Outcomes of laparoscopic hepatic resection versus percutaneous radiofrequency ablation for hepatocellular carcinoma located at the liver surface: A case-control study with propensity score matching.

AIM: Percutaneous radiofrequency ablation (P-RFA) therapy is a widely applied treatment for small hepatocellular carcinoma (HCC); however, local recurrence is a major issue of HCC located at the surface of the liver (surface HCC). The aim of this study was to compare the outcome of laparoscopic hepatic resection (LH) and P-RFA for surface HCC in case-control patient groups using the propensity score. METHODS: Between 2011 and 2013, 40 and 52 patients underwent LH and P-RFA for surface HCC (≤3 cm, 1-3 nodules). To correct the difference in clinicopathological factors between the two groups, propensity score matching was used at a 1:1 ratio, which resulted in a comparison of 27 patients/group. We compared outcomes between the two groups, with special reference to local recurrence. RESULTS: Clinicopathological variables were well balanced between the two groups. One patient in the LH group was converted to open surgery due to adhesion. The incidence of complications was 0% in the P-RFA group and 15% (four patients) in the LH group (P = 0.11); however, none of these four patients in the LH group sustained severe complications. The duration of hospitalization following treatment was longer in the LH group than in the P-RFA group (12.6 vs 7.6 days, P < 0.01). The incidence of local recurrence was lower in the LH group (0%) than in the P-RFA group (eight patients [30%], P = 0.004). CONCLUSION: LH is an effective treatment for surface HCC with regard to control of local recurrence.

Clinical characteristics and prognosis of non-B non-C hepatocellular carcinoma patients with modest alcohol consumption.

AIM: Alcoholic hepatocellular carcinoma (ALD-HCC) accounts for the majority of non-B non-C HCC (NBNC-HCC) cases. Although alcohol is a potent carcinogen, there have been few reports on the influence of modest alcohol consumption in NBNC-HCC. This study aimed to investigate the clinical characteristics and prognosis of NBNC-HCC patients with modest alcohol consumption. METHODS: From 2007 to 2010, 2283 HCC patients were evaluated at 10 hospitals. We collected detailed etiology data of 588 NBNC-HCC patients and compared the clinical characteristics and prognosis between ALD-HCC and modest alcohol-HCC patients. RESULTS: There were 69 HCC patients with modest alcohol consumption, accounting for 3% of all HCC patients evaluated. This patient group had significantly more women and higher prevalence of Child-Pugh class A, hypertension and advanced disease stage, and were diagnosed with HCC at an older age than the ALD-HCC group (266 patients). Additionally, among the modest alcohol-HCC patients, diabetes was significantly more common in the anti-hepatitis B core (HBc) negative subgroup than in the anti-HBc positive subgroup. However, no significant difference in survival was observed between the two patient groups regardless of significant differences in tumor staging. Alcohol consumption and metabolic factors were not significant independent predictors of survival. CONCLUSION: The clinical characteristics of modest alcohol-HCC included advanced staging, favorable liver reserve capacity and older age at diagnosis. HCC development in patients with modest alcohol consumption may relate to metabolic factors. Although approximately 30% of the evaluated HCC cases were in advanced stages, the prognosis of NBNC-HCC patients with modest alcohol consumption was relatively favorable.

Effects on anemia of drug adjustment in patients with chronic hepatitis C during telaprevir-combined therapy.

AIM: Anemia is the most common adverse event in patients with chronic hepatitis C virus (HCV) treated with telaprevir (TVR) combined triple therapy. We examined the effects of drug dose adjustment on anemia and a sustained viral response (SVR) during combination therapy. MATERIAL AND METHODS: This study enrolled 62 patients treated with TVR (2,250 mg) for 12 weeks plus pegylated interferon-alpha-2b and ribavirin for 24 weeks. The patients were assigned randomly to the TVR-standard or -reduced groups before treatment. At the occurrence of anemia (hemoglobin < 12 g/dL), the TVR-reduced group received 1500 mg TVR plus the standard dose of ribavirin, whereas the TVR-standard group received the standard TVR dose (2,250 mg) and a reduced dose of ribavirin (200 mg lower than prescribed originally). The safety and SVR at 24 weeks were compared between the TVR-standard (n = 28) and TVR-reduced (n = 25) groups. RESULTS: No differences in the proportion of patients who became HCV RNA-negative were detected between the TVR-standard and -reduced groups (72 and 72% at week 4, 79 and 84% at the end of treatment, and 76 and 80% at SVR24, respectively). Two groups had comparable numbers of adverse events, which led to the discontinuation of TVR in 14 patients of TVR-standard group and in 14 of TVR-reduced group. A lower incidence of renal impairment was observed in the TVR-reduced group (6%) than the TVR-standard group (11%, not statistically significant). CONCLUSIONS: TVR dose adjustment could prevent anemia progression without weakening the anti-viral effect during triple therapy in HCV-patients.

Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver.

Cytoglobin (CYGB) is ubiquitously expressed in the cytoplasm of fibroblastic cells in many organs, including hepatic stellate cells. As yet, there is no specific marker with which to distinguish stellate cells from myofibroblasts in the human liver. To investigate whether CYGB can be utilized to distinguish hepatic stellate cells from myofibroblasts in normal and fibrotic human liver, human liver tissues damaged by infection with hepatitis C virus (HCV) and at different stages of fibrosis were obtained by liver biopsy. Immunohistochemistry was performed on histological sections of liver tissues using antibodies against CYGB, cellular retinol-binding protein-1 (CRBP-1), α-smooth muscle actin (α-SMA), thymocyte differentiation antigen 1 (Thy-1), and fibulin-2 (FBLN2). CYGB- and CRBP-1-positive cells were counted around fibrotic portal tracts in histological sections of the samples. The expression of several of the proteins listed above was examined in cultured mouse stellate cells. Quiescent stellate cells, but not portal myofibroblasts, expressed both CYGB and CRBP-1 in normal livers. In fibrotic and cirrhotic livers, stellate cells expressed both CYGB and α-SMA, whereas myofibroblasts around the portal vein expressed α-SMA, Thy-1, and FBLN2, but not CYGB. Development of the fibrotic stage was positively correlated with increases in Sirius red-stained, α-SMA-positive, and Thy-1-positive areas, whereas the number of CYGB- and CRBP-1-positive cells decreased with fibrosis development. Primary cultured mouse stellate cells expressed cytoplasmic CYGB at day 1, whereas they began to express α-SMA at the cellular margins at day 4. Thy-1 was undetectable throughout the culture period. In human liver tissues, quiescent stellate cells are CYGB positive. When activated, they also become α-SMA positive; however, they are negative for Thy-1 and FBLN2. Thus, CYGB is a useful marker with which to distinguish stellate cells from portal myofibroblasts in the damaged human liver.

Positioning of 18F-fluorodeoxyglucose-positron emission tomography imaging in the management algorithm of hepatocellular carcinoma.

BACKGROUND AND AIM: (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) may detect primary lesions (PLs) and extrahepatic metastases (EHMs) only in advanced hepatocellular carcinoma (HCC) patients. We investigated the requirement of PET and the optimal timing of PET scanning for accurate staging and treatment planning. METHODS: We conducted a retrospective investigation of 64 HCC patients who underwent PET (median age, 74 years; male/female, 41/23; etiology, 46 hepatitis C virus/4 hepatitis B virus/4 alcoholic/10 others). To determine the best timing for PET examinations, we analyzed PET result-based recommended treatment changes and characteristics of patients with FDG-avid PLs or EHMs. RESULTS: FDG-avid PLs were detected by PET in 22 patients (34%): 18 with hypervascular PL, 11 with serum α-fetoprotein levels ≥ 200 ng/mL, and 11 beyond Milan criteria. EHMs were detected in 21 patients (33%: lymph nodes, 8; lung, 5; abdominal wall, 4; bone, 3; other organs, 4 [including overlapping]). Recommended treatments changed for 16 patients (25%) because of Barcelona Clinic Liver Cancer stage increases based on PET scanning. In multivariate analyses, serum α-fetoprotein levels ≥ 200 ng/mL and beyond Milan criteria were independent factors for FDG-avid PLs and a maximum standardized uptake value (SUVmax) of PLs of ≥ 4.0 was an independent factor for FDG-avid EHMs (P = 0.002, 0.008, and 0.045, respectively). CONCLUSIONS: PET allows detection of HCC spread in patients with elevated serum α-fetoprotein levels or those beyond Milan criteria and detects EHMs in patients with PLs with high SUVmax values. Optimally timed PET scans can complement conventional imaging for accurate staging and treatment strategy determination.

