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  <front>
    <journal-meta id="journal-meta-0670f057a0c74c1f9a0825922ca0aa99">
      <journal-id journal-id-type="nlm-ta">Sciresol</journal-id>
      <journal-id journal-id-type="publisher-id">Sciresol</journal-id>
      <journal-id journal-id-type="journal_submission_guidelines">https://jnutres.com/</journal-id>
      <journal-title-group>
        <journal-title>Journal of Nutrition Research</journal-title>
      </journal-title-group>
      <issn publication-format="electronic"> 2348-1064</issn>
      <issn publication-format="print"/>
    </journal-meta>
    <article-meta id="article-meta-41cfe9da6ae14f13a3d75569865f576d">
      <article-id pub-id-type="doi">10.55289/jnutres/v12i1_23.26</article-id>
      <article-categories>
        <subj-group>
          <subject>Guideline</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title id="article-title-41360aed8bb045868bbd839a6d634f42">
          <bold id="strong-11f75eb11d1340bc98a2a3ba4f7c6fc5">Nutritional </bold>
          <bold id="strong-791be5c52a544d9a996eed37d8fcc1dd">M</bold>
          <bold id="strong-49a2ed564d0d42f19525b5aab976874c">anagement in </bold>
          <bold id="strong-0b1cbcf26668436da042495fb57e5f65">C</bold>
          <bold id="strong-e542d11d4e774582a098a920b299bf2c">hronic </bold>
          <bold id="strong-4935ec33afe54758b43f66b1c71e5824">L</bold>
          <bold id="strong-6e147585765a46efb8f7d6d9a0a30774">iver </bold>
          <bold id="strong-d352baaca41b48408aeb60a4c715c78f">D</bold>
          <bold id="strong-802a10764cd54233819fbed5da87c6ad">iseases and </bold>
          <bold id="strong-3b8a1a04ba6142d58183c3684d44a31b">L</bold>
          <bold id="strong-06bde7e891704900b1ead48c9b45af56">iver </bold>
          <bold id="strong-a0a9290ee8e04c2c97147579abf4b0d6">Transplantation</bold>
        </article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <name id="name-6ac2d78ed834400f94caac6a66210c05">
            <surname>Ramachandran</surname>
            <given-names>Gokulapriya</given-names>
          </name>
          <email>rgp1979@gmail.com</email>
          <xref id="xref-5aed1beb352f4e9e98f91a41498dfe13" rid="aff-f0312e9b6a0046e193bd4d9f9a7a3762" ref-type="aff">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name id="name-1d76ca02c0554d92952dd28eb67cc7de">
            <surname>Tirou</surname>
            <given-names>Kannane</given-names>
          </name>
          <xref id="xref-6e8892a8f35e4d37be8bb7d59e86823b" rid="aff-abdd8c5faac140fcbf7eaccab64c4aac" ref-type="aff">2</xref>
        </contrib>
        <aff id="aff-f0312e9b6a0046e193bd4d9f9a7a3762">
          <institution>Department of Surgical Gastroenterology, JIPMER</institution>
          <addr-line>Puducherry</addr-line>
          <country country="IN">India</country>
        </aff>
        <aff id="aff-abdd8c5faac140fcbf7eaccab64c4aac">
          <institution>Consultant Gastroenterologist, Tirou Medical Centre and Pelican Gastro Clinic</institution>
          <addr-line>Puducherry</addr-line>
          <country country="IN">India</country>
        </aff>
      </contrib-group>
      <volume>12</volume>
      <issue>1</issue>
      <fpage>1</fpage>
      <permissions>
        <copyright-year>2024</copyright-year>
      </permissions>
      <abstract id="abstract-abstract-title-3c0daeeed68c43c4a46e77db3cd12f86">
        <title id="abstract-title-3c0daeeed68c43c4a46e77db3cd12f86">Abstract</title>
        <p id="paragraph-46ed71a42dc746e6b56e13b0cb4c20f7">Prevalence of malnutrition is most common in patients with chronic liver diseases. Malnutrition is associated with frequent infections, inflammations, long duration of hospitalisation and cause deep negative impact on disease progression and outcomes. Early screening and identifying the levels of malnutrition may help in initiating timely and focused care to prevent further complications.</p>
        <p id="p-4768d80412ec"/>
      </abstract>
      <kwd-group id="kwd-group-62086e81866f461e8ab94db5d204127c">
        <title>Keywords</title>
        <kwd>Nutrition</kwd>
        <kwd>Malnutrition</kwd>
        <kwd>Assessment</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement>Department of Science and Technology (DST/WOS-B/2018/1648), Government of India, New Delhi</funding-statement>
      </funding-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title id="title-7bc193bd4e904806bc4b0cfcf75de514">Introduction</title>
      <p id="paragraph-22d6f5974ade47a89bfd0d5d707771e6">Advanced liver disease patients are more prone to malnutrition and nutritional deficiencies. Prevalence of malnutrition increases with liver disease severity and raises the risk of mortality even in patients with Model for End-Stage Liver Disease – Sodium (MELD-Na) &lt; than 15 <xref id="xref-d09ba6631a794ab4ae542a28a82b7983" rid="R231809230707978" ref-type="bibr">1</xref>. Hospitalisation and risk of malnutrition elevates in malnourished patients than the well-nourished, and in some patients, malnutrition is masked by obesity. Hence, regular nutritional screening and diet therapy helps in identifying and treating malnutrition and improves the disease condition and quality of life of the patient <xref id="xref-646e7a335d464729a77f916156ede8e0" rid="R231809230707981" ref-type="bibr">2</xref>. But