Hepatitis E

　　In 1983, Balayan et al. were the first to detect HEV using immunoelectron microscopy from fecal specimens of infected individuals. In 1989, Reyes et al. obtained (HEV)cDNA clones using molecular cloning technology and officially named this virus as hepatitis E virus (HEV).

　　HEV is an enveloped spherical particle with a diameter of 27 to 34 nm, with protrusions and notches on the surface, and an uneven internal density. In 1989, Reyes et al. were the first to obtain the gene clone of HEV. Studies show that the HEV genome is a single-stranded positive-sense DNA, with a full length of 7.2 to 7.6 kb, encoding 2400 to 2533 amino acids, consisting of a 5' non-structural region (NS) and a 3' structural region (S). Both ends have non-coding regions (NC), with lengths of 28 bp and 68 bp, respectively. Additionally, there is a polyadenyl (A) tail consisting of 150 to 300 adenine residues at the 3' end. This virus is unstable and requires storage in liquid nitrogen for long-term preservation. Magnesium or manganese ions help maintain the integrity of the viral particles. It is sensitive to high salt, cesium chloride, and chloroform, and relatively stable in alkaline environments. The classification and attribution of HEV have not been finally confirmed. Initially, it was attributed to the minute RNA virus, but it was later found that its morphology and biological characteristics under electron microscopy are similar to those of calicivirus, so it was then classified into the calicivirus family. However, recent analysis of the nucleotide sequence homology of the HEV genome has found that it is different from calicivirus. Comparative analysis of the NS region genome sequence shows that it is similar to rubella virus and beet necrotic yellow vein virus, so some people suggest that HEV should be classified into the alpha virus subgroup of the rubella virus genus.

　　What diseases can hepatitis E trigger? The main complications include: 1. Hepatic encephalopathy. 2. Hemorrhage. 3. Hepatorenal syndrome. 4. Secondary infection. Hepatitis E affects people's daily lives and poses health hazards, so it is essential to seek timely treatment.

　　1. Incubation period

　　The duration of the incubation period for hepatitis E is not yet unified, with the incubation period during the 1955 Delhi outbreak being 18 to 62 days, averaging 40 days. In 1983, the incubation period observed in volunteer subjects was 36 days, and in 1986, Azamgsn, Kashmir, and Xinjiang, China reported an incubation period of 10 to 49 days, averaging 15 days. Zhuang Hui summarized the three outbreaks of hepatitis E with a similar origin, with an incubation period of 15 to 75 days, averaging 36 days. This is not entirely identical to the epidemiological characteristics of various regions, due to inconsistent statistical conditions, the number of viral infections, and certain differences in virus strains. A comprehensive analysis of foreign reports indicates that the incubation period of hepatitis E is slightly longer than that of hepatitis A, but shorter than that of hepatitis B, usually ranging from 2 to 9 weeks, with an average of 6 weeks.

　　2. Clinical manifestations

　　Currently, the clinically recognized types include acute hepatitis, severe hepatitis, and cholestatic hepatitis, while there is still controversy regarding chronic hepatitis.

　　1. Acute hepatitis E:

　　It accounts for 86.5% to 90.0% of acute hepatitis E, including acute icteric and acute anicteric types, with a ratio of about 1:5 to 10 between the two.

　　(1) Acute icteric type: Accounting for 75% of acute hepatitis E, the clinical manifestations are similar to those of hepatitis A, but the jaundice period is longer and the symptoms are more severe. A. Preicteric period: Mainly表现为an acute onset, with symptoms such as chills, fever, headache, sore throat, nasal congestion, etc. (with an incidence rate of about 20%), joint pain (7% to 8%), fatigue (60% to 70%), followed by loss of appetite (75% to 85%), nausea (60% to 80%), vomiting, upper abdominal discomfort, pain in the liver area, bloating, diarrhea, and other gastrointestinal symptoms. Some patients have mild liver enlargement with tenderness and percussion pain. This period lasts for several days to a month, and the urine color becomes darker at the end of this period. If tested, bilirubin and urobilinogen in urine can be detected positive, blood bilirubin (Bil) and alanine aminotransferase (ALT) rise. B. Jaundice period: Body temperature returns to normal, jaundice deepens rapidly, urine is as dark as strong tea, feces are light-colored, skin itching (29%), severe gastrointestinal symptoms, lasting until jaundice stops rising, this period is generally 2 to 4 weeks, some cases can last up to 8 weeks. Liver function tests also reach their peak at this stage, and then gradually subside. C. Recovery period: Symptoms, signs, and laboratory findings improve comprehensively, and various symptoms are reduced to disappear on average in about 15 days, liver shrinkage and liver function return to normal on average in about 27 days, this period is generally 2 to 3 weeks, a few cases can last up to 4 weeks.

　　(2) Acute anicteric type: There are also two stages, acute and convalescent, in clinical manifestation, but it is milder than the icteric type. Some patients have no clinical symptoms and present as subclinical type, with more subclinical infections, while adults mostly present with clinical infections.

