Nicoletta Sinelli

Chronic hepatitis induced by Jin Bu Huan

BACKGROUND/AIMSnJin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets.nnnMETHODSnThe patient, a 49-year-old man, developed biochemical signs of liver damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune, metabolic or other hepatotoxic causes were excluded. Liver function impairment was resolved by discontinuing Jin Bu Huan intake.nnnCONCLUSIONSnThis case reinforces the already known hepatotoxicity of this product and should make us think more about the uncontrolled use of alternative products.

HCV-RNA levels play an important role independently of genotype in predicting response to interferon therapy

Objective: To evaluate the relationship between hepatitis C virus (HCV)‐RNA levels and genotypes in order to establish their potentially predictive role in interferon (IFN) response. Design: To detect HCV genotype at baseline and HCV viraemia levels before and during IFN treatment in three groups of patients with different IFN response. Methods: Our study included 85 patients with biopsy‐proven chronic hepatitis C who underwent IFN therapy at standard schedule (3MU thrice weekly for 6 months). On the basis of IFN response they were subdivided into three groups as follows: non responders (NR: 27 cases) when alanine aminotransferase (ALT) values (normal value: 0‐40 IU) at the end of treatment were abnormal (101.7±10.4); responders relapsing (RR: 29 cases) when normal ALT values at the end of therapy (28.14±1.7) increased during follow‐up; sustained (long‐term) responders (LTR: 29 cases) when ALT values remained normal for at least 12 months of follow‐up (ALT values at the end of therapy: 21.8± 1.4). ALT activity was monitored monthly during therapy and each month during 12 months of follow‐up. HCV genotype was evaluated before starting treatment whereas HCV‐RNA viraemia was checked at baseline and at the 1st and 6th months of therapy. Results: The baseline viral load was higher in the NR group than in the RR and LTR groups independently of genotype; HCV‐RNA levels progressively decreased during therapy independently of response but the levels remained significantly higher in the NR group. Genotype 1b was prevalent in the NR group. However, levels of viraemia in genotype 1b LTR patients are significantly lower than in genotype 1b NR patients. Conclusion: These results suggest that among viral‐related parameters viraemia alone seems to play an important role in predicting response to IFN independently of genotype.

Hepatitis G Virus Infection in Haemodialysis and in Peritoneal Dialysis Patients

The aim of this study was to detect hepatitis G virus RNA (HGV RNA) and antibodies against the virus envelope protein E2 (anti-E2) in 107 patients either on maintenance haemodialysis (n = 78) or peritoneal dialysis (n = 29) to evaluate the prevalence of HGV infection and to establish its role in liver disease. The total prevalence of HGV infection was of 15.4% among haemodialysis patients, whereas it was 10.3% among peritoneal dialysis patients. HGV RNA was detected in 2 haemodialysis patients (2.6%) and in 3 peritoneal dialysis patients (10.3%). Anti-E2 was found in 10 haemodialysis patients (7.8%), whilst all peritoneal dialysis patients resulted negative. In only 1 patient the alanine aminotransferase level was elevated. This patient underwent liver biopsy that did not reveal evidence of chronic hepatitis. The lower HGV prevalence in haemodialysis patients, when compared with data reported by other European authors, should be related to the lower rate of polytransfused patients in our series (29.5%). Multiple blood transfusions should be considered as the main factor to explain the different prevalence of HGV infection among various European dialysis centres. Detection of both antibody and viraemia is important to establish the real rate of the infection.

Soluble β2-μ-Associated and β2-μ-Free HLA class I heavy chain serum levels in interferon-α nonresponder chronic hepatitis C patients. Markers of immune activation, and response to antiviral retreatment

The serum levels of soluble β2-μ-associated and β2-μ-free HLA class I heavy chains were determined in 28 interferon-α nonresponder chronic hepatitis C patients retreated with interferon-α plus ribavirin and in 70 healthy subjects. The baseline levels of β2-μ-associated and β2-μ-free HLA class I heavy chains were significantly higher in patients than in healthy controls(P = 0.001). The levels of β2-μ-associated HLA class I heavy chains significantly increased in responder patients with respect to nonresponders at the third month of treatment(P = 0.03). At the sixth month of treatment and after 6 months of follow up the levels of β2-μ-associated HLA class I heavy chains decreased in responder patients and increased in nonresponders. The levels of β2-μ-free HLA class I heavy chains showed only minor changes during and after treatment. We suggest that the determination of hepatitis C virus RNA levels combined with soluble β2-μ-associated HLA class I heavy chains, as a marker of immune activation, could identify interferon-α non responder chronic hepatitis C patients most likely to respond to a retreatment with interferon-α plus ribavirin.

