Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent ß-thalassemia intermedia.

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) ß-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11 years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis. Three groups of patients were identified: homozygous ß+ (N = 18), heterozygous ß0ß+ (N = 22), and homozygous ß0 (N = 20). The groups were homogeneous for sex, age, splenectomy, hematochemical parameters, chelation therapy, and iron levels. The homozygous ß° genotype was associated with significantly higher biventricular end-diastolic and end-systolic volume indexes and bi-atrial area indexes. No difference was detected in biventricular ejection fractions or myocardial fibrosis. Extramedullary hematopoiesis and leg ulcers were significantly more frequent in the homozygous ß° group compared to the homozygous ß+ group. No association was detected between genotype and liver cirrhosis, hypogonadism, hypothyroidism, osteoporosis, heart failure, arrhythmias, and pulmonary hypertension. Heart remodelling related to a high cardiac output state cardiomyopathy, extramedullary hematopoiesis, and leg ulcers were more pronounced in patients with the homozygous ß° genotype compared to the other genotypes analyzed. The knowledge of the genotype can assist in the clinical management of NTD ß-TI patients.

Idiopathic mesenteric phlebosclerosis occurring in a patient with liver cirrhosis: A case report.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare gastrointestinal disease with unclear etiology and pathogenesis. IMP occurring in a patient with liver cirrhosis is more scarcely reported than independent IMP. In this study, we reported a case of IMP occurring in a patient with liver cirrhosis, so as to provide a reference for understanding liver cirrhosis with IMP. METHOD: A 63-year-old man with liver cirrhosis was admitted in the hospital's department of infectious disease because of fatigue and constipation for 1 month. The patient had an irregular medical history of antivirus drug and Chinese herbal medicine intake because of the hepatitis B virus infection. No other abnormalities were found in the functions of the liver, coagulation, renal, or complete blood count. Fecal occult blood tests were all positive in 5 detections. Contrast-enhanced computed tomography revealed liver cirrhosis and showed thickening of the wall of the right hemicolon and multiple calcifications of the mesenteric veins. Mesenteric vein computed tomography venography displayed diffuse colon mural thickening of the right colon and tortuous linear calcification line in the right colic veins. Colonoscopy revealed a purple-blue, swollen, rough, and vanished vascular texture mucosa. He was finically diagnosed as liver cirrhosis with IMP by a series of examinations during hospitalization. RESULTS: His symptoms of fatigue and constipation subsided after conservative treatment and withdraw from Chinese herbal medicine. The patient experienced no obvious discomfort during the follow-up period. CONCLUSION: A comprehensive medical diagnosis is necessary for the discovery of IMP, especially IMP with liver cirrhosis. Liver cirrhosis maybe play a key role in the development of IMP. The regulatory mechanism of liver cirrhosis contributing to IMP needs to be further studied based on more clinical cases.

Branched-chain amino acid supplementation does not improve measures of sarcopenia in cirrhosis: results of a randomised controlled trial.

BACKGROUND: Sarcopenia is associated with adverse outcomes in cirrhosis. Branched-chain amino acids (BCAA) target several pathways that lead to muscle loss in this population. AIMS: We aimed to evaluate the impact of BCAA supplementation on sarcopenia measures in patients with cirrhosis. METHODS: We conducted a 12-month double-blinded, randomised, controlled trial of BCAA supplementation (30 g daily) compared to an equicaloric, equi-nitrogenous whey protein in volunteers with cirrhosis and reduced muscle strength. The primary endpoint was an increase in grip strength and upper limb lean mass measured on DEXA. Mean-adjusted differences (MAD, 95% CI) between groups at 6 and 12 months are reported as treatment effect using a linear mixed model for repeated measures. RESULTS: A total of 150 volunteers entered the trial (74 BCAA, 76 control), with a median age of 58 years [IQR 48; 63] and MELD of 14 [12; 17]. At 12 months, 57% in the BCAA arm and 61% in the control arm met the primary endpoint (p = 0.80). No significant between-group difference was found in grip strength (MAD -0.15 kg [-0.37; 0.06], p = 0.29) or upper limb lean mass (1.7 kg [-0.2; 3.6], p = 0.22) at 12 months. No significant differences in other body composition parameters, physical performance, frailty, rates of hospitalisation or mortality were found between the BCAA and the control group. Fatigue improved across the entire cohort, without significant between-group differences. 15% of volunteers reported side effects, with distaste higher in the BCAA arm (p = 0.045). CONCLUSION: BCAA supplementation did not improve measures of muscle strength, mass or performance or physical frailty compared to a whey protein supplement in a randomised controlled setting. ACTRN12618000802202.

