International Nonalcoholic Steatohepatitis (NASH) Day is a public education campaign launched by the Global Liver Institute. International NASH Day is observed on the second Thursday of June, every year, to raise visibility and urgency around fatty liver disease and its more advanced form, NASH, which affects more than 115 million people worldwide. This year, International NASH Day will be celebrated on June 8 with the theme #StepUpforNASH. On this day, several events, screenings, briefings, media outreach, and social media campaigns pertaining to liver health will be launched worldwide. INTERNATIONAL NASH DAY June 8, 2023
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 1 Editorial CONTENTS Research Update 2 Patient Education 13 Technologic Advances 9 Research at Himalaya 4 Doctors’ Feedback 17 Herb Facts 8 Expert Comments 10 The Liver and the Body 15 Dear Doctor, This year, World Hepatitis Day is observed to intensify the worldwide efforts in combating hepatitis by addressing the low coverage of testing and treatment, which will bring us one step closer to the goal of eliminating hepatitis globally by 2030. Research suggests that the development and progression of nonalcoholic fatty liver disease (NAFLD) is delicately orchestrated by the gut microbiome. A detailed article about the relationship between the dysregulation of the gut–liver axis and the onset of NAFLD is featured in the Research Update section. This issue also features insights and clinical experiences of Dr Sarva Jeet Singh about fatty liver and Dr GD Sharma about hepatitis B. Excerpts from clinical studies that prove the efficacy of Liv.52 DS in the management of NAFLD and Liv.52 HB in the management of hepatitis B are presented in the Research at Himalaya section. Furthermore, performance evaluation of the HelioLiver Test, the association between hyperthyroidism and liver dysfunction, trending news on the national- and global-level initiatives for the promotion of evidence-based research in traditional medicine, and facts on loss of appetite in children are presented in this issue. We hope you enjoy reading the collection of articles! — Editor Editor: Dr Jayashree B Keshav Editorial Team: Shruthi VB, Shruthi VK, Harika GS, Shruthi M, Priyakshi M, Keerthini D, Harshitha C Layout Artists: Dayananda RS, Santosh G, Monesh NP Copyright © 2023 Himalaya Wellness Company All content in this journal/publication is the property of Himalaya Wellness Company and is protected by Indian and international copyright laws. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance, of the content in this journal/publication, without written permission from the owner, is strictly prohibited. For permission to reproduce articles/information published in this journal/publication, please write to publications@himalayawellness.com SUBSCRIPTION If you would like to subscribe to Himalaya Livline, please fill an online form. You can access this form through https://tinyurl.com/LivlineSubscriptionForm OR Please share your views and suggestions about Himalaya Livline through an online form. You can access this form through https://tinyurl.com/LivlineFeedbackForm OR FEEDBACK
2 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 research update Role of Gut Microbiome Dysbiosis in the Pathogenesis of Nonalcoholic Fatty Liver Disease The diverse gut microbiome population is crucial for maintaining the integrity of the mucosal barrier function, absorption of nutrients, and maintaining energy balance. The predominant gut microbiome population comprises the Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia. Of these, Firmicutes and Bacteroidetes account for 90% of the gut microbiome. The liver has an intricate interaction with the gut, wherein it receives more than two-thirds of blood from the gastrointestinal tract through the portal system. The interaction between the gut and the liver occurs through hormones, inflammatory mediators, and products of digestion and absorption. Any disturbance/disruption in this communication and feedback loops between the gastrointestinal tract and the liver can affect the mucosal integrity, immunologic function, and metabolism, and hence, can lead to chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD). The Gut–Liver Axis NAFLD, involving a wide range of liver disorders that range from hepatic steatosis to nonalcoholic steatohepatitis, is characterized histologically by hepatocyte injury, inflammation, and varying degrees of fibrosis. Accumulating preclinical and clinical evidence suggests that the pathogenesis of NAFLD is delicately orchestrated by the gut microbiome. Gut dysbiosis serves as an important determinant for the development and progression of NAFLD. Research on NAFLD animal models shows a variety of changes in the relative abundances of Bacteroidetes, Firmicutes, and Ruminococcus. The composition of the gut microbiome is also observed to vary throughout different stages of NAFLD. Compositional Alteration in the Gut Microbiome in NAFLD: Research Findings A recent comprehensive review and meta-analysis on compositional alterations in the gut microbiome in patients with NAFLD found a characteristic compositional pattern and revealed the following findings: 1. The fecal microbiome constituted an increased number of Prevotella and species of Escherichia and Streptococcus, and fewer Coprococcus, Faecalibacterium, and Ruminococcus species. 2. The BMI may contribute to the change in the percentage of distribution (abundance) of Faecalibacterium species and Prevotella in patients with NAFLD, compared with healthy controls. 3. The change in the percentage of distribution of Streptococcus and Faecalibacterium species indicates increased systemic inflammation, which is a favorable index of progression of the NAFLD pathology. Pathomechanisms in the Dysregulation of the Gut– Liver Axis The following are the pathologic factors that dysregulate the equilibrium of the gut–liver axis and its relationship with the onset of NAFLD: Intestinal permeability Bacterial overgrowth in the intestine can affect the functionality of the tight
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 3 junctions that are crucial for preserving the integrity of the intestinal barrier. An impaired intestinal barrier function—also known as the leaky gut—is considered as a hallmark of dysbiosis in patients with NAFLD. Impaired gut permeability due to dysbiosis results in increased gut-derived toxins in the systemic circulation, which in turn contributes to the development of the chronic low-grade inflammation state observed in patients with NAFLD. Endotoxins and inflammation A tandem increase in the population of anaerobic gram-negative bacilli and the number of endotoxins impairs the intestinal barrier. An impaired intestinal barrier can overload the liver with endotoxins such as lipopolysaccharides and can cause loss of liver tolerance and establish a proinflammatory environment. The inflammatory state induced by endotoxins is also strongly linked to the immune response mediated by pattern recognition receptors and nucleotidebinding and oligomerization domainlike receptors. Further, inflammasomes also play a key role in the activation of lipid peroxidation and the production of reactive oxygen species, thereby contributing to gut microbiome dysbiosis and the advancement of NAFLD. Metabolites produced by the gut microbiome The metabolites in the gut can originate either from the microbiome itself, through microbial metabolism of food substrates, or by the alteration of bile acids. These metabolites that include endogenous ethanol, choline, and short-chain fatty acids can negatively affect the immune response and homeostasis, host energy metabolism, and mucosal integrity maintenance. Thus, it can be understood that the gut microbial health is important beyond localized gastrointestinal disorders and can influence systemic alterations. The rising prevalence of NAFLD is largely due to excessive calorie consumption, food additives and toxins, and antibiotic use, and decreased physical activity. Enhancement of the gut–liver axis through probiotics along with certain advantageous microbial products (such as baker’s yeast, kefir, and mushroom) can confer protection to the liver from the pathogenic constituents of the intestine. Further, advancing research about the gut–liver axis can contribute to the development of microbiota-based diagnostic, prognostic, and therapeutic tools for the treatment of NAFLD and other liver diseases. Sources: Pezzino S, et al. Biology. 2022;11(11):1622. Kaur KK, et al. J Hepatol Gastroint Dis. 2022;8(5):1000216. Summary • Gut dysbiosis serves as an important determinant for the development and progression of NAFLD. • An impaired intestinal barrier function—also known as the leaky gut—is considered as a hallmark of dysbiosis in patients with NAFLD. • Inflammasomes also play a key role in the activation of lipid peroxidation and the production of reactive oxygen species, thereby contributing to gut microbiome dysbiosis and the advancement of NAFLD. • Gut microbial health is important beyond localized gastrointestinal disorders and can influence systemic alterations.
