Export of intracellular HBsAg in chronic hepatitis B virus infection is related to viral replication.

Serum and liver HBsAg bear an inverse relation to each other during the evolution of chronic hepatitis B virus infection and the quantity of HBsAg in tissue rises gradually with time. In this study, intracellular and extracellular levels of HBsAg were measured by radioimmunoassay in primary culture of hepatocytes from 30 patients with chronic hepatitis B virus infection to determine a possible relationship with hepatitis B virus replication. Serum levels of HBsAg correlated with markers of active viral replication (serum hepatitis B virus DNA, p less than 0.005, and tissue HBcAg, p less than 0.02) but inversely with tissue HBsAg (p less than 0.05). In similar fashion, in vitro export of HBsAg was also related to the presence of active viral replication markers (serum hepatitis B virus DNA, p less than 0.02, and tissue HBcAg, p less than 0.05) and negatively with tissue HBsAg (p less than 0.001). Export of HBeAg also correlated positively with markers of active viral replication (serum hepatitis B virus DNA, p less than 0.05 and tissue HBcAg, p less than 0.05). Further experiments indicated that intrahepatic pre-S1 and pre-S2 correlated closely with intrahepatic HBsAg, indicating that a failure to export HBsAg was unlikely to be attributable to deficient intracellular expression of pre-S1 or pre-S2. These data indicate that in vitro primary hepatocyte culture of hepatitis B virus-infected cells provides an accurate reflection of in vivo export of HBsAg and that this is closely related to the presence of active viral replication.     

Increased tumor necrosis factor-alpha receptor number in chronic hepatitis B virus infection.

Production of the antiviral cytokine, tumor necrosis factor-alpha is increased in chronic hepatitis B virus infection, and clinical studies of tumor necrosis factor-alpha have indicated a proviral effect at higher doses. To determine whether this might be related to abnormal cell surface tumor necrosis factor-alpha receptor expression, binding characteristics of cell surface tumor necrosis factor-alpha receptor on peripheral blood mononuclear cells in chronic hepatitis B virus carriers were studied using radioiodinated recombinant tumor necrosis factor-alpha. The specific binding curves generated were analyzed according to the method of Scatchard to determine cell surface receptor numbers and dissociation constants. A single class of cell surface tumor necrosis factor-alpha receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. The median number (range) of cell surface tumor necrosis factor-alpha receptors on peripheral blood mononuclear cells from controls (n = 11), chronic hepatitis B virus patients seropositive for hepatitis B virus DNA (n = 8) and seronegative for hepatitis B virus DNA (n = 8) were 2,329 (range = 1,538 to 3,133), 3,375 (range = 2,300 to 6,718) (p less than 0.01) and 3,113 (range = 2,229 to 5,246) (p less than 0.05) sites/cell, respectively. They all had similar dissociation constants of 8.4 x 10(-10) mol/L (range = 4.1 to 16.9), respectively. Further dissection of the peripheral blood mononuclear cells showed that this increase in cell surface receptor number was confined to the monocyte fraction (p less than 0.01). Plasma tumor necrosis factor-alpha levels in five patients with increased monocyte cell surface tumor necrosis factor-alpha receptor numbers were also elevated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risks of immunosuppressive therapies including biologic agents in patients with rheumatic diseases and co-existing chronic viral infections

PURPOSE OF REVIEW: A number of chronic viral infections could be reactivated by immunosuppressive agents used in rheumatic diseases. In this review, we will focus on the complex effect of immunosuppressive agents, including biologic agents, on the natural course of chronic viral infections as well as an approach to the prevention and management of therapy-induced viral reactivation. RECENT FINDINGS: Chronic viral infections that are affected by immunosuppression in the setting of an underlying rheumatic disease include those due to hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, and latent infections from Epstein-Barr virus, JC virus, or varicella zoster virus. The most recent data of the effects of immunosuppressive agents are reviewed, with special emphasis on the effects of biologic therapies (anti-tumor necrosis factor, anti-B cell), on these viral agents. SUMMARY: Clinicians should be aware of the risk for viral reactivation of an underlying chronic viral infection during immunosuppressive therapy. Despite the existence of such risk, the presence of chronic viral infection is not a contraindication to immunosuppressive therapy, given that appropriate pretherapy screening and close monitoring is applied.     