Combination therapy of natural human interferon-beta and ribavirin for chronic hepatitis C patients with injection drug use.

AIM: The aim of this study was to evaluate the efficacy and safety of combination therapy using natural human interferon-ß and ribavirin (IFN-ß/RBV) for chronic hepatitis C patients who were injection drug users (IDU) and resident in the Airin district of Osaka, containing the biggest slums in Japan. METHODS: Twenty-nine IDU with chronic hepatitis C received combination therapy of IFN-ß/RBV. The psychiatrist in charge evaluated the scores of the Zung Self-rating Depression Scale (SDS), a self-rating scale based on 20 questions. Univariate logistic regression analyses were used to determine the factors that significantly contributed to complete treatment and a sustained virological response (SVR). RESULTS: Thirteen of the 29 patients achieved SVR according to the intention to treat analysis. All patients with a rapid virological response achieved SVR. No patient required a reduced dose of RBV because of a decrease in their hemoglobin level, or of IFN-ß because of a low level of white blood cells and platelet count. Two patients had psychological side-effects and stopped the therapy early in the treatment; one patient had depression and the other had anxious depression. Univariate logistic regression analyses indicated that the stage of fibrosis was the only factor that contributed to SVR, and that the SDS test and past drug abuse contributed to completion of the treatment. CONCLUSION: IFN-ß/RBV combination therapy is useful for treating IDU.

Physical inactivity and insufficient dietary intake are associated with the frequency of sarcopenia in patients with compensated viral liver cirrhosis.

AIM: The association between sarcopenia and nutritional status is thought to be an important problem in patients with cirrhosis. In this study, we investigated whether nutritional factors were related to sarcopenia in patients with liver cirrhosis. METHODS: The subjects were 50 patients with cirrhosis aged 41 years or older. In this study, the subjects were interviewed about their dietary habits, and their daily physical activity was surveyed using a pedometer. The skeletal muscle mass index (SMI) was calculated using the appendicular skeletal muscle mass (ASM) measured by bioelectric impedance analysis. The handgrip strength was measured using a hand dynamometer. Sarcopenia was defined by SMI and handgrip strength. The patients with cirrhosis were categorized as normal group or sarcopenia group, and the two groups were compared. Univariate and multivariate logistic regression modeling were used to identify the relevance for sarcopenia in patients with cirrhosis. RESULTS: Height (odds ratio (OR), 5.336; 95% confidence interval [CI], 1.063-26.784; P = 0.042), energy intake per ideal bodyweight (IBW) (OR, 5.882; 95% CI, 1.063-32.554; P = 0.042) and number of steps (OR, 4.767; 95% CI, 1.066-21.321; P = 0.041) were independent relevant factors for sarcopenia. Moreover, a significantly greater number of the patients in the sarcopenia group had low values for both parameters' energy intake per IBW and number of steps. CONCLUSION: Our results suggest that walking 5000 or more steps per day and maintaining a total energy intake of 30 kcal/IBW may serve as a reference for lifestyle guidelines for compensated cirrhotic patients.

Real-time PCR assays for hepatitis C virus RNA (genotype 1) is useful for evaluating virological response to the treatment with peginterferon-alpha2b and ribavirin.

BACKGROUND: The real-time PCR, such as Abbott RealTime assay, have replaced end-point PCR, such as Amplicor assays, for the measurement of HCV RNA. However, 'response-guided therapy' to use on-treatment response for tailoring the duration of treatment with peginterferon-alpha and ribavirin has not been fully evaluated for real-time PCR. METHODS: 43 patients with HCV genotype 1 (24 who had complete early virological responses (cEVR) on Amplicor assay and received 48-week therapy, and 19 who had late virological responses (LVR) and received 72-week therapy) were recruited. Using a RealTime assay, we retrospectively measured HCV RNA in stored sera. RESULTS: In 10 samples obtained during therapy, HCV RNA was undetectable on the Amplicor assay, but detectable on the RealTime assay. Among patients with cEVR on the Amplicor assay, those with detectable HCV RNA on the RealTime assay at week 12 were less likely to have a sustained virological response (SVR) than those without (2/4 vs 17/20, p = 0.116). Among patients with LVR on the Amplicor assay, those with HCV RNA detectable on the RealTime assay at week 24 were significantly less likely to have SVR than those without (1/4 vs 12/15, p = 0.041). CONCLUSIONS: The RealTime assay may be useful for tailoring duration of treatment for the patient with HCV genotype 1.

