Intrahepatic splenosis with severe iron deposition presenting with atypical magnetic resonance images.

An intrahepatic mass was incidentally found in a 41-year-old man with a history of a traffic accident injury which resulted in removal of a ruptured spleen. Hepatic splenosis was considered in the differential diagnosis but magnetic resonance imaging showed hypointensity on T2-weighted images, atypical for normal spleen. Histologically, the mass showed sinusoidal structures and lymphoid follicular aggregates. Immunohistochemical study showed that the phenotype of the vascular lining cells was CD8-positive, CD31-positive, and CD34 negative, the pattern diagnostic for ectopic spleen. In addition, severe iron deposition was histologically demonstrated, which was considered as the cause of the hypointense T2-weighted images.

First phase viral kinetic parameters and prediction of response to interferon alpha-2b/ribavirin combination therapy in patients with chronic hepatitis C.

The aim of the present study was to assess parameters in early phase HCV dynamics for predicting the outcome of interferon (IFN)/ribavirin combination therapy in patients with chronic hepatitis C (CH-C). Sixty-five CH-C patients who received IFN alpha-2b/ribavirin combination therapy were enrolled. The serum levels of HCV RNA 0h and 3 months after commencing therapy were serially quantified. HCV kinetic parameters such as quantity, ratio of decline, and half-life were analyzed. In genotype 1 patients, both the quantity and the ratio of decline of HCV RNA 24h after the start of therapy were useful predictors of a poor response. No patients who had serum HCV RNA above 200KIU/ml 24h after the start of therapy achieved a sustained viral response (SVR). In genotype 2 patients, conversely, these two parameters were predictors of a sustained viral response. The efficacy of these parameters in predicting the outcome of therapy was comparable to that of the disappearance of HCV RNA from sera at 4 weeks. These results demonstrate that parameters of HCV kinetics 24h after the start of therapy are useful for the early prediction of outcome in response to IFN alpha-2b/ribavirin combination therapy.

Prediction of breakthrough hepatitis due to lamivudine-resistant hepatitis B virus by a sensitive semiquantitative assay using peptide nucleic acids.

OBJECTIVE: The aim of this study was to predict breakthrough hepatitis and analyze the dynamics of lamivudine-resistant hepatitis B virus in patients treated with lamivudine. METHODS: Fifty-five chronic hepatitis B patients treated with lamivudine were included. The emergence of YMDD motif mutants was detected by peptide nucleic acid (PNA) mediated PCR clamping with a detection limit of 10(1) YMDD mutants. We then performed a semiquantitative PCR assay of subjects in whom YMDD mutants were detected. This assay detects 10(2.7)-10(7.7) copies of mutant virus per 1 ml of serum. RESULTS: YMDD mutants were detected in 28 (51%) of the 55 patients. Eight patients stopped medication before viral breakthrough. YMDD mutants appeared transiently despite the continuance of lamivudine therapy in 12 patients. In all 8 patients with breakthrough hepatitis, the quantities of YMDD mutants ranged from 10(2.7)-10(4.7) copies/ml in the two to three months before clinical breakthrough. In contrast, in 12 patients without viral breakthrough, there were always less than 10(2.7) copies/ml YMDD mutants. CONCLUSIONS: Lamivudine-resistant viruses sometimes disappear even during lamivudine administration. Our sensitive quantitative assay proved useful for early detection of YMDD mutants and a threshold of 10(2.7) copies/ml is suggested for predicting viral breakthrough.

Natural course of asymptomatic hepatitis C virus-infected patients and hepatocellular carcinoma after interferon therapy.

A long-term follow-up study was performed to identify the natural course of chronic HCV carriers with persistently normal serum ALT level (PNAL; < or =30 U/L) and to clarify the effect of interferon therapy on the inhibition of the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients with elevated ALT levels. One hundred twenty-nine HCV carriers with PNAL underwent liver biopsy, 69 were followed for more than 5 years, and 35 underwent serial liver biopsies. We included 1246 chronic hepatitis C patients (stage F1: 231, F2: 638, F3: 336, F4: 41) who received interferon therapy and were followed for more than 2 years (mean, 7.7 years). Approximately 90% of HCV carriers with PNAL had normal to mild liver histology, and 30% developed symptomatic chronic hepatitis C within 5 years. The frequency of steatosis and iron loading was significantly lower in these patients than in symptomatic chronic hepatitis C patients. The progression rate of fibrosis was slower than in chronic hepatitis C patients with elevated serum ALT levels. HCC was noted in 157 chronic hepatitis C patients after interferon therapy, and the development of HCC was significantly reduced in both sustained responders and transient biochemical responders compared with nonresponders. HCC in sustained responders mainly developed in male patients older than 55 years with advanced stage liver histology at entry. Approximately 30% of HCV-infected patients with PNAL become candidates for antiviral therapy within 5 years. Interferon therapy lowers the rate of the development of HCC in both sustained responders and transient biochemical responders.

A follow-up study to determine the value of liver biopsy and need for antiviral therapy for hepatitis C virus carriers with persistently normal serum aminotransferase.