Significance of anti-HBx antibodies in hepatitis B virus infection.

Serological responses to hepatitis B virus-X determinants have been noted in human sera, but conflicting findings concerning the correlation of anti-HBx antibodies with different stages of hepatitis B virus infection or pathological sequelae have been reported. Using an adenovirus-based eukaryotic vector, the 17 kD X protein was efficiently expressed in 293 cells. Cellular extracts containing the eukaryotic X protein have been used to screen for anti-HBx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis B virus chronic hepatitis, hepatocellular carcinoma and acute viral hepatitis. Sera from 32 of 171 (19%) chronic hepatitis B virus patients were positive for anti-HBx antibodies. Only one of thirty-two (3%) HBsAg-negative, anti-HBs/anti-HBc-positive chronic hepatitis serum was anti-HBx positive. Very few sera from primary hepatocellular carcinoma patients showed positivity for anti-HBx (8 of 149 or 5%). Anti-HBx were also detected in 8 of 48 (17%) acute viral hepatitis patients. In the four cases that were followed up weekly, anti-HBx antibodies appeared 3 to 4 wk after the onset of the clinical signs. To compare the X protein expressed in eukaryotic and prokaryotic cells as a substrate for anti-HBx antibody detection, 171 sera were screened with HBx fusion proteins expressed in Escherichia coli. The prokaryotic cell extract test seems to be more sensitive. During the chronic phase of hepatitis B virus infection, the presence of anti-HBx antibodies detected with the eukaryotic cell extract correlates with the presence of well-established markers of ongoing viral replication: serum hepatitis B virus-DNA (p less than 0.001) and intrahepatic HBcAg expression (p less than 0.001).     

Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy? A statistical analysis of predictive factors

Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti-human immunodeficiency virus antibody status (p less than 0.001), chronic active hepatitis on liver biopsy (p less than 0.005), high AST level (p less than 0.001), low hepatitis B virus DNA level (p less than 0.001) and a history of acute hepatitis (p less than 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p less than 0.05). The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter, which predicted response in 77% with a specificity of 79% (p less than 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration (p less than 0.001).     

Hepatitis C virus infection prevalence and liver dysfunction in a cohort of B-cell non-Hodgkin's lymphoma patients treated with immunochemotherapy

Several studies have reported a higher prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) than in the general population. Treatment for NHL includes the use of chemotherapeutic agents such as cytotoxic drugs, corticosteroids, and rituximab, which can be immunosuppressive and hepatotoxic. While reactivation of hepatitis B virus (HBV) when undergoing immunosuppressive therapy for haematological malignancies is a well-documented complication, data on HCV reactivation or liver function impairment after chemotherapy for NHL are controversial. From January 2006 to December 2009, 207 consecutive NHL patients treated with chemotherapy without rituximab (CHOP) or with rituximab (R-CHOP) were observed; screening for HCV infection and baseline liver function tests were performed in all patients. The prevalence of HCV infection was 9.2%. This prevalence is higher than that observed in the general population in Italy (3%). Among the HCV-infected subjects, the incidence of hepatitis flares was 26.3% vs 2.1% among the HCV-uninfected individuals. Although less frequent and less severe than in HBV-infected subjects, liver dysfunction can occur as a consequence of rituximab-containing regimens in HCV-infected patients with NHL. In the cases considered in this study, no patient treated with chemotherapy without rituximab developed hepatitis flares. The frequency and the severity of this complication vary in different reports. Therefore, we recommend the assessment of liver function and the screening of all patients with NHL for HCV infection before starting chemotherapy; we also recommend monitoring of liver function tests and HCV-RNA serum levels during treatment.     

