Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study.

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

Ectonucleotidases in Intestinal and Hepatic Inflammation.

Purinergic signaling modulates systemic and local inflammatory responses. Extracellular nucleotides, including eATP, promote inflammation, at least in part via the inflammasome upon engagement of P2 purinergic receptors. In contrast, adenosine generated during eATP phosphohydrolysis by ectonucleotidases, triggers immunosuppressive/anti-inflammatory pathways. Mounting evidence supports the role of ectonucleotidases, especially ENTPD1/CD39 and CD73, in the control of several inflammatory conditions, ranging from infectious disease, organ fibrosis to oncogenesis. Our experimental data generated over the years have indicated both CD39 and CD73 serve as pivotal regulators of intestinal and hepatic inflammation. In this context, immune cell responses are regulated by the balance between eATP and adenosine, potentially impacting disease outcomes as in gastrointestinal infection, inflammatory bowel disease, ischemia reperfusion injury of the bowel and liver, autoimmune or viral hepatitis and other inflammatory conditions, such as cancer. In this review, we report the most recent discoveries on the role of ENTPD1/CD39, CD73, and other ectonucleotidases in the regulation of intestinal and hepatic inflammation. We discuss the present knowledge, highlight the most intriguing and promising experimental data and comment on important aspects that still need to be addressed to develop purinergic-based therapies for these important illnesses.

An elderly man with syncytial giant cell hepatitis successfully treated by immunosuppressants.

Here, we report an elderly man with acute-on-chronic hepatitis accompanied by massive ascites. He showed elevated serum transaminase and anti-nuclear antibody (ANA) levels. Liver biopsy showed diffuse multinucleated giant hepatocytes with interface hepatitis, and he recovered with administration of azathioprine in addition to corticosteroids. Follow-up liver biopsy after recovery showed improvement of hepatic inflammation and reduction of giant hepatocyte formation. The patient is receiving low-dose corticosteroid maintenance therapy and he has remained healthy for 8 years to date. Active immunosuppressive treatment may be beneficial in patients with adult syncitial giant cell hepatitis (AGCH).

Human Th17 cells express high levels of enzymatically active dipeptidylpeptidase IV (CD26).

Dipeptidylpeptidase IV (CD26) is a multifunctional ectoenzyme involved in T cell activation that has been implicated in autoimmune pathophysiology. Because IL-17-producing CD4(+) T cells (Th17 cells) are important mediators of autoimmune disease, we analyzed the expression of CD26 and its enzymatic function on human Th17 cells. Analysis of CD26 expression on different CD4(+) T helper subsets showed that CD26 expression is highest on CD4(+) T cells producing type 17 cytokines (e.g., IL-22, IL-17, GM-CSF, or TNF) compared with Th1, Th2, and regulatory T cells. Phenotypic analysis revealed that CD26(++)CD4(+) T cells express the type 17 differentiation molecules CD161, CCR6, lL-23R, and retinoic acid-related orphan receptor-γt. Furthermore, sorted CD26(++)CD4(+) T cells contain >90-98% of Th17 cells, indicating that CD26(++) T cells harbor the Th17 lineage. A comparison with CD161 and CCR6 indicated that analysis of CD26 coexpression may improve the phenotypic characterization of Th17 cells. Of note, CD26(++) Th17 cells are enriched in the inflamed tissue of patients with hepatitis and inflammatory bowel disease. Functional analysis in migration assays revealed that CD26 expressed on Th17 cells is enzymatically active. Indeed, CD26 negatively regulates the chemotactic CD4(+) T cell response to the inflammatory chemokines CXCL9-12 that can be restored by pharmacological blockade of the enzymatic center of CD26. In summary, these results strongly suggest that CD26 may contribute to the orchestration of the immune response by Th17 cells in human inflammatory diseases. They also suggest that the phenotypic analysis of Th17 cells may be facilitated by determination of CD26 expression.

Relevance of the inner mitochondrial membrane enzyme F1F0-ATPase as an autoantigen in autoimmune liver disorders.

