Chronic hepatitis is hepatitis that lasts > 6 months. Common causes include hepatitis B and C viruses, metabolic dysfunction-associated steatohepatitis (MASH), alcohol-related liver disease, and autoimmune liver disease (autoimmune hepatitis). Many patients have no history of acute hepatitis, and the first indication is discovery of asymptomatic aminotransferase elevations. Some patients present with cirrhosis or its complications (eg, portal hypertension). Biopsy is sometimes necessary to confirm the diagnosis and to grade and stage the disease. Treatment is directed toward complications and the underlying condition (eg, glucocorticoids for autoimmune hepatitis, antiviral therapy for viral hepatitis). Liver transplantation is often indicated for decompensated cirrhosis.
Hepatitis lasting > 6 months is generally defined as chronic, although this duration is arbitrary.
Etiology of Chronic Hepatitis
Common causes
The most common causes of chronic hepatitis are (1):
Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH)
HBV and HCV are frequent causes of chronic hepatitis; up to 12% of cases of HBV infection (2), with or without hepatitis D virus (HDV) coinfection, and approximately 65 to 85% of cases of HCV infection become chronic (3). Rates are higher for developing chronic HBV infection in children. Although the mechanism of chronicity is uncertain, liver injury is mostly determined by the patient’s immune reaction to the infection.
Rarely, hepatitis E virus (HEV) genotype 3 has been implicated in chronic hepatitis (4, 5). Hepatitis A virus (HAV) does not cause chronic hepatitis.
Criteria for the diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) include the presence of steatosis in the liver in the setting of at least 1 of the following risk factors (6):
Insulin resistance
Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of MASLD that causes chronic hepatitis.
Alcohol-related liver disease (a combination of fatty liver, diffuse liver inflammation, and liver necrosis) results from excess alcohol consumption.
Less common causes
Autoimmune hepatitis (immune-mediated hepatocellular injury) accounts for a high proportion of hepatitis not caused by viruses or steatohepatitis; features of autoimmune hepatitis include the following (7):
The presence of serologic immune markers (eg, antinuclear antibodies, anti–smooth muscle antibodies, liver-kidney microsomal antibodies)
An association with histocompatibility haplotypes common in autoimmune disorders (eg, HLA-B1, HLA-B8, HLA-DR3, HLA-DR4)
A predominance of T cells and plasma cells in histologic liver lesions
Complex in vitro defects in cellular immunity and immunoregulatory functions
An association with other autoimmune disorders (eg, rheumatoid arthritis, autoimmune hemolytic anemia, proliferative glomerulonephritis)
A response to therapy with glucocorticoids or immunosuppressants
Primary biliary cholangitis is an immune-mediated process resulting in bile duct injury. Patients usually present with a positive antimitochondrial antibody (AMA) test and elevated alkaline phosphatase. Most patients with primary biliary cholangitis are women (8). Symptoms include fatigue, joint pain, and pruritus.
Sometimes chronic hepatitis has features of both autoimmune hepatitis and another immune-mediated chronic liver disorder (eg, primary biliary cholangitis, primary sclerosing cholangitis). These conditions are called overlap syndromes.
Many medications, including isoniazid, methotrexate, methyldopa, nitrofurantoin, tamoxifen, amiodarone, and rarely acetaminophen, can cause chronic hepatitis. The mechanism varies with the medication and may involve altered immune responses, development of steatohepatitis, cytotoxic intermediate metabolites, or genetically determined metabolic defects.
Less often, chronic hepatitis results from alpha-1 antitrypsin deficiency, celiac disease, a thyroid disorder, hereditary hemochromatosis, or Wilson disease.