BACKGROUND/AIMS: Long-term follow-up study was performed to identify the candidates for antiviral therapy for hepatitis C virus (HCV) infection among carriers with persistently normal aminotransferase (ALT< or = 30 U/L) levels (PNAL). METHODS: One hundred and twenty-nine HCV carriers with PNAL who underwent liver biopsy and had platelet count over 150,000/microl were entered and 69 were followed for over 5 years. Thirty-five patients underwent serial liver biopsies. Serum ferritin and thioredoxin levels were also determined. RESULTS: Seventeen patients had normal liver histology, 10 had moderate chronic hepatitis and the remainder 102 had mild hepatitis. Serum ferritin and thioredoxin levels were normal. The mean follow-up period for the 69 patients was 8.5 years. Of these 69 patients, 10 had persistently normal ALT levels (group A), 39 had transient elevation of ALT (group B), and 20 changed to symptomatic chronic hepatitis (group C). The rate of progression of fibrosis for groups A, B, and C were 0.05, 0.04, and 0.08, respectively. Hepatocellular carcinoma was not diagnosed in any of the patients. CONCLUSIONS: Around 90% of HCV carriers with PNAL have normal to mild liver histology. This long-term follow-up study demonstrated that 30% of such carriers became candidates for antiviral therapy within 5 years.

Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy.

BACKGROUND: The objective of the current study was to determine the characteristic features of sustained responders who develop hepatocellular carcinoma after treatment with interferon for chronic hepatitis C. METHODS: This study included 3626 patients with chronic hepatitis C who had received interferon monotherapy. Cox proportional hazards analysis was used to compare sustained responders who did and did not develop hepatocellular carcinoma, and nonsustained responders who developed hepatocellular carcinoma in a multicenter, retrospective cohort study. RESULTS: Among 1197 sustained responders, 27 patients developed hepatocellular carcinoma (2.3%). Compared with sustained responders who did not develop hepatocellular carcinoma, patients who developed disease more often were male (P = 0.0212), were older (P = 0.0068), and had advanced-stage histologic disease before interferon therapy (P = 0.0345). Conversely, compared with patients with hepatocellular carcinoma who were not sustained responders, patients who were sustained responders tended to be older at the time of the initiation of interferon therapy (P = 0.0552) and at the time hepatocellular carcinoma was detected (P = 0.0593), and they also were predominantly male (P = 0.0507). The histologic staging and serum aminotransferase levels at the initiation of interferon therapy, the interval to the detection of tumor, and the tumor size showed no significant differences between the two groups. CONCLUSIONS: Sustained responders in the group at high risk for developing hepatocellular carcinoma after interferon therapy were older, more often were male, and had more advanced histologic disease stage. Such patients should be followed carefully periodically for > 10 years after they complete interferon therapy.

Activated Kupffer cells play an important role in intra-hepatic Th1-associated necro-inflammation in Concanavalin A-induced hepatic injury in mice.

BACKGROUND/AIMS: To examine whether or not activated Kupffer cells play an important role in intra-hepatic Th1-associated necro-inflammation in Concanavalin A (Con A)-induced hepatic injury in mice. METHODS: Con A was administered to Balb/c mice pretreated with or without gadolinium chloride (GdCl(3)). Kupffer cell activation was evaluated by their ability to produce superoxide anions in situ under liver perfusion with nitro blue tetrazolium (NBT). Hepatic concentration of cytokines was measured by ELISA and the mRNA expression of CXC chemokine receptor 3 (CXCR3) was evaluated by RT-PCR. Immunohistochemical detection of CD4 positive lymphocytes in the liver was also performed. RESULTS: GdCl(3)-pretreatment significantly (P<0.01) reduced the serum levels of alanine aminotransferase (ALT) in Con A-treated mice. Formazan deposition in Kupffer cells, the hepatic concentration of tumor necrosis factor-alpha and interferon-gamma, the mRNA expression of CXCR3 and the CD4 positive lymphocytes in the liver were decreased in GdCl(3)-pretreated mice as compared with those without GdCl(3)-pretreatment (P<0.05, respectively). CONCLUSIONS: Activated Kupffer cells, which produce superoxide anions, are involved in Con A-induced hepatic necro-inflammation in mice possibly through the activation of Th1-associated immune response mediated by CD4 and/or CXCR3 positive cells recruited into the liver.

Tuberculous peritonitis.

We report a case of tuberculous peritonitis in a 24-year-old male patient. On admission, he was complaining of abdominal fullness and fever. Ultrasound tomography and computed tomography (CT) scan of the abdomen showed massive ascites with multiple septa. The most interesting feature of this case was the diffuse and intense uptake of gallium-67 in the abdomen. Though the initial chest X-ray showed only slight bilateral pleural effusion, and cultures from ascites, stool, sputum, and pleural effusion were negative for Mycobacterium tuberculosis, CT scan of the lung showed a small consolidation shadow with contractile change, similar to tuberculosis. A few days after the CT scan of the lung, the sputum was positive for Mycobacterium tuberculosis. Finally we diagnosed active tuberculous peritonitis, and then started antituberculous therapy. In patients with massive ascites and fever of unknown origin, tuberculous peritonitis must be considered. Gallium-67 scintigraphy has been shown to be useful when there is a high index of suspicion of tuberculous peritonitis.