4 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 Research at Himalaya Effect of Liv.52® DS on Various Liver Parameters in Nonalcoholic Fatty Liver Disease: A Cumulative Analysis Abstract Nonalcoholic fatty liver disease (NAFLD) is a clinical condition where excess fat accumulates within the liver and culminates in steatohepatitis, l iver failure, or hepatocellular carcinoma. A cumulative efficacy analysis of 4 clinical studies (2 controlled/comparative studies and 2 single-arm studies) that evaluated individuals with NAFLD post-Liv.52 DS administration was performed. A dosage of 2 tablets, BID, was recommended across the 4 studies. Treatment duration was 3 months in 3 studies and 2 months in 1 study. Improvements in clinical signs and symptoms, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT ) levels, hepatomegaly, NAFLD fibrosis scores (NFS), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis-4 (FIB-4) scores were considered for analysis. Reduced hepatomegaly and significant improvements in symptoms, levels of SGPT and SGOT, NFS, APRI, and FIB-4 scores were observed. Thus, the cumulative efficacy analysis confirmed that the recommended dosage of Liv.52 DS tablets was well-tolerated and showed beneficial improvement trends in individuals with NAFLD. An excerpt of the study conducted by Shah SC et al that was published in the International Journal of Pharmaceutical and Clinical Research is featured here. Aim To evaluate the effect of Liv.52 DS tablets on various liver parameters in NAFLD Materials and Methods Four clinical studies comprising 155 patients (aged 18–75 y; both sexes) who received 2 Liv.52 DS tablets, BID, orally, were considered for the cumulative efficacy analysis. Of the 4 studies, 2 were comparative, controlled clinical studies performed for 3 months (Liv.52 DS vs ursodeoxycholic acid and Liv.52 DS vs placebo, respectively), and the other 2 studies were single-arm clinical studies performed for 2 and 3 months, respectively, with Liv.52 DS alone. Clinical data specifically related to the Liv.52 DS arm of the studies were considered for the cumulative analysis. The studies’ outcomes were evaluated based on the improvement in the following parameters: NAFLD clinical signs and symptoms, hepatomegaly assessed using ultrasonography, SGOT and SGPT levels, NAFLD fibrosis scores, APRI, and fibrosis-4 score. Data were presented as mean ± standard deviation for quantitative variables, and as proportions and percentages for categorical variables. Comparisons of continuous variables within groups were performed using the paired t test. Comparisons of different categorical variables were performed using the c2 or Fisher’s exact tests. Results The cumulative analysis showed a significant reduction in SGPT (P < .0001) and SGOT (P < .0001) levels by the end of the study in 153 patients, compared with the baseline values (Figure 1). The ultrasonography results revealed a significantly improving trend in fatty liver grades by the end of the study in 90 patients. By the end of the study, 38% of the patients had grade 0, 60% had grade 1, 2% had grade 2, and no patients were reported with grade 3 fatty liver (Figure 2). The percentage of patients with hepatomegaly had reduced from 90% to 61.33%. A significant improvement
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 5 such as Capparis spinosa, Terminalia arjuna, Cichorium intybus, Cassia occidentalis, Achillea millefolium, Solanum nigrum, and Tamarix gallica. In NAFLD, the herbal constituents of Liv.52 DS decrease the uptake of free fatty acids by hepatocytes, leading to a reduction of fat deposition in the hepatocytes; decrease DNA fragmentation through antioxidant activity, leading to lesser cell death; downregulate inflammatory mediators like tumor necrosis factor-α and interluekin-8 and upregulate cytoprotective peroxisome proliferator activated receptors-γ, leading to a decrease in hepatic inflammation; increase urea and albumin secretion, suggesting cell proliferation; and decrease SGOT and SGPT levels, indicating normalization of biochemical parameters. Conclusion This cumulative analysis demonstrated that oral administration of Liv.52 DS tablets in patients with NAFLD, for 2 to 3 months, can cause significant symptomatic improvements, reduction in SGPT and SGOT levels, reduction in hepatomegaly, and a fibrosis-free state. Thus, it can be concluded that Liv.52 DS tablets are effective in the management of NAFLD. Table. Effect of Liv.52 DS Tablets on Signs and Symptoms of Nonalcoholic Fatty Liver Disease Abdominal