Hepatitis D

　　Hepatitis D is an infectious disease caused by the hepatitis D virus (HDV) and other hepatotropic DNA viruses such as hepatitis B virus (HBV). The complete HDV particle is spherical, with a diameter of 35-37 nm, containing HDV RNA and HDAg, and its shell is HBsAg. HDV RNA is the genome of HDV, consisting of 1679-1683 nucleotides, forming a single-stranded, circular structure, which can also fold into a non-branching rod-like structure. HDV-RNA has 9 coding regions (ORFs), and ORF5 can encode HDAg. HDAg is a nuclear protein that can induce the body to produce anti-HDIgM and anti-HDIgG. Anti-HDIgM appears earlier, generally positive in the early stage of acute HDV infection, and gradually disappears in the convalescent period. A high titer of anti-HDIgM indicates the chronicity of the disease. Anti-HDIgG appears later, often appearing 3-8 weeks after onset and can remain positive for many years with a low titer. The activity of the disease can increase the level of anti-HDIgG. The current infection often manifests as positive anti-HDIgM, while past infection shows negative anti-HDIgM and positive anti-HDIgG. Anti-HD is not a neutralizing antibody, and it can still be infectious when positive.

　　HDV infection can significantly inhibit the synthesis of HBV DNA. Serological testing has proven that the appearance of HDAg is consistent with the decrease of HBV DNA in the serum. When the expression of HDAg increases, HBV DNA decreases. At the peak of HDAg expression, HBV DNA is often already absent, but with the negativity of HDAg and the appearance of anti-HD, HBV DNA returns to the original level. It was previously believed that the assembly of HDV depends on the synthesis of HBsAg, and its replication and expression also require the assistance of HBV or other hepatotropic viruses. In vitro transfection experiments have proven that the replication of HDV-RNA and the expression of HDAg do not require the assistance of hepatotropic viruses, and HDV can complete it independently, but when forming a complete HDV, it must be provided with a coat by hepatotropic viruses to complete it.

　　Hepatitis D virus (HDV) is a defective virus that requires the assistance of hepatitis B virus (HBV) to replicate, so hepatitis D can only be infected on the basis of hepatitis B infection. Clinically, it can manifest as simultaneous infection or superinfection with HBV and HDV (first infected with HBV, then with HDV), which is prone to complications such as liver cirrhosis, severe hepatitis, chronic active hepatitis, etc., and can present as either acute or chronic course. Infection with HDV on the basis of HBV often leads to a worsening of the condition and is prone to develop into liver cirrhosis. It may even lead to primary liver cancer.

　　After human infection with hepatitis D virus (HDV), the clinical manifestations depend on the status of the pre-existing hepatitis B virus (HBV) infection, with an incubation period of 4 to 20 weeks, and there are two types:

　　One, Simultaneous infection of HDV and HBV

　　It occurs in patients who have never been infected with HDV, and are simultaneously infected with HDV and HBV, presenting as acute hepatitis D. The clinical symptoms are similar to those of acute hepatitis B, and in the course of the disease, there are two peaks of bilirubin and ALT elevation. HBsAg appears first in the serum, followed by the positivity of HDAg within the liver. In the acute phase, the positivity of HDAg in the serum persists for a few days and then becomes negative, followed by the positivity of anti-HDIgM, which is short-lived and of low titer. Anti-HDIgG is negative.

　　Two, HDV and HBV superinfection

　　Refers to the condition where the patient has an existing chronic HBV infection and is subsequently infected with HDV, the clinical course mainly depends on the state of HBV infection and the degree of liver damage at the time of HDV infection. It is more common in chronic HBV carriers, and the symptoms are mainly determined by whether the patient was a chronic HBsAg carrier or a chronic liver disease patient before the HDV infection. If the patient is a HBsAg carrier, after infection with HDV, it presents like an acute HBsAg-positive hepatitis, but with negative anti-HBVIgM, it is more severe than a simple HBV infection. If the patient has chronic liver disease due to HBV infection, due to the continuous infection of HBV and the continuous replication of HDV, the existing liver tissue lesions may worsen, and it may manifest as an acute hepatitis attack or accelerate the development of chronic active hepatitis and liver cirrhosis. Therefore, when encountering chronic hepatitis B, if the original condition is stable and the symptoms suddenly worsen, even leading to liver failure, which is very similar to severe hepatitis, it should be considered as a possible superinfection with HDV. The following manifestations may be present.