Natural history and prognostic factors for chronic hepatitis type B.

One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n = 46) or chronic active hepatitis without cirrhosis (n = 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3.7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p less than 0.0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p less than 0.0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis.     

Hepatitis B virus DNA, HBeAg and delta infection during the course from acute to chronic hepatitis B virus infection

The presence of hepatitis B virus DNA in serum was determined in 57 unselected patients during the course from acute to chronic hepatitis B infection. Forty-six (81%) patients were hepatitis B virus DNA-positive in the first available serum sample. Generally, hepatitis B virus DNA was cleared before or at the same time as HBeAg, but in two patients (4%), hepatitis B virus DNA could be demonstrated after HBeAg clearance. One of the latter patients had hepatitis B virus DNA in the presence of anti-HBe. Both patients became hepatitis B virus DNA-negative. Seven of the hepatitis B virus DNA-positive patients received long-term treatment with prednisone, and three of them continued to be hepatitis B virus DNA positive for more than 10 years. Among the untreated patients hepatitis B virus DNA could be detected for up to 7 years, and 10 patients were hepatitis B virus DNA-positive for three years or more. Twenty-four patients (42%) showed serological signs of delta agent infection. Hepatitis B virus DNA clearance was observed in a significantly higher proportion (87%) of delta-infected patients as compared to patients with no delta infection (45%) (p less than 0.05). In addition patients with delta infection had a significantly increased hepatitis B virus DNA clearance rate as compared to patients without delta markers in their serum (p less than 0.01). In one (8%) delta-infected patient, hepatitis B virus DNA clearance was followed by a fall in transaminases into the normal range as opposed to results in 86% of patients with pure hepatitis B (p less than 0.002).     

Antibodies to polymerized human serum albumin in acute and chronic liver disease

Since antibodies to polyalbumin have been noted to occur in patients with hepatitis or cirrhosis, we investigated sera from 219 patients with a variety of acute and chronic liver diseases with and without HBsAg using an ELISA. The prevalence of circulating polyalbumin antibodies was shown to be significantly increased over that of healthy controls (6.7%) in patients with autoimmune chronic active hepatitis (67%), acute viral hepatitis (41%) and fulminant hepatic necrosis (38%), but such antibodies were absent in chronic hepatitis B patients and other liver diseases. Serial studies in acute hepatitis showed evidence of antibodies early in the course of illness with disappearance prior to full recovery. In acute hepatitis B, the presence of polyalbumin antibodies was significantly associated with female sex (p less than 0.01), 3-fold higher transaminase levels and shorter duration of clinical illness (less than 4 weeks in all cases). Polyalbumin antibodies appear to be associated with diseases characterized by active hepatocyte necrosis. Since they are evident early in acute hepatitis B when complexes of polyalbumin and virus are likely, these antibodies may play an adjunctive role to other hepatitis B-related antibodies in the clearance of hepatitis B virus infection.     

Early and frequent detection of HBxAg and/or anti-HBx in hepatitis B virus infection

To clarify the significance of the X gene of hepatitis B virus, we have tested for anti-HBx in the serum and HBxAg in the liver at different stages of the natural history of hepatitis B virus infection. Sera were screened by enzyme-linked immunosorbent assay and positive results confirmed by immunoblot. Purified recombinant MS2 Pol-HBx fusion protein was used as target for both assays. Among serial sera of patients with nonfulminant acute hepatitis, 24 of 64 patients (37.5%) were positive for anti-HBx. In fulminant cases, 15 of 36 patients (42%) had anti-HBx. In chronic hepatitis patients with high rates of hepatitis B virus replication, we found a significantly (p less than 0.01) higher prevalence of anti-HBx, 14 of 25 patients (56%), than in those with low replication, 14 of 66 patients (21%), or among asymptomatic HBsAg carrier blood donors (20 of 126 = 16%) without detectable hepatitis B virus replication (p less than 0.0001). The highest prevalence of anti-HBx was found in HBsAg carriers with cirrhosis (41 of 54 patients = 76%) and/or with hepatocellular carcinoma (18 of 33 patients = 54%). The findings suggest that anti-HBx appears as a common and early marker of hepatitis B virus infection, transient in self-limited hepatitis but persisting with progression to chronicity. In chronic hepatitis, the prevalence of anti-HBx correlated with the intensity and duration of hepatitis B virus replication but neither with the severity of the liver disease nor with malignant transformation per se.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of interferon-gamma on hepatitis B viral antigen expression in primary hepatocyte culture

