Merck Manual

Please confirm that you are a health care professional

honeypot link

Overview of Chronic Hepatitis


Sonal Kumar

, MD, MPH, Weill Cornell Medical College

Reviewed/Revised Aug 2022 | Modified Sep 2022
Topic Resources

Chronic hepatitis is hepatitis that lasts > 6 months. Common causes include hepatitis B and C viruses, nonalcoholic steatohepatitis (NASH), 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, corticosteroids 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

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are frequent causes of chronic hepatitis; 5 to 10% of cases of HBV infection, with or without hepatitis D Hepatitis D Hepatitis D is caused by a defective RNA virus (delta agent) that can replicate only in the presence of hepatitis B virus. It occurs uncommonly as a coinfection with acute hepatitis B or as... read more virus (HDV) coinfection, and about 75% of cases of HCV infection become chronic. Rates are higher for developing chronic HBV infection in children (eg, up to 90% of infected neonates and 25 to 50% of young 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 genotype 3 has been implicated in chronic hepatitis.

Hepatitis A virus does not cause chronic hepatitis.

NAFLD develops most often in patients with at least one of the following risk factors:

  • Obesity

  • Dyslipidemia

  • Insulin resistance

NASH is the progressive form of NAFLD 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:

  • 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 corticosteroids or immunosuppressants

Primary biliary cholangitis Primary Biliary Cholangitis (PBC) Primary biliary cholangitis (PBC; formerly known as primary biliary cirrhosis) is an autoimmune liver disorder characterized by the progressive destruction of intrahepatic bile ducts, leading... read more (formerly, primary biliary cirrhosis) 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. 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 drugs, including isoniazid, methotrexate, methyldopa, nitrofurantoin, tamoxifen, amiodarone, and rarely acetaminophen, can cause chronic hepatitis. The mechanism varies with the drug and may involve altered immune responses, development of steatohepatitis, cytotoxic intermediate metabolites, or genetically determined metabolic defects.

Classification of Chronic Hepatitis

Cases of chronic hepatitis were once classified histologically as chronic persistent, chronic lobular, or chronic active hepatitis. Current classification specifies the following:

Symptoms and Signs of Chronic Hepatitis

Clinical features of chronic hepatitis vary widely. About one third of 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 low-grade fever and nonspecific upper abdominal discomfort. Jaundice is usually absent.

Often, the first findings are

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 Lichen Planus Lichen planus is a recurrent, pruritic, inflammatory eruption characterized by small, discrete, polygonal, flat-topped, violaceous papules that may coalesce into rough scaly plaques, often accompanied... read more Lichen Planus , mucocutaneous vasculitis Cutaneous Vasculitis Cutaneous vasculitis refers to vasculitis affecting small- or medium-sized vessels in the skin and subcutaneous tissue but not the internal organs. Cutaneous vasculitis may be limited to the... read more Cutaneous Vasculitis , glomerulonephritis Overview of Nephritic Syndrome Nephritic syndrome is defined by hematuria, variable degrees of proteinuria, usually dysmorphic red blood cells (RBCs), and often RBC casts on microscopic examination of urinary sediment. Often... read more , porphyria cutanea tarda Porphyria Cutanea Tarda Porphyria cutanea tarda (PCT) is a comparatively common hepatic porphyria affecting mainly the skin. Liver disease is also common. PCT is due to an acquired or inherited deficiency in the activity... read more Porphyria Cutanea Tarda , mixed cryoglobulinemia, and, perhaps, non-Hodgkin B-cell lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more Non-Hodgkin Lymphomas . 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 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)

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 addition, to identify asymptomatic patients, the Centers for Disease Control (CDC) recommends testing of all adults 18 years at least once for hepatitis C.

Liver tests

Liver tests are needed if not previously done 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 [ 1 Diagnosis reference Chronic hepatitis is hepatitis that lasts > 6 months. Common causes include hepatitis B and C viruses, nonalcoholic steatohepatitis (NASH), alcohol-related liver disease, and autoimmune liver... read more ]). ALT is usually higher than AST. Aminotransferase levels can be normal during chronic hepatitis if the disease is quiescent, particularly with HCV infection and nonalcoholic fatty liver disease Metabolic Dysfunction–Associated Liver Disease (MASLD) Steatotic liver disease is due to excessive accumulation of lipid in hepatocytes. Metabolic dysfunction–associated liver disease (MASLD) includes simple fatty infiltration (a benign condition... read more (NAFLD).

