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Review
. 2021 Jul;56(7):593-619.
doi: 10.1007/s00535-021-01788-x. Epub 2021 Jul 7.

Evidence-based clinical practice guidelines for Liver Cirrhosis 2020

Hitoshi Yoshiji  1   2 , Sumiko Nagoshi  3 , Takemi Akahane  3 , Yoshinari Asaoka  3 , Yoshiyuki Ueno  3 , Koji Ogawa  3 , Takumi Kawaguchi  3 , Masayuki Kurosaki  3 , Isao Sakaida  3 , Masahito Shimizu  3 , Makiko Taniai  3 , Shuji Terai  3 , Hiroki Nishikawa  3 , Yoichi Hiasa  3 , Hisashi Hidaka  3 , Hiroto Miwa  3 , Kazuaki Chayama  4 , Nobuyuki Enomoto  3 , Tooru Shimosegawa  3 , Tetsuo Takehara  4 , Kazuhiko Koike  3
Affiliations
Review

Evidence-based clinical practice guidelines for Liver Cirrhosis 2020

Hitoshi Yoshiji et al. J Gastroenterol. 2021 Jul.

Abstract

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

Keywords: Complications; Diagnosis; Guidelines; Liver cirrhosis; Treatment.

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Conflict of interest statement

Any financial relationship with enterprises, businesses or academic institutions in the subject matter or materials discussed in the manuscript are listed as follows: (1) those from which the enterprises and for-profit organizations received remuneration paid as patent royalties; SRL, (2) those from which the authors, the spouse, partner or immediate relatives of the authors have received individually any income, honoraria or any other type of renumeration; Abbvie, Otsuka Pharmaceutical, Gilead Sciences, Sumitomo Dainippon Pharma, MSD, Eisai, EA Pharma, Bristol Myers Squibb, Mitsubishi Tanabe Pharma, Bayer Yakuhin, ASKA Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Taiho Pharmaceutical, Chugai Pharmaceutical, (3) those from which the academic institutions of the authors received support (commercial/academic cooperation); Abbvie, Otsuka Pharmaceutical, EA Pharma, Gilead Sciences, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Bristol Myers Squibb, Eisai, MSD, Nippon Kayaku, Ono Pharmaceutical, Teijin Pharma, Novartis Pharma, ASKA Pharmaceutical, Astellas Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, Toray, Mochida Pharmaceutical, Interstem, Rohto Pharmaceutical, Towa Pharmaceutical, Nihon Pharmaceutical, Janssen Pharmaceutical, MIC Medical, Kowa, and 4)those from which the authors have received individually endowed chair;Shibuya Corporation.

