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The development and severity of liver fibrosis in patients with chronic HCV infection can be evaluated best according to the staging of fibrosis in blind liver biopsy. So far there is however no biochemical indicator suggesting advanced fibrosis or progression of fibrosis in chronic HCV infection. In 1997 - 1999 60 adult out-patients (32 women) with chronic HCV infection were examined by blind liver biopsy. The grading of hepatitis was scored according to Knodell and staging of fibrosis according to Desmet. All patients were anti-HCV positive, assessed by the ELISA-3 method and 48/60 had positive HCV RNA in serum. The main risk factor of HCV infection was blood transfusion (67%). Of 27 examined patients 20 (74%) had serotype HCV 1. Staging of fibrosis: histologically confirmed fibrosis was not recorded in 11 patients (18.3%), mild and medium fibrosis was recorded in 25 (42%), severe fibrosis in 14 (23%) and cirrhosis in 10 (17%). With confirmed fibrosis correlated more closely AST serum activity (p0.002) than ALT activity (p0.03). Steatosis of the liver was found in 25 (42%) patients. The mean age of patients with steatosis was significantly higher than that of patients without steatosis (p0.0008). Steatosis was more frequent in patients with fibrosis (p0.04), in particularin the age group above 60 years. The development of fibrosis in patients with chronic HCV infection is suggested by permanently elevated activity of both transaminases whereby AST has a higher predictive value than ALT activity. A total of 40% histologically tested patients had the highest staging of fibrosis (3 - 4). Steatosis is in chronic HCV infection a very frequent finding (42%), in particular in patients above 60 years and those with serious fibrosis. The finding of fibrosis should stimulate the initiation of antiviral treatment which can lead to regression of fibrosis and improvement of the histological finding.

At present standard treatment of patients with chronic hepatitis C is combined therapy with interferon-alpha and ribavirin which so far gives the best results. It is recommended in patients with resistance to interferon or a relapse after termination of treatment by interferon alone as well as in hitherto untreated patients. Combined treatment produces, however, not only common side-effects which are caused by interferon as well as ribavirin but rarely also serious side-effects produced by combined treatment which call for premature termination of therapy. The authors present an account on two patients who had serious side-effects during combined treatment: the first one was an intravenous drug addict who developed psychosis during combined treatment, the second one a female patient with cirrhosis and incipient portal hypertension who developed after nine months of combined treatment a severe biochemical relapse with jaundice, and treatment was also terminated. Both serious complications after treatment receded and in the first patient a sustained response to antiviral therapy persists for more than one year.

The aim of this study was to assess the rate of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection ("the coinfection") in chronic liver disease (CLD) and to reveal overt and hidden HBV infection in patients with antibodies to HCV (anti-HCV). A total of 209 untreated patients (64 with chronic hepatitis B, 79 with chronic hepatitis C and 66 with porphyria cutanea tarda (PCT)) were screened for serological markers of HBV and HCV infection in serum by third generation enzyme-linked immunosorbent assay (ELISA) methods and for HBV DNA and HCV RNA in serum by polymerase chain reaction (PCR). The rate of the overt coinfection in chronic hepatitis B was very low (2/64, 3%). However, in chronic hepatitis C, the rate of the hidden coinfection with HBV was relatively high (19/79, 24%); these patients had higher alanine transaminase (ALT) and asparagine transaminase (AST) levels in serum and a more advanced liver disease. In PCT patients, the rates of HBV and HCV infections were the same, 21% (14/66). In the PCT patients infected with HBV or HCV, the rate of the coinfection was 33% (7/21). The PCT patients with the coinfection had a high serum ALT level and the worst histological picture in the liver. The hidden HBV infection was more frequent than the overt one. The possibility of the overt or hidden coinfection in CLD renders a detailed analysis of all serum samples for both viruses mandatory. Vaccination against HBV infection should be offered to anti-HCV-positive individuals as well as to PCT patients not showing antibodies to HBV (anti-HBV).