A Prospective Open-Label Dose-Response Study to Correct Vitamin D Deficiency in Cirrhosis.

BACKGROUND: Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D3 needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown. OBJECTIVE: We aimed to establish the dose-response relationship between vitamin D3 and 25(OH)D in patients with liver cirrhosis. DESIGN: An open-label study of orally-administered vitamin D3 (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717). Supplementation continued for 6 months, or until liver transplantation. Changes in 25(OH)D were measured after ≥ 3 months. Dose-response data on 48 patients (21 receiving 4000 IU/d and 27 receiving 2,000 IU/d) reporting ≥ 80% adherence were analyzed using generalized estimating equations (GEE). RESULTS: Among the 48 patients, 39 (81%) had 25(OH)D > 20 ng/mL while on supplements, and none experienced hypercalcemia. The magnitude of the increase in 25(OH)D was approximately twofold greater in patients receiving the higher dose. The mean incremental increase was 5.1 ng/ml ± 3.9 of 25(OH)D per 1000 IU/d of vitamin D3. Multivariable models demonstrated a significant positive relationship between baseline 25(OH)D and serum albumin (p < 0.01) and hemoglobin (p = 0.01), and a negative relationship with the MELD score (p < 0.01) and total bilirubin (p < 0.01). CONCLUSIONS: A two-tiered dosing regimen of daily oral vitamin D3 supplementation safely raised 25(OH)D concentrations in the majority of adults with liver cirrhosis who were adherent to supplement use.

Evaluation of Vitamin D Levels in Children With Liver Transplant.

OBJECTIVES: Vitamin D deficiency is common in pediatric chronic liver disease despite oral replacement. We evaluated vitamin D deficiency before and after liver transplant and the relationship between posttransplant and pretransplant vitamin D deficiency and graft rejection. MATERIALS AND METHODS: Pediatric recipients with chronic liver disease (N =138) were divided into 4 groups: cholestatic liver diseases, cirrhosis, metabolic disorders, and acute liver failure. Pretransplant and posttransplant vitamin D levels, liver function tests, Pediatric End-Stage Liver Disease scores, rejection activity index scores by graft liver biopsy, and posttransplant patient survival were recorded. RESULTS: There were 62 (45%) female and 76 (55%) male participants (mean transplant age, 6.1 ± 5.6 years). Pretransplant mean available vitamin D of 90 patients was 25.2 ± 20.9 ng/mL, with 36 (40%) within reference range. Posttransplant level for 109 patients was 27.3 ± 18 ng/mL, with 64 (58.7%) within reference range. Pretransplant and posttransplant levels were available for 61 patients, and mean pretransplant levels were lower than posttransplant levels (23.7 ± 19.3 vs 28.3 ± 16.9 ng/mL; P = .01). Patients with cholestatic liver disease had lower pretransplant vitamin D levels (P = .04), which disappeared after transplant. Pretransplant vitamin D levels were positively correlated with serum albumin levels (r = 0.20) in all patients and negatively correlated with total/direct bilirubin (r = 0.29 and r = -0.30) in those with liver diseases and cirrhosis. No correlations were found between pretransplant vitamin D levels and Pediatric End-Stage Liver Disease scores, rejection activity index scores, and posttransplant mortality. CONCLUSIONS: Vitamin D deficiency is prevalent in pediatric chronic liver disease before and after transplant, especially for cholestatic liver diseases. However, no association between vitamin D levels and liver graft rejection or patient survival was noted. We recommend close monitoring and individualized vitamin D supplementation before and after liver transplant.

A Correlation Analysis Between Adult Hepatic Fibrosis and Bone Mineral Density of the Lumbar Spine and Hip.

