APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

Endoscopic Ultrasound Bubble Study for Detection of Extracardiac Shunting: Endohepatology in the Diagnosis of Hepatopulmonary Syndrome.

Contrast echo is often used to demonstrate extracardiac shunting for evaluation of hepatopulmonary syndrome. The same can also be performed via transesophageal route with endoscopic ultrasound. We here demonstrate this technique in a 58-year-old woman who underwent gastric variceal obliteration with endoscopic ultrasound. This technique can add another dimension to the "one-stop-shop" endohepatology evaluation of patients with cirrhosis in a single endoscopy appointment.

Prevalence of Frailty and Its Impact on Mortality and Hospitalization in Patients With Cirrhosis: A Systematic Review and Meta-analysis.

Background & aims: Frailty in patients with cirrhosis is associated with increased morbidity and mortality. In this study, we aimed to determine the prevalence of frailty and its impact on mortality and hospitalization in patients with cirrhosis. Methods: An elaborate search was undertaken in the databases "PubMed, Scopus, Web of Science, and Cochrane, and preprint servers", and an assessment of all published articles till 17 February 2023 was done. Studies that provided data on prevalence, mortality and hospitalization among frail patients with cirrhosis were included. The study characteristics and data on the prevalence, mortality, and hospitalization were extracted from included studies. The primary outcome was to estimate the pooled prevalence of frailty and determine its impact on mortality and hospitalization in patients with cirrhosis. Results: Overall, 12 studies were included. Data on prevalence of frailty and mortality were available in 11 studies, while seven studies reported data on hospitalization. The analysis conducted among 6126 patients with cirrhosis revealed pooled prevalence of frailty to be 32% (95% confidence interval [CI], 24-41). A total of 540 events of death revealed a pooled mortality rate of 29% (95% CI, 19-41). Six-month and twelve-month pooled estimates of mortality were found to be 24% (95% CI, 17-33) and 33% (95% CI, 23-45), respectively. The pooled hospitalization rate among the seven studies was 43% (95% CI, 21-68). Conclusion: The prevalence of frailty in patients with cirrhosis is high, leading to poor outcomes. Frailty assessment should become an integral part of cirrhosis evaluation. Registry and registration number of study: PROSPERO 2022 CRD42022377507.

Exploring the Prevalence, Predictors, and Impact of Bacterial Infections to Guide Empiric Antimicrobial Decisions in Cirrhosis (EPIC-AD).

Background/Aims: This study delved into cirrhosis-related infections to unveil their epidemiology, risk factors, and implications for antimicrobial decisions. Methods: We analyzed acutely decompensated cirrhosis patients (n = 971) from North India between 2013-2023 at a tertiary center. Microbiological and clinical features based on infection sites (EASL criteria) and patient outcomes were assessed. Results: Median age was 45 years; 87% were males with 47% having alcoholic hepatitis. Of these, 675 (69.5%) had infections; 305 (45%) were culture-confirmed. Notably, 71% of confirmed cases were multi-drug resistant organisms (MDRO)-related, chiefly carbapenem-resistant (48%). MDRO prevalence was highest in pulmonary (80.5%) and skin-soft-tissue infections (76.5%). Site-specific distribution and antimicrobials were suggested. Predictive models identified prior hospitalization [OR:2.23 (CI:1.58-3.14)], norfloxacin prophylaxis [OR:2.26 (CI:1.44-3.55)], prior broad-spectrum antibiotic exposure [OR:1.61 (CI:1.12-2.30)], presence of systemic inflammatory response-SIRS [OR:1.75 (CI: 1.23-2.47)], procalcitonin [OR:4.64 (CI:3.36-6.40)], and HE grade [OR:1.41 (CI:1.04-1.90)], with an area under curve; AUC of 0.891 for infection prediction. For MDRO infection prediction, second infection [OR: 7.19 (CI: 4.11-12.56)], norfloxacin prophylaxis [OR: 2.76 (CI: 1.84-4.13)], CLIF-C OF [OR: 1.10 (CI: 1.01-1.20)], prior broad-spectrum antibiotic exposure [OR: 1.66 (CI: 1.07-2.55)], rifaximin [OR: 040 (0.22-0.74)] multisite [OR: 3.67 (CI: 1.07-12.56)], and polymicrobial infection [OR: 4.55 (CI: 1.45-14.17)] yielded an AUC of 0.779 and 93% specificity. Norfloxacin prophylaxis, multisite infection, mechanical ventilation, prior broad-spectrum antibiotic exposure, and infection as acute precipitant predicted carbapenem-resistant infection (AUC: 0.821). Infections (culture-proven or probable), MDROs, carbapenem/pan-drug resistance, and second infections independently linked with mortality (P < 0.001), adjusted for age, leucocytosis, and organ failures. A model incorporating age [HR:1.02 (CI: 1.01-1.03), infection [HR:1.52 (CI: 1.05-2.20)], prior hospitalization [HR:5.33 (CI: 3.75-7.57)], norfloxacin [HR:1.29 (CI: 1.01-1.65)], multisite infection [HR:1.47 (CI:1.06-2.04)], and chronic liver failure consortium-organ failure score; CLIF-C OF [HR:1.17 (CI: 1.11-1.23)] predicted mortality with C-statistics of 0.782 (P < 0.05). Conclusion: High MDRO burden, especially carbapenem-resistant, necessitates urgent control measures in cirrhosis. Site-specific epidemiology and risk models can guide empirical antimicrobial choices in cirrhosis management.