Discomfort Due To Hepatomegaly Screening (n = 76) End of Study (n = 76) P Value Absent 0 (0%) 47 (62%) < .0001 Present 76 (100%) 29 (38%) Fatigue Screening (n = 53) End of Study (n = 53) Absent 0 (0%) 40 (75%) < .0001 Present 53 (100%) 13 (25%) Weakness Screening (n = 54) End of Study (n = 54) Absent 0 (0%) 34 (63%) < .0001 Present 54 (100%) 20 (37%) Fisher’s exact test. Significance < .05. Figure 1. Effect of Liv.52 DS Tablets on SGOT and SGPT Levels ALT, alanine transaminase; AST, aspartate transaminase; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase. Figure 2. Effect of Liv.52 DS Tablets on Fatty Liver Grades in abdominal discomfort due to hepatomegaly, fatigue, and weakness was also observed (Table). As per the cumulative data, by the end of the study, the NAFLD fibrosis score suggested no further progression to fibrosis. Some patients with an indeterminate NAFLD score at baseline also showed slight improvement toward normalcy by the end of the study. Further, the APRI score by the end of the study was 0.34, indicating no fibrosis progression in the liver. No clinically significant adverse events were either observed or reported in these studies. Discussion Liv.52 DS has a wide spectrum of therapeutic applications to correct hepatic dysfunction. The hepatoprotective, antioxidant, antimicrobial, antiviral, and antiinflammatory properties of Liv.52 DS tablets can be attributed to its constituents that primarily include herbs 500 0 1000 U/L Baseline P < .0001 P < .0001 End of Study End of Study Baseline SGOT (AST) SGPT (ALT) 55.56% 40% 4.44% 38% 60% 2% Grade 0 Grade 1 Grade 2 Grade 3 At Entry At the End of Study
6 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 HD-03/ES* in the Management of Chronic Hepatitis B Infection An excerpt of a study conducted by Rajkumar JS et al published in the World Journal of Gastroenterology is featured here. Aim To study the safety and efficacy of Liv.52 HB capsules in patients with chronic hepatitis B (CHB) infection Materials and Methods This was an open, prospective, controlled clinical trial. A total of 25 patients aged 18 to 60 years, with serum alanine transaminase (ALT) level of 41 to 200 IU/L and who were positive for serum hepatitis B surface antigen (HBsAg) were included in the study. The patients were administered 2 capsules of Liv.52 HB, BID, for 6 months. The signs and symptoms were clinically assessed on a regular basis. Serum assay was done for HBsAg, hepatitis B e-antigen (HBeAg), and hepatitis B virus (HBV) DNA at baseline and 4 and 6 months after therapy. The patients underwent liver function tests every month during the treatment. HBsAg clearance was considered as the primary end point. HBV DNA level and ALT level normalization to 40 IU/L were considered as the secondary end points. Results After 6 months of treatment with Liv.52 HB, there was a remarkable alleviation in the chief clinical symptoms such as abdominal pain and poor appetite in most of the patients. There was a trend toward normalization of liver function parameters in all patients (Table 1). A significant decrease in the HBeAg, HBsAg, and HBV DNA levels was observed in 60%, 52%, and 60% of the patients, respectively (Table 2). Liv.52 HB was well tolerated by the patients. Most of the observed side effects were mild (fatigue, headache, and insomnia). No serious biochemical abnormalities were noted in any patient. Conclusion Thus, Liv.52 HB is safe and effective in the treatment of CHB infection. Table 1. Effect of 6 Months of Treatment With Liv.52 HB on Liver Function Parameters Parameter Day 0 Month 4 Month 6 Alanine Aminotransferase, IU/L 66.5 ± 11.1 41.6 ± 05.1 39.1 ± 05.2 Aspartate Aminotransferase, IU/L 47.5 ± 9.5 42.4 ± 10.7 40.2 ± 10.1 Serum Albumin, g% 3.5 ± 0.8 3.5 ± 0.7 3.6 ± 0.7 Serum Globulin, g% 2.9 ± 0.3 3.1 ± 0.2 3.2 ± 0.2 Total Protein, g% 6.2 ± 0.7 6.5 ± 0.7 6.5 ± 0.7 Serum Bilirubin, mg% 1.3 ± 0.6 1.2 ± 0.5 1.1 ± 0.5 Alkaline Phosphatase, IU/L 155.5 ± 9.8 140.2 ± 9.0 127.0 ± 7.5 Values are expressed as mean ± SD. Table 2. Effect of 6 Months of Treatment With Liv.52 HB on Biochemical and Serological Parameters Parameter No. of Patients Alanine Aminotransferase Normalization, % Month 4 32 Month 6 56 Positive Negative HBsAg Day 0 25 0 Month 4 19 6 Month 6 12 13a HBeAg Day 0 16 9 Month 4 11 14 Month 6 10 15b HBV DNA Day 0 16 9 Month 4 11 14 Month 6 10 15b aP < .001 and bP < .05 vs day 0 value. HBeAg, hepatitis B e-antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus. Liv.52 HB in Chronic Hepatitis B Infection *HD-03/ES is marketed as Liv.52 HB.