Context: Osteoporosis (OP) is a common complication for patients who have liver cirrhosis or cholestatic liver disease or who have received a liver transplantation. Osteoporotic fractures are serious clinical consequences of OP, and they often occur in the spine, hip, and wrist; have a high disability and mortality rate; cause a serious, social, medical burden; and threaten people's health. Objective: The study intended to explore the correlation between different degrees of liver fibrosis and bone mineral density (BMD) of the lumbar spine and hip as well as the factors influencing those differences. Design: The research team performed a retrospective observational study. Setting: The study took place at the First Affiliated Hospital of the Medical College at Ningbo University (Bund Courtyard) in Ningbo, China. Participants: Participants were 164 patients who had received two-dimensional shear wave elastography (2D-SWE) to measure liver stiffness and dual-energy X-ray absorptiometry (DEXA) to measure bone density at the First Affiliated Hospital of Ningbo University (Bund Courtyard) in Ningbo from May 2020 to April 2022. Groups: According to the liver-stiffness value, the research team divided participants into three groups: (1) the F0-F1 group with no or mild liver fibrosis, (2) the F2 group with significant liver fibrosis, and (3) F3-F4 group with severe liver fibrosis. For the three groups, the research team also compared the differences between the groups-F0-F1 to F2, F0-F1 to F3-F4, and F2 to F3-F4-in the BMD of the lumbar spine-Total, L2, L3, L4-and of the hip-Total, Neck, and Troch. Outcome Measures: The research team: (1) determined participants' degrees of liver fibrosis to create the F0-F1, F2, and F3-F4 groups and compared the BMDs of the lumbar spine and hip among those groups; (2) compared the degrees of liver fibrosis for three age groups-<40, 40-60, and ≥60 years old; (3) compared the degrees of liver fibrosis for participants with two etiologies of the disease-hepatitis or other causes; and (4) analyzed the correlations between different degrees of liver fibrosis and BMD of the lumbar spine and hip and the factors influencing those relationships. Results: The study revealed significant differences among the F0-F1, F2, and F3-F4 groups in terms of age group, degree of liver fibrosis, and bone mineral density (BMD) at various sites. Specifically, there were significant age group differences between individuals aged 40-60 years and those aged ≥60 years (P < .05). There were also significant differences noted in the degree of liver fibrosis with mean values of 5.59 ± 0.81, 7.43 ± 0.26, and 15.48 ± 10.02 for the F0-F1, F2, and F3-F4 groups, respectively (P < .05). The BMDs of the lumbar spine (L2, L3, L4, and Total values) and hip (Total values, right femoral neck (Neck), and trochantor (Troch)) showed significant differences (all P < .05). However, no significant differences were found in the BMDs for the L1 vertebra and Ward's triangle among the groups (both P > .05). The analysis also revealed that the mean BMDs of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups. Furthermore, there was a positive correlation between the F2 and F0-F1 groups and a negative correlation between the F2 and F3-F4 groups (P < .05). The logistic regression analysis showed that age group (OR = 2.047, 95% CI: 0.135-1.298, P = .016) and Total BMD for the hip (OR = 176.368, 95% CI: 0.233-10.112, P = .040) were significantly, independently correlated with the degree of liver fibrosis. Conclusions: According to the findings of the present study, a positive correlation was observed between liver stiffness and bone mineral density (BMD) values in patients at the F0-F1 to F2 stage of liver fibrosis. In contrast, a significant negative correlation was identified between these parameters in patients at the F2 to F3-F4 stage, indicating that BMD tends to decrease as the degree of liver fibrosis increases. These results suggest a potential link between liver fibrosis and bone health. The comparisons between groups F0-F1 and F3-F4 with group F2. Specifically, the study found that the BMD values of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups.

An Emulated Clinical Trial of Deprescribing Proton Pump Inhibitors in Patients With Cirrhosis.

INTRODUCTION: Proton pump inhibitors (PPI) are overused and carry harms in cirrhosis. Deprescribing is advocated but has not been trialed. METHODS AND FINDINGS: We emulated a clinical trial using Medicare data. All patients were receiving chronic PPI therapy before a compensated cirrhosis diagnosis. We compared the risk death/decompensation over 3 years between continuous users and deprescribers. We find that PPI deprescription is associated with less ascites and that cumulative PPI use is associated with more ascites and encephalopathy. Ultimately, 71% of deprescribers restart PPIs. DISCUSSION: PPI deprescribing has benefits but requires ongoing support and alternative therapies for gastrointestinal symptoms.

The association of testosterone with sarcopenia and frailty in chronic liver disease.

BACKGROUND: Testosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin-bound, or sex hormone binding globulin (SHBG)-bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic-pituitary-gonadal axis, leading to diminished levels of free testosterone and hypogonadism. METHODS: We retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre-cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non-cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients. RESULTS: Low testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long-term safety of testosterone use remains an open question. CONCLUSION: Low serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver-related outcomes and complications.

Effects of Psychological Nursing Combined with Comprehensive Nursing on Gastrointestinal Bleeding and Nutritional Status in Cirrhosis.