intake of food is affected in liver disease patients due to various factors like feeling of fullness, decreased appetite, unpalatable food due to diet restrictions <xref id="xref-0875793294244c8e8fe28d12053e672c" rid="R231809230707977" ref-type="bibr">3</xref>, ascites and long hours of fasting for certain medical procedure <xref id="x-8746370a690e" rid="f-e4c352fa5fba" ref-type="fig">Figure 1</xref>. Diet for chronic liver diseases (CLD) patients should be a normal standard diet with supplements if necessary. Goals of diet therapy are to improve the status of malnutrition, to supply recommended macro and micronutrients, to correct nutritional deficiency diseases or clinical signs if any, to achieve positive nitrogen balance, to prevent muscle depletion, complications and to avoid hepato-toxic elements through diet<xref id="xref-776a218924a543299a2370a1481b2cc4" rid="R231809230707980" ref-type="bibr">4</xref>. </p>
      <p id="p-761a18f70e82"/>
      <p id="p-be9820dd106c"/>
      <fig id="f-e4c352fa5fba" orientation="portrait" fig-type="graphic" position="anchor">
        <label>Figure 1 </label>
        <caption id="c-d2128227473e">
          <title id="t-7303fefa8224">
            <bold id="s-0cdb55c2bcb9">Factors affecting food intake in chronic liver disease</bold>
          </title>
        </caption>
        <graphic id="g-6cd9d2a5d512" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/954b9e49-b7fe-4f72-8fea-59ae5393817f/image/4ae8bb48-0140-4a6b-b7ad-9c4d4d26283f-upicture1.png"/>
      </fig>
      <p id="p-da5a24c1eb06"/>
    </sec>
    <sec>
      <title id="title-958abdbf308241b2b4a21f51117713fc">Methodology</title>
      <p id="paragraph-df44da98545f47e6ae9d4fd7fc4a00ff">This paper addresses the guidelines on nutrition in chronic liver diseases and liver transplantation. Practical guidelines recommendations were initiated after critical evaluation of previous guidelines. Search was done<bold id="strong-06586af68c7645ada8bbafe8a8eb63c3"> </bold>for systematic reviews, randomized controlled clinical trials and original articles. These guidelines focus on the practical and feasible considerations in Indian scenario and after many deliberations by our expert group, these final recommendations were framed.</p>
      <sec>
        <title id="t-9dd6542ddb0a">
          <bold id="strong-84209a6d0fe340e19a52abdbd1ea2f7c">Recommendation 1</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-ce521992d296">
            <p><bold id="strong-9ba178dbc7ec4d8797e2b694f874467b">M</bold><bold id="strong-93822568c2c442c9a87500ba62527a48">alnutrition has </bold><bold id="strong-5c6e7e1bf498423fac38ed506d4362ac">many negative impacts</bold><bold id="strong-3ea623d853bc484aad8933e0a300691a"> </bold><bold id="strong-7b8ce66a3fb94531b607bbb9fa949019">in patients with CLD</bold><bold id="strong-b1bf68ba0f674778b3afefb8fabe2cb9">, hence nutritional assessment is </bold><bold id="strong-868a418c342e4b539a3a30e2b565eda5">required.</bold> </p>
            <list list-type="bullet">
              <list-item id="li-4a61107e29ba">
                <p>Malnutrition is a serious issue of concern in liver diseases, often undiagnosed and is associated with worse outcomes. Prevalence of malnutrition is around 5-92% in patients with liver diseases <xref id="xref-1c1fbc5b99f9485fb04edddcfa0e7a6a" rid="R231809230707977" ref-type="bibr">3</xref>. </p>
              </list-item>
              <list-item id="li-38bf85089c60">
                <p>Malnutrition is associated with loss of subcutaneous fat, muscle mass and muscle strength, increased risk of bacterial infections and complications, nutritional deficiency diseases, longer periods of hospitalization and/or ventilation.</p>
              </list-item>
              <list-item id="li-387db34522c8">
                <p>Malnutrition affects the overall survival and prognosis prior to and after liver transplantation (LT) <xref id="xref-5cfeac2d4a8f48dda8a1c0ceba0e6ebd" rid="R231809230707974" ref-type="bibr">5</xref>. </p>
              </list-item>
              <list-item id="li-af92f68b90e3">
                <p>High risk for malnutrition is also assumed if body mass index (BMI) &lt;18.5 kg/m<sup id="superscript-66aebd1e67184836876e8d95089deb68">2</sup>, or &gt;40kg/m<sup id="superscript-efa976fc3710419ba1e55f40c8b37482">2</sup> or Child Turcotte Pugh (CTP)-C. </p>
              </list-item>
              <list-item id="li-28e99305e286">
                <p>Detailed nutritional screening must be performed once in every three months for outpatients and on a monthly basis for those who are at risk for malnutrition and on a weekly basis for hospitalized patients.</p>
              </list-item>
              <list-item id="li-5cbfe0b59196">
                <p>Detailed nutritional screening includes global assessment tools viz., subjective global assessment (SGA), Royal Free Hospital Nutrition Prioritizing Tool (RFHNT), Nutrition Risk Screening (NRS)-2002 and Malnutrition Universal Screening Tool (MUST); anthropometry assessment like mid-arm muscle circumference (MAMC), mid-arm circumference (MAC), triceps skinfold thickness (TSF), BMI and muscle mass evaluation.</p>
              </list-item>
              <list-item id="li-c01cec2134be">
