Complementary and alternative medicines and liver disease.

Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations include asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, acute cholestatic liver disease (bland or with hepatitis), acute liver failure, severe hepatitis with features of portal hypertension, and acute decompensation of known or unknown cirrhosis that can lead to acute-on-chronic liver failure. Acute hepatitis with or without necrosis, hepatocellular and canalicular cholestasis, herb-induced or CAM-triggered autoimmune hepatitis, granulomatous hepatitis, severe steatohepatitis, and vanishing bile duct syndrome are common liver biopsy findings in CAM-DILI. The presence of preexisting liver disease predicts severe liver injury, risk of progression to liver failure, and decreased transplant-free survival in patients with CAM-DILI. This review discusses global epidemiology and trends in CAM-DILI, clinical presentation, assessment and outcomes, commonly emerging threats in the context of hepatotoxic herbs, pragmatic assessment of "liver beneficial" herbs and health care myths, patient communication, regulatory framework, and future directions on research in CAM.

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats.

BACKGROUND: Melissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation. METHODS: Hyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-ß1) were determined. RESULTS: MO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes' activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-ß1/Smad pathway. CONCLUSION: Accordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

Use of complementary and alternative medicine in children affected by oncologic, neurologic and liver diseases: a narrative review.

Complementary and alternative medicine (CAM) consist of a broad group of restorative resources often linked to existing local cultures and established health care systems and are also increasingly used in children with some serious illnesses. In this narrative review, we examine the epidemiology of the use, efficacy, and safety of complementary and alternative medicine in pediatric oncology, neurology, and hepatology. We searched for relevant articles published in Pubmed evaluating CAM use and its efficacy in safety in children affected by oncologic, neurologic and liver diseases. CAM is used to improve the success of conventional therapies, but also to alleviate the pain, discomfort, and suffering resulting from the diseases and their treatment, which are often associated with a significant burden of adverse effects. CAM use must be evaluated in children with neurological, oncological and liver diseases.

Liver Disease and Cell Therapy: Advances Made and Remaining Challenges.

The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for alternative therapies. Mesenchymal stromal cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties have therefore emerged as a promising therapeutic agent in treating inflammatory liver disease. Significant strides have been made in exploring their biological activity. Clinical application of MSC has shifted the paradigm from using their regenerative potential to one which harnesses their immunomodulatory properties. Reassuringly, MSCs have been extensively investigated for over 30 years with encouraging efficacy and safety data from translational and early phase clinical studies, but questions remain about their utility. Therefore, in this review, we examine the translational and clinical studies using MSCs in various liver diseases and their impact on dampening immune-mediated liver damage. Our key observations include progress made thus far with use of MSCs for clinical use, inconsistency in the literature to allow meaningful comparison between different studies and need for standardized protocols for MSC manufacture and administration. In addition, the emerging role of MSC-derived extracellular vesicles as an alternative to MSC has been reviewed. We have also highlighted some of the remaining clinical challenges that should be addressed before MSC can progress to be considered as therapy for patients with liver disease.

Hepatic dysfunction in patients receiving intravenous lipid emulsions.

PURPOSE OF REVIEW: Until recently, intravenous lipid emulsions (ILEs) have consisted of soybean oil (SO) only. This review addresses recent developments in the field, including the problem of intestinal failure associated liver disease (IFALD) that can occur with the use of ILEs in children and adults, and newer ILEs that may minimize and reverse IFALD. RECENT FINDINGS: Cholestasis is the primary manifestation of IFALD in premature infants receiving ILEs, whereas in older children and adults, steatosis is predominant. Two alternative ILEs have been extensively investigated for both safety and efficacy. SMOF, an ILE containing medium chain triglyceride, soybean oil, olive oil and fish oil (FO), is now widely used in both children and adults. A newer FO ILE is approved for use in children only. However, in case reports FO ILE has been shown to improve IFALD in adults. A number of new studies suggest that cholestasis from ILEs is dose-related. IFALD does not improve in many patients after transition from SO to SMOF, but partial or complete replacement with FO can halt and reverse IFALD. SUMMARY: Adverse hepatic effects from ILEs are to some extent dose-related. Overfeeding with fat or with carbohydrate, or simply providing excessive calories in general, may be responsible. More research is needed investigating dose-related effects of macronutrients on liver injury.

