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INTRODUCTION: Effect of long-term growth-hormone (GH) therapy in decompensated cirrhosis (DC) is unknown. We studied the safety and efficacy of GH therapy on malnutrition, nitrogen metabolism, and hormonal changes in patients with DC. METHODS: Patients with DC were randomized to standard medical therapy plus GH (group A; n = 38) or standard medical therapy alone (group B; n = 38). Body mass index, midarm muscle circumference (MAMC), hand grip strength (HGS), liver frailty index (LFI), skeletal muscle index (SMI), nitrogen balance, Child-Turcotte-Pugh, model for end-stage liver disease, quality of life (QOL), serum albumin, GH, insulin like growth factor-1, and acid labile subunit (ALS) were assessed at baseline and at 12 months. RESULTS: The mean difference between baseline and 12-months in SMI (-6.122 [-9.460 to -2.785] cm2/m2), body mass index (-2.078 [-3.584 to -0.5718] kg/m2), MAMC (-1.960 [-2.928 to -0.9908] cm), HGS (-5.595 [-7.159 to -4.031] kg), albumin (-0.3967 [-0.6876 to -0.1057] g/dL), LFI (0.3328 [0.07786-0.5878]), Child-Turcotte-Pugh (0.9624 [0.1435-1.781]), model for end-stage liver disease (1.401 [0.04698-2.75]), insulin-like growth factor-1 (-6.295 [-11.09 to -1.495] ng/dL), and ALS (-8.728 [-14.12 to -3.341] pg/mL) were statistically significantly better (P< 0.05) in group A. There was no improvement in nutritional parameters, clinical scores, QOL scores, or nitrogen balance in group B. The mean difference between group A and B in SMI, HGS, MAMC, LFI, ALS, physical component summary, and mental component summary at 12 months was also statistically significant. Survival at 12 months was similar in both groups (P = 0.35). No serious adverse events were observed. DISCUSSION: Long-term use of GH is safe in DC and leads to improvement in malnutrition and possibly QOL. However, there is no improvement in 12-month survival (NCT03420144). [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is more prevalent in people living with HIV‐AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first‐line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir‐based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir‐based ART. Forty‐five consecutive PLHA with HCV coinfection on dolutegravir‐based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty‐two (97.7%) of the remaining 43 patients attained SVR‐12. SVR‐12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan‐genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir‐based ART. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Verma et al papers. To view these articles, visit https://doi.org/10.1111/apt.17891 and https://doi.org/10.1111/apt.17902 [ABSTRACT FROM AUTHOR]

Introduction: Patients with cirrhosis have a higher risk of severe COVID-19 and mortality and are high-priority patients for vaccination. However, cirrhotics were excluded from the phase 2/3 vaccine trials. Hence, we aimed to assess the antibody response and safety of Covishield (ChAdOx1nCoV-19) among patients with cirrhosis. Methods: Patients who attended the tele-hepatology services at our institute from March 2020 to June 2021 and diagnosed with cirrhosis as per their medical records were telephonically interviewed in July 2021 using a pre-specified questionnaire. Patients who had completed 2 doses of ChAdOx1-nCOV (with the 2nd dose administered at least 2 weeks back) and without history of documented COVID-19 infection (pre- or post-vaccination) were tested for antibodies against the spike protein. Seropositive patients were divided into high, moderate, and low antibody responses based on the signal/cut-off. Results: We interviewed 784 patients with cirrhosis. At least 1 dose of ChAdOx1-nCOV was received by 231 patients among whom 134 (58%) had received 2 doses. Documented COVID-19 was reported in 3.9% patients who received at least 1 dose of ChAdOx1-nCOV including breakthrough infections in 3.7% patients vaccinated with 2 doses. Local and systemic adverse events were reported by 42% and 22.1% patients. None developed anaphylaxis, acute decompensation, acute-on-chronic liver failure, or other serious adverse events requiring hospitalization. Seroconversion was documented in 81 (92%) out of 88 patients. No difference was observed in level of antibody response between patients with compensated and decompensated cirrhosis (p = 0.12). Conclusion: Our preliminary data suggest that ChAdOx1-nCOV is safe with high seroconversion rates in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