[Tumor lysis syndrome after transarterial embolization for hepatocellular carcinoma].

A man in his 70's was admitted to our hospital for treatment of a huge hepatocellular carcinoma (HCC) by transcatheter hepatic arterial embolization (TAE). After treatment, anuria occurred, and laboratory examinations revealed a diagnosis of tumor lysis syndrome (TLS). He underwent conservative therapy including hemodialysis, resulting in complete remission of TLS. On the other hand, poor hepatic functional reserve was seen temporarily. After conservative therapy, biochemical markers returned dramatically. TLS is a group of metabolic complications in cancer therapy. It may occur in highly sensitive tumors, resulting from a rapid release of cytoplasmic degradation products of malignant cells. Generally it is rare in the treatment of solid tumors. In the case of TAE for huge HCC, we should keep the possibility of TLS in mind.

Effect of mosapride citrate on gastric emptying in interferon-induced gastroparesis.

BACKGROUND AND OBJECTIVES: Gastroparesis, a gastrointestinal autonomic neuropathy, is a common adverse reaction in chronic hepatitis C (CHC) patients receiving interferon therapy. Current therapeutic options are limited. We evaluated the efficacy of mosapride for IFN-induced gastroparesis. METHODS: Twenty-four consecutive CHC patients were randomly assigned to either the control group, which received pegylated interferon α-2b at 1.5 µg/kg/week and ribavirin at 600-1,000 mg/day, depending on body weight (PegIFN/RBV), or the mosapride group, which received PegIFN/RBV plus mosapride at 15 mg/person/day. The solid-phase gastric emptying half-times (T1/2) of the total, proximal, and distal stomach (scintigraphy) and digestive symptoms (questionnaire) were measured within one week before and four weeks after initiation of the assigned therapy. The test meal comprised a 200-g pancake containing Tc-99m diethylenetriamine pentaacetic acid. RESULTS: In the control group, after PegIFN/RBV initiation, a significant increase was observed in the total T1/2 (before: 84.0 ± 22.1 min versus after: 100.8 ± 28.9 min, P = 0.03), the distal T1/2 (before: 95.3 ± 32.2 min versus after: 115.3 ± 41.4 min, P = 0.03), and digestive symptom score (before: 3.2 ± 1.4 versus after: 8.1 ± 4.8, P = 0.02); proximal T1/2 change was not significant. In the mosapride group, no significant delays were observed in the total, proximal, and distal T1/2 values; the change in symptom scores was not significant. CONCLUSIONS: Mosapride improved total and distal gastric motility in IFN-induced gastroparesis, and consequently relieved symptoms.

Benefits of artificially induced pleural effusion and/or ascites for percutaneous radiofrequency ablation of hepatocellular carcinoma located on the liver surface and in the hepatic dome.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) with artificial pleural effusion and/or artificial ascites has recently been recognized as a useful device for the treatment of hepatocellular carcinoma (HCC). However, the indication of this technique is unclear and its therapeutic efficacy is undetermined. METHODOLOGY: We decided the precise indication for the use of artificial infusion. Artificial pleural effusion was indicated for tumors located on the dorsal side of the liver surface in the right lobe. Artificial ascites were indicated for (i) tumors located on the ventral side of the liver surface in the right lobe; (ii) tumors that could not be completely visualized but located near the liver surface in the right lobe; and (iii) tumors on the liver surface and adjacent to organs. RESULTS: The total local recurrence rates at 1 and 2 years were 4% and 22%, respectively. The estimated survival rates of 32 naïve patients at 1 and 3 years were 90% and 78%, respectively. The local recurrence rates of a tumor size of <3 cm and >3 cm at 2 years were 22% and 17%, respectively. CONCLUSIONS: RFA with artificial pleural effusion and/or ascites is effective for tumors located on the liver surface and in the hepatic dome.

Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus.