Objective: Cirrhosis of the upper GIB is a surgical emergency, PN and CN can reduce the risk of gastrointestinal bleeding, but there is a lack of analysis on PN combined with CN in Cirrhotic patients. This work explored the effects of psychological nursing (PN) combined with comprehensive nursing (CN) on gastrointestinal bleeding (GIB) and nutritional status of patients with cirrhosis. Methods: Total 80 patients with GIB and cirrhosis who received emergency treatment in the Affiliated Hospital of Shaoxing University from October 2019 to October 2022 were randomly rolled into two groups. Patients in the control group (Ctrl group) received CN (n = 40 cases), and those in the experimental group (Exp group) received PN combined CN (n = 40 cases). The Model for end-stage liver disease (MELD) score, self-rating anxiety scale (SAS), self-rating depression scale (SDS), SCL-90, complication rate, and nursing satisfaction of patients from different groups were analyzed and compared. MELD score effectively predicts short - and medium-term mortality in end-stage liver disease. SAS consisted of 20 questions related to anxiety symptoms, four-level scoring method was adopted. The SCL-90 scale included four aspects: somatic symptoms, interpersonal relationships, psychological emotions, and psychological needs. Results: The results disclosed that after nursing intervention, SAS, SDS, and MELD scores in the Exp group were remarkably lower than those in the Ctrl group (P < .05). The scores of SCL-90 somatic symptoms, interpersonal relationships, psychological emotion, and psychological needs of participants in the Exp group were much lower than those in the Ctrl group (P < .05). The complication rate was significantly lower in the Exp (30.0%) than in the Ctrl groups (72.5%) (P < .05). The total nursing satisfaction was increased, and it is significan higher in the Exp group (97.5%) than control group (87.5% ) (P < .05). Conclusions: In conclusion, PN combined with CN could effectively reduce the incidence of complications in patients with GIB and cirrhosis and improve nursing satisfaction. Therefore, such a method was worth promoting, which provides a reference for the clinical diagnosis and treatment of patients with GIB and cirrhosis.

Use of Branched-Chain Amino Acids as a Potential Treatment for Improving Nutrition-Related Outcomes in Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) represents a complex and multifactorial clinical entity characterized by liver dysfunction and associated complications. In recent years, the significance of nutritional status in ACLD prognosis has gained considerable attention. This review article delves into the multifactorial pathogenesis of malnutrition in ACLD and its profound consequences for health outcomes. We explore the clinical implications of secondary sarcopenia in ACLD and highlight the critical relevance of frailty in both decompensated and compensated ACLD. A specific focus of this review revolves around branched-chain amino acids (BCAAs) and their pivotal role in managing liver disease. We dissect the intricate relationship between low Fischer's ratio and BCAA metabolism in ACLD, shedding light on the molecular mechanisms involved. Furthermore, we critically evaluate the existing evidence regarding the effects of BCAA supplementation on outcomes in ACLD patients, examining their potential to ameliorate the nutritional deficiencies and associated complications in this population.

Management of minimal and overt hepatic encephalopathy with branched-chain amino acids: a review of the evidence.

Hepatic encephalopathy (HE) is a challenging complication of liver disease that is associated with substantial morbidity and mortality. Branched-chain amino acid (BCAA) supplementation in the management of HE is a debated topic. This narrative review aims to provide an up-to-date review of the topic and includes studies featuring patients with hepatocellular carcinoma. A review of the literature was performed using the online databases MEDLINE and EMBASE for studies between 2002 and December 2022. Keywords 'branched-chain amino acids', 'liver cirrhosis' and 'hepatic encephalopathy' were used. Studies were assessed for inclusion and exclusion criteria. Of 1045 citations, 8 studies met the inclusion criteria. The main outcomes reported for HE was changed in minimal HE (MHE) (n = 4) and/or incidence of overt HE (OHE) (n = 7). Two of the 4 studies reporting on MHE had improvement in psychometric testing in the BCAA group, but there was no change in the incidence of OHE in any of the 7 papers in the BCAA group. There were few adverse effects of BCAA supplementation. This review found weak evidence for BCAA supplementation for MHE, and no evidence for BCAAs for OHE. However, given the relative paucity and methodological heterogeneity of the current research, there is scope for future studies to examine the effects of varying timing, dosage, and frequency of BCAAs on outcomes such as HE. Importantly, research is also needed to examine BCAAs in conjunction with standard therapies for HE such as rifaximin and/or lactulose.