Incidence and development of cholestasis in surgical neonates receiving an intravenous mixed-oil lipid emulsion.

BACKGROUND: Intestinal failure-associated liver disease (IFALD), initially manifesting as cholestasis, is a complication in neonates receiving parenteral nutrition (PN). Soybean oil lipid emulsion (SOLE), though implicated in IFALD, was the only US Food and Drug Administration (FDA)-approved initial intravenous lipid emulsion (ILE) for infants and children in the United States. A mixed-oil lipid emulsion (MOLE) gained popularity in patients at risk for IFALD and was recently FDA approved as an initial ILE in children. Given the presence of soybean oil in MOLE, we hypothesized that MOLE would not be effective at preventing cholestasis in surgical neonates. METHODS: Neonates with gastrointestinal surgical conditions necessitating PN for ≥14 days and receiving MOLE (SMOFlipid) from July 2016 to July 2019 were analyzed retrospectively. Unpaired and pair-matched historical surgical neonates treated with SOLE (Intralipid) served as controls. The primary outcome measure was development of cholestasis (direct bilirubin ≥2 mg/dl). RESULTS: Overall, 63% (10 of 16) of MOLE patients and 22% (30 of 136) of SOLE patients developed cholestasis after ≥14 days of therapy (P = 0.005). The latency to developing cholestasis was significantly shorter in MOLE patients compared with SOLE patients. CONCLUSION: In surgical neonates, MOLE may not prevent cholestasis and should not be considered hepatoprotective. Regardless of ILE source, all surgical neonates should be closely monitored for development of IFALD. To date, there is still no ILE able to prevent IFALD.

Liver disease in adolescents.

In this article, we discuss common liver diseases in the adolescent population. We describe the initial evaluation of an adolescent presenting with new-onset liver enzyme abnormalities, based on the clinical history and physical examination. The management approach to the adolescent with liver disease is exemplified, including monitoring for adherence, risk-taking behaviours and focusing on psychosocial aspects of their care. Finally, we highlight the challenges of caring for the adolescent patient and the importance of addressing not only the liver disease but, more importantly, the holistic approach towards their management.

Current practices in lipid emulsion utilization in the prevention and treatment of intestinal failure-associated liver disease: A survey of pediatric intestinal rehabilitation and transplant centers.

BACKGROUND: Newer intravenous lipid emulsions (ILEs), such as fish oil-based intravenous lipid emulsions (FO-ILEs) and soybean oil, medium-chain triglycerides, olive oil, and fish oil-based intravenous lipid emulsions (SMOF-ILEs), provide alternatives to soybean oil-based intravenous lipid emulsions (SO-ILEs). We explored current ILE practice patterns among intestinal rehabilitation and transplant centers. METHODS: A survey was developed addressing ILE availability, ILE preference in clinical scenarios, and factors influencing ILE choice. This survey was reviewed locally and by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Intestinal Rehabilitation Special Interest Group, the Intestinal Rehabilitation and Transplant Association scientific committee, and the American Society of Parenteral and Enteral Nutrition pediatric intestinal failure section research committee. We recruited providers nationally and internationally from centers with and without intestinal transplant programs. RESULTS: We included 34 complete responses, 29 from the United States. Sixteen centers performed intestinal transplants. All centers had access to SMOF-ILEs, 85% had access to FO-ILEs, and 91% had access to SO-ILEs. In new patients, 85% use SMOF-ILEs as the first choice ILE. In those with new intestinal failure-associated liver disease (IFALD), FO-ILE was preferred to SMOF-ILE (56% vs 38%). In those developing IFALD on SMOF-ILE, 65% switched to FO-ILE, whereas 24% remained on SMOF-ILE. CONCLUSIONS: Centers have routine access to alternative ILEs, and these are quickly replacing SO-ILEs in all circumstances. Future work should focus on how this shift in practice affects outcomes to provide decision support in specific clinical scenarios.