Simultaneous Liver and Kidney Transplantation in a Patient With Telomere Biology Disorder: A Case Study.

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.

Algorithmic Approach to Deranged Liver Functions After Transplantation.

Liver transplant (LT) recipients require close follow-up with regular monitoring of the liver function tests (LFTs). Evaluation of deranged LFT should be individualized depending upon the time since LT, peri-operative events, clinical course, and any complications. These derangements can range from mild and asymptomatic to severe and symptomatic elevations requiring expedited personalized assessment and management. Pattern of LFT derangement (hepatocellular, cholestatic, or mixed), donor-recipient risk factors, timing after LT (post-operative, 1-12 months, and >12 months since LT) along with clinical context and symptomatology are important considerations before proceeding with the initial evaluation. Compliance to immunosuppression and drug interactions should be ascertained along with local epidemiology of infections. Essential initial evaluation must include an ultrasound abdomen with Doppler to rule out any structural causes such as biliary or vascular complications apart from focussed laboratory evaluation. Early allograft dysfunction, ischemia reperfusion injury, small-for-size syndrome, biliary leaks, hepatic artery, and portal vein thrombosis are usual culprits in the early post-operative period whereas viral hepatitis (acute or reactivation), opportunistic infections, and recurrence of the primary disease are more frequent in the later period. Graft rejection, biliary strictures, sepsis, and drug induced liver injury remain possible etiologies at all times points after LT. Initial evaluation algorithm must be customized based on history, clinical examination, risk factors, and pattern and severity of deranged LFT. Allograft rejection is a diagnosis of exclusion and requires liver biopsy to confirm and assess severity. Empirical treatment of rejection sans liver biopsy is discouraged.

Efficacy of Yttrium-90 Transarterial Radioembolisation in Advanced Hepatocellular Carcinoma: An Experience With Hybrid Angio-Computed Tomography and Glass Microspheres.