Indication Hepatitis B infection Dosage 1–2 capsules twice daily after meals. Effective management of hepatitis B Liv.52 HB® ( CA P S U L E ) An effective, safe, and affordable research-based product... ® Regd. Trademark Liv.52 HB Effective management of hepatitis B —World J Gastroenterol. 2007;13(30):4103–4107. —Antiviral Res. 2009;84(3):249–253. —World J Gastroenterol. 2007;13(46):6150–6155. Efficacy comparable to interferons and antivirals •Causes significant reduction of HBsAg, HBeAg, and HBV DNA levels •Significantly reduces the elevated ALT levels and normalizes liver function tests •Alleviates clinical symptoms such as abdominal pain and poor appetite Well tolerated and safe compared to interferons and antivirals •Free from harmful side effects such as: – Bone marrow depression – Pancreatitis and peripheral neuropathies – Neurovegetative syndrome Affordable cost of therapy
8 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 protective effect by lowering serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, and total bilirubin. The study concludes that the rhizome of C rotundus possesses hepatoprotective activity.3 References 1. Kamala A, et al. 3 Biotech. 2018;8(7):309. 2. Invasive Plant Atlas of the United States. Purple nutsedge. https://www.invasiveplantatlas.org/. Accessed February 28, 2023. 3. SVS Kumar, Mishra SH. Indian J Pharm Sci. 2005;67(1):84–88. In another study, pretreatment with C spinosa hydroalcoholic extract (400 mg/kg) protected the liver against tert-butyl hydroperoxide– induced hepatic injury in mice models. There was also a reduction in malondialdehyde levels and an increase in the activities of catalase and superoxide dismutase enzymes.5 References 1. Useful Tropical Plants. Capparis spinosa. http://tropical.theferns.info/. Accessed February 28, 2023. 2. Mohammad SM, et al. Life Sci J. 2012;9(4):684–686. 3. Rahnavard R, Razavi N. Adv Herb Med. 2016;2(1):44–53. 4. Aghela N, et al. Iranian J Pharm Res. 2007;6(4):285–290. 5. Kalantaria H, et al. J Tradit Complement Med. 2017;8(1):120–127. herb facts Cyperus rotundus Cyperus rotundus, commonly known as purple nutsedge, belongs to the family Cyperaceae. This perennial herb is 7 to 40 cm tall and has fibrous roots.1 It reproduces mainly through rhizomes, which are white and fleshy initially and become woody and wiry with age.2 C rotundus has anti-inflammatory, antioxidant, and hepatoprotective properties.1 A study evaluated the hepatoprotective activity of C rotundus in CCl4-induced liver damage in rats. The animals involved in the study received ethyl acetate rhizome extract orally, at a dose ranging from 100 to 1000 mg/kg body weight. The results revealed that the ethyl acetate extract at a dose of 100 mg/kg demonstrated a significant Capparis spinosa Sanskrit name: Himsra English name: The Caper Bush Capparis spinosa is a sprawling or erect evergreen shrub that grows in northern and eastern Africa, Madagascar, southern Europe, Philippines, southwestern and central Asia, Indonesia, and Australia.1 It has round fleshy leaves and pinkish white flowers.2 C spinosa has hepatoprotective,1 anti-inflammatory, antioxidant, and antimicrobial properties.3 In a study, in CCl4-treated animals, liver injury was reflected by increased levels of serum alanine aminotransferase and aspartate aminotransferase, which were normalized in animals treated with CCl4 plus C spinosa root bark extract (100, 200, and 400 mg/kg). C spinosa also reduced the thiopental-induced sleeping time, which was increased by CCl4 treatment. 4 Sanskrit name: Musta English name: Nut Grass Cyperus rotundus is an ingredient of Liv.52 HB. Capparis spinosa is an ingredient of Liv.52 DS.
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 9 Technologic Advances HelioLiver Test: A Multianalyte Blood Test for Early Detection of Hepatocellular Carcinoma The mortality rate in patients with hepatocellular carcinoma (HCC) has substantially increased over the past few decades due to delayed diagnosis (ie, usually diagnosed at a late noncurable stage). The performance of current HCC surveillance tests such as ultrasonography with or without serum a-fetoprotein (AFP) test is suboptimal in effective early tumor detection. Currently, liquid biopsies that assay the methylation of circulating cell–free DNA (cfDNA) released from cancer cells have been actively explored as a promising biomarker for sensitive detection of HCC at early stages. Further, by optimizing the cfDNA methylation panel, the HelioLiver test was designed for robust and accurate HCC detection. Performance Evaluation of the HelioLiver Test The HelioLiver test is a multianalyte blood test that combines cfDNA methylation markers with patient demographic information and clinically available HCC tumor markers. A prospective, blinded, multicenter phase 2 biomarker study was conducted to evaluate the performance of the HelioLiver test as an early detection marker of HCC. The study included 122 patients with HCC and 125 patients with a benign liver disease without HCC, in the test and control groups, respectively. Blood samples were collected from the patients to measure serum concentrations of AFP, Lens culinaris agglutininreactive AFP (AFP-L3%), and des-g-carboxy prothrombin (DCP), and to capture cfDNA methylation sequences. These sequences were included in a discovery methylated cell-free DNA (m-cfDNA) panel and further refined to generate a preliminary next-generation sequencing m-cfDNA panel. Finally, 28 gene (ie, 77 cytosine–guanine dinucleotide sites) m-cfDNA markers, 3 serum protein tumor markers (ie, AFP, AFP-L3%, and DCP), and patient demographics such as age and sex were combined to generate the results for the HelioLiver test. The primary end point was to compare the area under the receiver operating characteristic curve of the HelioLiver test with both AFP alone and the gender, age, AFP, AFP-L3%, and DCP (GALAD) score. The co-secondary end points were to compare the sensitivity and specificity of the HelioLiver test with both AFP alone and the GALAD score. In this study, the sensitivity of the HelioLiver test was found to be better than AFP, AFP-L3%, and DCP individually, and the GALAD score. The HelioLiver test, which incorporates components of the GALAD score, achieved improved performance over the GALAD score itself. The study confirmed that the HelioLiver test demonstrated superior sensitivity and similar specificity in detecting early-stage (1 and 2) HCC compared with clinically available tests. Thus, application of a blood test such as the HelioLiver test will enable easy and accurate HCC detection at early stages and will significantly improve treatment outcomes for a transformative reduction of HCC mortality. Source: Lin N, et al. Hepatol Commun. 2022;6(7):1753–1763. Disclaimer: The content in this section is for general information only, and holds no commercial interests.
