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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]

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]

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]

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]

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. 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. 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). The prevalence of frailty in patients with cirrhosis is high, leading to poor outcomes. Frailty assessment should become an integral part of cirrhosis evaluation. PROSPERO 2022 CRD42022377507. [Display omitted] [ABSTRACT FROM AUTHOR]

This study delved into cirrhosis-related infections to unveil their epidemiology, risk factors, and implications for antimicrobial decisions. 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. 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). 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [Display omitted] [ABSTRACT FROM AUTHOR]