Background: Hepatocellular carcinoma is one of the most common malignancies worldwide. Transarterial radioembolisation (TARE) involves selective intra-arterial administration of microspheres loaded with a radioactive compound like Yttrium-90 (Y-90). Conventionally, C-arm-based cone-beam computed tomography has been extensively used during TARE. However, angio-computed tomography (CT) is a relatively new modality which combines the advantages of both fluoroscopy and fCT. There is scarce literature detailing the use of angio-CT in Y90 TARE. Methods: This was a retrospective study of primary liver cancer cases in which the TARE procedure was done from November 2017 to December 2021. Glass-based Y-90 microspheres were used in all these cases. All the cases were performed in the hybrid angio-CT suite. A single photon emission computed tomography-computed comography (SPECT-CT) done postplanning session determined the lung shunt fraction and confirmed the accurate targeting of the lesion. Postdrug delivery, positron emission tomography-computed tomography (PET-CT) was obtained to confirm the distribution of the Y-90 particles. The technical success, median follow-up, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were recorded. Results: A total of 56 hepatocellular carcinoma patients underwent TARE during this period, out of which 36 patients (30 males and 6 females) underwent Y90 TARE. The aetiology of cirrhosis included non-alcoholic steatohepatitis (NASH) (11), hepatitis C (HCV) (11), hepatitis B (HBV) (9), metabolic dysfunction and alcohol-associated liver disease (MetALD) (2), alcoholic liver disease (ALD) (1), cryptogenic (1), and autoimmune hepatitis (AIH) (1). The technical success was 100 % and the median follow-up was 7 months (range: 1-32 months). The median OS was 15 months (range 10.73-19.27 months; 95 % CI) and the median local PFS was 4 months (range 3.03-4.97 months; 95 % CI). The ORR (best response, CR + PR) was 58 %. No major complications were seen in this study. Conclusion: TARE is a viable option for liver cancer in all stages, but more so in the advanced stages. The use of angio-CT in TARE aids in the precise delivery of the particles to the tumour and avoids non-target embolisation.

Bloody Lips - Gluing Bleeding Lower Lip Spider Angioma in Decompensated Cirrhosis.

Spider angiomas are dilated vascular channels in the skin. They have a central arteriole with surrounding vascular channels resembling legs of a spider, hence the name. They are frequently associated with liver cirrhosis, thyrotoxicosis, and pregnancy. We present the case of a 49-year-old gentleman who was referred to our liver clinic with complaints of jaundice and ascites of one-month duration. The patient was a chronic alcohol consumer, consuming country-made liquor, 80-100 grams/day for past 8-10 years. He was diagnosed with Acute on chronic liver failure with a model for end-stage liver disease score of 38. During his hospital stay, he developed active spurting from a spider angioma on his lower lip (video 1), which was initially tackled with hand compressions, which stopped bleeding for a few minutes, restarting again after the compressions were lifted. It was then decided to inject 0.1 mL cyanoacrylate glue injection using a 21-gauge needle, immediately stopping active spurt (video 2), (Figure 1). A small ulcer formed at the injection site, which healed in few days, and the patient was discharged to home. Spider angiomas are characteristic cutaneous manifestation of liver cirrhosis with a specificity of 95%.1 The prevalence of spider angiomas in cirrhosis is reported to be around 30-40%. Li Hongyu et al. in their study on 198 individuals reported the prevalence to be 47%.2 They can be graded from grade 1+ (readily recognizable containing a body, legs, and surrounding erythema) to grade 4+ (visible pulsations with a hand lens and raised central punctum with many obvious "spider legs" radiating from it).3 Underlying pathogenesis in cirrhosis is multifactorial including decrease levels of testosterone and high levels of estradiol,4 hyperdynamic circulation, high levels of substance-P, and vascular endothelial growth factor leading to angiogenesis and vasodilation.5,6 Spider angiomas can be single or multiple and are usually seen in the territory of superior vena cava-the face (nose, lips, forehead), upper chest, and arms.2 These lesions have been associated with bleeding esophageal varices and hepatopulmonary syndrome. Bleeding from spider angiomas is unusual. Rarely, fine-needle electrocautery, potassium-titanyl-phosphate (KTP) laser, or electro desiccation has been used to clear spider angiomas for cosmetic concerns. Treatment includes hand or ice compressions and treating the underlying cause. Use of cyanoacrylate glue for bleeding spider angioma has not been reported in the literature. We think this can be a handy bedside tool to combat an active spurt of bleeding when conventional methods have failed, as in our case; however, further studies are warranted.

Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography.

BACKGROUND AND AIMS: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers. APPROACH: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria. RESULTS: One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine. CONCLUSIONS: CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.

Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats.