The FibroScan-AST (FAST) score was recently described to detect patients with nonalcoholic steatohepatitis (NASH) having elevated nonalcoholic fatty liver disease (NAFLD) activity score (NAS ≥ 4) and significant fibrosis (≥ F2) on liver biopsy (NASH+ NAS ≥ 4 + F ≥ 2). The aim of this study was to validate the FAST score in Indian patients with NAFLD and to derive optimal cut-offs. Sixty patients with biopsy-proven NAFLD [men: 38 (63.3%), age 40 (32–52) years] with all parameters for assessing the FAST score within 3 months of liver histology were retrospectively analysed. Histological NASH was present in 17 patients (28.3%), while 11 (18.3%) patients had NASH + NAS ≥ 4 + F ≥ 2. The area under the curve (AUROC) of the FAST score for discriminating NASH + NAS ≥ 4 + F ≥ 2 was 0.81. Using cut-offs by Newsome et al , the rule-out cut-off (FAST: ≤ 0.35) had a negative predictive value (NPV) of 0.88 [sensitivity: 0.91, specificity: 0.14, negative likelihood ratio (LR): 0.64], while the rule-in cut-off (FAST: ≥ 0.67) had a positive predictive value (PPV) of 0.33 (sensitivity: 0.73, specificity: 0.67, positive LR: 2.22). Fifteen (25%) patients were correctly classified as per histology, while 28 (46.67%) patients fell in the grey zone. On recalculating the optimal cut-offs for our patients, the rule-out cut-off (FAST: ≤ 0.55) had an NPV of 0.95 (sensitivity: 0.90, specificity: 0.45, negative LR: 0.21), while the optimal rule-in cut-off (FAST: ≥ 0.78) had a PPV of 0.70 (sensitivity: 0.64, specificity 0.94, positive LR: 10.39). With these cut-offs, 27 (45%) patients fell in the grey zone and 29 (48.3%) were correctly classified as per histology, performing better than the cut-offs by Newsome et al (P < 0.001). The FAST score demonstrates good AUROC for detecting NASH with significant fibrosis and inflammation on histology. Cut-offs should be recalibrated based on prevalence of disease. India has a high burden of NAFLD with an estimated 25 million patients at potential risk for significant liver disease. Liver biopsy remains the gold standard for diagnosing NASH, although its application in routine clinical practice is limited. Noninvasive tests for the simultaneous detection of steatosis, inflammation and fibrosis are thus the need of the hour. The FAST score has been recently suggested for the noninvasive detection of NASH with significant fibrosis (≥ F2) and inflammation (NAS ≥ 4) on liver biopsy. We validated the utility of the FAST score for detecting NASH with significant fibrosis and inflammation on liver biopsy in Indian patients with NAFLD. This noninvasive, easy-to-use and nonproprietary FAST score can correctly classify disease severity in more than 50% patients. However, our results suggest that cut-offs should be recalibrated based on the anticipated prevalence of NASH + NAS ≥ 4 + F ≥ 2 in the given population. [ABSTRACT FROM AUTHOR]