10 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 expert comments Liv.52® (DROPS, SYRUP, TABLET, DS SYRUP, DS TABLET) Unparalleled in liver care Dosage Acute viral hepatitis Drops: 5 to 10 Drops TID (infants); 10 to 20 Drops TID (children) Syrup: 5 mL TID (children); 10 mL TID (adults) Tablet: 1 Tablet TID (children); 2 Tablets TID (adults) Syrup: 5 mL BID/TID (children); 10 mL BID/TID (adults) Tablet: 1 Tablet TID (children); 2 Tablets TID (adults) Drug-induced hepatitis DS Syrup/DS Tablet: 1 to 2 Teaspoonsful/Tablets BID with anti-TB/ Alcohol-induced liver damage Syrup: 10 to 15 mL TID Tablet: 2 to 3 Tablets TID Anorexia and suboptimal growth Drops: 5 to 10 Drops TID (infants); 10 to 20 Drops TID (children) Liv.52 is a hepatospecific formulation, designed for the treatment and management of liver disorders. An InterviewWith Dr Sarva Jeet Singh Doctor, how do lipids/fats accumulate in the liver? How does this lead to fatty liver? Fats can accumulate in the liver due to various reasons. Increased delivery of free fatty acids to the liver, increased synthesis of fatty acids in the liver, decreased oxidation of free fatty acids, or decreased assembly of very low-density lipoproteins leading to triglyceride accumulation are regarded as the primary factors that lead to fat accumulation in the liver. This impaired metabolism of lipids in the liver triggers oxidative stress, activation of stellate cells, and hepatocyte inflammation, resulting in fatty liver. Doctor, what are the most common signs and symptoms of fatty liver? Fatty liver is usually an incidental finding during other imaging analyses. Some patients with nonalcoholic fatty liver disease (NAFLD) present with thirst, bloating, fluctuations in body temperature, sleep disturbances, and anxiety. In progressed stages, a sharp or dull pain in the abdomen, in the right upper quadrant, is also reported. Doctor, what are the health complications associated with NAFLD? NAFLD is one of the most underdiagnosed liver conditions. Without timely diagnosis and management, NAFLD can result in long-term complications including hypertension, coronary artery disease, arrhythmia, chronic kidney disease, and extrahepatic malignancies. The chronic inflammatory state of NAFLD also contributes to the development and progression of cirrhosis and liver fibrosis. Doctor, what are the risk factors for NAFLD? NAFLD can stem from a wide range of factors. The most relevant factors include unhealthy dietary habits such as eating processed foods, nutrientdeficit foods, and high-sodium and high-fat foods, low physical activity and increased sitting time, presence of chronic metabolic abnormalities such as glycogen storage disorders and homocystinuria, and genetic polymorphisms that lead to impaired lipid metabolism. Doctor, how commonly does NAFLD progress further? NAFLD that coexists with other liver diseases such as hepatitis C, hemochromatosis, and alcoholic liver disease has shown to have more rapid disease progression. Approximately 10% to 30% of the patients with NAFLD could develop nonalcoholic
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 11 Chronic active hepatitis DS Syrup/DS Tablet: 2 Teaspoonsful/ Tablets BID for 6 months Early cirrhotic conditions DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet TID for 6 to 12 months statin/antiretroviral treatment and chemotherapy Jaundice and anorexia during pregnancy DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet BID for 8 weeks Nonalcoholic steatohepatitis (NASH) DS Tablet: 1 to 2 Tablets BID As a supportive treatment during hemodialysis DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet BID for 3 to 4 months As an adjuvant to anticancer drugs DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet BID for 4 months Dr Sarva Jeet Singh, MBBS, MD Senior Consultant Chest Physician Ursula District Hospital Kanpur 208001, Uttar Pradesh India steatohepatitis (NASH), and 25% to 40% of the patients with NASH could develop progressive liver fibrosis, ultimately resulting in cirrhosis. Doctor, can lifestyle management help reverse the fatty liver condition? Yes, dietary modifications and weight management could help alleviate fatty liver. Satisfactory reduction in liver fat can be achieved by engaging in regular exercise for 30 to 60 minutes for 3 to 5 days/week and by consuming foods enriched with hypocaloric high fibers, low saturated fats, and high proteins. Additionally, consumption of foods rich in ω-3 fatty acids, polyphenols, and vitamins E and D may be beneficial to protect against NAFLD. Can obesity exacerbate NAFLD? Yes, obesity is an established predisposing factor for NAFLD. The prevalence of NAFLD is known to increase with increasing BMI. Abdominal obesity along with insulin resistance results in the pathologic development of NAFLD because of the overproduction of glucose. Furthermore, release of tumor necrosis factor and leptin by the visceral fat tissues also increase the risk of NAFLD progression. Doctor, what therapeutics do you recommend for the management of fatty liver? I generally prescribe Liv.52 DS to patients diagnosed with NAFLD or NASH. Liv.52 DS is a hepatospecific formulation from Himalaya Wellness Company. The pharmacologic properties of the herbal constituents of Liv.52 DS decrease the uptake of free fatty acids, and thereby reduce fat deposition in the hepatocytes, downregulate inflammatory mediators and bring about a decline in hepatic inflammation, and normalize liver biochemical parameters. Our field correspondents: Hari Madhav Tripathi, Regional Manager Puneet Narayan Singh, Pharma Sales Officer HimalayaWellness Company
12 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 An InterviewWith Dr GD Sharma Doctor, what are the major routes of hepatitis B virus (HBV) transmission? Perinatal transmission and horizontal transmission, mainly due to exposure to infected blood, are the major routes of HBV transmission. Exposure to other body fluids including saliva, tears, and vaginal and seminal fluids can also transmit the virus. HBV transmission may also occur during surgical and dental procedures due to poor infection-control measures, unprotected sex, tattooing, and body piercing. Doctor, who is at risk of chronic HBV infection? The likelihood of chronic HBV infection can be determined based on the age at which an individual is infected. About 80% to 90% of infants in their first year of life and 30% to 50% of children younger than 6 years, who are infected with HBV, are likely to develop chronic infections. More than 5% of infected adults are at a risk of developing chronic infection, and 20% to 30% of adults who are chronically infected will develop cirrhosis and liver cancer. Doctor, what are the common symptoms of HBV infection? Although most individuals are asymptomatic, some experience symptoms within 60 to 150 days after infection. Jaundice, nausea, vomiting, abdominal pain, anorexia, fatigue, malaise, dark urine, fever, and headache are the common symptoms of an acute HBV infection. In some individuals, skin rashes, joint pains, and arthritis may also occur. Are there any coinfections associated with HBV infection, doctor? Hepatitis B coinfections occur with viruses that have similar transmission routes like hepatitis C