BACKGROUND AND AIMS: Recently, a non-M2-related mitochondrial 60 kDa protein found to be recognized by antimitochondrial antibody (AMA) negative sera from patients with primary biliary cirrhosis (PBC) has been shown to contain parts of the five F(1)-ATPase subunits α, ß, γ, δ and ε. In this study, we examined whether this enzyme is, indeed, a target antigen in PBC. METHODS: Analysed were 60 AMA-positive/anti-M2-negative and 103 anti-M2-positive PBC patients, 46 patients with autoimmune hepatitis (AIH), 35 patients with primary sclerosing cholangitis (PSC), 110 patients with viral hepatitis, 40 patients with inflammatory bowel diseases (IBD), 33 patients with connective tissue diseases (systemic lupus erythematosus, mixed connective tissue disease, Sjögren disease, systemic sclerosis) and 25 blood donors. The F(1)-ATPase-subunits α-δ were recombinantly expressed in Escherichia coli, purified and applied to ELISA and Western blotting. RESULTS: In all, 40 of the 60 AMA-positive/anti-M2-negative (67%) and 44 (43%) of the 103 anti-M2-positive PBC-sera reacted with at least one of the F(1)-subunits α-δ. The ß- and γ-subunits were preferentially recognized. However, also up to 57% of patients with AIH and 34% of patients with PSC had anti-ß- or γ-antibodies, while patients with viral hepatitis had these antibodies in up to 13%. Patients with IBD had anti-ß and anti-γ-antibodies in up to 20 and 5% respectively. None of the patients with connective tissue diseases had antibodies to the ß- and only 6% to the γ-subunit. Sera from healthy blood donors were negative. CONCLUSIONS: Antibodies to the ß- and γ-subunits of F(1)-ATPase are further AMAs in PBC but occur also in other autoimmune liver disorders; they may be, therefore, indicators for a general autoimmune process of the liver.

Adenosin deaminasa como molécula coestimuladora y marcador de inmunidad celular / Adenosine deaminase as costimulatory molecule and marker of cellular immunity

La adenosin deaminasa (ADA), es una enzima del metabolismo de las purinas que ha sido objeto de mucho interés debido a que el defecto congénito de esta enzima causa el síndrome de inmunodeficiencia combinada severa. Una de las tres isoformas de la enzima (ecto-ADA) es capaz de unirse a la glicoproteína CD26 y a los receptores de adenosina A1 y A2B. La interacción ADA-CD26 produce una señal coestimuladora en los eventos de activación de las células T y en la secreción de IFN-g, TNF-a e IL-6. Durante dicha activación la actividad de la enzima está regulada de manera positiva por IL-2 e IL-12 y negativamente por IL-4, basado en un mecanismo de translocación. Diversos estudios señalan que los niveles séricos y plasmáticos de ADA se elevan en algunas enfermedades causadas por microorganismos que infectan principalmente a los macrófagos; así como en trastornos hipertensivos, lo cual podría representar un mecanismo compensatorio como consecuencia de la elevación de los niveles de adenosina y la liberación de mediadores hormonales e inflamatorios estimulados por la hipoxia.

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-g, TNF-a and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia.

Diffuse pattern of transient hepatic attenuation differences in viral hepatitis: a sign of acute hepatic injury in patients without cirrhosis.

OBJECTIVES: Our objective was to describe the transient hepatic attenuation differences (THADs) on dynamic computed tomography in patients with viral hepatitis who had no evidence of cirrhosis. METHODS: After excluding patients who had known causative factors for the development of THAD, a retrospective review of dynamic CT scans in 67 patients with viral hepatitis was performed to determine whether THAD was present. The patients were assigned to 3 groups according to the magnitude of alanine aminotransferase (ALT) level alteration (normal to mild, moderate, and marked) or hepatitis type (acute hepatitis, acute exacerbation of chronic hepatitis, and chronic infection), and differences in the presence of various CT features including THAD among these groups were evaluated. RESULTS: Five THADs observed had a focal pattern, and 18 THADs had a diffuse pattern. All of the diffuse THADs were observed in patients with marked ALT level alteration (ALT level > 400 IU/L) and in patients with a clinical diagnosis of acute hepatitis or acute exacerbation of chronic hepatitis. In addition, there were significant differences of the presence of other CT findings including hepatomegaly, periportal tracking, gallbladder wall thickening, perihepatic lymphadenopathy, and splenomegaly among these groups (each P < 0.05). CONCLUSIONS: A diffuse THAD of the liver and other CT features indicates acute hepatic injury in patients with viral hepatitis who have no clinical evidence of cirrhosis.

[Adenosine deaminase as costimulatory molecule and marker of cellular immunity]. / Adenosin deaminasa como molécula coestimuladora y marcador de inmunidad celular.

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-gamma, TNF-alpha and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia.

Coordinate regulation of metabolic enzymes and transporters by nuclear transcription factors in human liver disease.

