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Chronic Hepatitis

Chapter 352 | Harrison's 22e

KEY CLINICAL POINTS

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[PAGE 2673] Chronic Hepatitis 2673 CHAPTER 352 TABLE 352-1 Clinical and Laboratory Features of Chronic Hepatitis 352 Chronic Hepatitis TYPE OF HEPATITIS DIAGNOSTIC TEST(S) THERAPY Chronic hepatitis B HBsAg, IgG anti-HBc, IFN- α , PEG IFN- α Esperance A. K. Schaefer, HBeAg, HBV DNA Oral agents: Raymond T. Chung, Jules L. Dienstag First-line: entecavir, tenofovir Chronic hepatitis C Anti-HCV, HCV RNA Sofosbuvir-ledipasvir, glecaprevir- pibrentasvir, sofosbuvir- Chronic hepatitis represents a series of liver disorders of varying causes velpatasvir, elbasvir-grazoprevir, and severity in which hepatic inflammation and necrosis continue sofosbuvir-velpatasvir-voxilaprevira for at least 6 months. Milder forms are nonprogressive or only slowly Chronic hepatitis D Anti-HDV, HDV RNA, IFN- α , PEG IFN- α c, bulevirtideb progressive, while more severe forms may be associated with scarring HBsAg, IgG anti-HBc and architectural reorganization, which, when advanced, lead ulti- Autoimmune ANA (homogeneous), First line: prednisone, azathioprine mately to cirrhosis. Several broad categories of chronic hepatitis have hepatitis anti-SMA, anti-SLA, Second line: mycophenolate been recognized. These include chronic viral hepatitis, drug-or toxin- anti-LKM1 (±) mofetil, tacrolimus, rituximab Hyperglobulinemia induced chronic hepatitis (Chap. 351), alcohol-associated liver disease (Chap. 353), metabolic dysfunction-related chronic hepatitis See www.hcvguidelines.org. (Chap 354), and autoimmune chronic hepatitis. In many cases, clinical aDetailed treatment recommendations can be found at www.hcvguidelines.org. and laboratory features are insufficient to allow assignment into one of bCurrently approved by European Medicines Agency, under review at the U.S. Food these distinct categories; these “idiopathic” cases are also believed to and Drug Administration. represent autoimmune chronic hepatitis. Moreover, because of the high Abbreviations: HBc, hepatitis B core; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis D prevalence of steatotic liver diseases (metabolic dysfunction-associated virus; IFN- α , interferon α ; IgG, immunoglobulin G; LKM, liver-kidney microsome; steatotic liver disease and alcohol-associated liver disease), patients PEG IFN- α , pegylated interferon α ; SLA, soluble liver antigen; SMA, smooth muscle with more than one, overlapping type of hepatitis are encountered not antibody. infrequently (e.g., viral and steatotic liver injury, alcohol-related and within the lobule; and the degree of portal inflammation. Several scor- nonalcohol-related steatotic liver injury). Finally, clinical and labora- ing systems for viral hepatitis that take these histologic features into tory features of chronic hepatitis are observed occasionally in patients account have been devised, and the most popular are the histologic with other hereditary/metabolic disorders, such as Wilson disease activity index (HAI), used commonly in the United States, and the (copper overload) and α antitrypsin deficiency (Chaps. 355 and 427). 1 METAVIR score, used in Europe (Table 352-2). Based on the presence Although all types of chronic hepatitis share certain clinical, laboratory, and degree of these features of histologic activity, chronic hepatitis can be and histopathologic features, chronic viral and chronic autoimmune graded as mild, moderate, or severe. hepatitis are sufficiently distinct to merit separate discussions. For dis- cussion of acute hepatitis, see Chap. 350. I CLASSIFICATION BY STAGE The stage of chronic hepatitis, which reflects the level of progression CLASSIFICATION OF CHRONIC HEPATITIS of the disease, is based on the degree of hepatic fibrosis. When fibro- Common to all forms of chronic hepatitis are histopathologic distinc- sis is so extensive that fibrous septa surround parenchymal nodules tions based on localization and extent of liver injury. These vary from and alter the normal architecture of the liver lobule, the histologic the milder forms, previously labeled chronic persistent hepatitis and lesion is defined as cirrhosis. Staging is based on the degree of fibrosis chronic lobular hepatitis, to the more severe form, formerly called as categorized on a numerical scale 0 − 6 (HAI) or 0 − 4 (METAVIR) chronic active hepatitis. When first defined, these designations were (Table 352-2). Several noninvasive approaches have been introduced believed to have prognostic implications, which were not corroborated to provide approximations of hepatic histologic stage, including serum by subsequent observations. Categorization of chronic hepatitis based biomarkers of fibrosis; fibrosis scores such as FIB-4, a validated algo- primarily on histopathologic features has been replaced by a more rithm based on such routine lab tests as aspartate and alanine amino- informative classification based on a combination of clinical, serologic, transferase (AST and ALT) levels and platelet counts (PLT) (age [years] and histologic variables. Classification of chronic hepatitis is based on × AST divided by PLT ×); the Enhanced Liver Fibrosis (ELF) score, a (1) its cause; (2) its histologic activity, or grade; and (3) its degree of proprietary score (applied more frequently in steatotic liver disease progression based on level of fibrosis, or stage. Thus, neither clinical than viral liver disease) based on a combination of three nonroutine features alone nor histologic features—requiring liver biopsy or non- blood tests (hyaluronic acid, procollagen III N-terminal peptide, and invasive markers of fibrosis—alone are sufficient to characterize and tissue inhibitor of metalloproteinase 1); and imaging determinations of distinguish among the several categories of chronic hepatitis. liver elasticity/stiffness. CLASSIFICATION BY CAUSE CHRONIC VIRAL HEPATITIS Clinical and serologic features allow the establishment of a diagnosis Both of the enterically transmitted forms of viral hepatitis, hepatitis A of chronic viral hepatitis, caused by hepatitis B, hepatitis B plus D, or and E, are self-limited and do not cause chronic hepatitis (rare reports hepatitis C; autoimmune hepatitis, including several subcategories, notwithstanding in which acute hepatitis A serves as a trigger for the I and II, based on serologic distinctions; drug-associated chronic hepatitis; onset of autoimmune hepatitis in genetically susceptible patients or and a category of unknown cause, or cryptogenic chronic hepatitis in which hepatitis E [Chap. 350] can cause chronic liver disease in (Table 352-1). These are addressed in more detail below. immunosuppressed hosts, for example, after liver transplantation). In contrast, the entire clinicopathologic spectrum of chronic hepatitis CLASSIFICATION BY GRADE occurs in patients with chronic viral hepatitis B and C as well as in Grade, a histologic assessment of necroinflammatory activity, is based patients with chronic hepatitis D superimposed on chronic hepatitis B. on examination of the liver biopsy. An assessment of important histo- logic features includes the degree of periportal necrosis and the disrup- I CHRONIC HEPATITIS B tion of the limiting plate of periportal hepatocytes by inflammatory The likelihood of chronicity after acute hepatitis B varies as a function cells (so-called piecemeal necrosis or interface hepatitis); the degree of age. Infection at birth is associated with clinically silent acute infec- of confluent necrosis that links or forms bridges between vascular tion but a 90% chance of chronic infection, whereas infection in young structures—between portal tract and portal tract or even more impor- adulthood in immunocompetent persons is typically associated with tant bridges between portal tract and central vein—referred to as bridging clinically apparent acute hepatitis but a risk of chronicity of only ~1%. necrosis; the degree of hepatocyte degeneration and focal necrosis Most cases of chronic hepat