virus (HCV), hepatitis D virus (HDV), and HIV. Coinfections increase the chances of complications. The incidence of HCC is higher in patients with both HBV and HCV infections. Coinfection with HDV and HBV results in liver failures in cases with acute infections and liver cancer in those with chronic infections. Doctor, what therapeutic strategy do you suggest for the management of hepatitis B? I generally prescribed Liv.52 HB to my patients with hepatitis B, and they have responded well to the therapy. Liv.52 HB is a phytopharmaceutical formulation from Himalaya Wellness Company. Liv.52 HB helps manage hepatitis B infection through its antiviral, immunomodulatory, antiinflammatory, and hepatoprotective actions. Liv.52 HB acts directly on the virus by binding directly to HBsAg and suppressing the replication of the viral DNA. It inhibits viral reverse transcriptase. It reverses the oxidative damage to the hepatocytes, hastens the recovery period, and ensures early restoration of hepatic functions. It also protects the hepatic parenchyma and promotes hepatocellular regeneration. Dr GD Sharma, MD Managing Director and Chairman PRP Multispeciality Hospital Kidney Center, Trauma Center, and Blood Bank Karnal 132001, Haryana India Our field correspondent: Mr Ritesh Kumar Dixit Area General Manager HimalayaWellness Company
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 13 Patient Education Managing Hypercholesterolemia for a Healthy Liver Several studies have proven that high cholesterol intake can worsen fatty liver disease that leads to inflammation and scarring of the liver.1 The accumulation of lipids in the hepatocytes can cause fibrosis and cirrhosis of the liver. Evidence proves that the increased accumulation of free cholesterol in the liver contributes to severe liver damage.2 Some of the causes of hypercholesterolemia include consumption of fat-rich foods, lack of exercise, being overweight, smoking, and drinking alcohol.3 Consuming nutritious food and adopting a healthy lifestyle help lower the cholesterol level. Here are some tips that can be recommended to patients to maintain healthy cholesterol levels. Reducing the intake of saturated fats and trans fats: Excessive intake of foods containing saturated fats and trans fats can increase the low-density lipoprotein (LDL) cholesterol level in the blood. High levels of saturated fat are present in animal foods such as red meat and dairy products, palm oil, and fried food (eg, chips, cakes, biscuits, and pastries). Trans fats, on the other hand, are present in margarine and processed and deep-fried foods. Some other foods that contain high cholesterol include egg yolk, processed meat (eg, bacon and ham), pizza, burger, doughnut and muffin, chocolate, and ice cream. Opting for foods rich in unsaturated fats will help maintain a healthy lipid profile. Healthy unsaturated fats are found in avocados, nuts, olives, oily fish (eg, salmon and sardines), seeds (flaxseeds, chia seeds, and sunflower seeds), and plant- and seed-based oils (eg, soybean oil, olive oil, peanut oil, canola oil, and avocado oil).4-6 Increasing intake of soluble fiber: Soluble fiber helps reduce the absorption of cholesterol into the bloodstream. Soluble fiber is present in foods such as oats, lentils, fruits and vegetables, barley, and sprouts.7 Increasing physical activity: Regular physical activity helps improve metabolism. Exercise also helps decrease the lipoprotein lipase activity, and thus, helps reduce the uptake of free fatty acids. This in turn enhances the upregulation of the enzymes involved in the metabolism of healthy fats in the body. Aerobics, resistance training and muscle training exercises, and yoga are some exercise forms that can be practiced.4,7,8 Following a healthy dietary regimen and engaging in regular physical activity thus play a key role in effectively managing hypercholesterolemia and keeping the liver healthy. References 1. Lewis W. High cholesterol leads to long-term liver scarring and immune cell dysfunction in lab study. https://keck.usc.edu/. Published September 16, 2022. Accessed February 7, 2023. 2. Malhotra P, et al. Front Med. 2020;7:467. 3. NHS. What is high cholesterol? https://www.nhs.uk/. Reviewed July 13, 2022. Accessed February 7, 2023. 4. healthdirect. How to lower your cholesterol. https://www.healthdirect.gov.au/. Reviewed August 2021. Accessed February 7, 2023. 5. healthdirect. Dietary fats. https://www.healthdirect.gov.au/. Reviewed October 2021. Accessed February 22, 2023. 6. Anderson E, Zagorski J. Cooking oils – plant-based oils. https://www.canr. msu.edu/. Published November 7, 2022. Accessed February 22, 2023. 7. Mayo Clinic. Top 5 lifestyle changes to improve your cholesterol. https://www.mayoclinic.org/. Published September 2, 2022. Accessed February 7, 2023. 8. Mika A, et al. Front Physiol. 2019;10:26.
14 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 health news Energy and Fatigue Traits May Be Driven By the Gut Microbiome Profile A Three-Minute Exposure to Sunlight Can Restore Color Vision The functionality of the rods and cones of the retina progressively decline with age. According to a study published in Scientific Reports, a single exposure of the aging retina to sunlight of long wavelength (650–900 nm), for 3 minutes, can partially restore color vision for a week. The dominant eye of healthy participants (34–70 y; both sexes), with normal color vision, was exposed to light of 670 nm wavelength, for 3 minutes, either in the morning (between 8 and 9 AM) or noon (between 12 and 1 PM). The color contrast sensitivity was measured using the ChromaTest, either 3 hours after exposure or 1 week later, and the threshold was determined. The results suggest that a single, 3-minute morning exposure of the eyes to sunlight can improve cone cells’ photoreceptor function in aged individuals for up to a week. A population-level adoption of this technique can minimize the problems associated with reduced vision and significantly improve the quality of life in the elderly. Source: Shinhmar H, et al. Sci Rep. 2021;11:22872. Recent evidence suggests that energy and fatigue are 2 distinct characteristics with different neurohormonal and physiologic connections. An exploratory study published in the journal Nutrients investigated the connection between mental energy, mental fatigue, physical energy, and physical fatigue with the gut microbiome. The 4 mood traits were assessed in 20 healthy, nonobese, and physically active individuals (aged 31 ± 5 y) through an online survey. Their mental and physical energy and mental and physical fatigue traits were distinguished using the respective energy and fatigue scales. Fecal samples were collected from the participants for the microbial community analysis (16s rRNA analysis). Results showed that the mental energy trait positively correlated with members of the Actinobacteria and Verrucomicrobia, the physical fatigue trait positively correlated with members of the Proteobacteria and Bacteroidetes, and at least 1 member of the Firmicutes positively correlated with all the 4 mood traits. Thus, this study confirms that the 4 mood traits are associated with unique gut bacterial profiles, with some overlaps. Source: Boolani A, et al. Nutrients. 2022;14(3):466.