Figures

Fig. 1
Fig. 1
Diagnostic algorithm for liver cirrhosis. After obtaining basic information on the cause of liver cirrhosis, characteristics of the patients, and physical examinations, we should combine several diagnostic tools, such as serum biomarkers, imaging modalities, and endoscopy, as noninvasive alternatives to liver biopsy. This algorithm diagnoses cirrhotic F4 fibrosis. A special blood test or histological characteristics are often needed to determine the cause of cirrhosis. APRI aspartate aminotransferase to platelet ratio index, FIB-4 fibrosis-4 index, HCV hepatitis C virus, hx history, M2BPGi Mac-2 binding protein glycosylation isomer
Fig. 2
Fig. 2
Nutritional therapy. *There is no gold standard for the assessment of nutritional status. It is recommended to comprehensively evaluate nutritional status by assessing dietary intake, body composition, and biochemical examinations. Measurement of non-protein respiratory quotient (npRQ) using indirect calorimetry is recommended for the assessment of energy malnutrition. However, the measurement of npRQ is limited in general medical practice. In patients with liver cirrhosis, %arm circumference (%AC) < 95 and fasting plasma free fatty acid (FFA) levels > 660 μEq/L are indices to predict npRQ < 0.85, which is a prognostic marker. Changes in fasting plasma FFA levels are useful for the dynamic assessment of nutritional status after dietary/nutritional intervention. However, the measurement of plasma FFA levels is not covered by the National Health Insurance of the Japanese Ministry of Health. For patients undergoing invasive treatment for hepatocellular carcinoma or esophagogastric varices, dietary/nutritional therapy is strongly recommended to improve protein-energy malnutrition. The diagnosis of sarcopenia is based on the Japan Society of Hepatology guidelines for sarcopenia in liver disease (Reference, CQ4-18). Measurement of grip strength is used to assess muscle strength. Muscle mass is assessed by skeletal muscle index based on bioelectrical impedance analyzer (BIA) or computed tomography (CT) scans at the lower border of the third lumbar vertebra (L3). Each assessment has advantages and disadvantages. **Based on required daily energy intake, it is recommended to treat cirrhotic patients by dietary/nutritional therapy, including divided meals (3–5 times/day), late evening snack, and BCAA-enriched enteral nutrients. Regular assessments of nutritional status are recommended. In patients with no improvement in nutritional status or energy intake, an oral BCAA supplement is recommended for patients with ascites or hepatic encephalopathy. Oral BCAA granules are recommended for patients with hypoalbuminemia. ***Patients with BMI < 18.5 kg/m2 are at high risk of protein-energy malnutrition or sarcopenia. It is recommended to perform regular nutritional assessments and dietary/nutritional intervention using enteral nutrients, including BCAA-enriched nutrients. ****Oral BCAA supplement is approved for “an improvement in the nutritional status of patients with chronic hepatic failure and hepatic encephalopathy.” Oral BCAA granules are approved for “an improvement in hypoalbuminemia in decompensated cirrhotic patients with sufficient energy intake and hypoalbuminemia.” Hypoalbuminemia is defined as a serum albumin level <3.5 g/dL. To prevent disease progression, it is recommended to change oral BCAA granules to alternative treatments in patients with no improvement of hypoalbuminemia 2 months after treatment with oral BCAA granules or no improvement of energy intake or BCAA to tyrosine ratio (BTR) 1 month after treatment with oral BCAA granules
Fig. 3
Fig. 3
Diagnostic algorithm for cirrhotic ascites. As a routine test, ascitic fluid obtained by diagnostic paracentesis should be examined for total protein, albumin, cell count, and differential cell count. The serum–ascites albumin gradient (SAAG) is an index for estimating the cause of ascites. Ascites can be diagnosed as leaky when it is 1.1 g/dL or more and exudative when it is less than 1.1 g/dL. SAAG is more reliable than the exudate-transudate concept, defined by transudate if the protein concentration of ascites is 2.5 g/dL or less and exudative if it is 4.0 g/dL or more. However, there are exceptions to these indicators; therefore, it is necessary to make a comprehensive judgment. Spontaneous bacterial peritonitis (SBP) is diagnosed when the bacterial culture is positive or when the neutrophil count is 250/mm3 or higher, even if the bacterial culture is negative. The leukocyte esterase test strip is a simple and rapid diagnostic tool for SBP and is useful in situations where it is difficult to calculate the number of neutrophils
Fig. 4
Fig. 4
Therapeutic algorithm for cirrhotic ascites. Grade 1 ascites is treated with sodium restriction (5–7 g/day) and, in some cases, diuretics. For grade 2 and 3 ascites, spironolactone (25–50 mg/day) is administered as a first-line drug with sodium restriction. When the effect is insufficient, furosemide (20–40 mg/day) is used in combination. In cases of resistant or intractable tolvaptan (3.75–7.5 mg/day) is additionally administered after hospitalization. For tolvaptan-resistant patients without renal dysfunction, intravenous injection of potassium canrenoate (100–200 mg) and furosemide (20 mg) is started. For severe hypoalbuminemia (< 2.5 g/dL), albumin infusion is considered. For refractory ascites, paracentesis or cell-free and concentrated ascites reinfusion therapy (CART) is recommended. Albumin infusion in large-volume paracentesis is effective in preventing paracentesis-induced circulatory dysfunction (PICD). Peritoneovenous shunts or transjugular intrahepatic portosystemic shunt (TIPS) are recommended for resistant cases. If these treatments are ineffective, liver transplantation should be considered
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References

    1. Fukui H, Saito H, Ueno Y, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51:629–650. doi: 10.1007/s00535-016-1216-y. - DOI - PubMed
    1. Higgins JPT, Thomas J, Chandler J. Cochrane Handbook for Systematic Reviews of Interventions version 6.0. https://training.cochrane.org/handbook/current. 2019.
    1. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–394. doi: 10.1016/j.jclinepi.2010.04.026. - DOI - PubMed
    1. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol. 2011;64:395–400. doi: 10.1016/j.jclinepi.2010.09.012. - DOI - PubMed
    1. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines 6. Rating the quality of evidence–imprecision. J Clin Epidemiol. 2011;64(12):1283–1293. doi: 10.1016/j.jclinepi.2011.01.012. - DOI - PubMed