Food aversion and intolerance in hepatitis C secondary to signs and symptoms of CLD such as nausea, anorexia, gastritis, and encephalopathy lead to a reduced dietary intake. Additionally, most patients with hepatitis C treated with interferons and direct acting antivirals tend to experience loss of appetite and metallic taste as adverse effects. Deficiencies in vitamin A and zinc lead to an altered sense of taste for food, already low in Sodium, further compounding the problem of reduced oral intake.Bile salt deficiency due to reduced entero-hepatic recycling in patients with impaired liver function has been proposed as the primary mechanism of Malabsorption in cirrhotic patients (Romiti et al. 1990). Other contributing factors include altered intestinal motility and mucosal injury that may be secondary to portal hypertension or bacterial overgrowth, which in itself impairs absorption of nutrients via small intestinal mucosal surface.In addition to depletion of glycogen stores, hepatocyte injury, in conjunction with insulin resistance,impairs glucose regulatory processes like gluconeogenesis further increasing reliance on alternative energy fuels such as lipids and fats, for the metabolic needs of the body. In addition to the depletion of vital macromolecules, preferential oxidation of lipids further reduces the respiratory quotient in CLD patients relative to those with normal liver function (Merli et al. 1990)A combination of reduced urea hepatic protein synthesis, impaired intestinal protein absorption, and increased urinary nitrogen excretion predispose cirrhotic patients to sarcopenia and also lead to a lowered ratio of branched-chain amino acids to aromatic acids in the blood.CLD patients often exhibit an increase in resting energy expenditure, as measured by indirect calorimetry. Hypermetabolism thought to be due to an increase in beta-adrenergic activity has been found to correlate well with a reduction in survival in CLD patients by some studies (Müller et al. 1999). The increased frequency of hypermetabolism in patients with complications like ascites and its negative impact on survival highlight the need to identify and address these complications earlier on in the disease course.Obesity is often associated with elevated circulating levels of cytokines like leptin released by adipocytes. These adipocytokines with pro-fibrogenic properties are thought to play an important role in inducing a state of low-grade inflammation and hepatic fibrosis due to their pro-fibrogenic properties (Saxena and Anania 2015), as shown in Fig. 3. Free fatty acids secreted by visceral adipocytes also impair insulin signaling in the skeletal muscle and liver by activating the lipid-activated protein kinase C family, contributing to insulin resistance in HCV patients (Kawaguchi and Mizuta 2014)Nutritional assessment of patients with hepatitis C allows for identification of nutritional risks that may contribute further to morbidity and mortality. Recognition of macro- and micronutrient deficiencies is important as their correction with supplemental nutrition can significantly reduce the risk of infections as well as in-hospital morbidity and improve liver function parameters of such patients. This assessment needs to be much more detailed in patients presenting with decompensated cirrhosis as they are more likely to be at risk for nutrient deprivation. In general, adequate assessment of the nutritional status requires a thorough history, detailed physical examination, and appropriate laboratory investigations.HistoryPertinent findings in patient history may include changes in weight, which can be quantified as the percentage of weight lost involuntarily over the preceding 6 months. Generally, weight loss > 10% is taken as severe. It is important to note however that a patient with decompensated cirrhosis, presenting with salt and water retention, may not be able to report an accurate history of weight changes.Dietary intake may be assessed using the 24-h dietary recall to identify incorrect dietary practices commonly observed in patients with CLD, who are often advised to consume a diet low in protein by ill-informed attendants as well as healthcare practitioners.Other symptoms to inquire about include gastrointestinal disturbances such as diarrhea, vomiting, or constipation that may indicate underlying malabsorption.The severity of the underlying liver disease can be assessed by inquiring about complications like ascites and encephalopathy that may manifest as increasing abdominal girth, respiratory difficulties, and altered mental status or disturbances in sleep wake cycle.Micronutrient deficiencies may present in advanced cases of liver disease with symptoms like night blindness or photophobia (vitamin A), burning of the mouth or tongue (vitamin B12, folate), easy bruising (vitamin C, K), paresthesias (thiamine, pyridoxine), or even skin lesions (zinc, vitamin A, niacin).Physical ExaminationA general physical examination should be performed on all patients at risk for nutritional deficiencies with particular attention to the presence of peripheral edema and ascites, muscle wasting, and signs of vitamin/mineral deficiencies such as pallor (iron deficiency), hyperkeratosis (vitamin A), dermatitis (vitamin A), bruising (vitamin C, vitamin K), glossitis (vitamin B12, folate, niacin), angular stomatitis (vitamin B12), and reduced lower extremity deep tendon reflexes (vitamins B12, B1).An accurate assessment of the patient’s weight and height needs to be performed and recorded for reference in future as it may facilitate tracking of the patient’s physical parameters.ScreeningTo date, several nutritional assessment tools have been developed, and although many of these remain in use in various parts of the world, no one tool has been accepted as the Gold standard yet.To be effective, a screening tool needs to be simple, easy to use, and patient-friendly, and for that reason, subjective global assessment is one of the most commonly employed scales to identify patients suffering from nutritional deprivation.It combines multiple elements of nutritional assessment to classify the severity of malnutrition from mild to severe. These components include recent weight loss, changes in dietary intake, gastrointestinal symptoms, functional capacity, signs of muscle wasting, and the presence of pre-sacral or pedal edema. On the basis of these assessments, patients are classified as well nourished (grade A), moderately malnourished (grade B), or severely malnourished (grade C)The SGA is a simple bedside method, proven to be adequate for the purpose of identification of malnutrition among patients with HCV. It is an excellent tool to assess nutritional status that can be applied on the bedside as it uses elements that can all be derived from a focused history and physical examination, rendering expensive, and time-consuming laboratory tests unnecessary.SGA, however, has not been found to be as reliable as handgrip strength, in predicting the complications of cirrhosis, as indicated by some studies (Alvares-da-Silva and Reverbel da Silveira 2005) (Table 1)Laboratory EvaluationSeveral laboratory and radiologic investigations may provide objective evidence of malnutrition in patients with HCV. Of these, specialized investigations like bioelectrical impedance analysis and dual-energy X-ray absorptiometry are not performed routinely but may be indicated in certain cases of an advanced liver disease, cirrhosis, or patients being evaluated for liver transplant.Serum levels of proteins including albumin, prealbumin, transferrin, and coagulation factors, which are generally regarded as useful indicators of nutritional status in the general population, are not as reliable in patients with decompensated cirrhosis due to hepatic synthetic dysfunction, limiting their use in HCV to patients with acute infection and early cirrhosis. Of these proteins, changes in levels of prealbumin are more reflective of acute changes in nutritional status owing to its relatively short half-life of two to three days, as compared to albumin which has a half-life of approximately 20 days.Reduced hepatic synthesis, decreased muscle mass, and increased tubular secretion are all responsible for decreased serum levels of creatinine, another marker of lean muscle mass, in cirrhosis.Serum levels of fat-soluble vitamins may be normal in HCV patients in the absence of advanced liver disease when fat malabsorption due to impaired entero-hepatic recirculation of bile salts leads to deficiencies of these vitamins. Plasma levels of vitamins A, D, and E, as well as INR, may be deranged in such patients.Levels of water-soluble vitamins such as folate and zinc may also be deranged. Serum vitamin B12 levels may be elevated in chronic HCV and cirrhosis due to hepatic cytolysis and release of stored vitamins and minerals. Patients with a history of concurrent alcohol abuse may also show decreased levels of thiamine. Deficiencies of other B complexes may present with decreased levels of hemoglobin and deranged mean corpuscular volume of RBC’s.Ancillary TestsAnthropometryAmong anthropometric measures used to identify malnutrition in HCV patients, mid-arm muscle circumference (MAMC) and hand-grip strength have been found to be the best indicators of protein-calorie malnutrition. Based on studies, a mid-arm muscle circumference of <23 cm in combination with a handgrip strength of <30 kg is thought to have a sensitivity of 94% and negative predictive value of 97% for diagnosing PCM.Meanwhile, body fat reserves have found to correlate best with skin-fold thickness, which has produced similar results as DEXA scans when used in studies on patients without ascites. For this purpose, the SFT over triceps may easily be measured at the midpoint between the acromion and olecranon using a caliper. A value lower than the 5th centile suggests severe malnutrition.Miscellaneous TestsSeveral other specialized tools for nutritional assessment can be used in certain cases of chronic liver disease, but are not routinely employed primarily due to their cost and limited availability.Bioelectrical impedance analysis (BIA) uses impedance which measures body water to estimate the fat content of the body. One of the limitations to its use is that even small variations in electrode placement tend to result in relatively large errors in measured impedance.Dual-energy X-ray absorptiometry (DEXA) scan can be used to accurately measure fat mass in patients with chronic liver disease but is unable to estimate the lean body mass due to increases in extracellular water in patients