Etiology references
1. Paik JM, Golabi P, Younossi Y, et al. Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD. Hepatology. 2020;72(5):1605-1616. doi:10.1002/hep.31173
2. Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67(1):1-31. Published 2018 Jan 12. doi:10.15585/mmwr.rr6701a1
3. Martinello M, Solomon SS, Terrault NA, et al. Hepatitis C. Lancet. 2023;402(10407):1085-1096. doi:10.1016/S0140-6736(23)01320-X
4. World Health Organization (WHO). Hepatitis E: Key Facts. Accessed May 13, 2026.
5. Narayanan S, Abutaleb A, Sherman KE, et al. Clinical features and determinants of chronicity in hepatitis E virus infection. J Viral Hepat. 2019;26(4):414-421. doi:10.1111/jvh.13059
6. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986. doi: 10.1097/HEP.000000000000052
7. Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology. 2020;72(2):671-722. doi:10.1002/hep.31065
8. Tana MM, Hirschfield GM. Primary Biliary Cholangitis. JAMA. 2026;335(3):269-270. doi:10.1001/jama.2025.20067
Classification of Chronic Hepatitis
Classification of chronic hepatitis specifies the following:
Etiology
Grade (intensity of histologic inflammation and necrosis)
Stage (degree of fibrosis, histologic or estimated noninvasively)
Inflammation and necrosis are potentially reversible. Fibrosis can be reversible if the cause is fully treated in patients who do not have cirrhosis.
Symptoms and Signs of Chronic Hepatitis
Clinical features of chronic hepatitis vary widely. Many cases develop after acute hepatitis, but most develop insidiously de novo.
Many patients are asymptomatic, regardless of the etiology. However, malaise, anorexia, and fatigue are common, sometimes with nonspecific upper abdominal discomfort. Jaundice is usually absent.
Often, the first findings are:
Signs of cirrhosis (eg, splenomegaly, spider nevi, palmar erythema)
Complications of cirrhosis (eg, portal hypertension, variceal bleeding, ascites, encephalopathy, liver cancer)
A few patients with chronic hepatitis develop manifestations of cholestasis (eg, jaundice, pruritus, pale stools, steatorrhea).
In autoimmune hepatitis, especially in young women, manifestations may involve virtually any body system and can include acne, amenorrhea, arthralgia, ulcerative colitis, pulmonary fibrosis, thyroiditis, nephritis, and hemolytic anemia.
Chronic hepatitis C is occasionally associated with lichen planus, cutaneous vasculitis, glomerulonephritis, porphyria cutanea tarda, mixed cryoglobulinemia, and, perhaps, non-Hodgkin B-cell lymphoma. Symptoms of cryoglobulinemia include fatigue, myalgias, arthralgias, neuropathy, glomerulonephritis, and rashes (urticaria, purpura, leukocytoclastic vasculitis); asymptomatic cryoglobulinemia is more common.
Diagnosis of Chronic Hepatitis
Liver test results compatible with hepatitis
Viral serologic and nucleic acid tests
Possibly autoantibodies, immunoglobulins, alpha-1 antitrypsin level, and other tests
Occasionally biopsy
Serum albumin, platelet count, and prothrombin time/international normalized ratio (PT/INR)
Evaluation for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH).
Chronic hepatitis is suspected in patients with any of the following:
Suggestive symptoms and signs
Incidentally noted elevations in aminotransferase levels
Previously diagnosed acute hepatitis
In the United States, testing of all adults ≥ 18 years at least once for hepatitis C is recommended (1).
MASLD and MASH should be considered in all patients with chronic hepatitis as metabolic dysfunction is a common cause of liver disease worldwide (2).
Liver tests
Liver tests are needed if not previously performed and include serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin.
Aminotransferase elevations are the most characteristic laboratory abnormalities (ALT normal values: 29 to 33 IU/L [0.48 to 55 microkat/L] for males and 19 to 25 IU/L [0.32 to 0.42 microkat/L] for females [3]). ALT is usually higher than AST. Aminotransferase levels can be normal during chronic hepatitis if the disease is quiescent, particularly with HCV infection and metabolic dysfunction-associated steatotic liver disease (MASLD).
Alkaline phosphatase is usually normal or only slightly elevated but is occasionally markedly high, particularly in primary biliary cholangitis.
Bilirubin is usually normal unless the disease is severe or advanced.
