with gallbladder mass lesions with biliary obstruction underwent EUS-FNA. The final diagnosis was malignancy in 98, benign disease in one, and two patients were lost to follow-up. EUS-FNA confirmed the diagnosis in 89 of 98 patients with malignancy (sensitivity 90.81 %); was false negative in nine of 98 cases with malignancy; and was truly negative in the solitary patient with benign disease (specificity 100 %). Positive predictive value, negative predictive value (NPV), and accuracy were 100 %, 10 %, and 90.90 %, respectively. Two patients had self-limiting pain. Conclusion EUS-FNA is a sensitive tool for evaluation of gallbladder mass lesions presenting with obstructive jaundice. However, because of low NPV, lesions in which FNA is negative should be further evaluated.

Predictors of 90-day mortality in patients with severe alcoholic hepatitis: Experience with 183 patients at a tertiary care center from India.

BACKGROUND: Severe alcoholic hepatitis (AH) is not an uncommon indication for hospital admission in India. However, there is limited data from India on predictors of mortality in patients of severe AH. We analyzed the data on patients with severe AH admitted to our institute and compared various parameters and severity scores in predicting 90-day mortality. METHODS: In this prospective study, we analyzed patients with severe AH (defined as discriminant function ≥ 32) admitted from January 2015 to February 2017 to our institute. All patients were administered standard treatment according to various guidelines, and their 90-day mortality was determined. Various hematologic, biochemical factors, and severity scores were compared between survivors and patients who died. RESULTS: A total of 183 patients (98% males, median age 41 years [range 20-70 years]) were included in our study. The median model for end-stage liver disease (MELD) was 26 (15-40). Ascites were present in 83% and hepatic encephalopathy in 38%. Only 21 (12%) could be offered steroid therapy, due to contraindications in the remaining. By 90 days, only 103 (56%) patients survived while 80 (44%) died. All patients died due to progressive liver failure and its complications. On multivariate analysis, presence of ascites, hepatic encephalopathy, high bilirubin, low albumin, high creatinine, high INR, and low potassium independently predicted 90-day mortality. All the scores performed significantly in predicting 90-day mortality with no statistically significant difference between them. MELD score had a maximum area under the curve 0.76 for 90-day mortality. A combination of Child class and presence of acute kidney injury (creatinine ≥ 1.35) was good in predicting 90-day mortality. CONCLUSION: Our patients had severe AH characterized by a median MELD score of 26 and had a 90-day mortality of 44%. Most patients were not eligible to receive corticosteroids. Presence of Child C status and high serum creatinine value (≥ 1.35 mg/dL) accurately predicted mortality. Newer treatment options need to be explored for these patients.

Kikuchi-Fujimoto Disease: A Rare Presentation with Localized Iliac Lymphadenitis.

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting disease characterized by histiocytic necrotising lymphadenitis. Though several viral agents or an autoimmune etiology has been proposed as causative, the exact cause remains unknown. It has a female predilection and most commonly seen among young Asian people. Patients usually present with a febrile illness and the presence of lymphadenopathy may provide a clue to diagnosis. The most common site of lymphadenopathy is cervical lymph nodes while intra-abdominal involvement is uncommon. Cases of KFD presenting with intra-abdominal lymphadenopathy have been reported to occur with equal frequency in both sexes. Abdominal tuberculosis, non-Hodgkin's lymphoma, and systemic lupus erythematosus are close differential diagnoses for this type of presentation. Treatment is mostly supportive as the disease usually resolves spontaneously; steroids are only required in severe cases. We report a 32-year-old male patient of intra-abdominal lymphadenitis that presented as fever of unknown origin (FUO) and diagnosed by excisional biopsy as a case of KFD.

Correlation of transient elastography with hepatic venous pressure gradient in patients with cirrhotic portal hypertension: A study of 326 patients from India.

AIM: To study the diagnostic accuracy of transient elastography (TE) for detecting clinically significant portal hypertension (CSPH) in Indian patients with cirrhotic portal hypertension. METHODS: This retrospective study was conducted at the Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, on consecutive patients with cirrhosis greater than 15 years of age who underwent hepatic venous pressure gradient (HVPG) and TE from July 2011 to May 2016. Correlation between HVPG and TE was analyzed using the Spearman's correlation test. Receiver operating characteristic (ROC) curves were prepared for determining the utility of TE in predicting various stages of portal hypertension. The best cut-off value of TE for the diagnosis of CSPH was obtained using the Youden index. RESULTS: The study included 326 patients [median age 52 (range 16-90) years; 81% males]. The most common etiology of cirrhosis was cryptogenic (45%) followed by alcohol (34%). The median HVPG was 16.0 (range 1.5 to 30.5) mmHg. Eighty-five percent of patients had CSPH. A significant positive correlation was noted between TE and HVPG (rho 0.361, P < 0.001). The area under ROC curve for TE in predicting CSPH was 0.740 (95%CI: 0.662-0.818) (P < 0.01). A cut-off value of TE of 21.6 kPa best predicted CSPH with a positive predictive value (PPV) of 93%. CONCLUSION: TE has a fair positive correlation with HVPG; thus, TE can be used as a non-invasive modality to assess the degree of portal hypertension. A cut-off TE value of 21.6 kPa identifies CSPH with a PPV of 93%.

Self-expanding plastic stent for esophageal leaks and fistulae.

BACKGROUND: Self-expanding plastic stents (SEPS) have emerged as a good alternative to surgery in esophageal leaks and fistulae. There is scarce published literature regarding its efficacy in these conditions. We present our experience with SEPS in treatment of esophageal leaks and fistulae. METHODS: Consecutive patients admitted in a tertiary referral center who underwent SEPS placement for esophageal leak or fistula between February 2012 and February 2015 were retrospectively evaluated. Patients underwent prior assessment with upper gastrointestinal endoscopic and thoracic contrast-enhanced computed tomography assessment. SEPS (25-mm flares, 21-mm diameter) were placed under fluoroscopic guidance. A silk thread tied to upper end was routed through nostril and fixed to prevent stent migration. Nasojejunal tube was inserted in all patients. Intercostal drain was inserted in the case of hydro/pyopneumothorax. RESULTS: Twelve patients [eight male, median age 45.3 years (19 to 65 years)] were included. Etiologies were spontaneous leaks due to Boerhaave syndrome (n = 2), corrosive fistulae (n = 2), tubercular fistulae (n = 4), invasive Candida esophagitis-induced fistula (n = 1), iatrogenic leaks (n = 2; one achalasia dilatation, one obesity surgery), and pancreaticoesophageal fistula due to ruptured pancreatic pseudocyst (n = 1). Stent placement was successful in all patients with no immediate postprocedure complications. Successful healing was seen in nine patients (75 %). Stents were removed after a median time of 83.5 days (13-190 days). Stent migration was seen in four patients (33.3 %), and in two of them, it was retrieved and redeployed; none had early migration (<72 h). Reasons for SEPS failure in our cohort were failure of effective sepsis control in two patients and poor wound healing seen in one patient having multiple tubercular fistulae. CONCLUSION: SEPS is a safe, well-tolerated treatment with good success rate (75 %) in treatment of esophageal leaks and fistulae.