                <p>NRS-2002 and MUST are validated tools to screen the risk of malnutrition in hospitalised patients and recommended by ESPEN <xref id="xref-55da66837e1d4d6ebaaea436ecda4747" rid="R231809230707976" ref-type="bibr">6</xref>. </p>
              </list-item>
              <list-item id="li-6e537a0fb8b0">
                <p>NRS-2002 is helpful in identifying malnutrition among liver cirrhosis patients with Hepatocellular carcinoma (HCC)<xref id="xref-7b54904577d54c65a1d9a7a9f3cca01c" rid="R231809230707976" ref-type="bibr">6</xref>. </p>
              </list-item>
              <list-item id="li-075c4224aa81">
                <p>RFH-NPT is considered the validated gold standard for malnutrition screening and to identify those at risk of malnutrition. It is considered more sensitive than NRS-2002<xref id="xref-5c077b5e64154e01b880d4856e487042" rid="R231809230707979" ref-type="bibr">7</xref>.</p>
              </list-item>
              <list-item id="li-5f3f494f3f54">
                <p>Dual-energy X-ray absorptiometry (DEXA) and Bioimpedance analysis (BIA) can also be used to estimate skeletal muscle mass. However, this leads to overestimation due to water retention<xref id="xref-ab3df8eb1a96424386ffac4859eac45b" rid="R231809230707981" ref-type="bibr">2</xref>.</p>
              </list-item>
              <list-item id="li-c5aaab01c273">
                <p>Physical frailty is a good predictor of adverse clinical outcomes in chronic liver diseases<bold id="strong-0a74707ce4f8427793bfd1e6866546bf"> </bold>(CLD). Patients referred for liver transplantation should be assessed both at baseline and during follow-up using objective performance frailty tools like liver frailty index.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-f1725ac9b667">
          <bold id="strong-a54eb649d06e49c1ba78b173049e623a">Recommendation 2</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-ce1b9914f6ce">
            <p><bold id="strong-5ed30cb526804843b7f6dd5ff6c0189a">Patient with chronic liver diseases requires high calorie diet</bold><bold id="strong-277acab8671a45918fe4a10bbd1997c4"> to </bold><bold id="strong-27cb16c56363485cbb9e828eb1070360">reverse</bold><bold id="strong-1c5be56946854e37a0e98dd73c79b2e9"> </bold><bold id="strong-e99482d2a1e1499a922ce604610acd1f">malnutrition.</bold> </p>
            <list list-type="bullet">
              <list-item id="li-6627180c31c8">
                <p>High calorie intake of about 30-35kcal/kg/day (1.2-1.3 times the REE) is recommended to improve their nutritional status, prevent catabolism and enhance liver regeneration<xref id="x-e4052fbdfc87" rid="f-454c87f1a3a2" ref-type="fig">Figure 2</xref>.</p>
              </list-item>
              <list-item id="li-b4b6f6965c96">
                <p>Calorie intake can be achieved by increasing the frequency of meals i.e. 5-7 small meals per day than three big meals a day.</p>
              </list-item>
              <list-item id="li-222795f93fcf">
                <p>50-60% of total calories should be provided from carbohydrates mainly complex carbohydrates, 20-30% of calories from fat, preferably MUFA and PUFA (saturated fat intake should be limited) and 20-30% of calories from proteins<xref id="xref-7a5e2ae7b89147458b8e1f3102311c0c" rid="R231809230707989" ref-type="bibr">8</xref>.</p>
              </list-item>
              <list-item id="li-c145311ba8da">
                <p>Excess intake of calories leads to lipogenesis and liver dysfunction.</p>
              </list-item>
            </list>
          </list-item>
        </list>
        <p id="p-0608aec2d005"/>
        <fig id="f-454c87f1a3a2" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 2 </label>
          <caption id="c-992156a022fd">
            <title id="t-7a05e705061f"><bold id="s-a7f05a90c91a">Effect of calorie intake in chronic liver disease patients</bold>  </title>
          </caption>
          <graphic id="g-11f2fb4a3cef" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/954b9e49-b7fe-4f72-8fea-59ae5393817f/image/d2e5993c-f070-4909-aa93-814f24f101cf-upicture2.png"/>
        </fig>
        <p id="p-2c7e053b23d9"/>
      </sec>
      <sec>
        <title id="t-da07a071ca73">
          <bold id="strong-7fda57315fcf486bae38d7222dc3ba1d">Recommendation</bold>
          <bold id="strong-af5c84aa11724a1c998330f52fb64483"> </bold>
          <bold id="strong-3cb219e4336a4c2b86802bf818e03f3c">3</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-ebef21676921">
            <p>
              <bold id="strong-9fb6731859ba484fb4ff467fc4a3969a">Optimal intake of protein</bold>
              <bold id="strong-25e29805b4b6448da7c7a91a6d14f0b6">, carbohydrate and fats </bold>
              <bold id="strong-ed52f03826eb4cbf87c3db5ad22592c4">are beneficial in cirrhotic patients.</bold>
            </p>
            <list list-type="bullet">
              <list-item id="li-49cd97f97a01">
                <p>Protein requirement in CLD patients who are not malnourished is 1.2 g/kg/day and in the presence of malnutrition 1.5g/kg/day is recommended<xref id="x-c97c812f2c3e" rid="R231809230707989" ref-type="bibr">8</xref> to prevent muscle loss, reduce lethargy and gain muscle mass<xref id="xref-a473b9f2b8b54672a251ba0a7b823e5e" rid="R231809230707984" ref-type="bibr">9</xref>.</p>
