Overview of Hepatitis
Various types of hepatitis with yellowing of the skin, mucous membranes and sclera can be characterized by fatigue, poor appetite, yellowing of the skin, mucous membranes and sclera, itchy skin, etc. The causes of the disease are related to viral infections, alcohol, drugs, autoimmune factors, etc. The mainstay of treatment is medication, and surgery is required when necessary.
Definition
Jaundice is a diagnosis of clinical symptoms rather than etiology. Jaundice is a clinical subtype of hepatitis, which is categorized into jaundiced and non-jaundiced hepatitis based on the presence or absence of jaundice and the presence or absence of elevated serum bilirubin in patients with hepatitis.
Jaundiced hepatitis is defined as inflammatory injury of the liver caused by various etiologies, accompanied by bilirubin metabolism disorders that increase serum bilirubin levels >17.1 μmol/L, and accompanied by yellowing of the skin and mucous membranes as well as some internal organs and body fluids, etc. [1-3].
Morbidity
The incidence of jaundice hepatitis varies considerably in different countries and regions.
It occurs mostly in patients with viral hepatitis, with viral hepatitis A and B being the most common [2, 4].
Causes
Causes
Various etiologic factors that can cause hepatitis may contribute to jaundice, such as viral infections, alcohol, abnormalities in lipid metabolism, pharmacologic factors, autoimmune factors, and parasitic infections such as schistosomiasis.
Viral infection
Hepatitis caused by hepatitis A, B, C, D and E viruses is an important causative factor of the disease.
Hepatitis viruses infect the human body, causing inflammation and necrosis of the liver, which further leads to a decrease in the ability of liver cells to process substances such as bilirubin and jaundice [4-5].
Alcohol
Chronic heavy alcohol consumption leads to steatosis, hypoxia, and immune damage to hepatocytes caused by ethanol and its metabolites, and extensive hepatocyte damage can be induced by short-term severe alcohol abuse [6].
Alcohol can also cause alcoholic fatty liver disease, which also causes damage to hepatocyte function and jaundice.
Abnormalities of lipid metabolism
It may be associated with insulin resistance, genetic predisposition, endocrine disorders, and simple obesity. Excess fat is deposited in the liver, causing liver damage.
With the change of lifestyle, the number of obese people in China, especially the number of abdominal obesity has increased dramatically compared with before, leading to a subsequent increase in the number of people suffering from fatty liver disease and an increase in the number of people suffering from hepatitis related to it [7].
Pharmacologic factors
Prolonged or repeated exposure to the presence of well-defined hepatotoxic poisons and drugs can easily cause pharmacologic liver injury, resulting in jaundiced hepatitis.
Common drugs that cause jaundice hepatitis include isoniazid, acetaminophen, lovastatin, quinolone, furotoxin, phenytoin sodium, ketoconazole, cyclosporine, diclofenac, and penicillin [8].
Common poisons causing jaundice hepatitis are carbon tetrachloride, dimethylnitramine, yellow phosphorus, herbs and fungal toxins.
Autoimmune factors
Caused by the body’s loss of tolerance to its own tissue proteins to produce autoantibodies and/or its own sensitized lymphocytes, which attack the tissues of its own target antigen cells.
Characterized by the presence of autoantibodies in the serum, increased serum transaminases and IgG [9].
Parasitic infections
Infections such as schistosomes, amoebas, echinococcus tapeworms, and liver fluke can cause mechanical destruction of liver tissue, biliary obstruction, and perihepatic effusion, resulting in a range of manifestations such as jaundice, fever, weight loss, and pruritus.
Predisposing factors
Jaundice may be induced by overeating, staying up late, overwork and mental stress.
Pathogenesis
The above etiologic factors may cause damage to the hepatocytes, resulting in the uptake, transport, binding, and excretion of bilirubin by the hepatocytes being affected, which may result in an increase in conjugated bilirubin as well as unconjugated bilirubin [1-3].
Mechanisms of increased bound bilirubin:
Hepatocyte excretion is impaired and bound bilirubin is retained in the liver and regurgitated into the blood.
Hepatocellular necrosis ruptures the capillary bile ducts and bile components regurgitate into the blood.
Increased permeability of capillary bile ducts and bile ducts, bile components enter the blood via hepatocytes.
Obstruction of the bile ducts due to sludge, inflammatory swelling, or compression by enlarged hepatocytes, resulting in regurgitation of bile into the blood.
Mechanism of increased unconjugated bilirubin:
Impaired excretion of bound bilirubin and decreased hepatic uptake of unconjugated bilirubin.