BACKGROUND: It has been hypothesised, mainly from studies with animal models of liver disease, that the transport of substrates for metabolic enzymes and their subsequent metabolism and elimination in hepatic bile or blood is co-ordinated, but there is little information on this process in diseased human liver. METHODS: In this study we have measured by reverse transcription polymerase chain reaction (RT-PCR) major genes involved in drug metabolism from UDP-glucuronosyltransferases (UGT1A1, UGT1A6, UGT1A9, and UGT2B4) and cytochrome P450 (CYP) families (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), transport (OATP-C, MRP2, MRP3, and MDR1) and major transcription factors (PXR, CAR, HNF1alpha, HNF4alpha, RXR, and AHR) involved in their regulation. Liver biopsy tissue from patients with viral hepatitis was scored for inflammation and fibrosis by the METAVIR system, and separated into groups with mild (A0-1; F0-1, n = 20) or severe (A2-3; F3-4, n = 19) liver disease. Correlation analysis (Spearman rank-test, P < 0.05) was used to identify metabolic enzymes and transporters which shared significant correlation with transcription factors. RESULTS: Our results show an extensive correlation between transcription factors, transporters, and metabolic enzymes. An unexpected finding was that this was substantially greater in the severely diseased liver. Cross-talk between transcription factors was markedly increased in tissue from patients with severe liver disease, particularly between CAR, HNF4alpha, and PXR. CONCLUSION: Our results support the hypothesis of co-ordinate regulation of metabolic enzymes and transporters in diseased human liver, as part of a widespread co-ordinated process under the control of nuclear receptor transcription factors.

Hepatitis G virus infection in multitransfused Egyptian children.

The purpose of this study was to identify the magnitude of the hepatitis G virus infection in 33 multitransfused cases and 20 matched controls. All were tested for liver biochemical profile, HBsAg, HCV-antibody, HGV-RNA, and antibody to envelop protein E(2). HGV was detected alone in 61% of the multitransfused cases and 15% of the controls. Hepatitis markers were negative in 21% of cases versus 70% of controls. HGV envelope antibody was detected in 12% of cases, and none of controls. Mean values of transaminases in HGV positives and negatives showed no significant differences. HGV infection is highly prevalent in Egyptian children with no impact in infected cases.

Acute hepatitis due to dengue virus in a chronic hepatitis patient

We present a case of acute hepatitis caused by dengue virus, with a significant increase in aspartate transferase and alanine transferase levels in a chronic hepatitis patient attended at the Cane Sugar Planters Hospital of Campos dos Goytacazes, RJ.

Assessment of liver fibrosis in co-infected patients.

The evaluation of liver injury in HIV patients co-infected with HBV and HCV should follow the same principles as the evaluation of any patient with chronic liver disease. The initial clinical evaluation should include documentation of risk factors for progressive disease. HIV history is important particularly with respect to a past history of significant or prolonged immunosuppression as this has been clinically correlated with more advanced liver disease. Liver transaminases are an important predictor of disease severity and progression in HIV patients. Liver biopsy has remained the 'gold standard' for the grading of inflammation and staging of disease. We would still recommend liver biopsy in HIV patients particularly those with HCV because recent community-based studies in the HAART era have suggested slower rates of progression for HIV/HCV than studies from tertiary care centres and older cohorts. Since, liver biopsy is invasive and expensive, non-invasive techniques including serological tests and novel imaging techniques have evolved to stage liver fibrosis. A novel technique for measuring hepatic elasticity has recently been validated alone and in combination with serum markers for HCV mono-infection. Future trends for staging liver disease must not only focus on cross sectional diagnosis but on utilizing novel techniques to stratify risk for disease progression over time.

Diverse cellular localizations of secretory phospholipase A2 enzymes in several human tissues.

The secretory phospholipase A2 (sPLA2) family in mammals contains more than 10 enzymes. In this study, we examined by immunohistochemistry the localization of six sPLA2s (IIA, IID, IIE, IIF, V and X) in human heart, kidney, liver and stomach. In normal hearts, sPLA2-IIA was detected in coronary vascular smooth muscle cells (VSMC) and sPLA2-V in cardiomyocytes beneath the endocardium. In infarcted hearts, expression of these two enzymes was markedly increased in damaged cardiomyocytes, and expression of sPLA2-IID and-IIE, which was undetectable in normal hearts, was elevated in damaged cardiomyocytes and VSMC, respectively. In infarcted kidneys, sPLA2-IIA and-V were markedly induced in the uriniferous tubular epithelium. In livers affected by viral hepatitis, sPLA2-IIA and-V were expressed in hepatocytes with fatty degeneration. In the gastric glands exhibiting intestinal metaplasia, sPLA2-IIA was localized in the glandular base, sPLA2-IID and-V in the glandular body epithelium, sPLA2-IIE and-IIF in goblet cells in the foveolar epithelium, and sPLA2-X in both glandular body epithelial cells and foveolar epithelial goblet cells. In the gastric submucosal tissues, sPLA2-IIA and-IIE were located in VSMC and sPLA2-V was in the interstitial fibroblasts. In addition, sPLA2-IIA,-IIE,-IIF and-X were highly expressed in gastric signet ring cell carcinoma. Thus, individual sPLA2s exhibit unique cellular localizations in each tissue, suggesting their distinct roles in pathophysiology.