It is known that in patients with porphyria cutanea tarda (PCT) there is an increased prevalence of the hepatitis B virus (HBV) and the hepatitis C virus (HCV). The incidence of anti-HCV in PCT in our country is 21.7% in estimations by the second generation method, however, the incidence of HBV in PCT was not assessed so far.In 60 patients with PCT antigens and antibodies against HBV and HCV were assessed (by the anti-HCV third generation ELISA method) and in subjects with signs of HBV or HCV. HBV DNA and HCV RNA were assessed by the method of the polymerase chain reaction. PCT without detectable HBV or HCV infection was found in 45 subjects (68%). HBV infection only was confirmed in seven subjects (10.6%), however none of the patients had positive HBsAg in serum. All had only antibodies against HBV. HCV infection only was detected in seven patients (10.6%) and HBV and HCV co-infection also in seven patients (10.6%). In the group of patients with HBV and HCV co-infection there was not a single HBsAg positive subject. The mean ALT serum activity was significantly higher as compared with subjects with HBV or HCV infection only (p0.05) and the histological finding on liver biopsy was more serious.HBV (21%) and HCV (21%) infection participates significantly in the clinical picture of PCT. A special subgroup is formed by patients with PCT and HBV and HCV co-infection who have as a rule a higher ALT activity and more severe histological changes in the liver. The incidence of HBV and HCV infection in PCT in the Czech Republic is double as compared with Germany or Great Britain.

In 1994 the authors published first results of anti-HCV antibodies in the group of 92 porphyria cutanea tarda patients, tested with ELISA second generation enzymatic method. Positivity, found in 21.7 per cent of them, was significantly higher when compared with the results of healthy blood-donors. Anti-HCV reactivity thus ascertained can be, however, non-specific in some cases and need not necessarily indicate existence of an active replication of hepatitis C-virus. The authors have therefore subsequently tried to verify the above results by the more sensitive polymerase chain reaction (PCR), enabling the proof of viral RNA and thus an assessment of the replication-activity of HCV. This study completes their previous findings for the evidence of viraemia in anti-HCV reactive PCT-patients.21 of 92 PCT-patients were reactive when examined with the second generation ELISA method (Sanofi, Pasteur). HCV RNA was examined in 20 subjects from the above group (one patient died in the meantime) by means of PCR. Positive HCV RNA was found in 17 patients, i.e. in 85 percent of them. Percutaneous liver biopsy without visual control was performed in 17 anti-HCV reactive and HCV RNA positive patients and in 46 anti-HCV negative porphyrics. The biopsy-findings were significantly worse in the HCV RNA-positive group. Also the average activity of ALT and AST was significantly higher in the patients with positive HCV RNA when compared with anti HCV-negative subjects.High frequency of HCV-infection (21.7 percent) was found in our group of 92 PCT-patients. Viraemia was present in the vast majority (85 per cent) of them, for they had also positive HCV RNA besides anti-HCV reactivity. These patients had also higher ALT- and AST-activity and more severe histological liver-changes. HCV-infection is the main virological cause of their liver lesion, beside ethylism. Hepatocellular carcinoma is rather exceptional in our porphyria patients in spite of their frequent HCV-infection.

In the majority of patients with acute viral hepatitis C the early antibody IgM anti-HCV in serum is positive. However, a substantial portion of the patients with chronic hepatitis C has also positive IgM anti-HCV as a sign of the continuing replication of the virus. The objective of the work was to assess the presence of IgM anti-HCV in patients with confirmed chronic hepatitis C, in subjects with HBsAg negative chronic hepatitis and in excluded blood donors. Moreover, the authors assessed the relationship between IgM anti-HCV positivity and the activity of serum transaminases and whether the presence of IgM anti-HCV has an impact on the histological finding in the liver.88 patients were examined (44 women and 44 men), average age 48 years. In 47 subjects histological examinations of the liver were made. IgG anti-HCV were assessed by the Monolisa anti-HCV Sanofi Pasteur test and IgM anti-c22 by an Abbott kit IgM HCV EIA: With regard to the results of the serological examination the patients were divided into three groups which were mutually compared. Group 1 comprised 24 patients with a positive IgG and IgM anti-HCV, group 2 38 patients with a positive IgG anti-HCV only and group 3 26 patients with a negative IgG and IgM anti-HCV. Of 88 examined patients 62 had positive IgG anti-HCV (70%). Of 62 IgG anti-HCV positive subjects 24 (39%) had positive IgM anti-c22. A total of 24 patients had blood transfusions (39%) but only 9 of them had positive IgM anti-c22 (37.5%). The mean ALT serum activity was significantly higher in subjects with positive IgM than in those without IgM (p = 0.006), however, for AST the difference was not significant (p = 0.09). Comparison of patients with a confirmed histological finding in the liver revealed that two-thirds of patients with a positive IgM anti-c22 either suffered from cirrhosis or chronic active hepatitis, while anti-HCV positive patients without IgM anti-c22 had cirrhosis or chronic active hepatitis only in one third of the cases.The results suggest that in chronic hepatitis C some 40% of the patients have positive IgM anti-c22; these subjects have a significantly higher serum ALT activity and a more advanced histological finding in the liver than subjects without IgM anti-c22. Assessment of IgM anti-c22 is important not only for diagnosis but also for treatment of chronic HCV infection with antiviral drugs.