              </list-item>
              <list-item id="li-08574bef22f9">
                <p>Inadequate protein intake of less than 0.8g/kg/day increases the risk of morbidity and mortality in cirrhotic patients <xref id="xref-b7bb2e4252204d5db78ac23326bd0917" rid="R231809230707986" ref-type="bibr">10</xref>. </p>
              </list-item>
              <list-item id="li-29dc3be0aff8">
                <p>Milk protein and vegetable proteins are well tolerated by cirrhotic patients, in addition, animal protein improves the protein quality and is well absorbed <xref id="xref-95852340d1c64460aed44178915521be" rid="R231809230707980" ref-type="bibr">4</xref>.</p>
              </list-item>
              <list-item id="li-ad07f76df887">
                <p>Branched-chain amino acids (BCAA) are a combination of dairy and plant protein, which helps in increasing appetite, restoring muscle mass, synthesizing skeletal muscle and maintaining Fischer ratio <xref id="xref-038f28b8eeb54848a1bdb3418bdbf0cd" rid="R231809230707988" ref-type="bibr">11</xref>. </p>
              </list-item>
              <list-item id="li-45d45642e6e7">
                <p>Limitation in glycogen storage increases the risk of hypoglycemia hence a liberal intake of carbohydrate is required to increase the glycogen stores to improve liver function. </p>
              </list-item>
              <list-item id="li-a3475c04ebcc">
                <p>300-400g/day of high complex and simple carbohydrates is suggested and can be obtained through 4-6 carbohydrate rich foods <xref id="xref-03197b1adfaa47109a61e2337c9f9813" rid="R231809230707969" ref-type="bibr">12</xref>.</p>
              </list-item>
              <list-item id="li-65c450958f54">
                <p>60-70% of calories should be obtained from carbohydrates to prevent ammonia accumulation <xref id="xref-8d7f9982d1aa4c1388e2ed8c41e0df0e" rid="R231809230707983" ref-type="bibr">13</xref>.</p>
              </list-item>
              <list-item id="li-423875a44f76">
                <p>Fat restriction is not advisable until slow gastric emptying and steatorrhea are reported <xref id="xref-510a60b5757f444ca19f14f2f70161b7" rid="R231809230707972" ref-type="bibr">14</xref>.</p>
              </list-item>
              <list-item id="li-f7ab26a5cddc">
                <p>Short chain and medium chain fatty acids can be supplemented as it does not require bile salts for absorption.</p>
              </list-item>
              <list-item id="li-d8b320c5e0f2">
                <p>Omega-3 fatty acids supplementations delay disease progression and are beneficial especially in the post-transplant period <xref id="xref-9721b731e027457d9f2a9fc16d55b305" rid="R231809230707987" ref-type="bibr">15</xref>.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-aefaa15e3ec7">
          <bold id="strong-52193aa978644aedb9392cb0ff62c1bf">Recommendation </bold>
          <bold id="strong-6066db7de4444584a8f6f1922ea8cc8a">4</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-edb07b7a1da3">
            <p>
              <bold id="strong-7440990e5c8448b9b3d873817e2e5c0c">Obesity </bold>
              <bold id="strong-8f707659e76f48c6bd0058dd0e6d6db1">increases the risk of morbidity and mortality, irrespective of its etiology, hence h</bold>
              <bold id="strong-2d49a994b2c44088b2541e5b69e59e2d">ypo-calorie diet with high protein is </bold>
              <bold id="strong-61756878afb94606880ec95d5b238359">recommended in patients with obesity.</bold>
            </p>
            <list list-type="bullet">
              <list-item id="li-f14347a6b7cf">
                <p>20-35% of CLD patients are obese irrespective of its etiology<bold id="strong-212ed95664e74ed081f8af39e6b4cb6f">. </bold>Increased obesity is observed in Non-alcoholic steatohepatitis (NASH) related cirrhosis.</p>
              </list-item>
              <list-item id="li-b4bb14cdcd4b">
                <p>Obesity in end-stage liver disease (ESLD) patient is associated with increased infection.</p>
              </list-item>
              <list-item id="li-bbb4e6a062ee">
                <p>A target of 5-10% weight loss can be achieved by reducing 500-800 kcal from their daily requirements. </p>
              </list-item>
              <list-item id="li-7dff9b6be4a0">
                <p>High protein diet of greater than 1.5g/kg/day is recommended.</p>
              </list-item>
              <list-item id="li-44d3a9814733">
                <p>Hypocaloric can be maintained by reducing the food portion size and the frequency of eating.</p>
              </list-item>
              <list-item id="li-5b9a48970185">
                <p>High protein intake helps in preventing muscle loss and promoting weight loss.</p>
              </list-item>
              <list-item id="li-808df62c2c5c">
                <p>Physical activity should be increased gradually and avoid hypomobility.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-7b9f0f81067c">
          <bold id="strong-31810b39506a49ceb1a11ec0fac7cfea">Recommendation 5</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-a67860195336">
            <p><bold id="strong-6c61716b105345bbb2e75b6e0194c20c">All patients with CLD should be identified for potential micronutrient status and if any deficiencies should be </bold><bold id="strong-c1ec4944e5274c6eba6f8a7de3b1313a">treated.</bold> </p>
