A broad body of evidence has accrued, demonstrating the role of endothelin-1 (ET-1) in the pathophysiology of pulmonary arterial hypertension. Furthermore, the role of ET-1 as a causative pathophysiological mechanism of portopulmonary hypertension (POPH) has been consistently implicated; however, there is a lack of satisfactory evidence supporting this assertion. Thus, the present study aims to determine the prevalence of POPH among patients with hepatic cirrhosis, determine the serum ET-1 levels among these patients, and investigate the association between ET-1 and POPH in subjects with hepatic cirrhosis. A prospective, observational study was conducted from September 2017 to August 2018. Detailed history and examination with relevant investigations, including echocardiography, were performed for patients with and without POHP. ET-1 levels were significantly higher among patients with POPH compared to those without POPH. Moreover, the ET-1 cut-off level of 82 pg/mL correctly predicted the 9.3% prevalence of POPH in patients with hepatic cirrhosis with 100% sensitivity and 100% negative predictive value. The ET-1 cut-off level of 82 pg/mL may be used as a biomarker of POPH in patients with hepatic cirrhosis.

Background and objectives- Occult Hepatitis B Virus infection (OBI)is defined as a condition when HBsAg virus infection is undetectable in serum, despite the presence of HBV DNA in liver or blood. This study was done to screen for occult hepatitis B infection among patients with CLD (chronic liver disease) attending gastroenterology OPD of tertiary care hospital. Materials and methods- Observational Cross-sectional study conducted for period of one year.All patients with history of chronic liver disease were tested for HBsAg by ELISA. All HBsAg negative patients were tested for total antiHBc antibody by ELISA and HBV DNA by real time PCR. Results- Prevalence of OBI(confirmed OBI) is 2.96% with isolated anti HBc positivity (probable OBI)being 7.24% in this study. Prevalence of seropositive OBI was 1.93% and prevalence of seronegative OBI was 0.96%. Fair agreement was observed between Total antibody against core antigen by ELISA and RTPCR for the diagnosis of OBI(k value=0.354). Conclusion It is recommended that Total Anti HBc by ELISA may be used as a surrogate marker for diagnosis of OBI in HBsAg negative patients with CLD and for confirmation HBV DNA PCR should be done if molecular facility is available.

BACKGROUND:Acute-on-chronic liver failure (ACLF) is a rapidly progressive syndrome marked by high short-term mortality. While diabetes mellitus (DM) is known to worsen liver-related outcomes, its specific impact on alcohol-related ACLF (ALD-ACLF) remains underexplored. This study aimed to assess the prognostic impact of DM on 90-day outcomes in ALD-ACLF using data from the APASL ACLF Research Consortium (AARC) database. METHODS:This observational study involved data from 5612 ACLF patients with documented 90-day outcomes. We identified 2096 patients with ALD-ACLF precipitated by alcoholic hepatitis. Patients with non-ALD etiologies, mixed etiologies, or non-alcoholic precipitants were excluded. Diabetic and non-diabetic patients were compared using 1:2 propensity score matching based on key baseline covariates. Survival outcomes were assessed using Kaplan-Meier analysis and multivariable Cox regression. RESULTS:After matching, 109 diabetic patients were compared with 218 well-matched non-diabetic controls. Diabetic patients had significantly lower overall survival (32 vs. 57%) and transplant-free survival (31 vs. 50%) compared to non-diabetics (log-rank p < 0.001). On multivariable Cox regression, DM was independently associated with increased 90-day mortality (HR 1.739, 95% CI 1.262-2.395, p < 0.001), along with elevated serum lactate (HR 1.187 per mmol/L, p < 0.001) and creatinine (HR 1.267 per mg/dL, p < 0.001). CONCLUSION:Diabetes mellitus is a significant independent predictor of mortality in patients with ALD-ACLF. These findings highlight the need for early identification and integrated management of diabetes in ACLF care pathways to improve clinical outcomes.

INTRODUCTION:The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS:Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS:The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. DISCUSSION:Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF.