Hepatocellular carcinoma (HCC) develops several years after the eradication of hepatitis C virus (HCV) by interferon therapy. Risk factors for the development of HCC are only partly understood. To elucidate the role of occult hepatitis B virus (HBV) infection in hepatocarcinogenesis in patients with sustained virologic response, the prevalences of HBV-related makers were examined. Study group comprised 16 patients with sustained virologic response (group A) and 50 with HCV (group B). Anti-HBc and anti-HBs in serum were examined by enzyme-linked immunoassay. HBV DNA in liver was examined by nested polymerase chain reaction, using primers specific for genes encoding for HBx, HBsAg, HBcAg, and HBV cccDNA. Sequence of the amplified HBV DNA for 'a' determinant of HBsAg was determined in HCC. Anti-HBc was positive in 10 of 16 in group A and 25 of 50 in group B. HBV DNA in liver was detected in 12 of 16 in group A and 21 of 50 in group B (P = 0.044). In group A, HBV DNA in liver was detected frequently in patients without cirrhosis and in those with a longer period from the time of HCV eradication to the development of HCC. Mutation in 'a' determinant of HBsAg was found in three HCC of group A. Occult HBV infection may be one of the most important risk factors in hepatocarcinogenesis of Japanese patients with sustained virologic response.

Noninvasive laboratory tests proposed for predicting cirrhosis in patients with chronic hepatitis C are also useful in patients with non-alcoholic steatohepatitis.

BACKGROUND: Several noninvasive tests have been proposed to predict cirrhosis in patients with chronic hepatitis C, but not in patients with non-alcoholic steatohepatitis (NASH). We assessed whether noninvasive laboratory tests designed to predict the risk of cirrhosis in patients with chronic hepatitis C virus (HCV) infection could be used in patients with NASH. METHODS: The subjects were 50 patients with biopsy-proved NASH and 100 age- and sex-matched patients with HCV. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST-to-platelet ratio index (APRI), cirrhosis discriminant score (CDS), and the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) model were calculated. RESULTS: The areas under the receiver-operating characteristic curves of the AAR, AP index, APRI, CDS, and HALT-C model for predicting cirrhosis were respectively 0.813, 0.877, 0.786, 0.949, and 0.908 in patients with NASH and 0.555, 0.652, 0.761, 0.782, and 0.782 in patients with HCV. A CDS cutoff value of less than 5 misclassified none of the 9 patients with NASH who had cirrhosis, while a value of more than 8 misclassified none of the 41 patients with NASH without cirrhosis. With the HALT-C model, a cutoff value of less than 0.6 classified non-cirrhotic NASH, while a cutoff value of 0.97 or higher classified cirrhotic NASH. The use of CDS and HALT-C model could avoid liver biopsy for predicting cirrhosis in 60 and 48% of the patients with NASH, respectively. CONCLUSIONS: Noninvasive laboratory tests designed to predict cirrhosis in patients with HCV are also useful in patients with NASH.

[Drug-induced liver injury caused by an herbal medicine, bofu-tsu-sho-san].

A 37-year-old woman was admitted to a hospital with jaundice. Within a couple of weeks, her liver function improved with only symptomatic therapy. About 30 to 60 days before admission, she had taken a herbal medicine, bofu-tsu-sho-san. A diagnosis of drug-induced liver injury was made according to the diagnostic scale proposed at the Digestive Disease Week-Japan 2004. A drug-lymphocyte stimulation test for each ingredient of bofu-tsu-sho-san; the results were positive for Cnidii Rhizoma, Angelicae Radix and Menthae Herba. The liver biopsy specimen revealed features of acute hepatitis. Physicians should be aware that bofu-tsu-sho-san can cause liver injury, as this drug is commonly used as an over-the-counter medicine.

High sensitivity of fatty liver Shionogi (FLS) mice to diethylnitrosamine hepatocarcinogenesis: comparison to C3H and C57 mice.

The fatty liver Shionogi (FLS) mouse is a new inbred strain that spontaneously develops fatty liver with infiltration of mononuclear cells. Moreover, this mouse is known to frequently develop spontaneous hepatic cancers. Recently, human non-alcholic steatohepatitis (NASH) has been focused of attention regarding hepatocellular carcinoma. Therefore, this mouse has potential as a model for human hepatic cancer due to steatosis. It is of interest therefore, whether it exhibits elevated susceptibility not only regarding spontaneous tumor development but also to chemical hepatocarcinogens. To examine this concern, we examined diethylnitrosamine (DEN) hepatocarcinogenesis in FLS mice with 30ppm in drinking water for 26 weeks in comparison to two other strains of mice, C3H and C57. The induction of spontaneous and DEN-induced hepatic tumors was clearly increased in the FLS case, along with levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, as compared to the other strains, with or without DEN treatment. These results indicate that the oxidative DNA stress is intimately involved in hepatocarcinogenesis in FLS mice and provide further support for use of this mouse as a useful model for investigating hepatocarcinogenesis due to human hepatic steatosis.