Prevalence and clinical significance of immunoglobulin A antibodies against tissue transglutaminase in patients with diverse chronic liver diseases.

The prevalence of celiac disease (CD) and the prevalence and clinical significance of anti-tissue transglutaminase (tTG) antibodies (tTGAbs) in a large series of patients with chronic liver diseases were assessed. We studied 738 patients (462 with chronic viral hepatitis, 117 with autoimmune liver diseases, 113 with alcoholic or nonalcoholic fatty liver disease, and 46 with other liver disorders) and 1,350 healthy controls (HC). Immunoglobulin A (IgA) tTGAbs were measured by enzyme-linked immunosorbent assay and a microsphere-based flow cytometric assay. Positive sera were investigated for IgA antiendomysial antibodies (EmA). IgA tTGAb-positive subjects were invited to undergo a small-intestinal biopsy and HLA-DQ allele typing. Four of 1,350 HC (0.3%) tested tTGAb(+) EmA(+) and underwent a biopsy (CD confirmation in all). Four of 738 liver disease patients tested tTGAbs(+) EmA(+) (0.54%; not statistically significant). Two were HCV infected (1.24%; not statistically significant), and two had transaminasemia of unknown origin. Forty-three patients tested tTGAbs(+) EmA(-) (5.8%; P<0.001 compared to HC). Inhibition experiments verified the existence of specific IgA anti-tTG reactivity. Twenty-six of 43 patients underwent a biopsy (all negative for CD). Binary logistic regression analysis revealed age (P=0.008), cirrhosis (P=0.004), alkaline phosphatase (P=0.026), and antinuclear antibodies (P=0.012) as independent risk factors for tTGAb reactivity among the patients. It was concluded that CD prevalence is the same in HC and patients with chronic liver diseases. The prevalence of tTGAbs is higher in hepatic patients compared to HC, but their specificity for CD diagnosis in this group of patients is low. tTGAbs in patients appear to be associated with the presence of autoimmunity, cirrhosis, and cholestasis, irrespective of the origin of the liver disease.

Differential expression of matrix metalloproteinases in viral and non-viral chronic liver diseases.

BACKGROUND: Fibrosis is a common consequence of chronic liver diseases irrespective of aetiology. Metalloproteinases play an important role in the fibrotic process participating in the balance between collagen synthesis and degradation. We examined whether matrix gelatinases and stromelysins are similarly involved in the development of viral (HCV, HBV) and non-viral (NASH) liver diseases. METHODS: Hepatic mRNA levels of matrix metalloproteinase MMP-2, MMP-9, MMP-10 and MMP-11 isolated from liver biopsies were measured by semi-quantitative RT-PCR. Seventy-three patients were examined in this study: non-diseased controls (10), patients with chronic hepatitis B (14), chronic hepatitis C (33) and non-alcoholic steatohepatitis (16). RESULTS: A significant increase of MMP-9 and MMP-10 expression was found in patients with non-viral (non-alcoholic steatohepatitis) liver disease. Patients with chronic hepatitis B and hepatitis C showed an increase in MMP-2 mRNA expression compared to controls. Moreover, chronic hepatitis B and hepatitis C patients had significantly different mRNA expression patterns. CONCLUSIONS: These findings indicate that matrix metalloproteinases are differentially involved in the fibrotic process of viral and non-viral chronic liver diseases. Differences exist between HBV and HCV chronic hepatitis. Differences between early and late fibrosis indicate that in future studies, careful staging of patients is mandatory for interpretation of results.

Dihydropyrimidine dehydrogenase and thymidylate synthase activities in hepatocellular carcinomas and in diseased livers.