　　2. Severe hepatitis E:

　　Accounting for about 5% of hepatitis E, it is more common than severe hepatitis A. Through the investigation of multiple outbreaks of hepatitis E in various parts of the world in the past ten years, it is universally recognized that severe hepatitis E is more common in women than in men (2:1 to 5:1); there are more pregnant women, and pregnant women account for 60% to 70% of severe hepatitis, followed by the elderly and those with viral superinfection, especially when hepatitis B patients are reinfected with HEV, it is easy to develop severe hepatitis. There are more acute severe cases in severe hepatitis E, and the ratio of acute severe to subacute severe is about 17:1. The difference between the two cannot be simply divided by time. According to the comprehensive clinical report data during the hepatitis E outbreak in Xinjiang, the following characteristics should also be referred to.

　　(1) Acute severe hepatitis E: Pregnant women are more common (57% to 60%), especially in the late stages of pregnancy (about 70%); the condition develops rapidly, and the condition of most pregnant women changes dramatically after normal delivery or early postpartum; blood bilirubin is still slightly or moderately elevated when a series of clinical manifestations of severe hepatitis can appear, and there is no enzyme bilirubin separation phenomenon; the liver dullness boundary is reduced and accounts for half of the normal ones; all cases have hepatic encephalopathy, and all cases of coma have cerebral edema, the survival rate of those with III degree or above coma is extremely low; the degree of hemorrhage is positively correlated with the depth of jaundice, and some cases have disseminated intravascular coagulation (DIC); the prognosis is positively correlated with the depth of coma, the degree of hemorrhage, the stage of pregnancy, and the frequency of organ failure, and there is no obvious correlation with the depth of jaundice. The survivors have a long course of disease, but no post-hepatitis cirrhosis has been observed.

　　(2) Subacute severe hepatitis: In addition to pregnant women, it also occurs in the elderly and other virus-infected individuals, especially HBV. The progression of the disease is relatively slower than that of acute severe hepatitis. The jaundice is deeper and lasts longer than that of acute severe hepatitis, and the phenomenon of enzyme-jaundice separation is more common. Most patients do not show a decrease in liver dullness, and some cases show mild enlargement of the liver and spleen, which often occurs in patients with hepatitis B who are infected with HEV. Almost all cases can present with ascites, lower limb edema, and hypoproteinemia, with rare cases of hepatic encephalopathy. The course of the disease is long, and various complications can occur during the course. The mortality rate is closely related to the number of organ failures, with the frequency of organ failure being liver, coagulation system, central nervous system, and kidney in order.

　　3. Cholestatic hepatitis E:

　　According to data from Xinjiang, it is rare, accounting for only 0.1%, and there are also reports showing that cholestatic hepatitis E is more common, with an incidence rate 7.5% higher than that of hepatitis A. The clinical manifestations are similar to those of cholestatic hepatitis A, with a longer jaundice period, but a good prognosis.

　　4. Chronic hepatitis E:

　　There is still no consensus on whether there is a chronic process in hepatitis E and whether there are chronic virus carriers. There are reports from Japan that 58.2% of cases during the epidemic period developed into chronic hepatitis. Zhao Suzhi from China followed up 500 cases of acute hepatitis E for 3 to 28 months and found that 12% of the patients had symptoms, signs, liver function tests, and liver tissue pathological examination that did not return to normal, and these changes were consistent with chronic persistent hepatitis. However, a one-year systematic follow-up of cases during the second hepatitis E epidemic in eastern Xinjiang did not find any cases of chronicization. Observations by Zhuang Hui from China and Khroo from India also did not find any cases of acute hepatitis E developing into chronicization. The inconsistency of these results may be related to the strain type of the virus, the immune level of the population, age, and other social factors, which all require further study.

　　5. Clinical characteristics of hepatitis E in different physiological stages:

　　(1) Acute hepatitis E during pregnancy: It has a high incidence and is prone to develop into severe disease. During the hepatitis E epidemic in Xinjiang from 1986 to 1988, pregnant women accounted for 24% of the cases, 27% of severe hepatitis cases, and 4.6% of non-pregnant women. The mortality rate is also high, with reports from multiple countries ranging from 10% to 20%, with the highest reaching 39%. The mortality rate in the late pregnancy stage is the highest (20.96%), followed by the middle stage (8.46%), and early stage (1.5%) is close to the general reproductive-age women (1.4%). The disease progresses rapidly, often leading to hepatic encephalopathy before jaundice reaches severe liver level. Half of the cases show liver shrinkage, and the liver tissue pathological examination shows that liver cells are mainly degenerated and swollen. The liver tissue after massive hemorrhage also shows ischemic and hypoxic changes, which are prone to cause miscarriage, preterm birth, stillbirth, and postpartum infection. The condition often deteriorates rapidly after delivery, with the main causes of death being cerebral edema, postpartum hemorrhage, hepatorenal syndrome, upper gastrointestinal hemorrhage, and cerebral hernia. During the process of developing into severe disease, a decrease in factors I, V, and VII is sequentially observed, and in most cases, platelets and fibrinogen are normal, with only a few cases developing disseminated intravascular coagulation (DIC).