with decompensated liver disease (McCullough et al. 1991).An accurate assessment of the nutritional needs using resting energy expenditure can significantly help in management of patients with chronic HCV as well as cirrhosis secondary to other causes. This can be done either using the Harris Benedict equation (HBE) that relies on factors like weight, age, gender, and height or using Indirect Calorimetry which is considered to be the gold standard assessment (Peng et al. 2007). Because it is not widely available though, its use has been limited to patients unable to meet their nutritional requirements despite adequate therapy (Fig. 5)ManagementEnsuring adequate nutrition can significantly improve quality of life in HCV patients. Good nutrition results in improved compliance with pharmacologic therapy and has also been found to hinder disease progression by preventing the development of HCV complications like cirrhosis and hepatic encephalopathy.In the absence of decompensated cirrhosis or comorbid conditions like diabetes mellitus, HCV patients usually do not require special diets. However, it is imperative that they consume a balanced diet, containing an adequate amount of calories and proteins to fight the infection as well as antioxidants to combat free radicals responsible for hepatocyte damage. In addition, frequent small meals have been found to improve nitrogen and substrate use, diminish fat and protein oxidation, and prevent depletion of glycogen stores.Major principles in management of malnutrition in chronic HCV revolve around restoring muscle health. In accordance with this, most interventions are focused on providing a diet that is adequate in proteins and calories and integrate physical activity into the patient's lifestyle. Because management of malnutrition in such patients is directed at addressing the underlying etiology, it is important to obtain a good understanding of the nutritional intake patterns and barriers to healthy eating. The best way to achieve that is through a detailed history and physical exam at each clinic visit, as well as counseling sessions with a dietician, who may be able to further draw up an individualized plan for each patient based on his/her need. Because a dietitian may not be available in many clinical settings, physicians may need to familiarize themselves with guideline recommendations for both diet and activity.HCV patients who are unable to meet their caloric requirements due to a diminished nutrient intake and early satiety should be advised to take frequent small volume meals up to 4–6 times/day (Amodio et al. 2013). Patients presenting with refractory ascites with a low MELD score and those suffering from portal hypertensive enteropathy may be offered TIPS in order to improve nutrient absorption. Replacement of trace elements such as zinc, magnesium, and vitamin A may be considered in patients presenting with food aversion due to micronutrient deficiencies, as per their symptoms and serum levels.Enteral feeding via a feeding tube is only recommended for patients who are unable to consume food orally despite the above interventions, as tolerance is often an important issue with a significant number of patients prematurely removing their feeding tubes themselves. Therefore, an oral route should be preferred as the first line intervention, even in the presence of complications like esophageal varices. Due to the high risk of complications, PEG tube placement is discouraged as well.Patients with cirrhosis are prone to fluctuating sugar levels and are thus advised to avoid fasting longer than 6 h as it may trigger a hypoglycemic episode and lead to additional complications. Cirrhotic patients are also advised to take small frequent meals throughout the day as well as an evening snack of complex carbohydrates to decrease lipid oxidation and reduce skeletal muscle proteolysis.It is generally recommended that HCV patients limit fat to 25% of the total calories in their diet. The general recommendation for diet composition is to limit carbohydrates to 50%, mostly in the form of complex sugars, protein to 20%, and total caloric intake to 30–40 kcal/Kg/day of the desirable body weight. It is also recommended that the consumption of processed sugars like fructose be avoided given its association with increases in the severity of liver fibrosis in HCV patients with genotype 1 (Petta et al. 2013). Substances like alcohol that can significantly enhance the rate of disease progression should also be avoided.Dietary SupplementationFor patients with advanced liver disease presenting with steatorrhea due to bile acid deficiency, fat-soluble vitamins and medium chain triglycerides that do not need bile for absorption may be supplemented in their diet. These are often available as nutritional drinks and can be easily taken even by patients with reduced tolerance to oral intake.Consuming vegetable-based proteins that contain fewer aromatic amino acids and supplementing the diet with branched chain amino acids should also be considered in patients at risk for hepatic encephalopathy, which is often accompanied by an impaired balance of these amino acids. Some studies have also implicated treatment with interferon and ribavirin in inducing this imbalance in the early stage of therapy, which further suggests