Introduction: Sofosbuvir (SOF) and velpatasvir (VEL) is a pan‐genotypic regimen for the treatment of Hepatitis C virus (HCV) infection. The data on the efficacy and safety of this regimen is end‐stage renal disease (ESRD) is scanty. This systematic review and meta‐analysis was done to ascertain the efficacy and safety of SOF and VEL in patients with chronic Hepatitis C (CHC) and ESRD on renal replacement therapy (RRT). Methods: Systematic search of Pubmed, Embase, Scopus, and Google Scholar was conducted using the search term (end‐stage renal disease OR renal replacement therapy OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR haemodialysis OR dialysis OR peritoneal dialysis) AND (sofosbuvir OR velpatasvir OR NS5A inhibitors OR directly acting antivirals). Pooled sustained virologic response (SVR) and adverse event rates with 95% confidence intervals were estimated. Results: Seven studies (410 patients with CHC and ESRD on RRT) fulfilled our eligibility criteria. The overall pooled SVR rate of SOF and VEL in patients with HCV on RRT was 97.69% (95% CI: 95.71 to 98.92). There was no significant heterogeneity (I2: 39.3%, p‐value of Cochran's Q = 0.13) among the studies. The pooled estimate of efficacy of SOF‐VEL combination among patients with cirrhosis was 91.94% (95% CI 77.03–98.52). Pooled SVR rates in genotype 3 infection [94.6%, (95%: CI 81.3–99.4)] was comparable to that in those with documented non‐genotype 3 infection [94.63%, (95% CI 87.12–98.44)]. No serious adverse event attributable to SOF and VEL was reported in the included studies. Conclusion: The fixed‐dose combination of SOF and VEL is effective and safe in CHC patients with ESRD on RRT. SUMMARY AT A GLANCE: This systematic review/meta‐analysis revealed collective evidence that the sofosbuvir/velpatasvir combination is efficacious and safe for HCV eradication in patients on kidney replacement therapy. [ABSTRACT FROM AUTHOR]

Background: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol‐associated acute‐on‐chronic liver failure (ACLF). Methodology: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. Results: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P =.007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P =.014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06‐2.24, P =.023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30‐day mortality (aHR 1.91, 95% CI 1.41‐2.59, P <.001), independent of age, CTP, MELD and AARC scores. Conclusion: Overweight/obesity and dyslipidaemia increase the severity of alcohol‐associated ACLF, and the former also increases the short‐term mortality in these patients. [ABSTRACT FROM AUTHOR]

The histological spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. Ballooning degeneration of hepatocytes with or without fibrosis is the key feature that differentiates NASH from NAFL. Liver biopsy is the only reliable method for diagnosing NAFL and differentiating it from NASH. Although the epidemiology of NAFLD is well described, the need for invasive biopsy limits our knowledge of the community prevalence of NAFL. Recent data suggest that the biochemical composition of hepatic steatosis may have a bearing on the disease. Triglycerides, the most commonly accumulated lipid, have a cytoprotective role because of their inert nature. Several paired liver biopsy studies and longitudinal follow-up studies have shown that NAFL is not completely benign as previously envisaged. NAFL can indeed progress to NASH and severe fibrosis, with progression being influenced by presence of baseline or worsening metabolic risk factors. Overall, NAFL carries a low risk of liver-related and overall mortality although the risk of cardiovascular mortality is similar to that of NASH. Current concepts suggest the presence of a dynamic bidirectional cycling between NAFL and NASH with slow progression of fibrosis in majority of the patients. The fact that ultimately it is the onset of progressive fibrosis that dictates clinical outcomes brings into question the relevance of distinguishing NAFL from NASH. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting. [ABSTRACT FROM AUTHOR]

Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000–1.003], P = 0.034), high albumin (OR 1.91 [1.05–3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33–0.91], P = 0.020) predicted complete response. AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response. [Display omitted] [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Moore et al papers. To view these articles, visit https://doi.org/10.1111/apt.15836 and https://doi.org/10.1111/apt.16001 [ABSTRACT FROM AUTHOR]