　　(2) Pediatric hepatitis E: With the increase of age, the incidence rate gradually increases. There have been no reports of neonatal onset. Cases aged 1 to 3 years account for 22.2% of the cases, and cases aged 7 to 14 years account for 77.8%. Compared with adults, the incidence rate in children is lower. Xinjiang has reported 3160 cases, with children accounting for 9.11% of the patients, mortality rate of 0.52%, which is also lower than that of adults. The onset is acute, symptoms are mild, and a large number of patients have respiratory symptoms in the early stage of onset (6.7% to 20.3%). The proportion of splenomegaly (19.8%) is higher than that in adults (0.22%). Although the majority of cases are jaundice (98.2%), the increase in jaundice is not as significant as in adults, and the duration is longer. Liver function changes are mainly characterized by increased ALT.

　　(3) Elderly hepatitis E: The incidence rate is about 3% to 10.9% of the total cases, lower than that of adults but higher than that of children. The onset is more insidious, and clinical symptoms are mainly jaundice. The proportion of cholestatic hepatitis is relatively high, with deep jaundice, long duration, relatively long course, slow recovery, hospital stay about twice as long as the adult group, relatively more severe hepatitis, higher than the adult group but lower than pregnant women, more complications, prone to secondary infection, good prognosis, low mortality rate, and no reports of chronic transformation.

　　Similar to hepatitis A, comprehensive measures are mainly taken to cut off the transmission routes. To prevent waterborne transmission, it is mainly to protect water sources and prevent fecal management; attention to food hygiene, improvement of sanitation facilities, and personal hygiene are also very important. Most reports show that the use of gamma immune globulin and human placental immune globulin for the prevention of hepatitis E is ineffective, and ultimately, it depends on vaccines. The success of HEV molecular cloning has provided a foundation for the development of vaccines.

　　Specific serological pathogen detection is the basis for diagnosis.

　　1. Enzyme-linked immunosorbent assay (ELISA) is used to detect anti-HEVIgM in serum, which is an indicator for the diagnosis of acute hepatitis E. This method uses recombinant or artificially synthesized peptides as antigens. In China, this method was used to test 111 cases of acute hepatitis E, with a positive rate of anti-HEV of 86.5%. In 32 cases of convalescent patients, the positive rate of anti-HEV was 6.3%, indicating that the duration of anti-HEV is relatively short, with 63% of patients turning negative after 5 to 6 months post-onset.

　　2. Protein blotting test (Western Blot, WB) This method is more sensitive and specific than the ELISA method, but the operation is more complex and the time required for detection is longer.

　　3. Polymerase Chain Reaction (PCR) is used to detect HEV-RNA in the serum and feces of patients with hepatitis E. This method has high sensitivity and specificity, but it is easy to cause laboratory contamination and false positives during the operation.

　　4. Immunoelectron microscopy (IEM) and immunofluorescence method (IF) are used to detect HEV particles and HEV antigens (HEAg) in the feces, bile, and liver tissue of patients with hepatitis E. However, both methods require special equipment and technology, and HEV exists for a short time in liver tissue, bile, and feces, with a low positive rate and should not be used as routine examination.

　　Dietary attention for Hepatitis E patients; 1. It is advisable to eat foods rich in vitamins and inorganic salts; 2. It is advisable to eat alkaline foods. 3. It is advisable to eat foods with high nutritional content. Smoking, drinking, spicy, and刺激性 foods should be avoided.

　　1. Alcohol should be avoided, overexertion should be prevented, and liver-damaging drugs should be avoided. Appropriate rest and reasonable nutrition should be the main focus, with selective drug use as a supplement. Medication should be simple rather than complex.

　　2. In the early stage, strict bed rest is required. As the symptoms improve significantly, the amount of activity can be gradually increased, and fatigue should be avoided. Treatment should continue until the symptoms disappear, the isolation period is over, and liver function is normal, then the patient can be discharged. After 1-3 months of rest, work can be gradually resumed.

　　3. Diet should be easy to digest and light. Avoid greasy foods, and should contain a variety of vitamins, sufficient calories, and appropriate amounts of protein; fat should not be restricted too strictly.

　　For those who have difficulty eating or eating little, or have vomiting, 10% glucose solution 1000-1500ml should be added with vitamin C 3g, Hepatol 400mg, and ordinary insulin 8-16U for intravenous infusion, once a day. Energy mixture and 10% potassium chloride can also be added. Chinese medicine for regulating the qi and harmonizing the middle can be appropriately used for treatment: for those with severe heat, Yu Chen胃Fen Decoction can be added or subtracted; for those with both heat and dampness, Yu Chen蒿Decoction and Wei Fen combined formula can be added or subtracted; for those with liver qi stagnation, Xiaoyao Powder can be used; for those with spleen deficiency and dampness, Ping Wei Powder can be used. Some people advocate using Da Chi for deep jaundice, which is effective. Generally, acute hepatitis can be cured.