            <list list-type="bullet">
              <list-item id="li-3120bd93536f">
                <p>Micronutrient deficiencies are very common among patients with liver diseases due to poor intake, depleted stores of nutrients and malabsorption and dysbiosis.</p>
              </list-item>
              <list-item id="li-6aabbb01dda9">
                <p>Fat soluble vitamin deficiencies are common due to inadequate bile secretion and decreased storage <xref id="xref-1bfef7fc274541b49b53ff91db53351e" rid="R231809230707970" ref-type="bibr">16</xref>.</p>
              </list-item>
              <list-item id="li-aff6aafbc185">
                <p>Inadequacies also occur due to less intake, malabsorption, and decreased synthesis of binding proteins (retinol binding protein for Vitamin A and Vitamin D binding proteins).</p>
              </list-item>
              <list-item id="li-a029085eb88d">
                <p>Daily oral supplementation of 2000-2,00,000 IU of vitamin A is suggested if serum retinol levels are &lt;10 µg/dL which reflects vitamin A deficiency<xref id="xref-195e753af8a049aa80a29a059209c5f1" rid="R231809230707973" ref-type="bibr">17</xref>.</p>
              </list-item>
              <list-item id="li-718203ad6bea">
                <p>Serum calcidiol (25‑hydroxy vitamin D [25(OH)D]) reflects vitamin D levels. The Endocrine society considers serum calcidiol levels between 20 - 30 ng/mL as insufficient and &lt;10 ng/mL as a risk factor for hepatic decompensation and mortality <xref id="xref-e1f906515b934bfdae5ab761ebdb94dd" rid="R231809230707985" ref-type="bibr">18</xref>.</p>
              </list-item>
              <list-item id="li-8171245de5d4">
                <p>Endocrine society also suggests oral dosage of 6000 IU/day or 50,000 IU/week to be supplemented during deficiency and oral maintenance dose of 1500-2000 IU/day can be continued until the normal serum levels are achieved <xref id="xref-2957d5d0c0314603bf5c410ae96e89e6" rid="R231809230707975" ref-type="bibr">19</xref>.</p>
              </list-item>
              <list-item id="li-6f599ceefbbd">
                <p>Vitamin E deficiency can cause hemolytic anaemia, platelet aggregation and peripheral neuropathy. During deficiency 400-800 IU/day is recommended as initial supplementation.</p>
              </list-item>
              <list-item id="li-dac4858c3709">
                <p>Vitamin K is common in decompensated disease mainly due to malabsorption and gut dysbiosis. Injection with the dosage of 10mg of Vitamin K for 3 days is helpful in treating the deficiency. </p>
              </list-item>
              <list-item id="li-d46f34ac7226">
                <p>Due to malabsorption and gut dysbiosis, oral supplement will not be beneficial in these patients.</p>
              </list-item>
              <list-item id="li-f605551c94d9">
                <p>In alcoholic liver disease, vitamin B deficiency cause Wernicke’s encephalopathy and Korsakoff’s dementia. Oral supplementation of 30-100 mg of thiamine twice/ thrice/day treats this condition<xref id="x-34e14fea9b94" rid="R231809230720815" ref-type="bibr">20</xref>.</p>
              </list-item>
              <list-item id="li-639006ddd9d6">
                <p>Folic acid deficiency causes microcytic anaemia. Intravenous supplementation of 400-1000 µg for 3days and 400 µg/day orally until normal levels of erythrocyte folate is achieved (140ng/ml) <xref id="xref-0d0dbaa148a04702bb7cc7a8466c816f" rid="R231809230707982" ref-type="bibr">21</xref>.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-47c714b91017">
          <bold id="strong-be66e77a105244099406ff4b6f1439db">Recommendation 6</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-811970f841b0">
            <p><bold id="strong-867bf923f81447acb705c2c76b0b67f0">Malnutrition and sarcopenia are associated with increased risk of morbidity and mortality.</bold> </p>
            <list list-type="bullet">
              <list-item id="li-6b9100416ff4">
                <p>Due to the limited capacity of hepatocytes to synthesize, store and breakdown of glycogen, carbohydrate utilization is reduced and fat depletion is increased for energy utilization. As the disease progresses, scarcity of fat leads to pronounced muscle protein breakdown that further leads to skeletal muscle loss contributing to sarcopenia <xref id="x-c02f2bd1bef6" rid="R231809230720819" ref-type="bibr">22</xref>.</p>
              </list-item>
              <list-item id="li-406f02ebcca5">
                <p>Prevalence (47% - 84%) of malnutrition and sarcopenia in cirrhosis is higher among the Indian population <xref id="xref-7a964b2a300340688d2786f3ed014749" rid="R231809230707989" ref-type="bibr">8</xref>. </p>
              </list-item>
              <list-item id="li-12ccfeb11126">
                <p>Sarcopenia in cirrhotic patients have an increased chance of developing hepatic encephalopathy (HE), refractory ascites and complications due to infection and inflammation.</p>
              </list-item>
              <list-item id="li-544f30c4160f">
                <p>Sarcopenia in Non-alcoholic fatty liver disease (NAFLD) patients likely increases the chance of steatohepatitis or advanced fibrosis.</p>