BACKGROUND/PURPOSE: Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are key enzymes for predicting the efficacy of 5-FU in the treatment of malignant tumors. However, 5-FU is not commonly commonly chosen for chemotherapeutic treatment of hepatocellular carcinoma (HCC) in practice. The aim of this study was to determine the activities of both DPD and TS in HCCs and corresponding liver parenchyma and to assess the correlation between the activities of these enzymes and clinicopathological features. The possibility of using 5-FU as a first-choice chemotherapeutic agent for HCC was also evaluated. METHODS: The study material comprised 33 pairs of hepatocellular carcinoma and noncancerous liver samples. The DPD and TS activities were quantified by a radiometric enzymatic assay and a 5-fluoro-2'-deoxyuridine-5'- monophosphate (FdUMP) ligand-binding assay, respectively. RESULTS: Pathologically invasive HCCs tended to show higher DPD activity and lower TS activity with some exceptions. DPD activity was lower in the HCCs regardless of their clinical features than in the noncancerous liver parenchyma, whereas TS activity was generally lower in HCCs except for those with certain clinical features. HCCs with multiple nodules showed lower DPD activity and those with a diameter of more than 5 cm showed lower TS activity. In the noncancerous liver parenchyma, a gradual decrease in DPD activity and an increase in TS activity were associated with the age of the patient, liver damage and z-factor. Of 30 HCC samples, 10 exhibited comparatively low DPD and TS activity, and these could be considered 5-FU-sensitive HCC. CONCLUSIONS: DPD and TS activity may be affected by the clinicopathological status in both the HCC and the corresponding liver parenchyma. However, further investigation is necessary. Some HCC patients may be good candidates for 5-FU-based chemotherapy based on measurements of tumor levels of DPD and TS.

Synergistic effect of hepatitis virus infection and occupational exposures to vinyl chloride monomer and ethylene dichloride on serum aminotransferase activity.

AIMS: To study the synergistic effect of occupational chemical exposure and hepatitis virus infection on serum aminotransferase activity. METHODS: A total of 568 male workers who were employed in five polyvinyl chloride (PVC) or four vinyl chloride monomer (VCM) manufacturing factories were studied. Information relating to current job title, alcohol consumption, and cigarette smoking was obtained. Exposure level of chemical mixtures was classified by hygienic effect (a summation of personal time weighted average/reference permissible exposure level of each chemical) into high, moderate, and low exposure groups. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-hepatitis C antibody were assayed. RESULTS: Hepatitis virus infection and increased body mass index were associated with abnormal serum aminotransferase activity. In workers with hepatitis virus infection, those with high exposure had a higher prevalence of abnormal AST and ALT compared to low exposure; among those without hepatitis virus infection, the differences of prevalence of abnormal AST and ALT were not significant between different chemical exposure groups. There was a significant trend of increasing risks of increased AST and ALT in moderate and high exposure groups with hepatitis virus infection. Such a synergistic effect was more prominent among HBeAg-positive workers. CONCLUSIONS: Mixed exposures to 1,2-ethylene dichloride and VCM have a positive synergistic effect with hepatitis virus infection on liver damage. Assessment of fitness for work should be considered in workers with hepatitis B and C infection, when they have potential exposure to hepatotoxins in the workplace.

[Perfluorocarbonic compounds application as a new approach in pathogenic treatment of severe forms of viral hepatitis]. / Perftoruglerodnye soedineniia kak novoe napravlenie patogeneticheskoi terapii tiazhelykh form virusnykh gepatitov.

Perfluorocarbonic blood substitute Perftoran (PF) was used in combined intensive therapy of 79 patients with severe viral hepatitis B as a polyfunctional pathogenetic drug according to the following scheme: intravenously 400 ml 1-2 times a day for 2-6 days (800-2400 ml per course). PF exhibited immunomodulating, antioxidant, membrane-stabilizing and disintoxicating properties. The immunomodulating effect of the drug manifested itself in its influence on functional activity of macrophages, reduction of their oversection of proinflammatory cytokines: IL-1 beta, IL-6, IL-8, TNF-alpha. Antioxidant properties were established on the basis of the ability of PF to lower activity of prooxidant factors (myeloperoxidase of neutrophilic granulocytes) and to stimulate antioxidant factors (catalase, glucose-6-phosphatedehydrogenase), reduced glutathione in erythrocytes). As a membranostabilizer, PF increased resistance of erythrocyte membranes to peroxide hemolysis and improved their rheological indices (deformability and viscosity). A disintoxication effect of PF led to reduction of middle-molecular peptides content in plasma. PF had a noticeable effect on basic clinicobiochemical indices in patients with a severe course of viral hepatitis B as well as the disease course and outcomes. Finally, PF reduced the duration of treatment of patients with severe viral hepatitis B in hospital and intensive care units. It is inferred that administration of infusion drugs on the basis of perfluorocarbonic compounds holds promise in pathogenetic therapy of viral hepatitides.