When hepatocytes are damaged, bound bilirubin is hydrolyzed to unconjugated bilirubin, which can regurgitate into the blood.
The shortened life span of erythrocytes in liver disease increases the production of unconjugated bilirubin [5].
Many biological, chemical, and physical factors can damage hepatocytes, and jaundice can occur when the damage is extensive or severe.
Symptoms
Main Symptoms
Symptoms of jaundice are mainly divided into a series of manifestations caused by hepatitis itself and jaundice caused by elevated bilirubin.
Hepatitis Symptoms
Fatigue: you may feel weak, continue to be weak for several days, feel tired easily, unable to engage in normal labor, etc.
Digestive tract symptoms: it can be manifested as distension and discomfort of the whole abdomen or epigastrium locally, hidden pain in the abdomen, and can also be accompanied by nausea, vomiting, belching, early satiety, diarrhea and other manifestations. It can also be manifested as obvious poor appetite, accompanied by anorexia of grease and other manifestations.
Bleeding tendency: due to the coagulation dysfunction, subcutaneous bruises, petechiae, bleeding from gums and nasal mucosa, etc. It may also cause gastrointestinal hemorrhage, which may be manifested as vomiting blood, blood in stools and black stools.
Others: Some patients may have polyuria and polyphagia due to hepatogenic diabetes mellitus; if combined with hepatorenal syndrome, oliguria and anuria may occur; in severe cases, severe infections and poisoning may occur, accompanied by fever.
Symptoms of elevated bilirubin
Jaundice: it can be manifested as yellow staining of skin, mucous membranes, sclera and other tissues and body fluids, deepening of urine color, or even strong tea color.
Itchy skin: elevated bilirubin can also stimulate nerve endings, causing generalized itchy skin [5].
Complications
Cirrhosis: various types of jaundice hepatitis may present with symptoms such as dizziness, fatigue, bleeding of skin and mucous membranes, etc. It may also present with obvious abdominal distension and manifestations such as splenomegaly and varicose veins of the abdominal wall may be seen.
Hepatic encephalopathy: it can be caused by severe liver disease, and often manifested as personality, behavior, intelligence changes and consciousness disorders and other manifestations.
Upper gastrointestinal hemorrhage: mainly manifested as sudden vomiting of blood, bright red or dark red, shock may occur when the bleeding is large.
Hepatorenal syndrome: oliguria, anuria, jaundice and ascites with varying degrees of yellowing of skin and mucous membranes and increasing abdominal circumference may appear suddenly.
Hepatopulmonary syndrome: dyspnea, cyanosis of skin and mucous membranes may occur.
Consultation
Department of Medicine
Gastroenterology
If nausea, poor appetite, jaundice, anorexia, fatigue and weakness occur, it is recommended to consult a doctor promptly.
Department of Infectious Diseases
If fever, chills, etc. appear, or if viral hepatitis is considered, it is recommended to consult a doctor immediately.
Emergency Medicine
In the event of severe abdominal pain, vomiting blood, black stools, or blurred consciousness, it is also advisable to consult the Emergency Department.
Preparation
Preparation for consultation: registration, preparation of documents, common problems
Tips for seeking medical treatment
If vomiting or black stools occur, take a picture of them for the doctor’s reference.
Try not to eat too much greasy food or drink alcohol for 3 days before the visit.
Try to keep a record of symptoms and their duration for the doctor’s reference.
Preparation List
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there any epigastric pain, bloating, belching, vomiting, fatigue, yellowing of the skin?
Is there any vomiting? When did the vomiting occur, what was vomited, and what was the color?
How is the appetite recently? Is there any significant weight loss?
Is there any blood in the stool or black stool? Are there bleeding gums when brushing teeth? Are there any bleeding spots on the skin?
How long have these symptoms been present? What conditions may aggravate or relieve them?
Medical History Checklist
Any previous diseases of the liver system such as viral hepatitis, fatty liver, etc.?
Does anyone in the family have liver disease?
Have you been vaccinated against hepatitis?
Has alcohol been consumed? How long have you been drinking alcohol? What is the amount of alcohol consumed per day?
Does one take medications such as isoniazid, acetaminophen, furotoxin, phenytoin sodium, etc.?
What is the occupation? Is there a history of toxic exposure?
Checklist
Test results from the last six months, which can be brought to your doctor’s appointment
Laboratory tests: routine blood, urine, stool, liver function, virology, coagulation, autoimmune antibodies, etc.
Imaging examination: abdominal ultrasound, abdominal CT, abdominal MRI, etc.
Pathologic examination by liver puncture.
Medication list
Medication used in the last 3 months, if there is a medicine box or package, you can bring it to the doctor
Hepatoprotective drugs: liver protection tablets, silymarin, dicyclomine, etc.
Antiviral drugs: tenofovir, entecavir, interferon, etc.
Antibacterial drugs: cefuroxime, amoxicillin, ceftazidime, etc.
Glucocorticoids: dexamethasone, prednisone acetate, etc.
Diagnosis
Diagnosis is based on
Medical history
Presence of viral hepatitis or family history of viral hepatitis or exposure to viral hepatitis.
Presence of diabetes mellitus, hyperlipidemia, fatty liver disease.
History of prolonged heavy alcohol consumption or short-term alcoholism.
Prolonged or repeated exposure to isoniazid, acetaminophen, lovastatin, furotoxin, phenytoin sodium, ketoconazole, cyclosporine, diclofenac, carbon tetrachloride, and other clearly hepatotoxic poisons and drugs.
Clinical manifestations
Symptoms
The main symptoms include poor appetite, nausea, vomiting, anorexia, fatigue, deepening of urine color, subcutaneous bruises and petechiae, bleeding from gums and nasal mucosa.
Physical signs
Some patients may have signs such as hepatic tenderness, splenomegaly, yellowing of skin and sclera.
Laboratory Tests
Routine blood tests
The levels of white blood cells, lymphocytes, hemoglobin and platelets can be changed, which are different in different etiologies of jaundice hepatitis.
Abnormal elevation of eosinophils may indicate the possibility of parasitic infection.
Infected patients may have elevated white blood cells, which can help to determine whether there is an infection and the severity of the infection.
Stool routine examination
Positive fecal occult blood suggests that the patient may have upper gastrointestinal bleeding.
Urine analysis
To find out whether the bilirubin and urobilinogen in urine are abnormal.
Liver function tests
The increase of alanine aminotransferase and aspartate aminotransferase can reflect the damage of liver cells. In addition, γ-glutamyl transpeptidase, serum alkaline phosphatase, bile acids and other values can also assist in determining liver reserve and the severity of the disease.
Serum bilirubin can help determine the presence of jaundice.
Liver failure is characterized by elevated serum bilirubin and decreased alanine aminotransferase and aspartate aminotransferase.
Decreased serum albumin and globulin may also reflect a decrease in the liver’s ability to synthesize proteins and may assist in determining hepatic impairment [5,10-11].
Virologic examination
Hepatitis virus-related antibody tests, such as the hepatitis A virus antibody test and the hepatitis B pentameter test, may be performed. Nucleic acid tests of the virus can also be performed, such as hepatitis B virus (HBV-DNA) test, hepatitis C virus (HCV-RNA) test and genotyping [5].
It can be used as a basis for confirming the diagnosis and provide reference for treatment.
Immunologic examination
Patients with autoimmune factors may show positive results for serum autoantibodies, such as anti-nuclear antibodies, anti-smooth muscle antibodies, and anti-type 1 liver and kidney microsomal antibodies. This is usually accompanied by elevated levels of immunoglobulin IgG.
Coagulation function tests
Abnormal liver function and decreased hepatic synthesis can lead to prolonged clotting time.
Imaging tests
Abdominal ultrasound
Ultrasonography is a simple, non-invasive and repeatable method of liver examination.
It can quickly differentiate obstructive and non-obstructive jaundice according to the presence or absence of bile duct dilatation, such as the initial judgment or exclusion of jaundice caused by stones and other factors.
Abdominal CT
It can further observe whether there is dilatation of the intrahepatic bile ducts, whether there is disruption of the bile duct structure, and whether there are space-occupying lesions, etc. The space-occupying lesions will be strengthened to varying degrees when enhanced scanning is performed.
Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging (MRI) is an ideal diagnostic method because it can obtain a complete and intuitive three-dimensional image of the pancreaticobiliary system, is not affected by the level of bilirubin in the liver, and requires no preoperative preparation.
Endoscopic ultrasound
Endoscopic ultrasound (EUS) can be used as an initial screening method for patients with a high suspicion of extrahepatic biliary obstruction. If ultrasound results are negative, follow-up endoscopic retrograde cholangiopancreatography (ERCP) is still needed.
Liver puncture biopsy for pathologic examination
It is important for making a definitive diagnosis and clarifying the degree of liver activity and fibrosis.