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 15 Effect of Hyperthyroidism on Liver Function Normal biosynthesis and functioning of the thyroid hormones thyroxine (T4), 3,5,3′-triiodothyronine (T3), and thyroid-stimulating hormone are critical for maintaining metabolic homeostasis in the body. An intricate relationship is known to exist between the thyroid gland and the liver in health and diseases. Thus, any disturbance in the metabolism of the thyroid hormones can affect liver function. Hyperthyroidism, a form of thyrotoxicosis, is caused by excessive production and secretion of T3 and T4 hormones into systemic circulation. Scientific evidence indicates that hyperthyroidism has a significant effect on the biosynthesis and functioning of liver enzymes, and thereby contributes to liver dysfunction. A recent meta-analysis reveals that 55% to 60% of the patients with untreated hyperthyroidism show at least one abnormality in the liver function biomarker levels. The highest abnormality was found in the level of alkaline phosphatase (ALP), followed by that of alanine transaminase, γ-glutamyl transferase (GGT), aspartate transaminase, and total bilirubin. Liver Injury Patterns A spectrum of pathological changes from focal necrosis with steatosis to cirrhosis can ensue from untreated hyperthyroidism. Several direct and indirect mechanisms that are involved in thyrotoxicosis-associated liver dysfunction exhibit either a hepatic pattern or a cholestatic pattern. Hepatic pattern: Prolonged exposure to excessive thyroid hormones, hypermetabolic state, accelerated liver glycogen and protein decomposition, autoimmunity, and underlying liver diseases may trigger hepatic dysfunction in patients with thyrotoxicosis. Cholestatic pattern: Hepatic dysfunction in Graves’ disease is predominantly a cholestatic pattern. Nonspecific histologic changes in the hepatocytes, centrilobular intrahepatic cholestasis, jaundice, and predominant elevation in ALP (due to increased osteoblastic activity) and GGT levels also trigger hepatic dysfunction in patients with thyrotoxicosis. Therefore, the examination of liver function upon diagnosis of hyperthyroidism is important to identify any hepatic abnormalities. Sources: Yorke E. Clin Med Insights Endocrinol Diabetes. 2022;15:1–3. Malik R, Hodgson H. QJM Int J Med. 2002;95(9):559–569. The Liver and the Body A spectrum of pathological changes from focal necrosis with steatosis to cirrhosis can result from untreated hyperthyroidism.
16 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 Liver Health Associations journal Facts Canadian Association of Gastroenterology Set up in 1962, the Canadian Association of Gastroenterology (CAG) comprises more than 1100 members, including gastroenterologists, surgeons, pediatricians, scientists, and nurses. The CAG imparts formal specialized training on gastrointestinal health to members. The association is known for providing improved, timely, and quality digestive health care for Canadians. The CAG researches on the organs of the digestive tract in both healthy and diseased conditions. By providing outstanding patient care and supporting research, teaching, and continuing professional development, the association supports the growth and development in the field of gastroenterology. It conducts educational events such as Canadian Digestive Diseases Week™ (CDDW™) and provides several online continuing medical education opportunities. Journal of Gastrointestinal and Liver Diseases Image source: https://www.jgld.ro/jgld/index. php/jgld Loss of Appetite and Poor Eating Behavior in Children • Children born preterm and those with developmental delays or inborn errors of metabolism are at an increased risk of loss of appetite, and they subsequently can develop poor eating behavior.1 • Small intestinal bacterial overgrowth (> 100,000 colony-forming units) can cause abdominal pain, eructation, bloating, and flatulence that often result in feeding difficulties and loss of appetite in children.2 • Loss of appetite in children can begin as oral texture aversion or sensory integration difficulty along with food selectivity.2 • Children with sensory food aversion refuse to eat certain foods because of their taste, texture, smell, temperature, or appearance.1 • Prolonged loss of appetite can result in short-term nutritional deficiency and weight loss and long-term deficits in physical growth, cognitive function, and neurologic development.1 References 1. Yang HR. Korean J Pediatr. 2017;60(12): 379–384. 2. Rivera-Nieves D, et al. Glob Pediatr Health. 2019;6:1–7. The Journal of Gastrointestinal and Liver Diseases is an open-access journal published quarterly by the Romanian Society of Gastroenterology. The journal publishes original clinical and scientific research papers that contribute to the advancement of knowledge in the fields of gastroenterology and hepatology. The topics covered include prevention, diagnosis, and management of gastrointestinal and hepatobiliary disorders and the associated molecular genetics, pathophysiology, and epidemiology aspects. The journal also publishes reviews, editorials, and short communications on topics related to gastrointestinal health.