OBJECTIVES: Preclinical evidence is needed to assess drug-metabolite behaviour in compromised liver function for developing the best antitubercular treatment (ATT) re-introduction regimen in drug-induced liver injury (DILI). The pharmacokinetic behavior of rifampicin (RMP) and its active metabolite des-acetyl-rifampicin (DARP) in DILI's presence is unknown. To study the pharmacokinetic behavior of RMP and DARP in the presence of carbon tetrachloride (CCl4) plus ATT-DILI in rats. METHODS: Thirty rats used in the experiment were divided equally into six groups. We administered a single 0.5 mL/kg CCl4 intraperitoneal injection in all rats. Groups II, III, IV, and V were started on daily oral RMP alone, RMP plus isoniazid (INH), RMP plus pyrazinamide (PZA), and the three drugs INH, RMP, and PZA together, respectively, for 21-days subsequently. Pharmacokinetic (PK) sampling was performed at 0, 0.5, 1, 3, 6, 12, and 24 h post-dosing on day 20. We monitored LFT at baseline on days-1, 7, and 21 and sacrificed the rats on the last day of the experiment. RESULTS: ATT treatment sustained the CCl4-induced liver injury changes. A significant rise in mean total bilirubin levels was observed in groups administered rifampicin. The triple drug combination group demonstrated 1.43- and 1.84-times higher area-under-the-curve values of RMP (234.56±30.66 vs. 163.55±36.14 µg h/mL) and DARP (16.15±4.50 vs. 8.75±2.79 µg h/mL) compared to RMP alone group. Histological and oxidative stress changes supported underlying liver injury and PK alterations. CONCLUSIONS: RMP metabolism inhibition by PZA, more than isoniazid, was well preserved in the presence of underlying liver injury.

Diagnostic Performance of Abbreviated MRI for HCC Detection in Patients with Non-alcoholic Fatty Liver Disease.

Background/Aim: Hepatocellular carcinoma (HCC) surveillance is recommended in nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The performance of ultrasound (US) is impaired in NAFLD. This study aimed to evaluate the diagnostic performance of non-contrast abbreviated magnetic resonance imaging (AMRI) for HCC detection in NAFLD. Methods: Consecutive contrast-enhanced magnetic resonance imaging (CE-MRI) scans of NAFLD patients between June 2017 and December 2021 were retrieved. A radiologist extracted and anonymized a noncontrast AMRI dataset comprising T2-weighted, T1-weighted, and diffusion-weighted imaging (DWI) sequences. Two radiologists blinded to CE-MRI reports and treatment details independently reviewed the AMRI for liver lesion and portal vein (PV) characteristics. HCC and malignant PV thrombosis were diagnosed based on the original dynamic CE-MRI diagnostic reports. The diagnostic performance of AMRI and the interobserver agreement for detecting HCC and malignant PV thrombosis were calculated. Results: Seventy-five patients (52 males; mean age (±SD), 56 ± 17.6 years; 61 cirrhotic) were included. Nine patients had HCC (14 HCCs). The sensitivity, specificity, positive predictive value, and negative predictive value of AMRI for detecting HCC were 100%, 93.9%, 69.2%, and 100%, respectively, and malignant PV thrombosis was 100%, 98.5%, 80%, and 100%, respectively. There was substantial interobserver agreement for detecting HCC (kappa = 0.721) and malignant PV thrombosis (kappa = 0.645) on AMRI. Conclusion: AMRI has high diagnostic performance in HCC detection in patients with NAFLD. However, prospective studies must compare the diagnostic performance of AMRI with that of US.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial.

Background: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. Patients and methods: European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Results: Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Conclusion: Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no: NCT04238416 (clinicaltrials.gov).

Survival of Trial-Like and Non-Trial-Like Patients With Immunotherapy in Advanced Hepatocellular Carcinoma in Real World: A Collaborative Multicenter Indian Study (IMHEP).