Acute jaundice rarely requires a liver puncture to assist in the diagnosis. Hepatic puncture is often used in persistent jaundice where intrahepatic cholestasis or hepatic parenchymal lesions are suspected.
Staging
Acute jaundice is relatively common in clinical practice, and its course can be divided into three phases based on clinical presentation.
Pre-jaundice
Hepatitis A and E have an acute onset, about 80% of patients have fever, accompanied by chills; hepatitis B, C and D have a relatively slower onset, and only a few have fever.
The main symptoms are generalized fatigue, poor appetite, anorexia, nausea, vomiting, abdominal distension, pain in the liver area and deepening of urine color.
This period usually lasts for 5 to 7 days.
Jaundice stage
Urine becomes yellow, color deepens, yellow staining of sclera and skin appears, and jaundice reaches the peak in 1～3 weeks.
Some patients may have obstructive jaundice with transient light-colored stools and itchy skin.
This period usually lasts for 2～6 weeks.
Recovery period
Symptoms gradually disappear and jaundice subsides.
This period usually lasts for 1 to 2 months [5].
Differential diagnosis
Pseudo jaundice
Similarities: Both may present with yellowing of the skin.
Differences: Pseudo jaundice is seen with excessive consumption of foods such as carrots, pumpkin, tomatoes and citrus. In pseudo jaundice, the serum bilirubin is normal and the sclera does not show yellowing and may improve on its own, while in jaundice hepatitis, the serum bilirubin is markedly elevated and may be accompanied by yellowing of the sclera.
Hemolytic jaundice
Similarity: Both patients may have symptoms such as yellowing of the skin and sclera.
Differences: hemolytic jaundice patients have lemon colored skin, not accompanied by skin itching, may be accompanied by conjunctival pallor, urine is soy sauce color or tea color and other manifestations. Blood routine, urine routine, liver function tests can be differentiated.
Obstructive jaundice
Similarity: both may present with symptoms such as yellowing of skin and sclera.
Differences: Obstructive jaundice is mainly caused by cholelithiasis, biliary ascariasis, bile duct stenosis due to surgery, or bile duct compression due to periampullary carcinoma, pancreatic head carcinoma, hepatocellular carcinoma, etc. It may present with white clay stool, and can be distinguished by ultrasonography, CT and other imaging examinations.
Treatment
Aim of treatment: remove the cause of disease, control the symptoms, prevent recurrence and avoid complications.
Treatment principle: According to different conditions, general treatment, medication and surgery are mainly adopted.
General treatment
Isolation: Viral hepatitis is mainly transmitted through digestive tract, body fluids, sexual contact, etc., so this kind of patients need to be isolated accordingly.
Patients need to take adequate bed rest and avoid overwork.
Light diet: Greasy diet will aggravate the burden of the liver. In addition, it is necessary to supplement the necessary vitamins.
Limit protein intake.
For patients with edema and ascites, attention should be paid to limiting the intake of sodium in the diet and controlling the amount of water in and out.
Avoid drugs that can damage the liver, such as anti-microbial drugs (anti-tuberculosis, antibiotics, etc.), non-steroidal anti-inflammatory drugs, immunosuppressants, anti-tumor-targeted drugs, and Chinese herbs (e.g., He Shouwu).
Abstinence from alcohol is a key measure.
Medications
Liver-protecting drugs
Protect liver cells and promote liver cell regeneration. The following types of liver-protecting drugs are commonly used:
Detoxifying agents: reduced glutathione.
Enzyme-lowering and anti-inflammatory: glycyrrhetinic acid, which improves histology and lowers enzymes.
Antiyellowing and choleretic: adenosylmethionine, which prevents cholestasis.
Hepatoprotective agents: silymarin, which stabilizes hepatocyte membranes.
Membrane repair agent: polyene phosphatidylcholine, which promotes regeneration of hepatocyte membranes.
Microcirculation improver: prostaglandin, which can increase hepatic blood supply [2-5].
Antiviral drugs
Nucleoside analogs such as entecavir, tenofovir, and propofol tenofovir are commonly used for viral hepatitis B. Interferons such as pegylated interferon and common interferon.
Viral hepatitis C commonly used asurevir, simeprevir, dalatasvir, ledipavir, sofosbuvir.
It can inhibit viral replication, reduce infectiousness and improve liver function. Antiviral therapy should be actively administered in cases of high viral load without contraindications [4-5].
Immunomodulatory drugs
Patients with autoimmune hepatitis need to be actively treated.
Commonly used drugs include prednisone, azathioprine, budesonide, morphimecrolate, tacrolimus and so on [9].