Background: Triple negative breast carcinoma (TNBC) has the highest mortality among all the breast carcinoma subtypes, but paradoxically, it shows the best response to neoadjuvant chemotherapy (NACT). Tumor infiltrating lymphocytes (TIL) density has been shown to have prognostic significance in TNBC. However, there are limited data on TIL subpopulation and their association with response to NACT in TNBC.Materials and Methods: The study included 80 consecutive patients with TNBC prospectively diagnosed for two and half years, who underwent tru-cut biopsy before NACT, followed by subsequent definite surgical procedures. Global TIL profile and immunohistochemistry (IHC) analysis of CD3, CD4, CD8, CD20, and CD56 were done on all baseline tru-cut biopsies and post-NACT surgical specimens.Results: Almost half the patients were postmenopausal with a mean age of 45.89 ± 4.62 years. The majority had low CD3, low CD4, low CD56, low CD20, and high CD8 positivity in both pre- and post-NACT specimens. On multivariate analysis, low CD3, CD4, CD56 and CD 20 were established as independent predictor of poor pathologic response (PR). Low CD4 (adjusted odds ratio [OR]: 228.46) was associated with the highest OR for poor PR. Low CD8 was associated with significantly decreased odds of poor PR on univariate analysis (OR: 0.26), but it was not been established as an independent predictor of PR on multivariate logistic regression. NACT did not significantly alter the profile of TILs.Conclusions: TIL profile with low CD3, CD4, CD20, and CD56 expression predicts PR to NACT in TNBC and may thus help in prognostication of these patients. [ABSTRACT FROM AUTHOR]

Background: Hyponatremia portends a poor prognosis in decompensated cirrhosis and is an independent predictor of mortality. Multiple modalities have been evaluated in the management of hyponatremia, including albumin infusion. However, the effect of albumin infusion on the resolution of hyponatremia is unclear. We conducted a systematic review to explore the available literature on the use of albumin infusion in hyponatremia. Methods: We performed a comprehensive search up to 31st December 2022 using MEDLINE, EMBASE, and Scopus for studies reporting the effectiveness of albumin infusion in the resolution of hyponatremia. The impact of albumin infusion of any dose, administration frequency, and duration of therapy was recorded. The study protocol was prospectively registered (CRD42021245914). Results: The literature search yielded 1322 references after duplicate removal. Only seven studies (three randomized trials, three cohort studies, and one case series) satisfied the predefined selection criteria after a full-text review. While hyponatremia was clearly defined as serum sodium < 130 meEq/L in all studies, two studies explicitly defined hyponatremia resolution (serum sodium > 135 mEq/L). No differentiation was made between the types of hyponatremia. The strength of the albumin infusion used was 5% and 20%. All but one study reported significant improvement in hyponatremia with albumin infusion. A subgroup analysis showed albumin infusion improved 30-day survival (odds ratio 0.43, 95% CI 0.25–0.74, I2 = 0.) No studies reported adverse events or the impact of concomitant associations (diuretic withdrawal, lactulose use, sepsis). Conclusion: Despite available literature on the use of albumin infusion for the resolution of hyponatremia, the level of evidence remains low. Large prospective studies with pre-defined selection criteria and endpoints are required to generate the evidence. [ABSTRACT FROM AUTHOR]

Background: Cyproheptadine is an easily available over-the-counter first-generation antihistaminic that is often used as an appetite stimulant. Although it is usually a safe drug, rare instances of drug-induced liver injury may occur. Case presentation: We report a case of cholestatic liver injury secondary to cyproheptadine in a young pharmacy student with chronic hepatitis B and review the literature of cyproheptadine-induced liver injury. Conclusion: Although cyproheptadine is largely a safe drug, its potential for significant liver toxicity cannot be ignored. [ABSTRACT FROM AUTHOR]

IgG4-related diseases are rare multisystem disorders involving salivary glands, retroperitoneum, pancreas, biliary tract, and liver. Isolated biliary strictures and gall bladder involvement are rare in such patients, and presentation with cholangitis and weight loss can misguide the diagnosis toward malignancy. Here, we report an interesting case of IgG4-related biliary stricture with gall bladder involvement, presented with cholangitis and weight loss. The initial symptoms and imaging were guided toward the malignant possibilities of cholangiocarcinoma and pancreatic carcinoma. However, endosonography, serology, and histopathology clinched the diagnosis of IgG4-related disease. The patient was managed without any biliary intervention and with antibiotics, steroids, and steroid-sparing agents. There was a relapse of disease during the steroids taper that improved after hiking its doses. The disease responded with medical management on follow-up. We demonstrated the effectiveness of steroid-sparing agents to treat IgG4-related diseases, especially to avert the steroid-related adverse effects. This case highlights the possible mislead for the diagnosis and delayed management of IgG4 disease due to shared clinical features with hepatobiliary malignancies and the effectiveness of noninvasive measures of management. [ABSTRACT FROM AUTHOR]