PURPOSE: Immune checkpoint inhibitors (ICIs) is the initial line of management in advanced hepatocellular carcinoma (HCC), but survivals in the real world are not known. MATERIALS AND METHODS: A retrospective study of patients with advanced HCC receiving ICIs (as first-line therapy or as later lines of therapy) across 11 Indian institutions was conducted. Patients were divided into either cohort 1 (trial-like receiving ICI as first-line therapy), with a Child Pugh score (CTP) of ≤6, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1, and no VP4 (main portal vein thrombosis [MPVT]) or cohort 2 (trial unlike) who did not satisfy at least one of the above criteria. The primary end point was 12-month overall survival (OS). RESULTS: Between January 2017 and January 2022, 133 patient data were analyzed. The presence of MPVT was seen in 33 patients (25%). The ICIs used were atezolizumab-bevacizumab, nivolumab, and pembrolizumab in 89 (66%), 44 (33%), and one (1%) patients, respectively. With a median follow-up of 13.8 months, the 12-month OS for the entire cohort was 33.4% (95% CI, 23.6 to 43.2). Patients in cohort 1 (n = 31) had a significantly improved OS compared with patients in cohort 2 (n = 102; 12-month OS, 57.9% [95% CI, 38.5 to 77.3] v 24% [95% CI, 13.4 to 34.6]; P = .005). Patients with CTP A as compared with CTP B (9.7 v 4.3 months; P < .001) and an ECOG PS of 0/1 as compared with a PS of ≥2 (8.7 v 7.2 months; P = .04) and without MPVT (9.4 v 4.0; P < .001) had superior survivals. CONCLUSION: Patients with advanced HCC in the real world, trial-like have survivals in consonance with trial data, whereas patients with features excluding them from trials, such as main portal vein thrombosis, poor ECOG PS, and child Pugh B status, have markedly inferior survivals, despite good tolerance to immunotherapy.

A chair-stand time of greater than 15 seconds is associated with an increased risk of death and hospitalization in cirrhosis.

Background: Frailty is a clinical state of increased vulnerability and is common in patients with cirrhosis. The liver frailty index (LFI) is a validated tool to evaluate frailty in cirrhosis, comprising of grip strength, chair stands, and balance tests. The chair-stand test is an easy to conduct frailty subcomponent that does not require specialized equipment and may be valuable to predict adverse clinical outcomes in cirrhosis. The objective of this study was to determine if the chair-stand test is an independent predictor of mortality and hospitalization in cirrhosis. Methods: A retrospective review of 787 patients with cirrhosis was conducted. Chair-stand times were collected at baseline in person and divided into three groups: <10 seconds (n = 276), 10-15 seconds (n = 290), and >15 seconds (n = 221). Fine-Gray proportional hazards regression models were used to evaluate the association between chair-stand times and the outcomes of mortality and non-elective hospitalization. Results: The hazard of mortality (HR 3.21, 95% CI 2.16%-4.78%, p <0.001) and non-elective hospitalization (HR 2.24, 95% CI 1.73%-2.91%, p <0.001) was increased in group 3 in comparison to group 1. A chair-stand test time >15 seconds had increased all-cause mortality (HR 2.78, 95% CI 2.01%-3.83%, p <0.001) and non-elective hospitalizations (HR 1.84, 95% CI 1.48%-2.29%, p <0.001) compared to <15 seconds. Conclusions: A chair-stand test time of >15 seconds is independently associated with mortality and non-elective hospitalizations. This test holds promise as a rapid prognostication tool in cirrhosis. Future work will include external validation and virtual assessment in this population.

NASH After Liver Transplantation: Impact of Immunosuppression.

Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the common causes of cirrhosis and hepatocellular carcinoma (HCC) and is a leading indication for liver transplantation (LT). Patients with NAFLD-related cirrhosis and HCC are at high risk for the development of recurrent NAFLD after LT. NAFLD can also develop de novo post-transplantation in patients subjected to LT for other indications. Besides the pretransplant presence of various components of metabolic syndrome (MS) use of immunosuppressive agents in the post-LT setting forms one of the major drivers for the development of post-LT NAFLD. Individual components of conventional immunosuppressive regimens (corticosteroids, calcineurin inhibitors, and m-TOR inhibitors) are all implicated in the development of post-LT metabolic derangement and follow unique mechanisms of action and degree of disturbances. The development of cardiovascular risk is associated with post-LT NAFLD, although graft outcomes do not seem to be influenced only by the presence of post-LT NAFLD. Measures in consonance with the management of NAFLD, in general, including lifestyle modifications and control of metabolic risk factors, hold true for post-LT NAFLD. Tailoring immunosuppression strategies with early corticosteroid withdrawal and calcineurin inhibitor minimization balancing against the risk of graft rejection constitutes important nuances in the individualized management of post-LT NAFLD.

Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats.

OBJECTIVES: The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any. METHODS: A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II-VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination. RESULTS: Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis. CONCLUSIONS: The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology.

Pharmacokinetic Assessment of Pyrazinamide and Pyrazinoic Acid in Carbon tetrachloride-induced Liver Injury Model in Wistar Rats.

Background: We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl4) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats. Methods: Thirty rats utilized in the experiment were separated equally into five groups. Each rat was injected with 0.5 ml/kg CCl4 intra-peritoneal injection on day zero. Group, I rats did receive only CCl4 (single i.p. injection, 0.5 ml/Kg in olive oil in a 1:1 ratio). Groups II, III, IV, and V did receive daily oral PZA, PZA plus isoniazid (INH), rifampicin (RMP) plus pyrazinamide (PZA), and three drugs together, respectively, for 21-days. Pharmacokinetic sampling was performed at 0, 0.5,1,3,6,12 and 24 hours post-dosing on day-20. Liver function test (LFT) was assessed at days 0,1,7, and 21 days after CCl4 and ATT administration, and rats were sacrificed on the last experiment day. Results: ATT treatment maintained the liver function changes initiated by CCl4 administration. An evidential LFT rise was observed in groups administered with pyrazinamide. Co-administration of Isoniazid caused a 2.02 and 1.78 times increase in Area-under-the-curve (AUC) values of PZA and PA, respectively (p < 0.05). Histological and oxidative-stress changes supported the biochemical and pharmacokinetic observations. Conclusion: The enzyme inhibitory capacity of isoniazid is well-preservd in CCl4-induced liver injury.

Evidence-Based Consensus Recommendations for Skin Care in Healthy, Full-Term Neonates in India.

Purpose: Neonatal skin care practices guided by personal experience and preferences might be substantially different across different hospital settings. The aim of this consensus recommendation is to provide clinical practice guidance to healthcare practitioners on evidence-based neonatal skin care practices from delivery-to-discharge, in hospital settings. Patients and Methods: A Scientific Advisory Board meeting on "Evidence-based Neonatal Skin Care Practices and Protocols" was held in December 2020 with an expert panel comprising neonatologists, pediatricians, obstetricians and gynecologists and pediatric dermatologist. Comprehensive literature search was performed up to 23 March 2021 using PubMed and Google Scholar to retrieve relevant evidence. Results: Recommendations were developed on critical aspects of skin care in healthy full-term neonates including cleansing at birth, skin-to-skin care, cord care, diaper area care, initial and routine bathing, cleansers and emollients use, and criteria to choose appropriate skin care products. Recommendations include inclusion of skin assessment in routine neonatal care, first bath timing after cardio-respiratory and thermal stabilization, 6-24 hours after birth; bathing with water alone or adding a mild liquid cleanser could be considered appropriate as it does not impact the developing skin barrier; use of emollients is recommended for neonates with higher risk of development of eczema to maintain and enhance skin barrier function and integrity; and inclusion of skin care advice in neonatal discharge checklist. Importance of rigorous quality control, high-quality clinical trials for assessment of baby products, usage of products that are formulated appropriately for newborns, and full label transparency for baby products were highlighted. The panel identified gaps in literature and discussed the scope for future research. Conclusion: These recommendations may help to standardize evidence-based skin care for healthy full-term neonates in Indian hospital settings to improve the quality of care that neonates receive in hospital and facilitate improvement in overall neonatal health outcomes.