In the majority of patients with acute hepatitis C the anti-HCV IgM antibodies in serum were present, however, some patients with chronic hepatitis C were positive for anti-HCV IgM too. The aim of this study was to assess the presence of anti-c22 IgM in patients with chronic hepatitis C and to determine whether the positivity for anti-c22 IgM has an impact on the histological finding in the liver. A total of 88 patients were examined (44 women, 44 men), mean age 48 years. The first group comprised 24 patients positive for both anti-HCV IgG and anti-c22 IgM, the second group 38 patients positive for anti-HCV IgG only, and the third group 26 patients negative for both anti-HCV IgG and anti-c22 IgM. Of 62 anti-HCV-IgG-positive subjects 24 (39%) were positive also for anti-c22 IgM. Of 24 patients who received a blood transfusion 9 (37.5%) were positive for anti-c22 IgM. The mean serum alanine aminotransferase (ALT) activity was significantly higher in subjects with anti-c22 IgM than that in subjects without them (p = 0.006), however, the difference in aspartate aminotransferase (AST) was not significant (p = 0.09). Histological examination was performed in 46 patients. Two-thirds of the patients with anti-c22 IgM had either cirrhosis or chronic active hepatitis (CAH) while only one third of the anti-HCV-positive patients without anti-c22 IgM had CAH or cirrhosis. The results showed that approximately 40% of the patients with CAH and cirrhosis had anti-c22 IgM, a significantly higher serum ALT activity and more serious histological finding in the liver than anti-HCV-positive patients without anti-c22 IgM.

Replication of the virus is in the majority of patients with chronic hepatitis B associated with permanent activity and progression of the inflammatory process. The change of the virus to the latent stage expressed by seroconversion of HBeAg to anti-HBe leads to a significant repression of inflammatory changes and has a favourable impact on the course of the disease. The morphological changes in the hepatic tissue after spontaneous seroconversion or after interferon treatment were investigated in specimens of needle biopsy in 18 patients with active chronic hepatitis B. In 10 of them the diagnosis of chronic hepatitis was confirmed by biopsy in the stage of replication of the virus. During the subsequent time interval after seroconversion of HBeAg, incl. two instances where interferon was administered, in the tissue of 14 HBsAg positive patients regression of inflammatory changes was apparent, in particular a lower incidence of piecemeal necroses. The regular finding of periportal and septal fibrosis in these patients is probably associated with a longer course of chronic active hepatitis and late spontaneous or therapeutically induced seroconversion of HBeAg. In one man, treated with interferon, morphological examination revealed one month after seroconversion of HBeAg an acute exacerbation of the disease. In another three patients, who at the time of the bioptic examination were HBsAg negative, in the hepatic tissue minor silent periportal and septal fibrosis persisted.

The authors analyzed acute exacerbations of chronic hepatitis B in 24 chronic HBsAg carriers (20 with positive HBeAg, 4 with anti-HBe), more than half of whom were treated with glucocorticoids, by examining specific antigens and antibodies of the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis delta virus (HDV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Of 38 observed exacerbations of the disease they found in 7 (18%) deterioration after discontinuation of glucocorticoids, in 7 (18%) seroconversion of HBeAg to anti-HBe, in 9 (24%) spontaneous exacerbation of chronic hepatitis B, in 11 (29%) chronic activation, reactivation of EBV superinfection, in 3 (8%) CMV reactivation or superinfection and in one (3%) HDV superinfection. In no instance HAV superinfection was observed. Exacerbations were found five times more frequently in subjects in the stage of active viral replication (in HBeAg+ subjects) than in subjects with anti-HBe. In eight patients EBV reactivation was found after glucocorticoids withdrawal: in five patients after an average period of 5 months (range 3-7) and in three patients after an average period of 33 months (range 22-48). The results provide evidence that in addition to already known causes of acute exacerbations of chronic hepatitis B in our geographical area probably an important cause of deterioration of hepatitis is reactivation or superinfection with EBV and CMV in some patients in conjunction with previous glucocorticoid treatment.