We read with great interest the study by Yeh ML et al. entitled "Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV coinfection".[1] The authors have tried to address an extremely relevant issue in the management of HBV/HCV coinfection in the direct-acting antiviral (DAA) era. Most international societies currently recommend nucleos(t)ide analogues (NUCs) in patients with compensated cirrhosis and detectable HBV DNA, irrespective of HBV DNA levels in decompensated cirrhosis.[2] SP , sp [3] Hence, information on the baseline virological, liver biochemistry profiles and presence of decompensations in these patients with cirrhosis would help elucidate many questions. References 1 M.L. Yeh, C.F. Huang, C.I. Huang, J.A. Holmes, M.H. Hsieh, Y.S. Tsai, Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection. [Extracted from the article]

Diagnosis and management of tuberculosis (TB) in patients with cirrhosis remains challenging. We studied the clinical spectrum, diagnosis, and management of TB along with the assessment of the diagnostic utility of various laboratory investigations in this cohort. A retrospective review of records of patients with cirrhosis (July 2017 and December 2019) was done. Out of 30 patients with cirrhosis and TB, 20 patients with pleural/peritoneal TB (cases) were compared with 20 consecutively selected spontaneous bacterial peritonitis (SBP) controls. Composite of clinical, laboratory, radiologic features and response to antituberculosis therapy (ATT) was taken as the gold standard to diagnose TB. Extrapulmonary TB (EPTB) (n = 23, 76.7%) was more common. Overall, 9 (30%) patients presented with ATT-induced hepatitis. Patients with pleural/peritoneal TB had less severe hepatic dysfunction as compared to SBP group with significantly lower CTP [8 ± 1.5 vs. 9 ± 1.7 (P = 0.01)], MELD [16.3 ± 5.8 vs. 20.2 ± 6.6 (P = 0.02)] and MELD-Na [18.8 ± 5.9 vs. 22.5 ± 7.1 (P = 0.03)] scores. Median ascitic/pleural fluid total protein [2.7 (2.4–3.1) vs. 1.1 (0.9–1.2); P < 0.0001] and adenosine deaminase (ADA) levels [34.5 (30.3–42.7) vs. 15 (13–16); P < 0.0001] were significantly higher in the TB group. Total protein levels had a sensitivity and specificity 81% and 93.3%, respectively, at cut off value of >2 g/dl with an AUROC of 0.89 [(0.79–0.96); P < 0.001] whereas ADA levels at cutoff >26 IU/L showed 80% sensitivity and 90% specificity to diagnose pleural/peritoneal TB with an AUROC of 0.93 [(0.82–0.97); P < 0.001]. Only 11 (36.7%), and 8 (26.6%) patients showed positivity on GeneXpert and mTB-PCR, respectively. Patients with Child-Turcotte-Pugh scores of ≤7 and 8–10 tolerated well two and one hepatotoxic drugs, respectively. EPTB is more frequent in patients with cirrhosis. Relatively lower cutoffs of ascitic/pleural fluid total protein and ADA may be useful to diagnose EPTB in patients with high pretest probability. Individualized ATT with close monitoring and dynamic modifications is effective and well-tolerated. [ABSTRACT FROM AUTHOR]