Interferon-alpha has been shown recently to selectively enhance hepatocyte expression of HBsAg/pre-S2 in chronic hepatitis B virus infection in a way that may enhance immune recognition. To determine the effect of interferon-gamma on hepatitis B virus antigen expression, hepatocytes isolated from patients with chronic hepatitis B virus infection were incubated in the absence or presence of interferon-gamma and viral antigen expression was assessed by both radioimmunoassay and immunocytochemistry using appropriate monoclonal antibodies. Interferon-gamma inhibited the expression of all hepatitis B virus antigens tested. Intracellular HBsAg measured by radioimmunoassay of sonicated hepatocytes fell by 29% with 1 U/ml (p less than 0.01) and 36% with 10 U/ml of interferon-gamma (p less than 0.001) compared with control treatment. Secreted HBsAg was reduced by 19% with 10 U/ml of interferon-gamma (p less than 0.01). Intracellular HBeAg was also decreased by 29% with 1 U/ml (p less than 0.05) and 42% with 10 U/ml of interferon-gamma (p less than 0.05), but no significant change was found in the amount of secreted HBeAg. The proportion of hepatocytes containing various hepatitis B virus antigens and the intracellular viral antigen staining densities also fell significantly with interferon-gamma incubation. Interestingly, the addition of interferon-gamma abolished the augmenting effect of interferon-alpha on intracellular HBsAg. These data indicate that interferon-gamma, in contrast to interferon-alpha, has an inhibitory effect on hepatocyte expression of all hepatitis B virus antigens including HBsAg/pre-S2, suggesting that this may be one factor that accounts for their difference in clinical activity in patients with chronic hepatitis B virus infection.     

Hepatitis B exposure in emergency medical personnel: Prevalence of serologic markers and need for immunization

To assess the occupational risk of hepatitis B infection in emergency medical personnel, a seroepidemiologic survey of 87 emergency medical technicians and paramedics was conducted. Serologic markers indicating exposure to hepatitis B virus were detected in 18 percent. The prevalence of markers was associated with race (p = 0.006), with a relative risk of 3.5 (95 percent confidence interval 1.42 to 8.63) for nonwhites. Seropositivity was not associated with age, sex, previous clinical hepatitis, or blood transfusion. There was a suggestion that duration of employment as an emergency medical technician was related to the prevalence of hepatitis B markers (p = 0.11). Efforts to control the risk of hepatitis B infection in this profession are complicated by unique problems with postexposure prophylaxis and uncontrolled exposure to blood. Immunization with hepatitis B vaccine would be the optimal strategy to reduce infection in this high-risk occupation.     

Intrahepatic expression of pre-S1 and pre-S2 antigens in chronic hepatitis B virus infection in relation to hepatitis B virus replication and hepatitis delta virus superinfection.