the importance of correcting this imbalance early in the course of the disease.Physical ActivityModerate physical activity is recommended for all HCV patients and has shown improvements in muscle mass, exercise capacity, and quality of life in general (Román et al. 2014; Zenith et al. 2014; Berzigotti et al. 2017). Exercise will not affect the course of infection, but it can help relieve fatigue, stress, and depression as well as improve appetite and strengthen immunity. HCV patients can also benefit from physical activity due to its effect on obesity. For patients with decompensated cirrhosis, however, physical activity needs to be carefully prescribed and individualized to each patient's exercise tolerance and presence of complications like esophageal varices. Deconditioning and fatigue are major issues for patients with cirrhosis that represent significant barriers to physical activity (Ney et al. 2017). Formal guidelines for physical activity in cirrhosis are not yet available. Therefore, it is important that all patients undergo screening for varices and the required variceal prophylaxis before an exercise regimen is initiated (García Pagan et al. 1996; Bandi et al. 1998) (Fig. 6)Policies and protocolsPoliciesRole of Health Care Providers and Local Government in Ensuring Food Security for All HCV PatientsIn this chapter, we have described some screening tools available for the identification of malnutrition as well as its management in HCV patients. Below, we talk about some policies that could be adopted to ensure adequate nutrition for patients with chronic liver disease, and the role of health care providers, as well as the local government in the implementation of these policies.HCV patients can be categorized as those with acute HCV, compensated cirrhosis, and decompensated cirrhosis. We recommend screening all HCV patients with a simple screening tool like SGA to identify patients suffering from nutritional impairment, and limiting the use of more specialized diagnostic measures, such as BIA and DEXA scans, to patients with an advanced form of liver disease, such as those with decompensated liver disease, awaiting liver transplantation.HCV patients should be offered counseling sessions with a dietician as well as a physical therapist, preferably at each clinical visit so that they may be screened for under-nutrition and managed appropriately, if at risk. In settings where a limitation of resources may present a barrier, physicians should take it upon themselves to familiarize themselves with the dietary needs of HCV patients, as well as the protocols in place, for dietary intervention in malnourished individuals. They should also take advantage of the clinic visits to obtain a dietary history from all patients to ensure an adequate provision of nutrients. It falls to the health divisions of local governments to ensure screening and management of under-nutrition at all healthcare facilities in that area. This can be achieved through regular audits by the concerned authorities as well as appointments of trained professionals by the government at each of these facilities.In addition to provision of antiviral medication, as is common practice in many third-world countries like Pakistan, local government should take also develop policies to provide aid, in the form of food packets, to HCV patients who may be unable to meet their nutritional needs on their own, due to financial constraints and the stress of their sickness. For the purpose of identification of such disadvantaged patients, the local government may rely on feedback from healthcare professionals as well as nongovernmental organizations, familiar with the socio-economic circumstances of these patientsESPEN Guidelines for Screening and Management of HCV Patients with Cirrhosis and Liver Transplant CandidatesUse SGA to identify malnutrition in patients with cirrhosis and bio-electric impedance analysis to quantify undernutrition in such patients.As per ESPEN guidelines, ensure energy intake of 35–40 kcal/kg/day, protein intake of 1.2–1.5 g/kg/day. For patients unable to meet these caloric requirements with normal daily food intake, supplementary nutrition may be provided, preferably via the enteral route. Tube feeding is only indicated in patients who are unable to maintain or tolerate oral intake. PEG tube is associated with adverse outcomes and should not be used until other options have been exhausted.For nutritional supplementation, whole protein formulas are generally recommended. In patients presenting with cirrhosis complicated with ascites, concentrated high energy formulas should generally be preferred. BCAA-enriched formulas have been found to improve outcomes in patients with encephalopathy and should, therefore, be supplemented in the diet of cirrhotic patients with concomitant encephalopathy.HCV is the most indication for liver transplantation as patients frequently progress to decompensated cirrhosis. For liver transplant candidates, in addition to the usual protocol for Cirrhotic patients, it is recommended that normal food/enteral nutrition be initiated within 12–24 h following liver transplantation. A nasogastric tube or catheter jejunostomy may be employed for early enteral nutrition posttransplant

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