Summary: Background: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non‐alcoholic fatty liver disease (NAFLD/MASLD). Aims: We evaluated the performance of machine learning (ML) and non‐patented scores for ruling out SF among NAFLD/MASLD patients. Methods: Twenty‐one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically‐proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological‐SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1‐score as model‐selection criteria). Results: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological‐SF were included in the study. Patients with SFvs.no‐SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p < 0.001, each). ML models showed 7%–12% better discrimination than FIB‐4 to detect SF. Optimised random forest (RF) yielded best NPV/F1 in overall set (0.947/0.754), test set (0.798/0.588) and validation set (0.852/0.559), as compared to FIB4 in overall set (0.744/0.499), test set (0.722/0.456), and validation set (0.806/0.507). Compared to FIB‐4, RF could pick 10 times more patients with SF, reduce unnecessary referrals by 28%, and prevent missed referrals by 78%. Age, AST, ALT fasting plasma glucose, and platelet count were top features determining the SF. Sequential use of SAFE < 140 and FIB4 < 1.2 (when SAFE > 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set). Conclusions: ML with clinical, anthropometric data and simple blood investigations perform better than FIB‐4 for ruling out SF in biopsy‐proven Asian NAFLD/MASLD patients. [ABSTRACT FROM AUTHOR]

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. 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). 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). Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. NCT04238416 (clinicaltrials.gov). • Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with high morbidity and mortality. • Oral branched-chain amino acids (BCAA) are helpful in HE in cirrhosis but role of intravenous BCAA in ACLF is unknown. • We describe the use of intravenous BCAA for HE in ACLF. • IV BCAA given in a short 3-day course helps in early resolution of HE which translated to shorter ICU stay. • The improvement in HE by IV BCAA was not sustained at day 3 or day 7 and there was no 28-day survival benefit. [ABSTRACT FROM AUTHOR]

Summary: Background: Point‐of‐care echocardiography (POC‐Echo) is an essential intensive care hemodynamic monitoring tool. Aims: To assess POC‐Echo parameters [i.e., cardiac index (CI), systemic vascular resistance index (SVRI) and cirrhotic cardiomyopathy (CCM) markers] and serum biomarkers in predicting circulatory failure (need for vasopressors) and mortality in patients with acute‐on‐chronic liver failure (ACLF) having sepsis‐induced hypotension. Methods: We performed serial POC‐Echo within 6 hours (h) of presentation and subsequently at 24, 48 and 72 h in patients with ACLF and sepsis‐induced hypotension admitted to our liver intensive care unit. Clinical data, POC‐Echo data and serum biomarkers were collected prospectively. Results: We enrolled 120 patients [59% men, aged 49 ± 12 years, 56% alcohol‐related disease and median MELDNa of 30 (27–32)], of whom 68 (56.6%) had circulatory failure, with overall mortality of 60%. CCM was present in 52.5%. The predictors of circulatory failure were CI (aHR −1.5; p = 0.021), N‐terminal brain natriuretic peptide (aHR −1.1; p = 0.007) and CCM markers; e′ septal mitral velocity (aHR −0.5; p = 0.039) and E/e′ ratio (aHR −1.2; p = 0.045). Reduction in CI by 20% and SVRI by 15% at 72 h predicted mortality with a sensitivity of 84% and 72%, and specificity 76% and 65%, respectively (p < 0.001). The MELD‐CCM model and CLIF‐CCM model were computed as MELDNa + 1.815 × E/e′ (septal) + 0.402 × e′ (septal) and CLIF‐C ACLF + 1.815 × E/e′ (septal) + 0.402 × e′ (septal), respectively, based on multivariable logistic regression. Both scores outperformed MELDNa (z‐score = −2.073, p = 0.038) and CLIF‐C ACLF score (z score = −2.683, p‐value = 0.007), respectively, in predicting 90‐day mortality. Conclusion: POC‐Echo measurements such as CCM markers (E/e' and e' velocity) and change in CI reliably predict circulatory failure and mortality in ACLF with severe sepsis. CCM markers significantly enhanced the CLIF‐C ACLF and MELDNa predictive performance. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Occlusion of spontaneous portosystemic shunts (SPSSs) in patients with cirrhosis may be required in recurrent or refractory hepatic encephalopathy. We describe a novel method for occlusion of SPSS using endoscopic ultrasound (EUS). METHODS: EUS-guided transgastric shunt obliteration was performed by injecting glue and coils directly into SPSS. RESULTS: EUS-guided transgasric shunt obliteration was performed for 7 patients in 9 sessions. Complete cessation of Doppler flow was achieved in 6/7 cases. Adequate clinical response was observed in 6/7 patients. No procedure-related severe adverse events were seen. DISCUSSION: This novel technique is a potentially effective and efficient method for shunt obliteration. [ABSTRACT FROM AUTHOR]