Bilirubin is usually normal unless the disease is severe or advanced.

Other laboratory tests

If laboratory results are compatible with hepatitis, viral serologic tests are done to exclude HBV and HCV (see tables Hepatitis B Serology Hepatitis B Serology* Hepatitis B Serology* and Hepatitis C Serology Hepatitis C Serology Hepatitis C Serology ). Unless these tests indicate viral etiology, further testing is required.

The next tests done include

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 at titers of 1:80 (in adults) or 1:20 (in children) and usually elevations in serum immunoglobulins. Antimitochondrial antibodies most often present in primary biliary cholangitis. (See also the American Association for the Study of Liver Disease's practice guideline 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.)

Serum transferrin saturation > 45% and elevated ferritin suggests hereditary hemochromatosis and should be followed by genetic testing for the hemochromatosis gene (HFE).


Unlike in acute hepatitis, 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 FIB4 index, which uses aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, and age to assess risk of advanced fibrosis. Other modalities include transient elastography or MR elastography

Screening for complications

If symptoms or signs of cryoglobulinemia Cryoglobulinemia Conditions that cause an abnormal protein content in the blood, typically in the form of immunoglobulins, can affect vascular fragility and lead to purpura. (See also Overview of Vascular Bleeding... read more 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 infection or cirrhosis due to any underlying liver disorder should be screened every 6 months for hepatocellular carcinoma Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) usually occurs in patients with cirrhosis and is common in areas where infection with hepatitis B and C viruses is prevalent. Symptoms and signs are usually nonspecific... read more with ultrasonography and sometimes serum alpha-fetoprotein measurement, although the cost-effectiveness of this practice, particularly alpha-fetoprotein measurement, is debated. (See also the Cochrane review abstract Alpha-foetoprotein and/or liver ultrasonography for liver cancer screening in patients with chronic hepatitis B.)

Diagnosis reference

  • 1. Kwo PY, Cohen SM, Lim JK: ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol 112 (1):18-35, 2017. doi: 10.1038/ajg.2016.517.

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 drug often regresses completely when the causative drug is withdrawn.

Without treatment, cases caused by HBV can resolve (uncommon), progress rapidly, or progress slowly to cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more 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 HDV causes the most severe form of chronic HBV infection; without treatment, cirrhosis develops in up to 70% of patients with coinfection.

Untreated chronic hepatitis due to HCV causes cirrhosis in 20 to 30% of 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 obesity.

Chronic autoimmune hepatitis usually responds to therapy but sometimes causes progressive fibrosis and eventual cirrhosis.

Treatment of Chronic Hepatitis

  • Supportive care

  • Treatment of cause (eg, corticosteroids for autoimmune hepatitis, antivirals for HBV and HCV infection)

General treatment

Drugs 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.

Chronic hepatitis B and C

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.

Corticosteroids and immunosuppressants should be avoided in chronic hepatitis B and C because these drugs enhance viral replication. If patients with chronic hepatitis B have other disorders that require treatment with corticosteroids, immunosuppressive therapies, or cytotoxic chemotherapy, they should be treated with antiviral drugs at the same time to prevent a flare or reactivation of hepatitis B or acute liver failure due to hepatitis B. A similar situation with hepatitis C being activated or causing acute liver failure has not been described.

Nonalcoholic steatohepatitis (NASH)

  • Reduce weight

  • Control risk factors and comorbidities

It may involve

  • Recommending weight loss of 7 to 10% of body weight via dietary changes and exercise

  • Treating concomitant metabolic risk factors such as hyperlipidemias and insulin resistance

  • Stopping drugs associated with NASH (eg, amiodarone, tamoxifen, methotrexate, corticosteroids such as prednisone or hydrocortisone, synthetic estrogens)

  • Avoiding exposure to toxins (eg, pesticides)

  • No pharmacotherapy is currently recommended specifically for the treatment of NASH

Autoimmune hepatitis

(See also the American Association for the Study of Liver Disease’s practice guideline Diagnosis and Management of Autoimmune Hepatitis.)

Corticosteroids, with or without azathioprine, prolong survival. Prednisone is usually started at 30 to 60 mg orally once a day, then tapered to the lowest dose that maintains aminotransferases at normal or near-normal levels. To prevent long-term need for corticosteroid treatment, clinicians can transition to azathioprine 1 to 1.5 mg/kg orally once a day or mycophenolate mofetil 1000 mg twice a day after corticosteroid induction is complete and then gradually taper the corticosteroid. Most patients require long-term, low-dose, corticosteroid-free maintenance treatment.