Albumin and PT/INR, while not evaluating directly for hepatic or hepatobiliary inflammation, are important in assessing hepatic synthetic function.
Other laboratory and imaging tests
If laboratory results are compatible with hepatitis, viral serologic tests are performed to exclude viral hepatitis (B, C, and sometimes E for chronic hepatitis). Unless these tests indicate viral etiology, further testing is required.
The next tests performed include:
Autoantibodies (antinuclear antibody, anti–smooth muscle antibody, antimitochondrial antibody, liver-kidney microsomal antibody)
Immunoglobulins
Serum transferrin saturation and ferritin
Thyroid tests (thyroid-stimulating hormone)
Tests for celiac disease (tissue transglutaminase antibody)
Alpha-1 antitrypsin level
Ceruloplasmin
Children and young adults are screened for Wilson disease by measuring the ceruloplasmin level.
Autoimmune hepatitis is normally diagnosed based on the presence of antinuclear (ANA), anti–smooth muscle (ASMA), or anti-liver/kidney microsomal type 1 (anti-LKM1) antibodies and usually elevations in serum immunoglobulin G (IgG). Antimitochondrial antibodies most often are positive in primary biliary cholangitis (4).
Serum transferrin saturation > 45% and elevated serum ferritin suggest hereditary hemochromatosis and should be followed by genetic testing for the hemochromatosis gene (HFE).
Serum albumin, platelet count, and PT should be measured to assess liver function and disease severity; low serum albumin, a low platelet count, or prolonged PT may suggest cirrhosis and even portal hypertension.
If the cause of hepatitis is identified, noninvasive tests (eg, ultrasound, elastography, FIB-4 and other blood based tests) can be performed to assess the degree of liver fibrosis (5, 6).
Biopsy
Biopsy may be necessary to confirm the diagnosis or etiology of chronic hepatitis.
Mild cases may have only minor hepatocellular necrosis and inflammatory cell infiltration, usually in portal regions, with normal acinar architecture and little or no fibrosis. Such cases rarely develop into clinically important liver disease or cirrhosis.
In more severe cases, biopsy typically shows periportal necrosis with mononuclear cell infiltrates (piecemeal necrosis) accompanied by variable periportal fibrosis and bile duct proliferation. The acinar architecture may be distorted by zones of collapse and fibrosis, and frank cirrhosis sometimes coexists with signs of ongoing hepatitis.
Biopsy is also used to grade and stage the disease, although noninvasive testing (serum markers or elastrography) is now often used instead of liver biopsy to stage fibrosis. One of the simplest markers to stage fibrosis is the FIB-4 index, which uses aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, and age to assess risk of advanced fibrosis (5, 6). Other modalities include transient elastography or MR elastography
Screening for complications
If symptoms or signs of cryoglobulinemia develop during chronic hepatitis, particularly with HCV, cryoglobulin levels and rheumatoid factor should be measured; high levels of rheumatoid factor and low levels of complement suggest cryoglobulinemia.
Patients with chronic HBV or HCV infection or cirrhosis due to any underlying liver disorder should be screened every 6 months for hepatocellular carcinoma with ultrasound and sometimes serum alpha-fetoprotein measurement (7).
Diagnosis references
1. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Hepatitis C Virus Infection in Adolescents and Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2020;323(10):970-975. doi:10.1001/jama.2020.1123
2. Targher G, Valenti L, Byrne CD. Metabolic Dysfunction-Associated Steatotic Liver Disease. N Engl J Med. 2025;393(7):683-698. doi:10.1056/NEJMra2412865
3. Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35. doi: 10.1038/ajg.2016.517
4. Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology. 2020;72(2):671-722. doi:10.1002/hep.31065
5. Castera L, Rinella ME, Tsochatzis EA. Noninvasive Assessment of Liver Fibrosis. N Engl J Med. 2025;393(17):1715-1729. doi:10.1056/NEJMra2403308
6. Sterling RK, Patel K, Duarte-Rojo A, et al. AASLD Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis. Hepatology. 2025;81(1):321-357. doi:10.1097/HEP.0000000000000845
7. Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78(6):1922-1965. doi:10.1097/HEP.0000000000000466
Treatment of Chronic Hepatitis
Supportive care
Treatment of cause (eg, glucocorticoids for autoimmune hepatitis, antivirals for hepatitis B virus [HBV] and hepatitis C virus [HCV] infection)
General treatment
Treatment goals for chronic hepatitis include treating the cause and, if cirrhosis and portal hypertension have developed, managing complications (eg, ascites, encephalopathy).