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 17 DOCTORS’ FEEDBACK Liv.52 is a hepatospecific formulation, designed for the treatment and management of liver disorders. Liv.52 has a wide spectrum of therapeutic applications. Liv.52 restores the metabolic efficiency of the liver, minimizes damage to the hepatic parenchyma, and accelerates the rate of recovery in various liver disorders like infectious hepatitis, drug-induced hepatitis, and alcoholic liver diseases. Liv.52 is a valuable adjuvant during prolonged illness. In anorexia, Liv.52 improves appetite, digestion, and assimilation. Liv.52 also prevents the complications of nonalcoholic steatohepatitis (NASH). Liv.52 is one of the world’s most enduring phytomedicines, accredited with more than 250 studies, and is available in a wide range of dosage forms to suit the requirement of patients of all age groups. Liv.52 is safe even for long-term use. Here are some clinical experiences with Liv.52, shared by a few eminent doctors. I have been prescribing Liv.52 for 20 years. Liv.52 is very effective in the management of hepatitis, fatty liver, and indigestion. I have been prescribing Liv.52 since the time I started practicing medicine. In my clinical experience, Liv.52 is an effective hepatoprotective agent for both adults and children. I recommend Liv.52 in cases of hepatomegaly and fatty liver. I have been prescribing Liv.52 from the past 15 years. Liv.52 is effective in the management of anorexia, indigestion, and mild cases of hepatitis. The results are good in chronic patients. I have been prescribing Liv.52 for 20 years. Liv.52 has shown excellent results in the management of viral hepatitis. Dr Ashok Kumar Gupta MBBS, MD (Med) Delhi 110095, India Dr Prashant MD New Delhi 110078, India Dr Juthika Ghosh Maity MBBS New Delhi 110075, India Dr Rajeshwar Shah MS Delhi 110043, India
18 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 Ayurveda trends Ministry of Ayush Appoints an Academic Chair for Ayurveda Studies at Western Sydney University, Australia The Ministry of Ayush (MoA), with an aim to strengthen international collaborations and promote collaborative research, has formally announced the setting up of an Ayurveda Academic Chair for a tenure of 3 years at Western Sydney University’s NICM Health Research Institute. Dr Rajagopala S (Associate Professor and Head, Department of Kaumarabhritya [Pediatrics], All India Institute of Ayurveda [AIIA], New Delhi, India) has been selected as the Academic Chair. The Academic Chair will be responsible for undertaking academic and collaborative research activities in Ayurveda (including Yoga), and designing short- and long-term courses, defining their academic standards, and formulating guidelines for imparting education. This will serve as a means for demonstrating and fostering excellence in teaching, research, and policy development related to Ayurveda in the setting of the robust Australian regulatory framework. Further, the MoA aims to develop strategies to promote the integration of evidence-based Ayurvedic medicines into conventional health care. Professor Barney Grover (Vice Chancellor and President, Western Sydney University) said, “The collaboration strengthens the University’s reputation as Australia’s leader in integrative and complementary medicine and is a significant step towards developing a new research stream for the NICMHealth Research Institute.” Source: Ayush Ministry appoints Academic Chair in Ayurvedic science at Western Sydney University. BioSpectrum. November 22, 2022. https://www.biospectrumindia.com/news/68/22279/ ayush-ministry-appoints-academic-chair-in-ayurvedic-science-at-western-sydney-university. html?_sm_au_=iVV3DbQKKDKMSqPbf1HqkKQJBMVpq. Accessed February 10, 2023. Ministry of Ayush and DST Sign MoU for the Promotion of Evidence-Based Research Image source: https://ddnews.gov.in/international/ayush-ministry-announces-setting- academic-chair-ayurvedic-science-western-sydney Image source: https://www.pib.gov.in/PressReleasePage.aspx?PRID=1878834 An MoU was signed between the Ministry of Ayush (MoA) and the Department of Science and Technology (DST), Ministry of Science and Technology, and Ministry of Earth Sciences, Government of India. The MoU was signed by Vaidya Rajesh Kotecha (Secretary, MoA) and Dr Srivari Chandrasekhar (Secretary, DST) in the presence of senior officials from the MoA and scientists of DST. The MoU will identify the potential areas of research to explore cooperation, convergence, and synergy for evidence-based scientific intervention in the Ayush sector and the various means of utilizing them in the public health care system. It will be a platform for the MoA and DST to jointly undertake R&D activities for the scientific validation of the concepts, procedures, and products of Ayush. Moreover, initiatives will be taken by the MoA to identify all the thrust areas of the Ayush-related systems that involve understanding the basic concepts, procedures, and development of new tools in modern science. The DST through the Science and Engineering Research Board (SERB) will be responsible for coordinating the implementation of thrust areas using well-chartered plans and actions. Source: Department of Science &Technology. MoU signed between Ministry of Ayush and Department of Science and Technology. https://dst.gov.in/mou-signed-between-ministryayush-and-department-science-and-technology. Accessed February 10, 2023.
Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 19 movies and medics Books When Breath Becomes Air Gifted Hands: The Ben Carson Story The movie Gifted Hands revolves around the true story of Ben Carson. Raised by a single mother, he has a difficult childhood, struggling amid poverty and prejudice. He performs poorly at school and faces racist treatment by his classmates. Ben’s mother always encourages him to use his Godgiven gifts. The continual support from his mother helps Ben to instill belief in himself. He works hard to become the best student in his school, and later pursues a career in medicine. Gifted Hands is an inspiring story that shows how believing in oneself helps overcome any obstacle in life. The story revolves around Ben who, instead of considering himself inferior, underprivileged, and discriminated, fights hard to finally become a world-renowned neurosurgeon. Details Genre: Drama, Biography Director: Thomas Carter Year: 2009 Runtime: 1 hour 30 minutes Cast: Cuba Gooding Jr., Kimberly Elise, Aunjanue Ellis, Jaishon Fisher, and Gus Hoffman Source: Movieguide. Gifted Hands: The Ben Carson Story. https://www.movieguide.org/. Accessed February 9, 2023. Image source: https://www.imdb.com/title/tt1295085/mediaviewer/rm3135342848?ref_=ttmi_mi_all_prd_12 Author: Paul Kalanithi Publication date: January 12, 2016 Number of pages: 208 Publisher: Random House When Breath Becomes Air is a nonfiction autobiography written by Paul Kalanithi, a young neurosurgeon. At the age of 36, when he is in his last year of training as a neurosurgeon, Paul starts experiencing negative changes in his body. His and his wife Lucy’s world turns upside down when he is diagnosed with stage IV lung cancer and has to go through a rigorous treatment regimen. Paul who was once a doctor helping patients recover suddenly turns into a patient struggling to survive. This book chronicles Paul’s transformation from a naïve medical student, to a neurosurgeon at Stanford University, to finally being a patient himself. When Breath Becomes Air depicts the relationship between a doctor and a patient, and is a memoir on the life of a brilliant writer who ends up becoming both. Image source: https://nerdybookarazzi.wordpress.com/ 2020/11/17/book-review-when-breath-becomes-air- by-paul-kalanithi-rocketgirlmd-singh_nikita- hinatekchandani/
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