              </list-item>
              <list-item id="li-90641d69412b">
                <p>In HCC patients, sarcopenia is associated with poor survival, tumor recurrence and mortality.</p>
              </list-item>
              <list-item id="li-ca872a296c62">
                <p>Sarcopenia and malnutrition, during pre-transplant period increase the risk of decompensation, morbidity and mortality.</p>
              </list-item>
              <list-item id="li-6a309821fb52">
                <p>Sarcopenia in post-transplant period increase post operative infections, increase the duration of hospitalisation and poor outcomes.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-ae8820747f73">
          <bold id="strong-d93f37dcfd714d78919b3cfdba706da8">Recommendation </bold>
          <bold id="strong-b6c0b331ac9c4c78b84bae79b6fea4a9">7</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-b1181568bbda">
            <p>
              <bold id="strong-91557dc996c64c90a36d52a60e987e25">Bone disease </bold>
              <bold id="strong-2eec498dc1f34a74a60f6530d0959216">should be identified and treated mainly in cholestatic liver disease and liver transplantation waiting patients.</bold>
            </p>
            <list list-type="bullet">
              <list-item id="li-81a44bd828e0">
                <p>Patients with liver damage are more prone to hepatic osteodystrophy, which includes osteoporosis and osteomalacia.</p>
              </list-item>
              <list-item id="li-dccb97ffba84">
                <p>Osteoporosis is loss of muscle mass causing fragility fractures; Osteomalacia is demineralization of bone due to Vitamin D deficiency.</p>
              </list-item>
              <list-item id="li-ae2968284940">
                <p>Higher prevalence of osteoporosis (30%) is noticed in cholestasis including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) and in patients waiting for liver transplantation. </p>
              </list-item>
              <list-item id="li-1c562e99a320">
                <p>A balanced diet with optimal nutrient intake is suggested in addition to 1000-1500 mg/d calcium supplements and 400-800 IU/day of 25-hydroxy vitamin D/calcidiol until the normal levels are reached.</p>
              </list-item>
              <list-item id="li-105614ddcc5f">
                <p>Lifestyle changes like increased physical activity, exercise and cessation of alcohol and tobacco are helpful.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-3bd4789a5610">
          <bold id="strong-0f93a1c867dc4701b41b44facce15920">Recommendation </bold>
          <bold id="strong-75c135985ed74828bf1c23fbdc991dab">8</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-a3819fd6fe80">
            <p><bold id="strong-dcd515c67c0d42dfbe924db52c3ddffc">F</bold><bold id="strong-5350097a0e1e4f708736c84c45990dee">luid restrictions </bold><bold id="strong-e822f9820e1d4c88b045e4e7c9f247d6">is not required in patients with chronic liver disease.</bold> </p>
            <list list-type="bullet">
              <list-item id="li-683d0b0041fb">
                <p>As a rule, fluid intake is not restricted until the sodium levels are &lt;125mEq/L, or in the presence of uncontrolled ascites or the patient also have renal failure.</p>
              </list-item>
              <list-item id="li-aef02be437a8">
                <p>Fluid accumulates since the blood vessels lose the capabilities to retain fluids due to impaired protein synthesis and albumin synthesis <xref id="xref-ca971a98259f4ebfbdfca331f36d8330" rid="R231809230707969" ref-type="bibr">12</xref>.</p>
              </list-item>
              <list-item id="li-6bccbd428b03">
                <p>Sodium intake is restricted to 2g/day to prevent fluid build-up especially in ascites.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-3dd0c6066c40">
          <bold id="strong-34c9555f05f442878184fa3a5834ff73">Recommendation</bold>
          <bold id="strong-f437550c97eb4827bfa6a3d372f1de4a"> </bold>
          <bold id="strong-6064d55ea46446e88fe5491212425f28">9</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-9b4de618a772">
            <p>
              <bold id="strong-8ffeed4f60ab47ff8385c757e65b8828">Timings and mode of feeding is also a vital component in reducing malnutrition and </bold>
              <bold id="strong-ba0a5a6332b44e42ab52532557f66440">sarcopenia.</bold>
            </p>
            <list list-type="bullet">
              <list-item id="li-78d75e619e8d">
                <p>Long hours of fasting in CLD patients affects protein synthesis, increases muscle proteolysis and gluconeogenesis (especially from amino acids) thus increasing the risk for sarcopenia. </p>
              </list-item>
              <list-item id="li-0e9940f6461b">
                <p>Long fasting hours should be avoided, and frequent intake of small meals prevent catabolic state. Long hours of starvation are usually possible during night hours and hence nocturnal supplementation rich in carbohydrates and proteins are beneficial.</p>
              </list-item>
              <list-item id="li-c114fca0fc59">