Patients using glucocorticoid hormones for a long period of time need to pay attention to the detection of bone mineral density to prevent the occurrence of osteoporosis and so on. Patients using immunosuppressants such as azathioprine need to monitor blood counts to prevent infections, etc.
Others
For alcoholic liver disease with difficulty in quitting alcohol, oral baclofen treatment is available. Those with concurrent alcohol withdrawal symptoms may also be treated with sedatives such as diazepam [6].
Jaundice hepatitis is often combined with multivitamin and trace element deficiencies, and multivitamins can be taken as prescribed.
For those with combined ascites and edema, diuretics such as furosemide and spironolactone can be used to assist diuresis. can also be intravenous infusion of albumin, in order to improve the colloid osmotic pressure, reduce the generation of ascites.
Comorbid hepatic encephalopathy requires treatment with medications such as lactulose, branched-chain amino acids, and menthol ornithine.
Combined hepatorenal syndrome may be treated with volume expansion, treatment with diuretics, dopamine, prostaglandins, terlipressin, and other vasoactive drugs as prescribed. Sometimes dialysis may also be administered.
Surgery
Liver transplantation
In principle, progressive, irreversible, and lethal end-stage liver disease that cannot be effectively cured with other medical and surgical treatments are indications for liver transplantation [2-3].
Liver transplantation can help patients with end-stage liver disease regain their lives.
Traditional Chinese medicine (TCM)
Some traditional Chinese medicine (TCM) treatments or medications can relieve the symptoms, and it is recommended to go to a regular medical institution for treatment under the guidance of a physician.
Prognosis
Cure
The prognosis of jaundice hepatitis needs to be judged according to the cause of the disease and one’s own condition. Acute jaundiced liver has a better prognosis and can usually recover within 3 months.
For jaundice caused by viral hepatitis and autoimmune hepatitis, medication can slow down the progression of liver disease to a certain extent, but it is not a cure.
For those with alcoholic hepatitis, drug-induced liver disease, and non-alcoholic steatohepatitis, the prognosis is generally better or even curable after timely removal of the causative factors.
Some people with recurrent and poorly controlled liver disease may further develop into cirrhosis, liver cancer, etc., with a poorer prognosis.
Daily
Daily Management
Dietary management
Diet should be nutritious, with easy-to-digest fluids or semi-fluids, and protein intake needs to be limited to control the source of ammonia in the intestines to avoid hepatic encephalopathy.
Eat a light diet rich in legumes, fish, vegetables, fruits and other foods that contain lots of vitamins.
Avoid rough and hard foods, as well as fried and spicy foods.
Eat regular meals and chew slowly.
Life management
Those with obvious symptoms and jaundice should rest in bed. Appropriate physical exercise during the recovery period to improve body immunity and reduce mental stress.
Quit smoking and drinking.
Patients with fatty liver disease should pay attention to weight reduction.
Viral hepatitis A and E should be isolated during the period of illness, and personal hygiene should be maintained at the same time.
Follow-up review
Pay attention to the degree of yellowing of the skin, the color of urine, stool and the progress of other symptoms. If the symptoms worsen significantly, or new symptoms appear, such as fever, nausea, vomiting, aversion to oil and grease, or even a change in mental status, timely medical attention should be sought.
Follow-up liver function, liver ultrasound and other tests are needed. For patients with viral hepatitis need to review the pathogenetic tests, etc.
Prevention
Prevention of viral hepatitis
Control of infectious sources: Patients with viral hepatitis and virus carriers are infectious sources. Viral hepatitis A and E are transmitted through the digestive tract and need to be isolated in the acute stage. Patients with viral hepatitis B, D and E need timely antiviral treatment to reduce the risk of transmission.
Cut off the transmission route: maintain environmental and personal hygiene, do a good job in managing feces and water sources, strictly disinfect tableware, hairdressing and other items, and use disposable syringes.
Protect susceptible groups: avoid contact with patients with acute phase hepatitis, newborns and children need to be vaccinated. Encourage high-risk groups to get vaccinated.
Prevention of non-viral hepatitis
Abstain from alcohol.
Control weight and avoid overweight and obesity.
Avoid unnecessary medications, especially those determined to be damaging to the liver.
Do not take prescriptions and herbal tonics that have not been directed by a medical professional.
Pay attention to food hygiene and hand hygiene, and do not consume raw water, raw food and half-cooked products.
Not to perform invasive operations such as tattooing and ear piercing in stores without formal qualifications.