　　1. Self-limiting hepatitis D: The course of the disease is short, and the clinical symptoms are generally not severe, with a tendency to self-limiting recovery. It can also manifest as typical acute HBsAg-positive hepatitis. After HBsAg carriers are infected with HDV, HDAg appears first within the liver, followed by HDAgemia, and the serum anti-HDIgM and IgG sequentially become positive. Once HDV is cleared, anti-HDIgM decreases accordingly, while anti-HDIgG can maintain a high level for several years. Most patients with overlapping infection are prone to develop chronic hepatitis, but only patients with this self-limiting course recover.

　　2. Chronic progressive hepatitis D: When chronic hepatitis B or HBsAg carriers are reinfected with HDV, the clinical manifestations are often deterioration, or similar to acute hepatitis attacks during the chronic process. HDAg remains positive within the nuclei of liver cells, but serum HDAg appears transiently, and anti-HDIgM and anti-HDIgG show high titer and persistent positivity. The most common histological changes are chronic hepatitis or liver cirrhosis. Clinical observations show that the age of patients in the HDV-positive liver cirrhosis group is significantly younger than that of the HDV-negative group, indicating that HDV-positive hepatitis is more likely to progress to liver cirrhosis.

　　3. HDV and severe hepatitis: Li Qifeng reported that among 105 cases of severe hepatitis, 36 cases (34.3% of the patients) were co-infected with HDV/HBV. Govindarajan reported that among 71 cases of acute severe hepatitis, 24 cases (33.8% of the patients) had HDV markers in their serum, while in the control group of 118 cases of ordinary acute jaundice type hepatitis B, only 5 cases (4.2% of the patients) had HDV markers. Other authors have also found similar situations, suggesting that the overlapping HDV infection in severe hepatitis should be paid considerable attention to.

　　When the condition of HBsAg carriers, hepatitis B patients, or severe hepatitis patients shows significant fluctuations or progressive deterioration, the possibility of simultaneous or overlapping HDV infection should be considered, and confirmed through laboratory tests.

　　Simultaneous infection of acute HDV/HBV: Acute hepatitis patients, in addition to positive markers of acute HBV infection, with positive serum anti-HDIgM and low titer positivity of anti-HDIgG; or positive HDAg and HDV-RNA in serum and/or within the liver.

　　Overlapping infection of HDV/HBV: Chronic hepatitis B patients or chronic HBsAg carriers, with positive serum HDV-RNA and/or HDAg; or high titer positivity of anti-HDIgM and anti-HDIgG; or positive HDV-RNA and/or HDAg within the liver.

　　The prevention of hepatitis D virus (HDV) mainly focuses on preventing the pathways of viral infection.

　　1. Strictly screen blood donors to ensure the quality of blood and blood products, which is an effective method to reduce the incidence of Hepatitis D after blood transfusion.

　　2. For susceptible individuals to hepatitis B virus (HBV), widespread vaccination with the hepatitis B vaccine is a powerful measure to ultimately eliminate the HBsAg carrier state and is also a feasible method to control HDV infection.

　　1. Strictly screen blood donors to ensure the quality of blood and blood products, which is an effective method to reduce the incidence of Hepatitis D after blood transfusion.

　　The routine examination for Hepatitis D is abdominal ultrasound, which can detect liver lesions. To further confirm the diagnosis, liver function and serum tests are required.

　　1. Serum tests

　　Serum hepatitis D virus antigen (HDAg) and hepatitis D virus antibody (anti-HD).

　　2. Liver function tests

　　Including bilirubin, turmeric turbidity test, AST, ALT, A/G, prothrombin time, serum protein electrophoresis, etc.

　　3. Specific serological pathogenic examination

　　Including HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HBcIgM. If conditions permit, HBV-DNA, DNA-p, Pre-S1, Pre-S2, etc., can be detected.