Successful Treatment of Cirrhotic Chylous Ascites using Orlistat and Dietary Modifications: A Case Study and Literature Review.

BACKGROUND Chylous ascites (chyloperitoneum), a condition arising from lymphatic leakage in the peritoneal cavity, is rare in liver cirrhosis patients, accounting for less than 1% of cases. Treatment typically involves therapeutic paracentesis, dietary modifications, a low-fat, high-protein diet, and medium-chain triglyceride (MCT) supplementation. Orlistat, a fat absorption inhibitor, has been reported to show potential efficacy in treating chylous ascites. CASE REPORT We detail the case of a 59-year-old male patient admitted for decompensated liver disease and worsening ascites. Diagnostic paracentesis identified chylous ascites, indicated by a 3.5 mmol/L triglyceride level. Despite administering therapeutic paracentesis, dietary modifications, MCT supplementation, Spironolactone, and Terlipressin for a presumed hepatorenal syndrome, the patient's ascites remained chylous for two weeks. On administering orlistat, a significant reduction in ascites volume and chylous content was observed, with triglyceride levels dropping to 0.7 mmol/L. CONCLUSIONS Our case illustrates the potential of orlistat in managing chylous ascites in liver cirrhosis patients, marking only the second such case reported in the existing literature. It encourages further exploration of orlistat's therapeutic potential in treating chylous ascites.

Nutritional therapy for persistent cognitive impairment after resolution of overt hepatic encephalopathy in patients with cirrhosis: A double-blind randomized controlled trial.

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) reflects cognitive impairment in patients with liver cirrhosis and is associated with poor prognosis. We assessed the effects of nutritional therapy on cognitive functions, health-related quality of life (HRQOL), anthropometry, endotoxins, and inflammatory markers in cirrhotic patients with MHE. METHODS: In a double-blind randomized controlled trial, cirrhotic patients with MHE were randomized to nutritional therapy (group I: 30-35 kcal/kg/day and 1.0-1.5 g of protein/kg/day) and no nutritional therapy (group II: diet as patients were taking before) for 6 months. MHE was diagnosed based on psychometric hepatic encephalopathy score (PHES). Anthropometry, ammonia, endotoxins, inflammatory markers, myostatin, and HRQOL were assessed at baseline and after 6 months. Primary endpoints were improvement or worsening in MHE and HRQOL. RESULTS: A total of 150 patients were randomized to group I (n = 75, age 46.3 ± 12.5 years, 58 men) and group II (n = 75, age 45.2 ± 9.3 years, 56 men). Baseline PHES (-8.16 ± 1.42 vs -8.24 ± 1.43; P = 0.54) was comparable in both groups. Reversal of MHE was higher in group I (73.2% vs 21.4%; P = 0.001) than group II. Improvement in PHES (Δ PHES 4.0 ± 0.60 vs -4.18 ± 0.40; P = 0.001), HRQOL (Δ Sickness Impact Profile 3.24 ± 3.63 vs 0.54 ± 3.58; P = 0.001), anthropometry, ammonia, endotoxins, cytokines, and myostatin levels was also significantly higher in group I than group II. Overt hepatic encephalopathy developed in 6 patients in group I and 13 in group II (P = 0.04). CONCLUSIONS: Nutritional therapy is effective in treatment of MHE and associated with improvement in nutritional status, HRQOL, ammonia, endotoxins, inflammatory markers, and myostatin levels.

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis. METHODS: This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed. RESULTS: Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment. CONCLUSION: BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

Sarcopenia and Frailty in Cirrhosis: Assessment and Management.

Sarcopenia and frailty are frequent in cirrhosis, and both contribute to increased morbidity and mortality. The complex pathogenesis of sarcopenia in cirrhosis is mainly determined by hyperammonemia and malnutrition. Sarcopenia/frailty screening and reevaluation should be undertaken in all cirrhotic patients. Frailty tests are useful in the ambulatory setting, whereas the computed tomography scan is the diagnostic gold standard for sarcopenia. To manage sarcopenia/frailty, a multidisciplinary team should develop a personalized comprehensive care plan that includes patient education, protein/calorie intake goals, late evening meals, exercise programs, and micronutrient replenishment. In selected patients, branched-chain amino acid and testosterone supplements may also be beneficial.

Clinical outcomes associated with complementary and alternative medicine-related "immunity-boosting" practices in patients with cirrhosis during the COVID-19 pandemic - an observational study.

During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden.