Effect of interferon therapy on serum alpha-fetoprotein levels in patients with chronic hepatitis C virus infection

Serum alpha-fetoprotein (AFP) levels were determined monthly for 1 year in 30 patients with biopsy-proven chronic hepatitis C virus (HCV) infection before, during, and after recombinant interferon alfa-2b (IFN) therapy. On the basis of their response to therapy, as evaluated by serum alanine aminotransferase levels, patients were classified as responders (10 patients), partial responders (10), and nonresponders (10). Ten healthy subjects comprised the control group. In patients with chronic HCV infection, baseline serum AFP levels (7.2 ± 1.0 ng/mL, 5.2 ± 0.4 ng/mL, and 6.2 ± 0.7 ng/mL in responders, partial responders, and nonresponders, respectively) were slightly but significantly higher than those recorded in healthy subjects (2.2 ± 0.3 ng/mL). Furthermore, IFN therapy caused a decrease in serum AFP levels that was more evident and prolonged in responders but that also occurred in partial responders and nonresponders. However, in the latter groups, this reduction in serum AFP levels was evident only during IFN therapy. These data suggest that IFN therapy may affect AFP secretion, possibly throughout the improvement of hepatic necrosis and, consequently, of hepatic regeneration.

Prevalence of TT virus (TTV) infection in patients at high risk of parenterally transmitted viruses

Aim: To evaluate: I) TTV infection prevalence in a group o f patients (pts) with high risk o f parenteral exposure such as intravenous drug users 0DUs) and haemodialysed pts (HDs); 2) the clinical relevance o f TTV and the correlation with other hepatitis virus coinfection~ Mater ia l s and Methods: We studied 118 pts:40 with previous or ongoing history o f IDU and 78 HDs. All IDUs were anti-HCV+ve and 20 out them were HIV ceinfected. TTV-DNA was tested by semi-nested PCR using primers open reading flame 1 (ORF). HGV-RNA analysis was performed by PCR using specific primers for the NS3 and 5UTR.The presence o f anti-E2 Ab was tested by ELISA assay. Qualitative HCV-RNA was performed by nested (in h o u s e ) R T PCR. R~ n l t s : Our data showed a lower prevalence o f TTV (21/118; 17.8%) as compared to HGV infection (38/118; 32.2%). In particular TTV-DNA was detected in 6 cases (15%) among IDUs and in 15 cases (19%) among HDs, while an higher prevalence (65%) o f HGV was present in IDUs group. TI V infection alone was present in few pts (4 l i d s ) which showed normal ALT levels while in all TTV+ve cases with ALT increase HCV-RNA was detected. Rarely we observed TTV and HGV coinfection in both groups. Conclusions: The prevalence o f TI V infection was lower when compared to HGV. These data suggest the lower importance o f parenteral route for TTV. As far as the clinical impact o f TTV is concerned, the data showed that in the TTV+ve pts ALT increase may be related to HCV activity, [ eo o3s I Viral hepatitis. clinical aspects

Effect of therapy with combined interferon and tauroursodeoxycholic acid in chronic hepatitis C: Biochemical and virologic evaluation

Abstract Sixty men and women with biopsy-proven chronic hepatitis C were randomized to receive interferon (IFN) subcutaneously 3 million units three times a week (n=30) or 3 million units three times a week with tauroursodeoxycholic acid (TUDCA) 250 mg BID (n=30) for 6 months. A follow-up period of 3 months at the end of therapy was scheduled. Thirty-four patients (56.7%) had normalized serum alanine aminotransferase levels at the end of therapy; 16 received IFN alone and 18 received IFN plus TUDCA. Sixteen of these 34 patients (47.1%) relapsed in the follow-up period. No significant difference in relapse rate was observed between the two treatment groups. The overall percentage of nonresponders was 36.6%. Treatment was discontinued for noncompliance and/or side effects in four patients (6.7%), two in the IFN group and two in the IFN plus TUDCA group. Hepatitis C virus-ribonucleic acid was evident at the start of treatment in all patients and became undetectable in almost all responders. In some cases there was no correlation between viremia and biochemical signs of liver disease. No virologic differences were found between treatment groups. The tendency toward a reduced, but not significant, relapse rate in patients treated with IFN plus TUDCA must be confirmed in studies using a larger sample size.

High-dose interferon therapy in patients with chronic hepatitis C: A biochemical and virologic evaluation

Abstract Sixty patients of both sexes with biopsy-proven chronic hepatitis C were randomized to receive recombinant alpha-2b interferon 3 million IU or 10 million IU three times a week for 4 months. A 6-month follow-up period was scheduled for the end of therapy. Eighteen patients (30.0%) had normalized alanine aminotransferase (ALT) levels at the end of therapy and during the follow-up period. Of these, 10 received 3 million IU (33.3%) and 8 (26.7%) received 10 million IU. Twenty-three (38.3%) of the 60 patients relapsed during the follow-up period. No significant difference in relapse rate was observed between the two groups. The overall percentage of nonresponder patients was 31.7%. Treatment was discontinued because of noncompliance and/or side effects in 7 patients (11.7%), 1 in the 3-million IU group and 6 in the 10-million IU group. All patients were positive for hepatitis C virus—RNA at the beginning of the study, and it became undetectable in almost all responder patients. No correlation between viremia and biochemical signs of liver disease was observed in some cases. No virologic differences were found between the two treatment groups. Our study shows that 10 million IU does not increase the response or the relapse rate compared with 3 million IU in the treatment of patients with chronic hepatitis C.