　　4. Serological detection

　　Some patients with HDV infection can be detected, but a considerable number of patients can only be diagnosed by detecting HDAg in liver tissue.

　　There should be a scientific understanding of the diet for Hepatitis D. The high-calorie therapy for hepatitis advocated in the past is not scientific. The following are dietary recommendations for and against Hepatitis D:

　　1. What is good for the body for patients with Hepatitis D?

　　1. Ensure adequate calorie intake, with an appropriate daily intake of 8400-10500 kilojoules (2000-2500 calories).

　　2. Carbohydrates can generally account for 60-70% of total energy intake.

　　3. To promote the repair and regeneration of liver cells, increase the supply of protein, which should generally account for 15% of total energy intake. Special attention should be given to ensuring a certain amount of high-quality protein, such as animal protein and soy products.

　　4. Ensure the supply of vitamins. B vitamins such as Vitamin B1, Vitamin B2, Niacin, as well as Vitamin C, play an important role in improving symptoms. In addition to choosing foods rich in these vitamins, multiple vitamin preparations can also be taken orally.

　　5. Provide adequate fluids. Drinking more fruit juices, rice porridge, honey water, watermelon juice, etc., can accelerate the excretion of toxins and ensure the normal metabolic function of the liver.

　　6. Prioritize the intake of high-quality protein foods such as fish, lean meat, eggs, dairy products, and soy products.主食 should be ensured.

　　7. Increase the intake of fresh vegetables and fruits.

　　2. What foods should be avoided for patients with Hepatitis D?

　　1. The high-calorie therapy for hepatitis advocated in the past is not advisable, because although high calories can improve clinical symptoms, they can ultimately lead to fatty liver, which may worsen the condition, so the disadvantages outweigh the benefits.

　　2. The high-sugar diet used in the past should also be corrected, because a high-sugar diet, especially excessive glucose, fructose, and sucrose, can affect the appetite of patients, worsen gastrointestinal bloating, increase fat storage in the body, and are prone to obesity and fatty liver. The supply of carbohydrates should mainly be through staple foods.

　　3. Avoid deep-fried, fried, and other strongly irritating foods, limit foods high in nitrogen extracts such as broths and soups, to reduce the burden on the liver.

　　4. Alcohol consumption is strictly prohibited.

　　5. Caution should be exercised when consuming spicy and other irritant foods.

　　Currently, there is no effective treatment for hepatitis D virus (HDV) infection, the key is prevention. Clinical treatment mainly focuses on liver protection and symptomatic treatment, antiviral drugs such as interferon mainly interfere with the synthesis of HBV-DNA, and have no inhibitory effect on the synthesis of HDV-RNA. IfHepatitis B Virus (. The reduction of HBV replication can increase the synthesis of HDV-RNA, and the use of immunomodulators has not improved it.

　　To date, there is no satisfactory treatment drug for hepatitis D virus. There have been cases of using recombinant interferon α to treat chronic HDV/HBV infection abroad, with a very high dose of 9×10^6U, injected intramuscularly 3 times a week, for 12 months as a course, which can sustainably alleviate biochemical abnormalities in 50% of patients, suppress HDVRNA, and improve liver tissue pathology. However, long-term efficacy is still difficult to consolidate. The combination of interferon with other antiviral agents also cannot improve efficacy. There have been reports of using phosphonoacetic acid to treat acute severe hepatitis caused by simultaneous infection with HDV/HBV, with 6 of 8 patients with grade II or higher hepatic encephalopathy surviving after 12 to 14 days of treatment at a dose of 160mg/(kg/d). However, the efficacy for chronic HDV/HBV hepatitis is still difficult to confirm. In 1996, Zavaglia et al. reported 12 cases of chronic hepatitis with both hepatitis B and D superinfection, randomly divided into two groups, 6 cases were treated with thymosin a, 900μg/m2, injected subcutaneously twice a week for 6 months, and the other 6 cases were used as a blank control. Follow-up was conducted up to 12 months after discontinuation of medication, and 2 cases in the treatment group had ALT normalization and HDVRNA negativity, while none in the control group had ALT normalization or HDVRNA negativity. Due to the small number of cases, further data accumulation is needed.