COVID-19 and liver dysfunction: What nutritionists need to know.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 has brought serious challenges for the medical field. Patients with COVID-19 usually have respiratory symptoms. However, liver dysfunction is not an uncommon presentation. Additionally, the degree of liver dysfunction is associated with the severity and prognosis of COVID-19. Prevention, diagnosis, and treatment of malnutrition should be routinely recommended in the management of patients with COVID-19, especially in those with liver dysfunction. Recently, a large number of studies have reported that nutrition therapy measures, including natural dietary supplements, vitamins, minerals and trace elements, and probiotics, might have potential hepatoprotective effects against COVID-19-related liver dysfunction via their antioxidant, antiviral, anti-inflammatory, and positive immunomodulatory effects. This review mainly focuses on the possible relationship between COVID-19 and liver dysfunction, nutritional and metabolic characteristics, nutritional status assessment, and nutrition therapy to provide a reference for the nutritionists while making evidence-based nutritional decisions during the COVID-19 pandemic.

Intestinal failure-associated liver disease in the neonatal ICU: what we know and where we're going.

PURPOSE OF REVIEW: Parenteral nutrition is an integral part of the care of infants in the neonatal ICU. However, prolonged use of parenteral nutrition can be associated with adverse outcomes, most notably parenteral nutrition-associated liver disease, now known as intestinal failure-associated liver disease (IFALD). This review highlights pertinent developments in the epidemiology of IFALD as it pertains to neonates and showcases recent advances in the pathophysiology, treatment, and outcomes of neonates with IFALD. RECENT FINDINGS: The role of intravenous lipid emulsions in the pathogenesis, prevention, and treatment of IFALD remains a target for investigative studies. Recent data continues to support the use of fish-oil based intravenous lipids, but its use is limited due to concerns for essential fatty acid deficiency. Use of soy-based lipids and mixed lipids is not wrought with such concerns as these are often used at greater doses but their use is limited due to higher proinflammatory fatty acid content, increased phytosterols and decreased antioxidants, risk factors for the development of IFALD. SUMMARY: Hepatic complications may limit the use of parenteral nutrition in the neonatal ICU. However, the pathophysiology of IFALD is continuing to be further elucidated and novel targets are being developed for the treatment of IFALD. As noninvasive disease monitoring strategies continue to be developed, early enteral nutrition ameliorates the risk of IFALD and should be considered when possible.

Biological therapies in patients with liver disease: are they really lifesavers?

INTRODUCTION: The liver plays a key role in the setting of immune tolerance. Targeting antigens for presentation by antigen-presenting cells in the liver can induce immune tolerance to either autoantigens from the liver itself or organs outside of the liver. Despite its non-conventional capacity for tolerance induction, the liver remains a target organ for autoimmune diseases. Whereas chronic inflammation and intra-hepatic immuno-suppressive microenvironment occurring during liver fibrosis lead to hepatocellular carcinoma. Monoclonal antibodies have revolutionized the therapeutic strategies of many autoimmune diseases and some cancers. AREAS COVERED: We review data from literature regarding the safety and efficacy of biologics in treating hepatobiliary autoimmune diseases and primary liver cancers. Furthermore, we describe their potential use in the setting of liver transplants and their main immune-related liver adverse events. EXPERT OPINION: Biological therapies have changed the natural history of main autoimmune diseases and solid cancers. Compared to other organs and disease settings, the liver lags behind in biologics and their applications. The development of novel diagnostic and therapeutic strategies based on the immunological and antigenic characteristics of the hepatobiliary system could reduce mortality and transplant rates linked to chronic liver diseases.