Background: We evaluated the prevalence, risk factors, and impact of bacterial/fungal infections in acute liver failure (ALF) patients. Methods: We analyzed clinical, biochemical, and microbiological data of ALF patients with and without bacterial/fungal infections admitted at an institute over the last 5 years. Results: We enrolled 143 patients, 50% males, median age 25 years, with acute viral hepatitis (32.2%), drug-induced injury (18.2%), and tropical illness (14%) as aetiologies of ALF. 110 patients (76.9%) developed bacterial/fungal infections [Bacterial infection: MDR: 70%, PDR: 7%, ESBL: 40%, CRE: 30%, CRAB: 26.6%, MDR-EF: 13.3% and fungal infection: 19 (17.3%)]. On univariable analysis, SIRS (33.6% vs.3%), ICU admission (78.2% vs. 45.5%), mechanical ventilation (88.2% vs. 51.5%), inotropes (39.1% vs. 6.1%), invasive catheters (91.8% vs. 39.4%), and prolonged catheterization (6 days vs. 0 days) were significant risk factors for infections (p < 0.05, each). In contrast, SIRS and catheterization independently predicted infection on multivariable regression. Organ failures [3 (2–4) vs. 1 (0–2)], grade-III–IV HE (67.3% vs. 33.3%), circulatory failure (39.1% vs. 6.1%), coagulopathy (INR > 2.5: 58.2% vs. 33.3%), renal injury (28.2% vs. 6.1%) (p < 0.05), MELD (32.9 ± 8.2 vs. 26.7 ± 8.3) and CPIS [3(2–4) vs. 2(0–2)] were higher in infected vs. non-infected patients (p < 0.001). 30-day survival was significantly lower in infected vs. non-infected patients (17.3% vs. 75.8%, p < 0.001), while no patient survived with fungal infections. Refractory septic shock was the commonest cause of mortality in patients. Conclusions: Infections due to MDR organisms are high, fungal infections are fatal, and refractory septic shock is the dominant reason for mortality, implying bacterial and fungal infections as the major killer in ALF patients. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses various reports in the issue on the topics including body mass index, sarcopenia related to increased mortality, and assessment of survival in patients with lung or gastrointestinal cancers.

Background: Terlipressin is a commonly used drug in cirrhotic patients with acute variceal bleed (AVB) due to its vasoconstrictor effects. Ischemic complications are uncommon adverse events associated with worse outcomes. Case presentation: We present a case of alcohol-related cirrhosis, who was started on terlipressin for AVB. However, he developed bilateral lower limb gangrene with ischemic skin necrosis and ultimately succumbed to death. Conclusion: Although ischemic adverse events are uncommon with terlipressin, it is important to be aware of these complications as they may be severe and potentially life threatening. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aims: The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia‐Pacific region. The aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. Methods: A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016. Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography (Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24 weeks. Twenty‐two patients received Sofosbuvir and Ledipasvir and 12 patients received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data were analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. Results: The median baseline HCV RNA concentration in the whole group was 7.38 × 106 IU/mL (1.23 × 104–6.36 × 107). The SVR12 rates were 100% in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient Elastography revealed minimal or no fibrosis (F0‐F1) in 31 (65.96%) patients, moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in five (10.64%) patients. The only serious adverse effect was anaemia observed in eight (57%) patients in the Sofosbuvir and Ribavirin group. Conclusion: DAAs including Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and effective for the treatment of chronic hepatitis C in renal transplant recipients. [ABSTRACT FROM AUTHOR]