Update in the Treatment of the Complications of Cirrhosis.

Cirrhosis consists of 2 main stages: compensated and decompensated, the latter defined by the development/presence of ascites, variceal hemorrhage, and hepatic encephalopathy. The survival rate is entirely different, depending on the stage. Treatment with nonselective ß-blockers prevents decompensation in patients with clinically significant portal hypertension, changing the previous paradigm based on the presence of varices. In patients with acute variceal hemorrhage at high risk of failure with standard treatment (defined as those with a Child-Pugh score of 10-13 or those with a Child-Pugh score of 8-9 with active bleeding at endoscopy), a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) improves the mortality rate and has become the standard of care in many centers. In patients with bleeding from gastrofundal varices, retrograde transvenous obliteration (in those with a gastrorenal shunt) and/or variceal cyanoacrylate injection have emerged as alternatives to TIPS. In patients with ascites, emerging evidence suggests that TIPS might be used earlier, before strict criteria for refractory ascites are met. Long-term albumin use is under assessment for improving the prognosis of patients with uncomplicated ascites and confirmatory studies are ongoing. Hepatorenal syndrome is the least common cause of acute kidney injury in cirrhosis, and first-line treatment is the combination of terlipressin and albumin. Hepatic encephalopathy has a profound impact on the quality of life of patients with cirrhosis. Lactulose and rifaximin are first- and second-line treatments for hepatic encephalopathy, respectively. Newer therapies such as L-ornithine L-aspartate and albumin require further assessment.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Low 25 (OH) vitamin D levels are associated with increased prevalence of nonalcoholic fatty liver disease and significant liver fibrosis.

AIMS: Evidence on the role of 25-Hydroxyvitamin D (25(OH)D) in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) is conflicting and population-based data are scarce. Here, we assess the association between 25(OH)D levels, NAFLD and liver fibrosis in the general population. MATERIALS AND METHODS: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included adult participants with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. 25(OH)D was measured by high performance liquid chromatography-tandem mass spectrometry. RESULTS: A total of 3970 participants (1928 men and 2042 women) were included in the study. The prevalence of NAFLD (CAP ≥ 274 dB/m) and significant liver fibrosis (LSM ≥ 8 kPa) were 41.7% (95% CI 39.4-44.0) and 8.4% (95% CI 7.0-9.9), respectively, while 21.1% (95% CI 17.3-25.4) of participants had low 25(OH)D levels (<50 nmol/L). A multivariable logistic regression model adjusted for age, sex, race-ethnicity, body mass index, waist circumference, calendar period, diabetes, chronic kidney disease, and vitamin D supplementation showed that compared with participants with low 25(OH)D, those with optimal levels (≥75 nmol/L) had lower odds of both NAFLD (OR 0.73, 95% CI 0.55-0.98 p = 0.038) and significant liver fibrosis (OR 0.65, 95% CI 0.44-0.96, p = 0.033). CONCLUSIONS: An inverse relationship was found between 25(OH)D and NAFLD and fibrosis, suggesting a possible role of vitamin D in NAFLD occurrence and progression.

Case Report: Nyctalopia Due to Severe Liver Cirrhosis-induced Vitamin A Deficiency.

SIGNIFICANCE: Vitamin A is a micronutrient critical for retinal function. Patients with a deficiency may notice a progressive decline in night vision as rod photoreceptors become unable to regenerate rhodopsin. Although uncommon in developed nations, vitamin A deficiency should be considered in symptomatic patients with chronic, severe liver disease. PURPOSE: This report presents a rare case of night blindness secondary to poor vitamin A metabolism due to severe liver cirrhosis. CASE REPORT: A 62-year-old White woman presented with progressively worsening vision in dim lighting over the past 6 to 8 months. She was asymptomatic in daylight but "blind in the dark" to the extent that she was afraid to go outside at night. She had no personal or family history of night blindness or retinal disorders. Ocular health was unremarkable with dilation. Given her medical history of severe nonalcoholic liver cirrhosis, malabsorption of vitamin A was suspected and subsequently confirmed by the very low vitamin A level in her serum analysis. The patient was sent to endocrinology for evaluation, and appropriate repletion therapy was implemented. Subjective improvement in symptoms, along with better performance on visual field testing, was noted after initiating oral vitamin A supplementation for 5 months. CONCLUSIONS: Although vitamin A deficiency is a relatively rare disorder in the United States, it should be suspected in patients with severe liver disease or other conditions causing malabsorption who experience a loss of night vision.