Medications that cause hepatitis should be stopped. Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease. NSAIDs should also be avoided in patients with severe hepatic impairment.
Underlying disorders should be treated. Lifestyle changes should be recommended for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-related liver disease.
Liver transplantation may be required for decompensated cirrhosis.
Chronic hepatitis B and C
There are specific antiviral treatments for chronic hepatitis B (eg, nucleoside/nucleotide analogues as first-line therapies) and antiviral treatments for chronic hepatitis C (eg, direct-acting antivirals).
In chronic hepatitis due to HBV, prophylaxis (including immunoprophylaxis) for contacts of patients may be helpful. No vaccination is available for contacts of patients with HCV infection.
Glucocorticoids and other immunosuppressants should be avoided in chronic hepatitis B and C because these medications enhance viral replication. If patients with chronic hepatitis B have other disorders that require treatment with glucocorticoids, other immunosuppressive therapies, or cytotoxic chemotherapy, they should be treated with antiviral medications at the same time to prevent a flare or reactivation of hepatitis B or acute liver failure due to hepatitis B (1). A similar situation with hepatitis C being activated or causing acute liver failure has not been described.
Metabolic dysfunction-associated steatohepatitis (MASH)
Treatment of MASH involves:
Reducing weight and controlling metabolic risk factors
Sometimes resmetirom or semaglutide
Treatment of MASH includes lifestyle modifications and control of metabolic risk factors (2). This may include discontinuation of medications or toxins, weight loss, and treatment for dyslipidemia and/or hyperglycemia. Weight loss interventions can reduce hepatic inflammation, steatosis, and fibrosis. (3, 4, 5).
Pharmacotherapy is recommended as an adjunct to lifestyle modifications for patients with biopsy-confirmed or noninvasively diagnosed steatohepatitis with moderate to severe (F2 and F3) fibrosis. Resmetirom, a thyroid beta receptor agonist has been shown to resolve steatohepatitis and improve fibrosis in some patients, and is discussed further separately (6, 7). Semaglutide, a GLP-1 receptor agonist, also resolved steatohepatitis and improved fibrosis in some patients along with cardiometabolic benefits (8).
Autoimmune hepatitis
Glucocorticoids (eg, prednisone, prednisolone, or budesonide in patients without cirrhosis) with or without azathioprine are the first-line treatment for autoimmune hepatitis, with the goal of inducing and maintaining biochemical remission and preventing progression to cirrhosis (9). Second-line treatments include mycophenolate mofetil (preferred) and tacrolimus; multiple salvage therapies have been described. Most patients ultimately require lifelong maintenance therapy, ideally with a glucocorticoid-sparing agent (eg, azathioprine).
Hereditary hemochromatosis
Hereditary hemochromatosis is treated with phlebotomy to achieve and maintain a ferritin level of 50 to 100 mcg/L (10, 11).