Hepatocyte expression of pre-S1 and pre-S2 in relation to hepatitis B virus replication (hepatitis B virus-DNA in serum and HBcAg in the liver), histological activity and hepatitis delta virus superinfection was studied by indirect immunofluorescence on frozen sections of liver specimens from 68 patients with chronic hepatitis B virus infection. All 44 patients with chronic type B hepatitis had pre-S1 and pre-S2 display in the liver. The distribution of pre-S1 in the liver was membranous in one, mixed membranous and cytoplasmic in 12, and cytoplasmic in 31. The distribution of pre-S2 was membranous in one, mixed membranous and cytoplasmic in 26, and cytoplasmic in 17. Membranous expression of pre-S1 was significantly more prevalent in patients with active hepatitis B virus replication than in those without (13/28 v 0/16, p < 0.001), regardless of the histological activity, as was membranous expression of pre-S2 (27/28 v 0/16, p < 0.001). In contrast, a significantly higher extent of cytoplasmic expression of pre-S1 and pre-S2 was noted in patients without active hepatitis B virus replication than in those with. Of 24 patients with chronic type D hepatitis virus, eight had active hepatitis B virus replication, and the other 16 did not. The distribution and quantitative expression of pre-S1 and pre-S2 in the liver in these patients also correlated significantly with the status of hepatitis B virus replication and, moreover, showed little or no difference from those without hepatitis delta virus infection. In conclusion, all patients with chronic type B hepatitis had synthesis and display of pre-S1 and pre-S2 in the liver. The distribution and quantitative expression of pre-S1 and pre-S2, however, were closely related to the status of hepatitis B virus replication, but not to the histological activity. Hepatocyte expression of pre-S1 and pre-S2 in chronic type D hepatitis also correlated significantly with status of hepatitis B virus replication, and was not modulated by concurrent hepatitis delta virus infection.     

Effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 and hepatitis B viral replication.

This study examined the effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 infection and hepatitis B viral replication. Twenty-five chronic HBsAg carriers were studied. Presence of hepatitis B virus DNA and expression of HBeAg were more frequent among 20 chronic HBsAg carriers positive for human immunodeficiency virus type-1 antibody compared with five chronic HBsAg carriers negative for human immunodeficiency virus type-1 antibody, but the associations were not statistically significant. Hepatitis B virus DNA and HBeAg were inversely related to duration of hepatitis B virus infection (p less than 0.001). Stratifying for duration of hepatitis B virus infection, the presence of viral replication was similar among patients negative and positive for antibody to human immunodeficiency virus type-1. Hepatitis B virus DNA levels did not increase with the decline of cellular immunity over time. In conclusion, hepatitis B virus replication among chronic carriers may be a function of duration of hepatitis B virus infection rather than of an effect of human immunodeficiency virus type-1.     

Detection of antibody to calmodulin in chronic viral hepatitis: lack of correlation with virus replication and hepatocellular damage.

We have analyzed the presence of IgG and IgM anti-calmodulin antibodies (anti-CaM) by ELISA in patients with chronic hepatitis due to B, delta and C viruses as well as in patients with other liver diseases. The specificity of the assay was demonstrated by preadsorption of positive serum with calmodulin (CaM) but not with myosin light chain. Among 164 patients with chronic viral hepatitis (B, delta and C) and 50 with non-viral hepatitis, 27 and 26%, respectively, had auto antibodies against CaM. There was a significantly increased frequency (37%) of these auto-antibodies in chronic delta infection as compared to that (21%) of patients with chronic B hepatitis (p less than 0.05). An intermediate incidence of anti-CaM, (24%) was found in chronic C infection. The frequency of anti-CaM was not related to the level of hepatitis B virus (HBV) or hepatitis delta virus (HDV) replication. A high occurrence of anti-CaM in the presence of liver membrane antibody (p less than 0.03) was observed. During follow-up of patients with chronic delta-hepatitis, the presence of anti-CaM was consistently observed, when the isotype was IgM, but transiently when it was IgG. The occurrence of anti-CaM correlated neither with ALT levels nor with histological diagnosis. Antibodies to CaM, are present in liver diseases especially in chronic delta-hepatitis, and do not play a pathogenic role on hepatocellular damage.     

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.     

Changes in hepatitis B virus DNA polymerase in relation to the outcome of acute hepatitis type B.