In 1985-1993 in the out-patient clinic in Prague 8 a total of 59 patients died from cirrhosis of the liver, incl. 30 who were for prolonged periods HBsAg positive and 29 who were HBsAg negative. In the group of cirrhotics with positive HBsAg who died 19 of 29 (66%) were also HBeAg positive which suggested advanced HBV replication during the period of reconstruction of the liver. 43% of those who died and had HBV infection, had glucocorticoid treatment. Only one female patient of 13 had positive anti-HD in serum. In HBsAg negative cirrhotics the main cause of development of cirrhosis was ingestion of alcohol, but at that time it was not possible to assess antibodies against HCV. The most frequent cause of death in cirrhotics was haemorrhage into the digestive tract (25%), hepatic failure (20%) and a malignant tumour (12%). The most frequently encountered malignant tumour was primary carcinoma of the liver (in 8 of 11, 73%). Because in chronic hepatitis the replication activity of HBV is high and can persist also in advanced cirrhosis of the liver, patients with hepatitis B in the stage of active viral replication must be treated in time with interferon to prevent the development of the disease into cirrhosis of the liver and its complications.

In serum of patients with chronic hepatitis B (HB) in the stage of active viral replication HBsAg/IgM complexes were detected. Using a commercial kit AU-IGM-K Sorin Biomedica HBsAg/IgM complexes in 136 patients with chronic HB and cirrhosis of the liver were examined, incl. 89 men, 42 women and 5 children, mean age 48 +/- 17 years. With regard to the results of the serological examination for HB virus (HBV) markers the results in 54 patients with positive HBeAg and HBsAg in serum (group 1) were compared with 68 patients with positive HBsAg only (group 2) and with 14 patients with positive antibodies against HBV or unrelated to HBV (group 3). The mean positivity index of HBsAg/IgM complexes in group 1, 2 and 3 was 9.89, 1.85 and 0.50, respectively. The results suggest a significant predominance of HBsAg/IgM complexes in patients during the stage of active viral replication with positive HBeAg in serum, as compared with patients without HBeAg (p = 0.001) and the control group (p = 0.001). A similar significant difference between groups was found as regards to ALT and AST activities. We conclude that in patients with chronic HBeAg positive hepatitis and a moderately elevated transaminase activity usually also HBsAg/IgM complexes, which are closely correlated with HBeAg, are positive.

Alpha-fetoprotein (AFP) was assessed in 159 subjects with chronic liver disease, incl. 125 chronic HBsAg carriers (42 suffered from cirrhosis of the liver) and in 34 HbsAg negative cirrhotic patients. In the group of 83 patients with chronic hepatitis B a slightly elevated AFP value was recorded in 7.2%, however, during the check-up examination it was already normal. During a one-year follow up hepatocellular carcinoma (HCC) was revealed in 4 of 42 HBsAg positive cirrhoses (9.5%) and in 2 of 34 (5.9%) HBsAg negative cirrhoses, the difference was not, however, significant. Five patients with HCC had markedly elevated or rising AFP value, one patient had abnormal AFP level despite advanced HCC. All cases of HCC were diagnosed late, in one patient radical treatment was not successful. We conclude that to improve the adverse prognosis of patients with HCC it is necessary to follow-up prospectively all patients with cirrhosis of the liver by sonography twice a year and examine after the same time intervals serum AFP to detect early stages HCC where there is still some chance of successful treatment.

In 37 patients with chronic hepatitis B in the stage of active viral replication the authors tried to assess the time of seroconversion of HBeAg to anti-HBe and HBsAg to anti-HBs (21 men, 13 women and 3 boys, mean age of adults 44 years). During the 8-years investigation period seroconversion of HBeAg occurred in 19 of 37 patients (51.3%) which is an annual rate of seroconversion 6.4%. HBeAg disappeared from serum after a mean period of 82 months (range 29-228 months). After seroconversion of HBeAg the ALT and AST activity declined significantly. Acute exacerbation of hepatitis before seroconversion of HBeAg was recorded in 13 of 37 patients (35%). The mean ALT activity at the peak of exacerbation was 7.93 mu kat/l, the average duration of exacerbation was 9.8 months. Seroconversion of HBsAg occurred in 7 of 37 patients (19%). The mean annual rate of seroconversion of HBsAg was 2.4% after an average period of 98 months. During the investigation period 7 patients died (19%), four of them had a constantly positive HBeAg. The authors conclude that very low annual average seroconversion of HBeAg (6.4%) and HBsAg (2.4%) in patients with chronic hepatitis B is probably caused by previous glucocorticoid treatment.

Electron microscopy of 57 needle biopsies from livers of 55 patients with chronic hepatitis, mostly of type B, revealed, in addition to typical hepatitis B virus nucleocapsids in 34 cases, also atypical intranuclear inclusions in 9 biopsies. These inclusions consisted of electron-dense particles similar in size to hepatitis B virus nucleocapsids. The possibility of an involvement of a hepatitis non-A non-B virus is discussed.