Zinc supplementation and its benefits in the management of chronic liver disease: An in-depth literature review.

Malnutrition among patients with chronic liver disease (CLD) is a common complication with significant prognostic implications for patients with liver cirrhosis. Micronutrient deficiency has been associated with an increased risk of hepatic decompensation and is an independent risk factor for mortality among cirrhotic patients. Micronutrient deficiencies in patients with CLD include zinc, vitamin A, vitamin D and selenium. This review article aims to evaluate the literature to date on the complications of zinc deficiency in patients with CLD. A management algorithm for zinc replacement has also been proposed.

Human Pluripotent Stem Cell-Derived Hepatocyte-Like Cells and Organoids for Liver Disease and Therapy.

Liver disease is a global health issue that has caused an economic burden worldwide. Organ transplantation is the only effective therapy for end-stage liver disease; however, it has been hampered by a shortage of donors. Human pluripotent stem cells (hPSCs) have been widely used for studying liver biology and pathology as well as facilitating the development of alternative therapies. hPSCs can differentiate into multiple types of cells, which enables the generation of various models that can be applied to investigate and recapitulate a range of biological activities in vitro. Here, we summarize the recent development of hPSC-derived hepatocytes and their applications in disease modeling, cell therapy, and drug discovery. We also discuss the advantages and limitations of these applications and critical challenges for further development.

[Hepatic glycogen storage diseases: Symptoms, management and associated mutations]. / Enfermedades por depósito de glucógeno hepático: Clínica, manejo y mutaciones asociadas.

Glycogen storage diseases (GSD) are rare diseases derived from altered glycogen metabolism. This leads to glycogen storage in different organs such as muscle, kidney, and liver, resulting in a variety of clinical manifestations. GSD with liver involvement are classified into types I, III, IV, VI, and IX, depending on the enzymes affected. They are clinically characterized by hypoglycemia and hepato megaly as cardinal signs. Their diagnosis is initially based on clinical manifestations and laboratory test results. Nevertheless, diagnostic certainty requires a genetic study that identifies the specific mutation. Multiple mutations have been associated with each GSD. In Chile, since patients often lack the genetic study, the GSD genetic local characteristics are unknown. The treatment is based on dietary restrictions modulated according to the identified mutation. Today, the international consen sus indicates that early diagnosis allows better metabolic control and improves the patient's quality of life and prognosis. In this review, the information on GSD with liver involvement is updated to optimize the diagnosis, treatment, and follow-up of these patients, emphasizing specific nutritional and gastroenterological management.

Liver injury in COVID-19: clinical features and treatment management.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread to many countries around the world. In addition to lung disease, severe cases also displayed varying degrees of liver injury. This article will describe the latest developments regarding coronavirus and the pathogenesis of liver injury, the prone population and clinical characteristics of these patients, as well as providing some suggestions for clinical treatment.

Clinical study on acupuncture treatment of hypertension with hyperactivity of liver yang.

INTRODUCTION: Hypertension can lead to different degrees complications of cardiovascular and cerebrovascular, and increase the risk of sudden death. Acupuncture has become a complementary alternative therapy for hypertension because of its antihypertensive and nontoxic side effects. However, there is still lack of evidence-based medicine evidence for an effective acupuncture antihypertensive prescription. The purpose of this study is to evaluate the effect of a special acupuncture prescription on hypertension with hyperactivity of liver yang. METHODS: In this randomized controlled trial, we will recruit 56 hypertensive patients with hyperactivity of liver yang. Then the patients will be randomly divided into control group and experimental group. The control group will be treated with western medicine, and the experimental group will be treated with medicine combined with acupuncture. The intervention will last 4 weeks. The indices will be collected before acupuncture, after acupuncture, and 2 weeks after acupuncture. The primary outcome will be 24-hour ambulatory blood pressure. The secondary outcomes will be clinic blood pressure, anxiety and depression score, and the syndrome score of hyperactivity of liver yang. The auxiliary indicators will be blood pressure load values and salt sensitivity risk rate. The exploratory indicator will be acupoint diagnosis. The safety evaluation indicator will be incidence of adverse events. DISCUSSION: The results of this study will provide favorable evidence for the efficacy and safety of acupuncture in reducing blood pressure, and explore the positive reaction acupoints which related to hypertension.

Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure.

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil-based lipid therapy should be implemented in order to successfully halt and reverse IFALD.

Systematic review on percutaneous aspiration and sclerotherapy versus surgery in symptomatic simple hepatic cysts.

BACKGROUND: Simple hepatic cysts (SHC) may cause pain and bloating and thus impair quality of life. Whereas current guidelines recommend laparoscopic cyst deroofing, percutaneous aspiration and sclerotherapy (PAS) may be used as a less invasive alternative. This review aimed to assess the efficacy of PAS and surgical management in patients with symptomatic SHC. METHODS: A systematic search in PubMed and Embase was performed according to PRISMA-guidelines. Studies reporting symptoms were included. Methodological quality was assessed by the MINORS-tool. Primary outcomes were symptom relief, symptomatic recurrence and quality of life, for which a meta-analysis of proportions was performed. RESULTS: In total, 736 patients from 34 studies were included of whom 265 (36%) underwent PAS, 348 (47%) laparoscopic cyst deroofing, and 123 (17%) open surgical management. During weighted mean follow-up of 26.1, 38.2 and 21.3 months, symptoms persisted in 3.5%, 2.1%, 4.2%, for PAS, laparoscopic and open surgical management, respectively. Major complication rates were 0.8%, 1.7%, and 2.4% and cyst recurrence rates were 0.0%, 5.6%, and 7.7%, respectively. CONCLUSION: Outcomes of PAS for symptomatic SHC appear to be excellent. Studies including a step-up approach which reserves laparoscopic cyst deroofing for symptomatic recurrence after one or two PAS procedures are needed.

Neonatal liver disease.

Neonatal liver disease encompasses many diagnoses, including structural and genetic aetiologies. Many have significant health implications requiring long-term specialist treatment including liver transplantation. Jaundice is a common presenting feature. The ability of health-care professionals to differentiate neonatal liver disease from benign diagnoses such as physiological jaundice is very important. Persistent (more than 2 weeks) of conjugated jaundice always warrants investigation. Severe unconjugated jaundice (requiring prolonged phototherapy) should also be promptly investigated. Recent advances in genomics have enabled previously elusive, precise diagnoses in some patients with neonatal liver disease. This review paper discusses the commoner causes, with a focus on early detection and need for referral to paediatric liver services.

Probiotics: Versatile Bioactive Components in Promoting Human Health.

The positive impact of probiotic strains on human health has become more evident than ever before. Often delivered through food, dietary products, supplements, and drugs, different legislations for safety and efficacy issues have been prepared. Furthermore, regulatory agencies have addressed various approaches toward these products, whether they authorize claims mentioning a disease's diagnosis, prevention, or treatment. Due to the diversity of bacteria and yeast strains, strict approaches have been designed to assess for side effects and post-market surveillance. One of the most essential delivery systems of probiotics is within food, due to the great beneficial health effects of this system compared to pharmaceutical products and also due to the increasing importance of food and nutrition. Modern lifestyle or various diseases lead to an imbalance of the intestinal flora. Nonetheless, as the amount of probiotic use needs accurate calculations, different factors should also be taken into consideration. One of the novelties of this review is the presentation of the beneficial effects of the administration of probiotics as a potential adjuvant therapy in COVID-19. Thus, this paper provides an integrative overview of different aspects of probiotics, from human health care applications to safety, quality, and control.