Treatment references
1. Ali FS, Nguyen MH, Hernaez R, et al. AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals. Gastroenterology. 2025;168(2):267-284. doi:10.1053/j.gastro.2024.11.008
2. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323
3. Koutoukidis DA, Koshiaris C, Henry JA, et al. The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: A systematic review and meta-analysis. Metabolism. 2021;115:154455. doi:10.1016/j.metabol.2020.154455
4. American Diabetes Association Professional Practice Committee. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S59-S85. doi:10.2337/dc25-S004
5. Koutoukidis DA, Astbury NM, Tudor KE, et al. Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. JAMA Intern Med. 2019;179(9):1262-1271. doi:10.1001/jamainternmed.2019.2248
6. Chen VL, Morgan TR, Rotman Y, et al. Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD Practice Guidance. Hepatology. 2025;81(1):312-320. doi:10.1097/HEP.0000000000001112
7. Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000
8. Newsome PN, Sanyal AJ, Engebretsen KA, et al. Semaglutide 2.4 mg in Participants With Metabolic Dysfunction-Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial. Aliment Pharmacol Ther. 2024;60(11-12):1525-1533. doi:10.1111/apt.18331
9. Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology. 2020;72(2):671-722. doi:10.1002/hep.31065
10. Bacon BR, Adams PC, Kowdley KV, et al; American Association for the Study of Liver Diseases. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(1):328-343. doi:10.1002/hep.24330.
11. Kowdley KV, Brown KE, Ahn J, Sundaram V. ACG Clinical Guideline: Hereditary Hemochromatosis. Am J Gastroenterol. 2019;114(8):1202-1218. doi:10.14309/ajg.0000000000000315
Prognosis for Chronic Hepatitis
Prognosis for patients with chronic hepatitis is highly variable and often depends on the cause and availability of treatment.
Chronic hepatitis caused by a medication often regresses completely when the causative medication is withdrawn.
Without treatment, cases caused by hepatitis B virus (HBV) can resolve (uncommon), progress rapidly, or progress slowly to cirrhosis over decades. Resolution often begins with a transient increase in disease severity and results in seroconversion from hepatitis B e antigen (HBeAg) to antibody to hepatitis B e antigen (anti-HBe) followed by the loss of hepatitis B surface antigen (HBsAg). Coinfection with hepatitis D virus (HDV) causes the most severe form of chronic HBV infection, with 2 to 4 times the rate of cirrhosis, hepatocellular carcinoma, and mortality compared with HBV alone (1).
Chronic HBV infection, even in the absence of cirrhosis, increases the risk of hepatocellular carcinoma (2). The risk is also increased in other liver disorders (eg, HCV infection, metabolic dysfunction-associated steatotic liver disease [MASLD]), but usually when cirrhosis or advanced fibrosis has developed.
Untreated chronic hepatitis due to HCV causes cirrhosis in some patients, although development may take decades and varies because it is often related to a patient's other risk factors for chronic liver disease, including alcohol use and having obesity.
Chronic autoimmune hepatitis usually responds to therapy but sometimes causes progressive fibrosis and eventual cirrhosis (3).
Prognosis references
1. Kushner T, Cohen SM, Ahn J, et al. AGA Clinical Practice Update on Management of Hepatitis Delta: Commentary. Gastroenterology. 2025;169(5):1063-1069. doi:10.1053/j.gastro.2025.07.037
2. Wang J, Qiu K, Zhou S, et al. Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis. Ann Med. 2025;57(1):2455539. doi:10.1080/07853890.2025.2455539
3. Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology. 2020;72(2):671-722. doi:10.1002/hep.31065
Key Points
Chronic hepatitis is usually not preceded by acute hepatitis and is often asymptomatic.
If liver test results (eg, unexplained elevations in aminotransferase levels) are compatible with chronic hepatitis, do serologic tests for hepatitis B, C, and possibly E.
If serologic results are negative, do tests (eg, autoantibodies, immunoglobulins, alpha-1 antitrypsin level) for other forms of hepatitis.
Consider a liver biopsy to confirm the diagnosis and assess the severity of chronic hepatitis if noninvasive testing is nondiagnostic.
Noninvasive tests (eg, elastography, serum markers) can be used to assess the degree of liver fibrosis.
Use recommended antiviral treatment regimens for chronic hepatitis B and C.
Treat autoimmune hepatitis with glucocorticoids and transition to steroid-sparing maintenance treatment.
Encourage diet and exercise for weight loss in patients with metabolic dysfunction-associated steatohepatitis (MASH); resmetirom may be useful.
Treat hereditary hemochromatosis with phlebotomy.
Drug Information for the Topic
