Needle Liver Biopsy Specimens Research Articles

Validation of whole-slide imaging in the primary diagnosis of liver biopsies in a University Hospital

BackgroundExperience in the use of whole slide imaging (WSI) for primary diagnosis is limited and there are no comprehensive reports evaluating this technology in liver biopsy specimens. AimsTo determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of needle liver biopsies. MethodsTwo experienced liver pathologists blindly analyzed 176 consecutive biopsies from the Pathology Department at the Hospital Clinic of Barcelona. One of the observers performed the initial evaluation with CLM, and the second evaluation with WSI, whereas the second observer performed the first evaluation with WSI and the second with CLM. All slides were digitized in a Ventana iScan HT at 400× and evaluated with the Virtuoso viewer (Roche diagnostics). We used kappa statistics (κ) for two observations. ResultsIntra-observer agreement between WSI and CLM evaluations was almost perfect (96.6%, κ=0.9; 95% confidence interval [95% CI]: 0.9–1 for observer 1, and 90.3%, κ=0.9; 95%CI: 0.8-0.9 for observer 2). Both native and transplantation biopsies showed an almost perfect concordance in the diagnosis. ConclusionDiagnosis of needle liver biopsy specimens using WSI is accurate. This technology can reliably be introduced in routine diagnosis.

Element bioimaging of liver needle biopsy specimens from patients with Wilson’s disease by laser ablation-inductively coupled plasma-mass spectrometry

A laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) method is developed and applied for the analysis of paraffin-embedded liver needle biopsy specimens of patients with Wilson’s disease (WD), a rare autosomal recessive disorder of the copper metabolism causing various hepatic, neurological and psychiatric symptoms due to a copper accumulation in the liver and the central nervous system. The sample set includes two WD liver samples and one negative control sample. The imaging analysis was performed with a spatial resolution of 10 μm. Besides copper, iron was monitored because an elevated iron concentration in the liver is known for WD. In addition to this, both elements were quantified using an external calibration based on matrix-matched gelatine standards. The presented method offers low limits of detection of 1 and 5 μg/g for copper and iron, respectively. The high detection power and good spatial resolution allow the analysis of small needle biopsy specimen using this method. The two analyzed WD samples can be well differentiated from the control sample due to their inhomogeneous copper distribution and high copper concentrations of up to 1200μg/g. Interestingly, the WD samples show an inverse correlation of regions with elevated copper concentrations and regions with high iron concentrations.

Interleukin-6 (-174G>C) promoter polymorphism in patients infected by hepatitis B virus

Objective: Hepatitis B virus (HBV) infection is one of the most important health problems in the world. Interleukin-6 (IL-6) has been shown to be a major inflammatory cytokine, inducing cell proliferation and expression of acute response genes, such as fibrinogen and C-reactive protein in hepatocytes. IL-6 levels are elevated in patients acutely infected with HBV and have been associated with progression of infection to chronic hepatitis. Methods: In the present study, the role of IL-6 (-174G/C) polymorphism was investigated on individuals which are diagnosed as hepatitis B virus carrier (n=19), chronic hepatitis (n=10) and cirrhosis (n=13), and non-infected individuals with HBV (n=8). In order to determine IL-6 polymorphism, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied using genomic DNA extracted from paraffin embedded liver needle biopsy specimens. Results: The genotype frequencies in 50 samples were observed as follows: 76% homozygote typical (GG), 22% heterozygote (GC) and 2% homozygote atypical (CC). In this study, limited statistical association was observed between IL-6 polymorphism (GG, GC and CC genotype) and chronic hepatitis/cirrhosis compared to hepatitis B virus carriers and non-infected individuals with HBV (p=0.045). Conclusion: As observed in only one patient with chronic hepatitis, IL-6 (-174C/C) genotype is very rare in this study group. Because of lower frequency of -174C/C phenotype, studies in larger series can give statistically more precise conclusions.

Preactivation of the interferon signalling in liver is correlated with nonresponse to interferon alpha therapy in patients chronically infected with hepatitis B virus

Interferon alpha (IFN-α) therapy is widely used to treat patients with chronic hepatitis B (CHB) but the sustained response rate is low, and the molecular mechanisms for the ineffectiveness of IFN-α treatments are not known. We screened differentially expressed genes between responders (Rs) and nonresponders (NRs) in patients with CHB treated with IFN-α to explore the molecular basis for treatment failure. Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared between seven patients who did not respond to therapy (NR) and six who did respond (R). Gene ontology category and KEGG pathway were analysed for differentially expressed genes, and the selected differentially expressed genes were confirmed using real-time polymerase chain reaction. We identified 3592 genes whose expression levels differed significantly between all Rs and NRs (P < 0.05); many of these genes are IFN-stimulated genes (ISGs) and immune-related genes. The ISGs were more highly expressed, while immune-related genes were inhibited in NRs before IFN-α treatment. Two ISGs (CEB1 and USP18) that are linked in an IFN inhibitory pathway are highly expressed in NRs, and a potential antiviral gene ISG20 was inhibited in NRs, suggesting a possible rationale for treatment nonresponse. Patients who do or do not respond to IFN have different liver gene expression profiles before IFN-α treatment. Preactivation of the IFN signalling pathway leading to the increased expression of inhibitory ISGs and inhibition of immune response in the pretreatment livers was associated with treatment failure.

Rolls Royce for everybody? Diagnosing liver disease by mini-laparoscopy

Rolls Royce for everybody? Diagnosing liver disease by mini-laparoscopy

Non–Viral-Related Pathologic Findings in Liver Needle Biopsy Specimens From Patients With Chronic Viral HepatitisThe Author’s Reply

To the Editor I read with great interest the article by Nair et al1 published in the Journal. It presents valuable information on the prevalence of so-called other diagnoses revealed in liver needle biopsies performed for staging of chronic viral hepatitis. As such, it sheds light on an important aspect of liver biopsy interpretation by pathologists. Somewhat similar findings were also observed by Spycher et al2 in their retrospective review of liver biopsy specimens. The authors of the latter study found “incidental diagnoses” in more than half of the specimens from biopsies performed for staging of chronic hepatitis C infection.2 We also receive and interpret hundreds of liver biopsy specimens yearly, predominantly …

Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement

Recently the authors proposed a new staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histological heterogeneity. Herein is proposed a convenient version of this system. Scores for fibrosis, bile duct loss, and chronic cholestasis were combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity (CA) and hepatitis activity (HA) were graded as CA0-3, and HA0-3, respectively. Analysis of interobserver agreement was then conducted. Digital images of 62 needle liver biopsy specimens of PBC were recorded as virtual slides on DVDs that were sent to 28 pathologists, including five located overseas. All participants were able to apply this version in all 62 cases. For staging, kappa was 0.385 (fair agreement) and the concordance rate was 63.9%. For necroinflammatory activity, the kappa and concordance rate were 0.110 (slight agreement) and 36.9% for CA, and 0.197 (slight agreement) and 47% for HA, respectively. In conclusion, this new staging and grading system for PBC seems to be more convenient and practical than those used at present, but more instruction and guidance are recommended for the grading of necroinflammatory activity in practice.

Efficacy of Entecavir for patients of chronic severe-degree hepatitis B with HBeAg-posi-tive

Objective To evaluate the effects of Entecavir for patients of chronic severe-degree hepatitis B with HBeAg-positive.Methods 58 patients with chronic severe-degree hepatitis B were randomly divided into two groups (treatment group and control group ).29 patients in the treatment group were treated with Entecavir 0.5mg/d for 48 weeks and protect-liver drug for the first 4 weeks.29 patients in control group were treated with protect-liver drug for 48 weeks.Results After therapy for 48 weeks, ALT normalization-rate, the negative-rate of serum HBV DNA and HBeAg, the transition-rate of serum HBeAg/ Anti-Hbe in the treated group were all significantly higher than that of the control group( 93.1%vs593%, 93.1%vs11.1%, 44.8%vs11.1%, 41.4%vs11.1%, respectively,χ2-value were 8.98, 37.79, 7.79,6.53. P< 0.005, <0.001, <0.01, <0.05, respectively ).The improve-rate of hepatic histological activity and hepatic fibrosis in needle liver biopsy specimens in the treatment group were all significantly higher than that in the control group ( 93.1 %vs44.4%, 72.4%vs33.3%, respectively, x2-value were 15.66, 8.58, P <0.001, <0.005, respectively ).Conclusion The clinical efficacy of entecavir were better than protect-liver drug in patients of chronic severe-degree hepatitis B with HBeAg-positive.Entecavir can prevent severe hepatitis and hepatocirrhosis in these patients. Key words: Entecavir; HBeAg-positive ; Chronic hepatitis B; Severe-degree

Non–Viral-Related Pathologic Findings in Liver Needle Biopsy Specimens From Patients With Chronic Viral Hepatitis

Liver biopsy is a vital part of chronic viral hepatitis management. Pathologists should view these biopsies as screening tools for other liver diseases. We describe our experience in a 6-year period and discuss the pathologist's role. Liver biopsies of 1,842 patients with hepatitis B or C, for the 2001-2007 period at the University Health Network, Toronto, Canada, were reviewed; 410 other diagnoses were documented in 377 patients (20.5%; mean age, 25.4 years; range, 15-80 years). These diagnoses included 58 hepatocellular carcinomas and 16 dysplastic nodules, which are recognized complications of chronic viral hepatitis. The remaining findings included the following: steatosis/steatohepatitis, 251; hemosiderosis, 62; granulomatous disease, 7; drug-induced hepatitis, 4; primary biliary cirrhosis, 3; Wilson disease, 2; metastases, 2; and cholangiocarcinoma, atypical lymphoid proliferation, alpha(1)-antitrypsin deficiency, cystic fibrosis, and schistosomiasis, 1 each. Liver biopsies in patients with viral hepatitis revealed other processes with the potential to modify disease progression and/or the management strategy in 20.5% of patients.

Recurrence of primary biliary cirrhosis and development of autoimmune hepatitis after liver transplant: A blind histologic study

This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT). We reviewed "blindly" allograft biopsy specimens of women who underwent transplantation for PBC (n = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV ) (n = 108). All needle liver biopsy specimens obtained more than 6 months post-OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients. Granulomatous destructive cholangitis was found in five biopsies from four PBC patients (P = 0.0048). Non-necrotizing epithelioid cell granulomas were present in four biopsies from four PBC patients, and in two biopsies from one CHCV patient. Piecemeal necrosis (P = 0.0002), lobular necroinflammatory activity (P < 0.0001), steatosis (P < 0.0001) and fibrosis (P < 0.0001) were more prevalent in CHCV patients than PBC patients. Four PBC patients developed histologic evidence of autoimmune hepatitis (AIH), at a mean time of 3.66 years post-OLT. One of these patients had histologic features of AIH/PBC overlap syndrome. All four patients developed bridging fibrosis (n = 2) or cirrhosis (n = 2). No other PBC patient had evidence of cirrhosis after OLT. Histologic findings indicative of recurrent PBC were present in 15.9% of the PBC patients undergoing biopsy in this series. However, this group of patients did not suffer significant bile duct loss or fibrosis, as compared to the control group, suggesting that recurrent PBC is a mild or slowly progressive disease. Histologic evidence of AIH was observed in allograft biopsies of some PBC patients.

Value of Glypican 3 Immunostaining in the Diagnosis of Hepatocellular Carcinoma on Needle Biopsy

The diagnostic value of glypican 3 (GPC3) immunostaining on needle biopsy specimens has not been well assessed. In this study, 120 liver needle biopsy specimens, including 46 from cirrhotic livers and 74 hepatocellular carcinomas (HCCs), were immunohistochemically examined for expression of GPC3. The results showed strong cytoplasmic and membranous staining in 36 HCCs (49%), among which 20 cases (56%) showed diffuse immunoreactivity. None of the 46 cirrhotic livers exhibited positive GPC3 immunostaining. The nonneoplastic liver tissues (cirrhotic or noncirrhotic) that were present in the majority of the HCC cases were also completely negative for GPC3 expression. These data demonstrate that GPC3 is a reliable immunohistochemical marker for the diagnosis of HCC on needle biopsy specimens when positive. However, the detection rate in our series seems lower than that reported in studies using resection specimens as the study materials. Our findings emphasize that GPC3 immunoreactivity can be focal and that negative staining should not be viewed as evidence to exclude the diagnosis of HCC in challenging needle biopsy specimens.

Presence of perivenular elastic fibers in nonalcoholic steatohepatitis Fibrosis Stage III.

Elastic fibers appear in extensive old fibrotic foci in general. We examined an association between hepatic fibrosis stage and the presence of perivenular elastic fibers in nonalcoholic steatohepatitis (NASH). A total of 48 liver needle biopsy specimens were used, taken from 48 cases with NASH. Fibrosis Stage (Brunt E, et al. Am. J. Gastroenterol. 1999) of the cases was as follows; six Fibrosis Stage I, twenty-two Fibrosis Stage II, and twenty Fibrosis Stage III. We examined Orcein stain sections in all of the liver needle biopsy specimens. In all twenty Fibrosis Stage III cases, perivenular elastic fiber bundles were observed. In contrast, perivenular elastic fibers were detected only in one of the six Fibrosis Stage I and two of the twenty-two Fibrosis Stage II cases. In liver needle biopsy specimens of NASH, detection of perivenular elastic fibers is useful in deciding Fibrosis Stage III.

Experimental poisoning by Senecio brasiliensis in calves: quantitative and semi-quantitative study on changes in the hepatic extracellular matrix and sinusoidal cells

Extracellular matrix plays an important role in chronic hepatic lesions and has been studied in experimental intoxication models. However in cattle, studies on chronic disease have focused on the hepatocellular damage and extracellular matrix (ECM) changes are usually overlooked. There are no specific studies on the hepatic ECM in either normal or chronically damaged bovine liver. Thus an experimental model of hepatic toxicity model using Senecio brasiliensis poisoned calves was designed. Senecio brasiliensis contains pyrrolizidine alkaloids which cause either acute or chronic progressive dose dependent liver damage. Five calves were orally fed with 0.38g of dry leaves of S. brasiliensis/kg/day for 24 days. Liver needle biopsy specimens were obtained every 15 days for 60 days. Clinical signs of digestive complications appeared at 3rd week. One calf died on 45th day and four were evaluated up to 60th day. Biopsy samples were processed for routine light microscopy, immuno-histochemistry and transmission electron microscopy. From 30th day on progressive liver damage characterized by hepatocellular ballooning, necrosis, apoptosis and megalocytosis, centrilobular, pericellular and portal fibrosis were seen by light microscopy. Quantitative and semi-quantitative measurements of hepatic ECM components were performed before and after the onset of lesions. Morphometric analysis of total collagen and elastic fiber system was conducted. Total collagen and I and III collagen types progressively increased in throughout the liver of affected calves. Changes in location, amount and disposition of the elastic fiber system were also observed. Then numbers of Kupffer cells were significantly increased at 30th day and total numbers of sinusoidal cells were significantly increased at 45th and 60th days. Liver damage was progressive and irreversible even after the exposure to the plant was discontinued. Severe fibrotic lesions occurred mainly in portal tracts, followed by veno-occlusive and pericellular fibrosis. Collagen types I and III s were present in every normal and damaged liver, with predominance of type I. In affected calves the increase of total collagen and elastic fibers system paralleled the number of total sinusoidal cells.

Analysis of occult hepatitis B virus infection in liver tissue of HIV patients with chronic hepatitis C

Current data on the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals conflict. As occult HBV infection could have an impact on the outcome of liver disease in HIV-positive patients, we investigated a large number of HIV-positive/HBV-surface-antigen (HBsAg) negative subjects with hepatitis C virus (HCV) infection by using the 'gold standard' approach for occult HBV detection--analysis of liver DNA extracts. The presence or absence of HBV DNA was determined by PCR testing of four different viral genomic regions in DNA extracts of needle liver biopsy specimens of 101 HBsAg negative individuals with HIV/HCV co-infection. HBV genotyping was performed by sequencing analysis of the preS-S gene in occult HBV isolates from 18 cases. Occult HBV infection was diagnosed in 42 of the 101 cases (41%). No clinically relevant difference was found between occult HBV-positive and -negative patients. HBV genotype D and A were detected, respectively, in 11 (61%) and 7 (39%) of 18 cases analysed. Occult HBV infection frequently occurs in HIV/HCV co-infected patients indicating the importance of performing prospective studies able to clarify its clinical impact in these patients. HBV genotype A is highly prevalent in HIV-infected subjects with occult HBV infection in a similar way to HBsAg/HIV-positive individuals.

Proposal of a new staging and grading system of the liver for primary biliary cirrhosis

To define a new histological staging and grading system for primary biliary cirrhosis (PBC), to provide more information reflecting clinical laboratory data and the prognosis to hepatologists. First, 17 histological lesions of PBC were scored in 188 needle liver biopsy specimens. Factor analysis yielded three independent groups of factors: factor 1 (fibrosis, fibrous piecemeal necrosis, orcein-positive granules, bile plugs, Mallory bodies, feathery degeneration, bile duct loss and atypical ductular proliferation); factor 2 (portal inflammation, eosinophilic infiltration, lymphoid follicles, epithelioid granulomas, interface hepatitis and chronic cholangitis); and factor 3 (interface hepatitis, lobular hepatitis, acidophilic bodies and pigmented macrophages). The eight findings of factor 1, but not factors 2 and 3, were significantly correlated with clinical laboratory data and scores in the Mayo Clinic's prognostic model. Factor 1 lesions may reflect histological progression (staging), while factor 2 and 3 lesions may relate to necroinflammatory activity (grading). Then, we devised a staging and grading system using three lesions (bile duct loss, fibrosis and orcein-positive granules) from factor 1 and three from factors 2 and 3 (chronic cholangitis, interface hepatitis and lobular hepatitis). This new system might provide more pathological information on PBC patients for hepatologists.

Correlation between acute rejection severity and CD8-positive T cells in living related liver transplantation

The Banff schema is the most widely used standard grading system for liver allograft rejection. To investigate the relationship between the Banff rejection activity index (RAI) and the presence of lymphocyte subpopulations in allograft liver tissue, assuming these cells to probably play an important role in the mechanism of acute cellular rejection (ACR), we performed immunohistological examinations using liver tissues with various ACR severities after living related liver transplantation (LRLT). In total, 37 needle liver biopsy specimens with ACR in LRLT were examined using antibodies to CD4, CD8, and CD20. Formalin-fixed and paraffin-embedded liver tissues were used to maintain morphology. Immunohistological findings and RAI score according to the Banff schema were compared. In the results, mainly CD8-positive (CD8+), rather than CD4-positive (CD4+), cells were detected in the portal tract and were also found in bile duct epithelium and subendothelial areas of portal veins. The number of CD8+ cells increased according to ACR grade, whereas CD4+ cells tended to decrease. There were significant correlations between the presence of CD8+ cells ( p = 0.0006) and CD4+ cells ( p = 0.0003) and ACR severity. On the other hand, CD20-positive cells did not correlate with ACR severity ( p = 0.472). The results indicate that CD8+ cells play important roles in ACR severity of LRLT, suggesting the number of CD8+ cells in liver tissue to be useful as a supplementary tool, in addition to RAI of the Banff schema, for objective evaluation of ACR severity.

Frequency of Recipient-Derived Chimerism and Relationship With Acute Rejection and HLA Tissue Typing in Transplanted Livers

Background We sought to determine the extent and time course of recipient-derived chimerism after transplantation and the relationship with acute rejection episodes (ARE) and HLA typing in hepatic allograft patients. Patients and Methods We studied 18 needle liver biopsy specimens from patients who had undergone orthotopic liver transplantation. Fluorescent in situ hybridization (FISH) analysis for X and Y chromosomes was performed in all cases with a sex mismatch. To evaluate the HLA matching, we used serological and polymerase chain reaction (PCR) methodology. Results There was a sex mismatch between the recipients and donors in all cases. X and Y chromosome chimerism was detected in 14 of 18 (83%; 31.14 ± 27.4) patients. Also, no statistical association was found between the presence and the extent of chimerism and clinicopathological parameters ( P < .05). Conclusions Our results suggest that chimerism was frequently seen in liver allografts, but it did not influence the occurrence of ARE, tissue compatibility, or histopathological changes in the posttransplantation period. The clinical, immunological, and histopathological relevance of chimerism remain unclear. These results may relate to the small number of patients and disproportion of chimerism-positive versus-negative cases. Further prospective studies will be required to clarify these findings in a larger population of liver transplant patients.

Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis

The sustained antibody response to nuclear envelope gp210 antigen indicates a group of primary biliary cirrhosis (PBC) patients at high risk for the progression to end-stage hepatic failure. To address this issue, we immunohistochemically studied the expression of gp210 antigen in needle liver biopsy specimens from PBC patients using a monoclonal antibody specific for gp210 antigen. The specimens from autoimmune hepatitis (AIH), chronic viral hepatitis B (CHB) and C (CHC) patients served as disease controls. The expression of gp210 antigen was apparently increased on the nuclear envelope of biliary epithelial cells (BECs) of small bile ducts in almost all specimens from PBC. In contrast, the expression of gp210 antigen was negative in BECs of small bile ducts in normal liver, while relatively weak anti-gp210 immunostaining was observed in AIH, CHC and CHB. In addition, the degree of gp210 expression in BECs of small bile ducts was positively correlated to that of portal inflammation, interface hepatitis and lobular inflammation in PBC. These results indicate that the increased expression of gp210 in small bile ducts, which is probably associated with damage to BECs by inflammation, is possibly involved in autoimmune response to gp210 leading to the progression to end-stage hepatic failure in PBC.

Hepatic Gene Expression Discriminates Responders and Nonresponders in Treatment of Chronic Hepatitis C Viral Infection

Pegylated interferon (IFN)-alpha plus ribavirin is the most effective treatment of chronic hepatitis C but has unpleasant side effects and high costs. A large proportion of patients do not respond to therapy for reasons that are unclear. We used gene expression profiling to investigate the molecular basis for treatment failure. Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared among 15 nonresponder, 16 responder, and 20 normal liver biopsy specimens. Differential gene expression was confirmed using real-time polymerase chain reaction. We identified 18 genes whose expression differed significantly between all responders and all nonresponders (P < .005). Many of these 18 genes are IFN sensitive and 2 (ISG15/USP18) are linked in a novel IFN-regulatory pathway, suggesting a possible rationale for treatment resistance. Using a number of independent classifier analyses, an 8-gene subset accurately predicted treatment response for 30 of 31 patients. The classifier analyses were applicable to patients with genotype 1 infection and were not correlated with viral load, disease activity, or fibrosis. Hepatic gene expression profiling identified consistent differences in patients who subsequently fail treatment with pegylated IFN-alpha plus ribavirin: up-regulation of a specific set of IFN-responsive genes predicts nonresponse to exogenous therapy. These data may be of use in predicting clinical responses to treatment.

Clinicopathological features of eight Korean cases of primary hepatic lymphoma

Primary hepatic lymphoma is very rare, accounting for less than 0.4% of extranodal lymphomas. Furthermore, hepatic lymphoma, either primary or metastatic, is infrequently confirmed histopathologically in needle biopsy specimens. The aim of the current study is to assess the clinicopathological characteristics of primary hepatic lymphomas in Korea, which is an endemic area of chronic B viral hepatitis. In total, 17 cases with liver needle biopsy specimens with involvement of malignant lymphoma, from whom eight cases met the criteria for primary hepatic lymphoma, were selected. The clinicopathological features were reviewed. Five of eight (62.5%) cases were T cell lymphoma, including three cases (37.5%) of hepatosplenic T cell lymphoma. Three cases (37.5%) were diffuse large B cell lymphomas. Seven patients had follow-up data from 25 days to 50 months that was available for evaluation. The partial remission was present in two of seven patients (28.6%) and five patients (71%) died of disease 25 days to 7 months after the diagnosis. The data indicate that the relatively high incidence of T-cell type in Korean cases of primary hepatic lymphoma may be related to its aggressive behavior and poor prognosis despite combination chemotherapy.