| Hepatitis E Virus (HEV) infection may cause acute inflammation of liver. The diseaseis mostly self-limited, and most patients can be cured without treatment. However, for theelderly, pregnant women and patients with initial liver diseases, HEV infection can acutelyworsen their condition, leading to acute decompensation of liver function and even liverfailure with poor prognosis. Chronic hepatitis B virus (HBV) infection is very common inChina, and its overlapping with acute hepatitis E (AHE) causes severe illness and severeeconomic and health burden. The natural history of chronic HBV infection contains twostable states: immune tolerance and inactive carrier. Immune tolerance is featured bypositive serum HBeAg, and high-level replication of HBV (＞105IU/mL) withoutinflammatory of liver. Inactive carrier is featured by negative HBeAg. In this state, HBV islower than lower limit of detection, and the inflammatory activity is absent. At present, fewresearches focus on the effect of overlapping acute HEV infection in stable state of chronicHBV infection on the progression of liver diseases and HBV replication. Meanwhile, due toprolonged HBV infection, chronic liver injury and tissue fibrosis progress alternately, andthe annual and cumulative incidence rates of cirrhosis of patients with chronic HBVinfection grow year by year in China. Previous researches indicate that patients withHBV-related cirrhosis can have overlapping HEV infection, which is an important causeacute decompensation. After acute HEV infection, once severe acute decompensation ofliver functions occurs, the outcomes of decompensated patients are not optimistic, and themortality may increase. Therefore, in-depth research should be performed to investigateclinical characteristics and the factors that worsen the acute liver diseases of patients withstable chronic liver diseases (especially cirrhosis) after overlapping acute HEV infection.Seeking effective antiviral therapy and exploring noninvasive indicators are very important for diagnosis and treatment.Similar to other hepatitis viruses, pathopoiesia of HEV is mainly virus-mediatedimmune response injury, but the specific mechanism has not been illustrated. IL-22is animportant effecter molecule secreted by Th17and Th22cells, and plays an important role inliver inflammation and regeneration. Currently, researches on the expression level of IL-22in viral hepatitis mainly focus on acute and chronic infection of HBV and HCV, while studyof IL-22in acute HEV infection is lacking. Analyzing different levels and clinicalsignificance of IL-22and related cytokines between patients with overlapping HEVinfection will help us understand the immune states and possible mechanisms underlyingacute exacerbation of the diseases, and identify and establish sero-immunity indicatorsrelated to disease progression.Therefore, this paper retrospectively includes149patients with acute HEV infectionfrom March2003to June2013, and groups them according to whether they have chronicHBV infection previously, state of HBV stable infection, and whether there is HBV-relateddecompensated cirrhosis. We collected patients’ medical records and routine laboratoryindexes during hospitalization, and observed themduring follow-up. Meanwhile, weselected serum samples of some patients, detected levels of IL-22and some relatedcytokines in serum by ELISA, and analyzed how they are related with outcomes.Results:1. ALT, TBIL, ALB, PTA and other indicators that reflect liver functions of the patientswith stable chronic HBV infection (immune tolerance and inactive carrier) and overlappingacute HEV infection were not significantly different from those of patients with acute HEVinfection (P＞0.05). So was the incidence rate of severe complications related to liverdiseases (P＞0.05).2. The patients with HBV-related liver cirrhosis and overlapping acute HEV infectionhad significantly higher TBIL, and lower ALB and PTA than those with pure acute HEVinfection (P＜0.01). The former also had a higher incidence rate of severe complicationsrelated to liver diseases (P＜0.01) with a hospital mortality of8.3%, and lower recoveryratio of TBIL in a short period of time (60days)(P＜0.05). Advanced age, positive HBVDNA in serum and prolonged drinking are risk factors for acute-on-chronic liver failure(ACLF) of patients with cirrhosis after having overlapping acute HEV infection. 3. After having overlapping acute HEV infection under immune tolerance of chronicHBV infection, patients had a lower serum HBV DNA level in a short period of time (1.5months), no matter anti-HBV drugs (nucleoside analogs and interferon) were used or not,71.4%of patients had the serum HBV DNA level lower than lower limit of detection; aftermedian1.5years of follow-up, patients’ HBV DNA level was slightly decreased comparedwith that in initial treatment (P=0.004), but was still in a high-level replication status, andALT was restored to a normal level (＜40IU/L); and HBeAg serological conversion wasabsent in all patients.4. The patients with decompensated liver cirrhosis and overlapping acute HEVinfection had higher levels of serum IL-22, IL-17, IL-6and TNF-α than those with pureHEV infection,, and patients with ACLF had a higher incidence rate during the course ofdisease than those without ACLF (P＜0.001); serum IL-22and IL-17levels were positivelycorrelated with the TBIL level and MLED score, and negatively correlated with PTA (P＜0.001).5. Cox regression was used to analyze and compare the effect of five types of cytokinelevels on ALT and TBIL recovery, and variables of equations were IL-22and IL-6concentrations, where variable coefficient B of IL-22was-0.017(P=0.029). Tip: with ahigher IL-22level, the risk that ALT and TBIL can not be restored timely was greater.Longitudinal observation indicates that IL-22level decreases with the improvement ofdisease.Conclusion:1. Stable chronic HBV infection will not lead to further worsening of liver dysfunctionwhen the patients have overlapping acute HEV infection. Short-term serum HBV DNAclearance can occur no matter anti-HBV drugs are used or not after overlapping acute HEVinfection under immune tolerance state, and immune tolerance state of chronic HBVinfection has not been ended and active replication of HBV DNA may still occur after HEVclearance.2. Due to the existence of basic diseases of HBV-related cirrhosis, overlapping acuteHEV infection may lead to more severe clinical manifestation and prognosis of pure HEVinfection, and liver functions recover more slowly, and the course of disease will bedelayed. 3. IL-22is involved in liver inflammatory injury and intensive process after acuteHEV infection, serum IL-22level is related to disease severity and prognosis and can be animmunological indicator for evaluating degree of disease progress. Further study should becarried on body immune state and mutual influence that IL-22and related cytokines havereflected during acute hepatitis virus infection. |
PDF Full Text Request