Serum levels of hepatitis B virus specific DNA polymerase and hepatitis B e antigen were studied serially in 34 patients with hepatitis B virus infection--20 who had the acute illness and recovered, seven who died with fulminant disease, three who died as a result of subacute hepatic necrosis, and four who went on to develop chronic active hepatitis. DNA polymerase activity was present in 16 (80%) and HBeAg in 13 (65%) of the uncomplicated cases at presentation and in all of those patients from whom the initial sample was obtained before the peak in aminotransferase. Both markers disappeared after 30 days from the onset but DNAP remained persistently positive during a follow-up period of four to 10 months in the four patients who progressed to chronic hepatitis. These results indicate that DNAP and HBeAg are transiently present in all cases of acute hepatitis B. Only their persistence after the acute episode could represent a useful prognostic marker of chronically. In this respect, DNAP was more reliable in our patients than HBeAg. In uncomplicated acute hepatitis, the peak in DNAP levels, which defines the time of maximum virus replication in the liver, preceded the peak in aminotransferase levels. Among the 10 patients who developed massive liver damage after hepatitis B infection, DNAP was detected in five of the seven with fluminant hepatitis, with enzyme levels that were comparable with those observed in uncomplicated acute hepatitis and presentation, but not in the cases of subacute hepatic necrosis. These findings are consistent with the hypothesis that in hepatitis B infection, liver damage, whatever the severity, is not directly related to the degree of virus replication.     

Management of chronic hepatitis B in treatment-experienced patients

Current monotherapy with interferon (IFN), lamivudine, or adefovir remains unsatisfactory for most patients with chronic hepatitis B infection. Prolonged treatment with lamivudine monotherapy is needed in most patients with chronic hepatitis B infection and leads to an increased risk of developing lamivudine resistance. Recent data suggest that lamivudine resistance occasionally can result in serious clinical sequelae. On the other hand, conventional IFN treatment is ineffective in up to 70% of chronic hepatitis B patients. Adefovir resistance, although less frequent than lamivudine resistance,also has been identified. With the introduction of new nucleoside/nucleotide analogs such as entacavir, clevudine, LFd4C,tenofovir, and immunomodulatory agents such as pegylated IFN, new treatment options, either alone or in combination, are being investigated to increase the response rate in treatment-na?ve and treatment-experienced chronic hepatitis B patients.     

Interleukin-1 and interleukin-2 activity in chronic hepatitis B virus infection

Abnormalities of lymphocyte proliferation in chronic hepatitis B virus infection are well documented, although the underlying mechanisms are poorly understood. To determine whether these defects may be secondary to disordered lymphokine production, we have simultaneously assayed interleukin-1 and interleukin-2 production in 31 chronic carriers of the hepatitis B virus. Supernatants from mononuclear cells cultured both in the presence and absence of lipopolysaccharide contained significantly increased quantities of interleukin-1 activity in patients compared with normal controls (p less than 0.01). Lysates of monocytes from patients also contained more interleukin-1 than those of controls (p less than 0.05) in the presence of lipopolysaccharide or silica, or both. These results indicate that interleukin-1 production is markedly elevated in patients with chronic hepatitis B virus infection, whereas in contrast, interleukin-2 production was found to be reduced in these patients (p less than 0.01). As one of the biological properties of interleukin-1 is to stimulate fibroblasts to produce collagen, the relationship between fibrosis in the liver biopsy specimen and interleukin production was examined. There was a highly significant correlation (p less than 0.001) between interleukin-1 production and the severity of fibrosis, suggesting that this lymphokine may be closely related to the development of cirrhosis in such patients.     

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis(PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs(c DMARDs) or biological ones(b DMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus(HBV) and hepatitis C virus(HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen(anti-HBs Ag), HBs Ag, and antibody to HCV(anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a(Cy A) or b DMARDs(etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBs Ag and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV.In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.