                <p>Multigrain bread or nut bread sandwich may be a healthy option for late evening snacks (LES), this provides 700 calories and 25g protein, helps in preventing catabolism and maintaining muscle mass<xref id="x-6c8543d767d4" rid="R231809230720957" ref-type="bibr">23</xref>.</p>
              </list-item>
              <list-item id="li-0e986f4cb424">
                <p>LES enriched with BCAA improves serum albumin levels, glucose tolerance and Fischer ratio thus reducing the mortality among cirrhotic patients. </p>
              </list-item>
              <list-item id="li-5fa1ca1bcd3a">
                <p>LES helps in reversing anabolic resistance and sarcopenia.</p>
              </list-item>
              <list-item id="li-fcdf3e5ef1a7">
                <p>In gastrointestinal bleeding, early feeding within 24 hours after the bleed reduces the risk of rebleeding<xref id="x-a8df51b8cfed" rid="R231809230720980" ref-type="bibr">24</xref>.</p>
              </list-item>
              <list-item id="li-4f2f7b2908a6">
                <p>Enteral nutrition may be the preferable route to deliver the nutrients since it maintains the integrity of gastric mucosa and gut barrier function, and less expensive with very few complications<xref id="x-156dfef4c2ee" rid="R231809230707971" ref-type="bibr">25</xref>. </p>
              </list-item>
              <list-item id="li-bd8c60114ae8">
                <p>Parenteral route is indicated to patients unable to achieve optimal nutritional requirement orally for more than 12 h or in moderate or severe malnutrition.</p>
              </list-item>
              <list-item id="li-af1031442eb1">
                <p>Long term use of parenteral nutrition may also worsen liver function.</p>
              </list-item>
              <list-item id="li-cfcf8eb9699e">
                <p>Parenteral nutrition carries the risk of infection, electrolyte imbalance and fluid over-load. Hence it is important to initiate enteral or oral nutrition during the early recovery period<xref id="xref-f393d63878da42a1b7c804a24086d2b2" rid="R231809230707971" ref-type="bibr">25</xref>.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-ab3a8213c3c1">
          <bold id="strong-23ee267426454d8da5d0dfdd79493021">Recommendation </bold>
          <bold id="strong-7b9ca5708c404a48a1a703e128e39c61">10</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-02462c83a515">
            <p>
              <bold id="strong-d865ba135e374704a1595b4596cc8406">Physical activity and exercises are recommended to improve muscle contractile function and muscle mass in patients with CLD</bold>
            </p>
            <list list-type="bullet">
              <list-item id="li-85cdc3558bbf">
                <p>Physical inactivity and sedentary lifestyle are associated with frailty, sarcopenia and mortality in CLD patients [26]. Physical activity and exercise are physiological anabolic stimuli that can reverse protein synthesis and increase muscle mass <xref id="x-28a5c78e67e9" rid="R231809230721130" ref-type="bibr">26</xref>.</p>
              </list-item>
              <list-item id="li-573ed2bbe110">
                <p>Exercises increase plasma testosterone concentrations which stimulate amino acid uptake and protein synthesis and inhibits protein degradation <xref id="x-7d810fb85213" rid="R231809230721131" ref-type="bibr">27</xref>.</p>
              </list-item>
              <list-item id="li-a49f43392644">
                <p>In adults, 150-300min / week of moderate-intensity of physical activity or 75-150 mins of vigorous-intensity of physical activity is recommended <xref id="x-d0982ac7c83a" rid="R231809230721120" ref-type="bibr">28</xref>.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
      <sec>
        <title id="t-81e3a73244d2">
          <bold id="strong-1ea152c7808d4d85a9bd78ff9329ade5">Disease specific recommendation</bold>
        </title>
        <list list-type="bullet">
          <list-item id="li-fc4226588a0d">
            <p><bold id="strong-149f28ca45cc41f796cd34549ed27cc2">HE</bold>  </p>
            <list list-type="bullet">
              <list-item id="li-cc09c80177d7">
                <p>Protein restriction does not benefit in HE, as it worsens, HE outcomes.</p>
              </list-item>
              <list-item id="li-0a741c05d2dc">
                <p>Intake of 1.2g/kg/day of protein reduces lethargy and is safe in cirrhotic patients with episodic encephalopathy but should not be restricted beyond 0.8g/kg/day as it imposes the risk of mortality and morbidity <xref id="x-cc27c65a3a4b" rid="R231809230721126" ref-type="bibr">29</xref>.</p>
              </list-item>
              <list-item id="li-89370d15eaac">
                <p>25-45 g/ day of fibre intake (non- digestible carbohydrate) alters gut microbiota, prevents bacterial translocation, increases ammonia excretion via stools and prevents constipation<xref rid="R231809230707980" ref-type="bibr">4</xref>, <xref rid="R231809230721122" ref-type="bibr">30</xref>.</p>
              </list-item>
              <list-item id="li-800f754b2393">
                <p>Intake of probiotics, BCAA, fibre and supplements for vitamins and minerals should be ensured for patients’ wellbeing Impact of SARS CoV-2 /COVID-19 infection on the course of advanced chronic<xref id="x-6157cace058d" rid="R231809230721123" ref-type="bibr">31</xref>.</p>
              </list-item>