Hereditary hemochromatosis

Hereditary hemochromatosis is treated with phlebotomy.

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 and C.

  • 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.

  • Consider entecavir or tenofovir as first-line therapies for chronic hepatitis B.

  • Treat chronic hepatitis C of all genotypes with interferon-free regimens of direct-acting antivirals.

  • Treat autoimmune hepatitis with corticosteroids and transition to maintenance treatment with azathioprine or mycophenolate mofetil.

  • Encourage diet and exercise for weight loss (10% if possible) in patients with nonalcoholic fatty liver disease (NAFLD).

  • Treat hereditary hemochromatosis with phlebotomy.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

Drug Name Select Trade
Otrexup, Rasuvo, RediTrex, Rheumatrex, Trexall, Xatmep
Furadantin, Macrobid, Macrodantin, Urotoin
Nolvadex, Soltamox
Cordarone, Nexterone, Pacerone
7T Gummy ES, Acephen, Aceta, Actamin, Adult Pain Relief, Anacin Aspirin Free, Apra, Children's Acetaminophen, Children's Pain & Fever , Comtrex Sore Throat Relief, ED-APAP, ElixSure Fever/Pain, Feverall, Genapap, Genebs, Goody's Back & Body Pain, Infantaire, Infants' Acetaminophen, LIQUID PAIN RELIEF, Little Fevers, Little Remedies Infant Fever + Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Infants, Mapap Junior, M-PAP, Nortemp, Ofirmev, Pain & Fever , Pain and Fever , PAIN RELIEF , PAIN RELIEF Extra Strength, Panadol, PediaCare Children's Fever Reducer/Pain Reliever, PediaCare Children's Smooth Metls Fever Reducer/Pain Reliever, PediaCare Infant's Fever Reducer/Pain Reliever, Pediaphen, PHARBETOL, Plus PHARMA, Q-Pap, Q-Pap Extra Strength, Silapap, Triaminic Fever Reducer and Pain Reliever, Triaminic Infant Fever Reducer and Pain Reliever, Tylenol, Tylenol 8 Hour, Tylenol 8 Hour Arthritis Pain, Tylenol 8 Hour Muscle Aches & Pain, Tylenol Arthritis Pain, Tylenol Children's, Tylenol Children's Pain+Fever, Tylenol CrushableTablet, Tylenol Extra Strength, Tylenol Infants', Tylenol Infants Pain + Fever, Tylenol Junior Strength, Tylenol Pain + Fever, Tylenol Regular Strength, Tylenol Sore Throat, XS No Aspirin, XS Pain Reliever
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20
Afrezza, Exubera
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
A-Hydrocort, Ala-Cort, Ala-Scalp, Alkindi, Anucort-HC, Anumed-HC, Anusol HC, Aquaphor Children's Itch Relief, Aquaphor Itch Relief, Balneol for Her, Caldecort , Cetacort, Colocort , Cortaid, Cortaid Advanced, Cortaid Intensive Therapy, Cortaid Sensitive Skin, CortAlo, Cortef, Cortenema, Corticaine, Corticool, Cortifoam, Cortizone-10, Cortizone-10 Cooling Relief, Cortizone-10 External Itch Relief, Cortizone-10 Intensive Healing, Cortizone-10 Plus, Cortizone-10 Quick Shot, Cortizone-5 , Dermarest Dricort, Dermarest Eczema, Dermarest Itch Relief, Encort, First - Hydrocortisone, Gly-Cort , GRx HiCort, Hemmorex-HC, Hemorrhoidal-HC, Hemril , Hycort, Hydro Skin, Hydrocortisone in Absorbase, Hydrocortone, Hydroskin , Hydroxym, Hytone, Instacort, Lacticare HC, Locoid, Locoid Lipocream, MiCort-HC , Monistat Complete Care Instant Itch Relief Cream, Neosporin Eczema, NuCort , Nutracort, NuZon, Pandel, Penecort, Preparation H Hydrocortisone, Proctocort, Proctocream-HC, Procto-Kit, Procto-Med HC , Procto-Pak, Proctosert HC , Proctosol-HC, Proctozone-HC, Rectacort HC, Rectasol-HC, Rederm, Sarnol-HC, Scalacort, Scalpicin Anti-Itch, Solu-Cortef, Texacort, Tucks HC, Vagisil Anti-Itch, Walgreens Intensive Healing, Westcort
Azasan, Imuran
CellCept, Myfortic
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz!