Chronic Hepatitis

Overview

Hepatitis is an inflammation of the liver. Some individuals or animals with hepatitis have no symptoms, while others develop jaundice (yellow staining of the skin and whites of the eyes), a loss of appetite, vomiting, fatigue, stomach discomfort, and diarrhea. Hepatitis is classified as acute if it clears up within six months and chronic if it lasts longer than six months. Chronic hepatitis can lead to liver scarring (cirrhosis), liver failure, and liver cancer.

What is Chronic Hepatitis?

Hepatitis is a liver inflammation. The liver is inflamed for at least six months in chronic hepatitis. This disorder can be modest, producing only minor damage, or severe, causing the destruction of numerous liver cells. Cirrhosis and liver failure can occur in some cases.

Causes of Chronic Hepatitis

The most common causes of chronic hepatitis are:

• Hepatitis C virus

Hepatitis C virus causes 60 to 70% of chronic hepatitis cases, while at least 75% of acute hepatitis C infections become chronic.

• Hepatitis B virus

In adults, between 5 to 10% of hepatitis B infections develop chronic, frequently in conjunction with hepatitis D. Acute hepatitis B can develop chronic in up to 90% of infected infants and 25% to 50% of young children.

Note!

Hepatitis D does not develop on its own. It only arises as a result of a hepatitis B coinfection.

• Hepatitis E virus 

Hepatitis E virus causes chronic hepatitis in persons with impaired immune systems, such as those receiving immunosuppressive medicines after an organ transplant, those receiving cancer treatment, or those infected with HIV. Chronic hepatitis is not caused by the Hepatitis A virus.

• Fatty liver not due to alcohol use (nonalcoholic steatohepatitis)

Nonalcoholic steatohepatitis is a kind of chronic liver inflammation that commonly arises in persons who are overweight (obese), have diabetes, and/or have abnormal amounts of cholesterol and other fats (lipids) in their blood. All of these situations lead the body to produce more fat or to digest (metabolize) and excrete fat at a slower rate. As a result, fat builds up and is deposited inside liver cells (called fatty liver). Fatty liver can cause persistent inflammation and, eventually, cirrhosis.

 Note!

Nonalcoholic fatty liver disease refers to fatty liver caused by conditions other than excessive alcohol intake.

• Alcohol-related liver disease

After being absorbed in the digestive system, alcohol is typically digested (metabolized) in the liver. Substances that might harm the liver are created during the processing of alcohol. People who drink heavily for several months or years are more likely to develop alcohol-related liver damage. Alcohol-related liver disease is distinguished by fatty liver and extensive liver inflammation, which can result in liver cell death. If people continue to drink, scar tissue in the liver can grow and eventually replace a considerable percentage of normal liver tissue, culminating in cirrhosis.

• Rare causes of chronic hepatitis

Less often, chronic hepatitis results from:

• Autoimmune hepatitis

Chronic inflammation in autoimmune hepatitis is similar to inflammation generated by the body attacking its own tissues. Women are more likely than males to have autoimmune hepatitis.

• Drugs

Certain medicines, especially those taken for an extended period of time, can induce chronic hepatitis. Amiodarone, isoniazid, methotrexate, methyldopa, nitrofurantoin, tamoxifen, and, in rare cases, acetaminophen is among them.

• Alpha-1 antitrypsin deficiency (a hereditary disorder)
• Celiac disease
• Hemochromatosis (a hereditary disorder that causes the body to absorb too much iron)
• Primary biliary cholangitis
• A thyroid disorder
• Wilson disease (a rare hereditary disorder involving abnormal retention of copper in the liver)

Symptoms of Chronic Hepatitis

Chronic hepatitis develops gradually in roughly two-thirds of people, typically without showing any signs of a liver condition until cirrhosis occurs. It arises following an episode of acute viral hepatitis that lasts or returns in the remaining one-third of cases (often several weeks later).

Chronic hepatitis frequently produces nonspecific symptoms such as malaise, loss of appetite, and weariness. A low-grade fever and upper abdominal pain are also common in those who are afflicted. Jaundice (a yellow coloring of the skin and whites of the eyes caused by bilirubin accumulation) is uncommon unless liver failure occurs. Many persons with chronic hepatitis do not exhibit any symptoms.

When liver disease has progressed and there is evidence of cirrhosis, the first particular symptoms are frequently seen. Symptoms include:

• An enlarged spleen
• Small spiderlike blood vessels visible in the skin (called spider angiomas)
• Redness of the palms
• Accumulation of fluid within the abdomen (Ascites)
• A tendency to bleed (coagulopathy)
• Jaundice
• Deterioration of brain function (hepatic encephalopathy)

Because the severely damaged liver is unable to eliminate hazardous compounds from the blood as it should, brain function suffers. These toxins then accumulate in the blood and go to the brain. Normally, they are removed from the blood by the liver, broken down, and excreted as harmless by-products into the bile (the greenish yellow fluid that assists digestion) or blood. Treatment for hepatic encephalopathy can save brain function from deteriorating permanently.

Blood cannot clot normally because the injured liver can no longer produce enough of the proteins that aid in blood clotting.

Some patients are experiencing jaundice, itching, and light-colored feces. Jaundice and itching arise as a result of the damaged liver's inability to eliminate bilirubin from the blood as it should. Bilirubin then accumulates in the blood and deposits on the skin. Bilirubin is a yellow pigment that is created as a byproduct of the regular breakdown of red blood cells. Because the passage of bile out of the liver is inhibited, less bilirubin is removed in the stool. Bilirubin is the substance that gives feces its characteristic brown color.

Different symptoms of autoimmune hepatitis may include other bodily systems. Menstrual cycle cessation, joint discomfort and swelling, lack of appetite, and nausea are some of the symptoms. People who have autoimmune hepatitis may also have type 1 diabetes, ulcerative colitis, celiac disease, or autoimmune illnesses that cause anemia or inflammation of the thyroid gland or kidneys.

Chronic hepatitis in many patients does not progress for years. In others, it worsens with time. The prognosis is contingent on which virus is to blame and whether therapy is available:

• Untreated chronic hepatitis C produces cirrhosis in 20 to 30 percent of patients. Cirrhosis, on the other hand, can take decades to develop. Cirrhosis typically increases the chance of developing liver cancer.
• Chronic hepatitis B worsens over time, sometimes fast, sometimes slowly, eventually leading to cirrhosis. Chronic hepatitis B raises the risk of liver cancer whether or not cirrhosis develops. (In persons with other types of liver illness, liver cancer is typically only a concern if cirrhosis develops.) Chronic hepatitis B seldom cures on its own without therapy.
• Chronic coinfection with hepatitis B and D, if untreated, causes cirrhosis in up to 70%.
• Autoimmune hepatitis can be effectively treated in most people, but some develop cirrhosis.
• Chronic hepatitis caused by a drug often completely resolves once the drug is stopped.

Autoimmune Hepatitis

Autoimmune hepatitis is a chronic condition with an unknown origin that is distinguished by persistent hepatic inflammation and necrosis. Cirrhosis can develop as a result of progressive fibrosis. Immune serum indicators, such as autoantibodies against liver-specific and non-liver-specific antigens and elevated immunoglobulin G (IgG) levels, are frequently observed. Although autoimmune hepatitis is frequently linked with other autoimmune disorders, it cannot be explained by persistent viral infection, alcohol usage, or exposure to hepatotoxic medicines or chemicals.

In every patient with acute hepatitis or acute liver failure, clinicians must examine the possibility of autoimmune hepatitis (defined by the new onset of coagulopathy and hepatic encephalopathy). Serum autoantibodies, serum protein electrophoresis, and quantitative immunoglobulins should all be tested in such individuals. A transjugular liver biopsy, if necessary, may aid to confirm the clinical suspicion of acute autoimmune hepatitis.

Rapid initiation of high-dose corticosteroid therapy may save individuals whose autoimmune hepatitis would otherwise have advanced to acute liver failure or cirrhosis. Other patients' conditions worsen despite immunosuppressive medication. As a result, there should be a low barrier for moving patients with acute liver failure to tertiary care facilities capable of performing urgent liver transplantation.

Diagnosis of Chronic Hepatitis

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

Furthermore, to identify asymptomatic individuals, the CDC advises testing all persons over the age of 18 at least once.

Liver tests

If no prior tests have been performed, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin levels are required.

The most common laboratory abnormalities are aminotransferase increases (ALT normal values: 29 to 33 IU/L for men and 19 to 25 IU/L for females). ALT is often greater than AST. Aminotransferase levels in chronic hepatitis can be normal if the illness is dormant, especially with HCV infection and nonalcoholic fatty liver disease (NAFLD).

Alkaline phosphatase is normally normal or slightly increased, although it can be significantly elevated, especially in primary biliary cholangitis. Unless the condition is severe or progressed, bilirubin levels are normally normal.

Other laboratory tests

If the laboratory results are consistent with hepatitis, viral serologic testing are performed to rule out HBV and HCV. Unless these tests reveal a viral etiology, more testing is necessary.

The next tests done 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

The ceruloplasmin level is used to test children and young adults for Wilson disease.

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 generally rises in blood immunoglobulins are used to identify autoimmune hepatitis. Antimitochondrial antibodies are frequently seen in primary biliary cholangitis.

Serum transferrin saturation more than 45 percent and increased ferritin are indicators of hereditary hemochromatosis and should be followed by genetic testing for the hemochromatosis gene (HFE).

To assess liver function and disease severity, serum albumin, platelet count, and PT should be examined; low serum albumin, a low platelet count, or prolonged PT may indicate cirrhosis and even portal hypertension. If the etiology of hepatitis is determined, noninvasive diagnostics such as ultrasound elastography and blood markers can be used to determine the extent of liver fibrosis.

Biopsy

In contrast to acute hepatitis, a biopsy may be required to establish the diagnosis or the pathogenesis of chronic hepatitis.

Mild instances may only exhibit minimal hepatocellular necrosis and inflammatory cell infiltration, often in portal areas, with normal acinar architecture and little or no fibrosis. Such instances seldom progress to clinically significant liver disease or cirrhosis.

Biopsy often reveals periportal necrosis with mononuclear cell infiltrates (piecemeal necrosis), variable periportal fibrosis, and bile duct growth in more severe instances. Zones of collapse and fibrosis can deform acinar architecture, and cirrhosis can coexist with symptoms of continuing hepatitis.

Biopsy is also used to grade and stage the disease.

Screening for complications

Cryoglobulin levels and rheumatoid factor should be examined if symptoms or indications of cryoglobulinemia develop during chronic hepatitis, particularly with HCV; 

• High levels of rheumatoid factor and
• Low levels of complement imply cryoglobulinemia.

Patients with chronic HBV infection or cirrhosis due to any underlying liver disorder should be screened for hepatocellular carcinoma every 6 months using ultrasonography and occasionally serum alpha-fetoprotein measurement, though the cost-effectiveness of this practice, particularly alpha-fetoprotein measurement, is debatable.

Treatment of Chronic Hepatitis

Chronic hepatitis treatment focuses on treating the underlying cause and controlling consequences such as ascites and hepatic encephalopathy in persons with cirrhosis.

If a drug is the root reason, the medication is discontinued. If another disorder is the source of the problem, it is addressed. If the reason is alcohol-related liver disease, doctors prescribe lifestyle adjustments, most notably abstinence from alcohol.

• Hepatitis B and C

People are frequently given antiviral medicines if their chronic hepatitis B is progressing or if their liver enzyme levels are high. Hepatitis B can return and become more severe in some persons when pharmacological therapy is stopped. As a result, these folks may need to take an antiviral medication indefinitely.

Treatment with antiviral medicines is advised for all people with chronic hepatitis C, unless their life expectancy is very short. Treatment might last anywhere from 8 and 24 weeks. Hepatitis C treatment can eradicate the virus from the body, halting inflammation and preventing scarring and development to cirrhosis.

• Nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis treatment focuses on controlling the circumstances that lead to it. Treatment may, for example, comprise

• Losing weight
• Eating a healthy diet (which can help control weight, diabetes, and possibly lipid levels)
• Taking drugs to treat diabetes
• Taking drugs to lower lipid levels
• Not taking drugs that can contribute to the disorder (such as tamoxifen, corticosteroids, and synthetic estrogens)
• Avoiding toxins, such as pesticides

• Autoimmune hepatitis

Corticosteroids (such as prednisone or budesonide) are typically used in conjunction with azathioprine, a medication that suppresses the immune system, to treat autoimmune hepatitis. These medications reduce inflammation, alleviate symptoms, and increase long-term survival. Nonetheless, scarring in the liver may worsen with time.

Stopping these medications frequently causes the inflammation to return, so most individuals must take them continuously. However, using corticosteroids for an extended period of time might have serious negative effects. As a result, doctors generally progressively lower the amount of the corticosteroid so that patients can discontinue use. People are subsequently prescribed azathioprine or mycophenolate (both immune suppressants) forever.

• Treatment of complications

Chronic hepatitis, cirrhosis, liver failure, and associated sequelae require therapy regardless of the cause or kind. Ascites is treated by limiting salt consumption and taking a medication that helps the kidneys flush more sodium and water into the urine (a diuretic). Taking medications to assist the body clear harmful compounds that might cause brain function to degrade is part of treating hepatic encephalopathy.

• Liver transplantation

People with severe liver failure may be candidates for liver transplantation.

Prognosis for Chronic Hepatitis

The prognosis for chronic hepatitis patients is very diverse and frequently relies on the etiology and availability of therapy. Chronic hepatitis induced by a drug frequently resolves entirely when the causative substance is discontinued.

Without therapy, HBV cases might resolve (rarely), develop fast, or proceed slowly over decades to cirrhosis. Resolution frequently begins with a brief rise in disease severity, followed by seroconversion from hepatitis B e antigen (HBeAg) to antibody to hepatitis B e antigen (HBeAg) (anti-HBe). HDV coinfection produces the most severe type of chronic HBV infection; without treatment, cirrhosis develops in up to 70% of coinfected individuals.

Cirrhosis is caused by untreated chronic hepatitis caused by HCV in 20 to 30 percent of individuals, however development can take decades and varies since it is commonly linked to a patient's other risk factors for chronic liver disease, such as alcohol use and obesity.

Chronic autoimmune hepatitis normally responds to treatment, however it can occasionally lead to progressive fibrosis and eventually cirrhosis. Chronic HBV infection raises the chance of developing hepatocellular carcinoma. Other liver problems (e.g., HCV infection, NAFLD) also increase the risk, but mainly when cirrhosis or severe fibrosis has occurred.

Prevention

Chronic hepatitis is often caused by infection with the hepatitis B or C virus. These viruses are typically transmitted from person to person through sexual contact or contact with blood or other body fluids when needles are shared or blood transfusions are performed. It is unknown why some instances of viral hepatitis progress to chronic hepatitis while others do not.

If these tests reveal evidence of liver inflammation or failure, you will be tested for hepatitis B and C, as well as antibodies that indicate autoimmune hepatitis. Your doctor will examine any drugs you are now taking or have previously taken to see if they are the source of your chronic hepatitis. If the cause is still unknown, more blood tests will be requested to rule out unusual factors. To determine the size of the liver, an ultrasound or computed tomography (CT) scan may be performed. Cirrhosis is indicated by a tiny liver that seems scarred.

A liver biopsy may be advised. A little bit of tissue from your liver will be taken during a biopsy.

Conclusion 

Chronic hepatitis is characterized as widespread chronic liver illness that has lasted at least 6 months. Cirrhosis is a follow-up. It has several etiologies. A liver biopsy is required for accurate diagnosis and prognosis. Chronic hepatitis caused by Hepatitis B progresses slowly. Corticosteroid treatment is ineffective. Current antiviral treatment converts around 50% of hepatitis B e antigen-positive patients to anti-HBe. A diagnostic marker for non-A, non-B viral hepatitis-related chronic hepatitis is lacking.

There is no current therapy that has been shown to be beneficial. The biochemical and immunological profile of autoimmune lupoid chronic active hepatitis is particularly active. Prednisolone medication extends life but does not prevent cirrhosis from developing. Associations recognize drug-related liver disease. Withdrawal from the substance is followed by recovery. Deaths frequently occur as a result of the drug's continued use.