            </list>
          </list-item>
          <list-item id="li-b7aa8cacf8b5">
            <p>
              <bold id="strong-917598905edc4402b44157475cc75d00">NAFLD</bold>
            </p>
            <list list-type="bullet">
              <list-item id="li-5709c4252387">
                <p>High protein intake of 2-2.5 g/kg/day help in reducing weight loss. Majority of calories should be contributed by proteins <xref id="x-14c4d945ca2d" rid="R231809230721129" ref-type="bibr">32</xref>.</p>
              </list-item>
              <list-item id="li-31560f2a4b75">
                <p>Hypo-caloric, high fibre, high protein diet significantly reduced liver fat content, liver stiffness, GGT and serum lipids <xref id="x-e658980ce0ab" rid="R231809230721124" ref-type="bibr">33</xref>. </p>
              </list-item>
              <list-item id="li-bd25d754a440">
                <p>Food intake should be once in every 2-3 hours; hence 5-6 meals/ day is recommended<xref id="x-a02f9fcfc2c8" rid="R231809230721129" ref-type="bibr">32</xref> .</p>
              </list-item>
              <list-item id="li-cf5c99475e81">
                <p>Boiled, steamed, and baked foods are allowed and avoid soft drinks, fried and fast foods.</p>
              </list-item>
              <list-item id="li-4f9e385484c9">
                <p>Regular coffee consumption decreases the risk of NAFLD by 29%, liver fibrosis by 30-39% and cirrhosis by 39%<xref id="x-991bc7be4ac6" rid="R231809230721127" ref-type="bibr">34</xref>.</p>
              </list-item>
            </list>
          </list-item>
          <list-item id="li-d98a10f9ece2">
            <p>
              <bold id="strong-51fa613e09664e228b1017432428539f">NASH</bold>
              <bold id="strong-f8eb3688638941a089218ce09811d961"> </bold>
            </p>
            <list list-type="bullet">
              <list-item id="li-86a0fa11303b">
                <p>Weight loss is encouraged, targeting a reduction of 7-10% weight loss improves liver fat content, inflammation and fibrosis. A reduction in 5% of BMI is associated with 25% relative reduction in liver fat<xref id="x-c796e388193c" rid="R231809230721128" ref-type="bibr">35</xref>.</p>
              </list-item>
              <list-item id="li-8bf09c202e0b">
                <p>20-25kcal/kg/day is recommended and helps in reducing 5-10% of body weight.</p>
              </list-item>
              <list-item id="li-06afe1968847">
                <p>Alcohol abstinence helps in decreasing the comorbidity risk and improves liver biochemistry and histology<xref id="x-b82865a8a3df" rid="R231809230721125" ref-type="bibr">36</xref>.</p>
              </list-item>
              <list-item id="li-f8f108524301">
                <p>Vitamin E supplementation of 400-800 IU / day improves liver enzymes, steatosis, and inflammation as well<xref id="x-829d58b53ae8" rid="R231809230721121" ref-type="bibr">37</xref>.</p>
              </list-item>
              <list-item id="li-61d97770a60e">
                <p>Water soluble vitamin deficiencies are common in alcoholic hepatitis and NASH.</p>
              </list-item>
            </list>
          </list-item>
          <list-item id="li-4c615b610802">
            <p><bold id="strong-ab368273bcd84bd1ae0ca19afea5168a">HCC</bold> </p>
            <list list-type="bullet">
              <list-item id="li-407dbe66fdba">
                <p>Vitamin A and D deficiency are contributing factors of HCC development. </p>
              </list-item>
              <list-item id="li-776b52240b68">
                <p>The endocrine society warns that serum calcidiol concentrations &lt;10 ng/mL is a high risk for HCC patients.</p>
              </list-item>
              <list-item id="li-ca790c5897b7">
                <p>Vitamin D has to be supplemented until the normal range is achieved (normal serum calcidiol concentrations &gt;30 ng/mL)<xref id="xref-c462eb5e08de4571951e29f0a89ea15e" rid="R231809230707975" ref-type="bibr">19</xref>.</p>
              </list-item>
              <list-item id="li-f8e8d413ef03">
                <p>BCAA supplementation improves nutritional status, prevents reduction in residual liver function, and prevents recurrence.</p>
              </list-item>
            </list>
          </list-item>
        </list>
      </sec>
    </sec>
    <sec>
      <title id="title-ce98fe53889f4c38b584de1ee1e4bfb6">Conclusion</title>
      <p id="paragraph-c605f6713cf942c7b0a5410872671664">Malnutrition is very commonly observed in chronic liver disease. Assessing the nutritional status, timely identification of risks and deficiencies, and proper planning of diet in addition to treatment have a positive impact on the prognosis of health condition of decompensated liver failure patients. Proper care during the liver transplant waiting period helps in improving their nutritional status, improves survival, decrease morbidity, and improves the quality of life.</p>
      <sec>
        <title id="t-390c60afcfc7">Acknowledgment</title>
        <p id="t-00814da45f92">Department of Science and Technology (DST/WOS-B/2018/1648), Government of India, New Delhi.</p>
        <p id="p-09ed27fe7d1e"/>
      </sec>
    </sec>
  </body>
  <back>
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