Background and Aim: Telemedicine is an evolving tool to provide health‐care services. We evaluated the suitability of telemedicine to deliver effective consultation for hepatobiliary disorders. Methods: In this prospective study spanning over a year, we interviewed hepatologists delivering the teleconsultations through a pre‐validated questionnaire. A consult was deemed suitable based on the physician's judgment in the absence of unplanned hospitalization. We evaluated factors determining the suitability through inferential statistics and machine learning models, namely, extreme gradient boosting (XGB) and decision tree (DT). Results: Of 1118 consultations, 917 (82.0%) were deemed suitable. On univariable analysis, patients with skilled occupation, higher education, out‐of‐pocket expenses, and diseases such as chronic hepatitis B, C, and non‐alcoholic fatty liver disease (NAFLD) without cirrhosis were associated with suitability (P < 0.05). Patients with cirrhosis (compensated or decompensated), acute‐on‐chronic liver failure (ACLF), and biliary obstruction were likely unsuitable (P < 0.05). XGB and DT models predicted suitability with an area under the receiver operating curve of 0.808 and 0.780, respectively. DT demonstrated that compensated cirrhosis with higher education or skilled occupation with age < 55 years had 78% chance of suitability whereas hepatocellular carcinoma, decompensated cirrhosis, and ACLF patients were unsuitable with a 60–95% probability. In non‐cirrhotic liver diseases, hepatitis B, C, and NAFLD were suitable, with a probability of 89.7%. Biliary obstruction and previous failure of teleconsultation were unsuitable, with a probability of 70%. Non‐cirrhotic portal fibrosis, dyspepsia, and dysphagia not requiring intervention were suitable (probability: 88%). Conclusion: A simple decision tree can guide the referral of unsuitable and the management of suitable patients with hepatobiliary diseases through telemedicine. [ABSTRACT FROM AUTHOR]

There is an ongoing debate on the change of terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). Experts from the Indian National Association for Study of the Liver (INASL) and the South Asian Association for Study of the Liver (SAASL) involved in diagnosing, managing, and preventing NAFLD met in March 2022 to deliberate if the name change from NAFLD to MAFLD is appropriate, as proposed by a group of experts who published a "consensus" statement in 2020. Proponents of name change to MAFLD opined that NAFLD does not reflect current knowledge, and the term MAFLD was suggested as a more appropriate overarching term. However, this "consensus" group which proposed the name change to MAFLD did not represent the views and opinions of gastroenterologists and hepatologists, as well as perceptions of patients across the globe, given the fact that change of nomenclature for any disease entity is bound to have multidimensional impact on all aspects of patient care. This statement is the culmination of the participants' combined efforts who presented recommendations on specific issues concerning the proposed name change. The recommendations were then circulated to all the core group members and updated based on a systematic literature search. Finally, all the members voted on them using the nominal voting technique as per the standard guidelines. The quality of evidence was adapted from the Grades of Recommendation, Assessment, Development and Evaluation system. [Display omitted] • INASL–SAASL consensus group was constituted with experts from different parts of India and South Asia. • They participated in a consensus development process on name change of NAFLD, to enable establishment of an updated document on nomenclature of NAFLD. • The INASL–SAASL consensus group felt that proponents of MAFLD neither represented views of hepatologists nor perceptions of patients across the globe. • The group resolved that the term NAFLD should not be changed to MAFLD since there are no cogent reasons to justify a name change. • The INASL–SAASL consensus group also felt that a name change from NAFLD to MAFLD is replete with demerits. [ABSTRACT FROM AUTHOR]