Background Portal hypertension leads to the formation of portosystemic collateral veins, of which esophageal varices (EV) are the most severe complications and have the greatest clinical impact. The possibility of identifying cirrhotic patients with varices by non-invasive tests is appealing, as they can lead to reduced healthcare costs and can be done in resource-limited settings. In this study, we investigated ammonia as a potential non-invasive predictor of EV. Methods This was a single-center cross-sectional observational study that was done at a tertiary health care hospital in north India. It included 97 chronic liver disease patients irrespective of etiology after excluding patients with portal vein thrombosis and hepatocellular carcinoma to participate in endoscopic screening for the presence of EV and correlate it with various non-invasive markers like serum ammonia levels, thrombocytopenia and aspartate aminotransferase to platelet ratio index (APRI ). On the basis of endoscopy, enrolled patients were divided into two groups, i.e., group A consisting of large varices (grade III and grade IV) and group B consisting of patients with low-grade varices and no varices (grade II, grade I, and no varices). Results This study included 97 patients, out of which 81 patients have varices on endoscopy, and mean serum ammonia levels were found to be significantly higher in cases with varices (135 ±69.70 ) vs. those without varices (94±43) (p value=0.026). Further, on comparing serum ammonia values between patients with large varices (Grade III/IV) (Group A) with a mean value of 176 ± 83 vs. Grade I/II/No varices (Group B) with a mean value of 107±47, which were significantly higher in Group A patients (<0.001). In our study, we also found a correlation between blood urea level as a non-invasive predictor of varices, but no statistically significant relation was found between thrombocytopenia and APRI. Conclusion This study found that serum ammonia can be used as a useful marker for the prediction of EV and can also be used to determine the severity of varices. Apart from ammonia, serum urea levels can also prove to be a good non-invasive marker for the prediction of varices although further multicentric studies are warranted to reach this conclusion.

Background: Diagnostic and therapeutic algorithms given by various societies for hepatitis B are fragmented and complex. The clinico-epidemiologic spectrum of hepatitis B is not studied with large-scale data from our region. We aimed to develop a comprehensive algorithm for the treatment of hepatitis B and study its clinico-epidemiological spectrum. Methods: From 2014-2019, the clinico-laboratory data of hepatitis B surface antigen (HbsAg)-positive patients were prospectively recorded. King George's Medical University hepatitis B therapeutic algorithm (KGHeBTA) was developed on the basis of the standard existing guidelines. The prevalence of different clinical stages of HBsAg-positive patients was calculated and their treatment records reviewed. Testing circumstances and risk factors were noted. Results: Among 1,508 data record sheets, 421 were complete. According to the KGHeBTA algorithm, 221 had detectable hepatitis B virus DNA. 21% were cirrhotic and 79% non-cirrhotic. 72% were incidentally detected asymptomatic hepatitis B, 7% were hepatitis B with acute symptoms, 0.7% were acute hepatitis B, and 22% were chronic hepatitis B. 20% patients were eligible for antivirals and 80% patients were not eligible. 32% patients were actually treated with antivirals due to the inclusion of some special indica-tions as pregnancy and family history. Screening during various medical illnesses (40%) was the most common and during health camps (0.2%), the least common testing approach. Road-side shaving (52%) was the most com-mon and intravenous drug abuse (0.2%) and the least common risk factor for the detection of hepatitis B in our data pool. Conclusions: HBsAg-positive patients can be easily worked up and treated based on the proposed algo-rithm (KGHeBTA). About one fourth to one fifth of all HBsAg-positive patients were eligible and treated with oral antivirals. Most of the patients were incidentally detected asymptomatic hepatitis B screened during med-ical illnesses. Roadside shaving and intravenous drug abuse were the most and the least common risk factors. ( J CLIN EXP HEPATOL 2023;13:629-63 7)

Background: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by SARS CoV-2 that emerged in Wuhan, China, and has rapidly spread worldwide. The mortality rate of critically ill COVID-19 patients is high. Objective: To assess the severity, different clinical symptoms, and comorbidities of COVID-19 pneumonia in vaccinated vs. non-vaccinated patients. Methods: In this single-center, cross-sectional study, 142 patients with COVID-19 were enrolled. The clinical characteristics, comorbidities, severity, and outcomes were also assessed. Results: Of the 142 patients, 92 (64.8%) were males, with a mean age of (56.00±14.81) years. Among them, 62 (43.7%) were aged above 60 years. Of these, 92 (64.7%) had comorbidities. The patients were divided into two groups: unvaccinated and those who received at least one dose of the vaccine within six months. The demographic characteristics of the two groups were similar except for gender. In the vaccinated group, most of the patients were males. Most patients in the non-vaccinated group had a severe illness, whereas most patients in the vaccinated group had mild to moderate disease. Only 26% of the vaccinated group experienced severe illness compared to 71.5% in the unvaccinated group. In addition, the all-cause 30-day mortality in the non-vaccinated population was higher than that in the vaccinated population. However, this difference was not statistically significant (12.5% vs. 7.1%). On the contrary, there was no difference in the length of the intensive care unit or total hospital stay between the two groups. Conclusion: Severe COVID-19 had the worst outcome in the unvaccinated patients. Most partially vaccinated patients got infected before developing immunity, and a small percentage of completely immunized patients who were infected were likely non-responders. Receiving at least one vaccination dose significantly reduced illness severity.

Objective The present study was conducted to delineate the prevalence and clinical features of portopulmonary hypertension in patients with hepatic cirrhosis. Possible associations between echocardiographic variables and portopulmonary hypertension were also explored. Methods A prospective, observational study was conducted between September 2017 and August 2018. Differences in demographics, clinical presentation, laboratory findings, and echocardiographic findings in cirrhosis patients with and without portopulmonary hypertension were compared. Results The prevalence of portopulmonary hypertension in patients with hepatic cirrhosis was found to be 9.3%. Hemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension (5.50±0.68 g/dl vs. 7.26±1.43 g/dl, p=0.001). All patients with portopulmonary hypertension displayed right atrial (major: p=0.0001 and minor: p=0.001) and right ventricular (basal, p=0.0001; longitudinal, p=0.0001) dilation. Several variables such as right ventricular systolic pressure (p=0.0001), pulmonary artery diameter (major: p=0.0001; right: p=0.0001; and left: p=0.007), pulmonary vascular resistance (p=0.0001), tricuspid regurgitation (p=0.0001), pulmonary regurgitation peak pressure gradient (p=0.0001), pulmonary regurgitation end diastolic gradient (p=0.0001), left atrial dimension (major axis: p=0.002), left atrial volume (p=0.04), left ventricular outflow tract (p=0.001), inferior vena cava diameter (p=0.001), and inferior vena cava collapsibility (p=0.001) were higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension. Conclusions The present study revealed a 9.3% prevalence of portopulmonary hypertension among patients with hepatic cirrhosis. Patients with portopulmonary hypertension displayed significantly lower haemoglobin levels, right and left ventricular dilation, and higher values of several echocardiographic variables as compared to those without portopulmonary hypertension.

Subba et al.[1] review ways to empower primary health care institutions against the COVID-19 pandemic, and they suggest a health system–based approach. They underscore a pressing need to empower primary health centers (PHCs) in COVID-19 preparedness and response as they conclude by stating that these institutions are going to play an indispensable role in this fight. Under the heading of Health Information System (HIS), they write that verbal autopsy of severe acute respiratory illness (SARI)/influenza-like illness (ILI) cases into facility-level data can help to improve the quality of HIS reporting. However, we want to highlight that verbal autopsy can only reveal what we already know about an illness. In conversation with relatives of a deceased person, when some points appear in front of us, we can surmise and imagine only that sequence of events, which we have witnessed before. But in this pandemic when our colleagues conducted an analysis of the morbid -anatomy of expired ones suffering from the disease, novel facts were emerging. A few months ago, while dissecting bodies of such cadavers, we came to know that there is a tendency for blood to clot inside veins[2] and that is why now we recommend anticoagulant drugs in this group.[3] What we want to underline is that study by any other method in these circumstances may not have provided such an insight into the pathogenesis of the viral illness. Hence, while verbal autopsy has its own value in discovering the cause of death when it is not known, it cannot replace the conventional knife. Then, under the heading of Leadership and Governance, the authors write that governance at any level should be based on a proper Planning- Implementation- Monitoring- Evaluation framework. In this respect, we want to emphasize that issue of governance has been marred in the times of this pandemic by loss of trust not only in our own country but also at other places. While Anoop Saraya at the AIIMS, New Delhi vouches for expertise and transparency while making a decision at the top level of governance, we observe that several government orders leave a lot of relevant issues to be fixed.[4] Similarly, across the oceans, we observed that time-tested agency having the stature of the Food and Drug Administration, the US was fighting to win the trust of its stakeholders at perhaps one of the most crucial moments of history.[5] Due to political meddling, when certain unscientific decisions were made at these federal bodies, we witnessed after-effects in the form of some of the record number of infections/deaths per day resulting in overwhelming of the health care system and for the first time after World War 2, erection of tents in grounds and stadiums to accommodate an excessive number of patients. Hence, while leadership is necessary to give impetus to mitigation efforts, domain experts should be in harness to steer the wheel. While bureaucrats provide support by arranging resources, specialists provide an avenue for their best and maximum utilization. And both are complementary and indispensable to each other. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Introduction: Government runs teaching hospitals to impart a high-quality medical education to budding medicos and paramedical students in training. The experiences these trainees at various tenure positions get then and there shape their worldview for rest of the life and have an indelible impression. The Covid-19 pandemic disrupted all the routines at the hospitals around the world—including ours—and we make an attempt to measure it in one dimension in this study. Materials and Methods: We obtained attendance data of patients at out patient department and in patient department of our hospital. During the pandemic for a certain duration offline (physical) registrations were closed and they were attended only by online ones. Hence that data (actually a part of it) got captured electronically and we analyzed it to get an idea of the traversed course of the scourge. Results: When the pandemic surged during the spring and summer of 2021, our hospital was turned into a Covid facility. Hence average routine attendance of patients got reduced to a significant extent, elective surgeries/interventions and procedures were postponed and this data is reflected in an electronic system, perhaps making a long-lasting effect on the budding trainees. This fact needs to be realized so as to take appropriate action. Conclusion: We need to realize that the effects of the viral communicable disease may be enduring, not only for the infected patients and their families but also for those who learn on those patients. Therefore, the transmissible diseases disabled not only our society, economy, and health care services when they ascended but pedagogy too. Online learning came to rescue but only up to a certain extent and with several caveats and limitations.

Krishna et al.,[1] wrote in the November issue of the journal about Covid-19 re-infection and assessed its linked possibilities and future outlook. They cite various reported cases in medical literature when someone got re-infected and then provided their references. However, we humbly submit that that is selective reading of literature. Now, when detected cases have reached every territory of the globe and millions of them are detected on a daily basis, the number of re-infections is minute in comparison. At our hospital in UP, there were hardly any such reported cases and among the healthcare workers, with whom we have a good follow up, the incidence was negligible. Various hypotheses are emerging about its rarity and possible causations and time will tell the truth. This month an editorial in Lancet provides various cues on this important aspect.[2] In the fourth paragraph of their review under the heading ‘Mystery behind reinfections’, the authors mention the discharge criteria of Covid-19 patients. They mention that when 2 consecutive tests are found to be negative, they are discharged. However, we want to highlight that in mid-May, our government changed its discharge policy. As per the changed policy, for mild/very mild and pre-symptomatic cases, now we don’t need any such testing.[34] Now we presume that in mild cases, immunity takes precedence over the virus, clears it from the respiratory system and then the patient is eligible to be discharged. Our government clarifies that even after symptomatic improvement, a patient may keep on shedding the virus in samples drawn and that fragment may be picked up by the highly sensitive rRT PCR tests. But as that virus may not be viable, the patient is considered non-infectious. As viability is a crucial issue to determine the infectiousness, we need to have a simple culture test to settle the riddle. But at present that is a tedious and cumbersome process, the jury is still out on the issue. Moreover, we also need to have good sample collection methods so as not to break the delicate virus during collection, then we have to maintain it during transport. All of these issues hinder the resolution of the point at present. But after discharge he/she is advised to self-isolate for one week. And several experts have raised the question over the effect of the exercise.[5] How long does the virus remain viable and when does the patient become non-infectious, remains the impugned and debatable issue. At the end of their review, the authors recommend under point number 5 that they (the recovered patients) should follow all the precautionary measures to prevent Coronavirus infection. Here we want to highlight that these precautionary measures not only protect those recovered patients from re-infection but also their contacts from getting infected. Today the unsolved puzzle remains; how long should they follow these recommended measures. And what is the risk of household contacts to get infected from such apparently recovered patients. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. We accessed all the webpages at the time of submission of this Letter to the Editor.

Sureka et al.[1] modelled a suraksha chakra (safety circle) by designing a new scoring system to protect healthcare workers from COVID. They published the scoring system in the April 2021 issue of the Journal and assessed implementation of the protocol in regular and surprise rounds. What its approach is, is that by constantly nudging our fellow workers, we can motivate them to follow the best practices and hence, in the process, can protect ourselves and those around us.

Introduction: Covid-19 is an unprecedented challenge in our times leaving a trail of destruction and mayhem affecting almost all of us during the last 2 years. Various data sources are available around the globe to measure its impact using various yardsticks. Material and Methods: By carefully looking at data available at the website maintained by Government of India, we can draw some useful conclusions. Results: There is a dip in the number of online registrations at our hospital coinciding with second wave and resultant lockdown. Conclusion: Tracing digital footprints of an event as huge as the Covid pandemic may help us for future planning when we learn its lessons well.