Role of oxidative DNA damage caused by carbon tetrachloride-induced liver injury -- enhancement of MeIQ-induced glutathione S-transferase placental form-positive foci in rats.

The strong association between chronic inflammation and development of cancer is well-established in chronic inflammatory states. Nitric oxide (NO) is generated by inflammatory cytokines due to the action of inducible nitric oxide (iNOS), oxidizing DNA to form 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts, a major species of oxidative DNA damage. In the present study, we investigated the enhancing effect of carbon tetrachloride, a typical hepatotoxic chemical, on rat 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) hepato-carcinogenesis. A total of 420, 21-day-old, male Fisher 344 rats were given MeIQx at a concentration of 0, 0.001 ppm (human exposure level), 0.01, 0.1, 1, 10 and 100 ppm in the diet, and each group was separated into carbon tetrachloride-treated and vehicle-treated subgroups. Carbon tetrachloride was given by subcutaneous (s.c.) injection twice a week at a dose of 0.125 ml/kg body weight (b.w.) for the first 10 weeks and then at 0.25 ml/kg b.w. during the next 10 weeks. All rats were sacrificed at the end of week 22. In the vehicle-treated animals, only 100 ppm MeIQx significantly increased the number of glutathione S-transferase placental form (GST-P)-positive foci in the liver compared with 0 ppm MeIQx. Co-administration of carbon tetrachloride enhanced the induction of GST-P-positive foci by MeIQx in each group and the curve was almost the same pattern as that of vehicle-treated group but their numbers were significantly enhanced with 10 ppm and above compared with 0 ppm MeIQx. Persistent liver injury and liver cell proliferation were histopathologically observed in carbon tetrachloride-treated groups. Increase of 8-hydroxydeoxyguanosine (8-OHdG) formation and iNOS overexpression were observed by co-administration of carbon tetrachloride in MeIQx-treated rat liver. Our results indicate that carbon tetrachloride enhances MeIQx hepato-carcinogenicity through increase in oxidative DNA damage but non-effect levels of MeIQx carcinogenic activity still exist.

Expression of progenitor cell markers in livers with fulminant massive necrosis.

Studies of stem cells in various organs have greatly progressed, and progenitor cells have been confirmed even in liver by recognition of cytokeratin 14 (CK14), c-kit, flt-3, and CD34. We, therefore, immunohistochemically examined the expression of these progenitor cell markers in patients with confluent or massive necrosis, in addition to CK19, albumin, vimentin, and Ki-67. Our subjects were six survivors and 14 deceased patients. Expression of CK14 and c-kit was found in a small number of cells lining biliary ductule-like structures, and that of flt-3 was found in many lining cells in two deceased patients with multi-lobular necrosis. CK14 positive cells were positive for c-kit, flt-3, and CK19 in semi-serial sections, but were negative for albumin, Ki-67, and CD34. In conclusion, expression of CK14 and c-kit was found in a small number of cells lining biliary ductule-like structures, and that of flt-3 was found in many cells lining biliary ductule-like structures. CK14-positive cells were positive for c-kit, but negative for CD34. Since c-kit is a hematopoietic marker, our study suggests that CK14- and c-kit-positive cells may be derived from bone marrow in liver with fulminant hepatitis.

Immunohistochemical detection of Fas and apoptosis in type-1 autoimmune hepatitis.

BACKGROUND/AIMS: Although Fas expression has been reported in liver with chronic viral hepatitis and primary biliary cirrhosis, little is known about Fas expression and apoptosis in type-1 autoimmune hepatitis. The aim of this study was to investigate whether the expression of Fas and apoptosis are found in liver with autoimmune hepatitis. The relationship between Fas expression and clinicopathological findings including the occurrence of apoptosis was also investigated. METHODOLOGY: Fas expression and apoptosis were immunohistochemically examined in liver tissues from 20 patients with autoimmune hepatitis and five control subjects using specific antibodies against Fas and single-stranded DNA. The grade of expression of Fas and apoptosis was evaluated and compared with histological findings and the results of liver function tests in each patient. RESULTS: Fas expression in hepatocytes was detected in all patients with autoimmune hepatitis, while Fas expression was not detected in control livers. The Fas-positive hepatocytes were particularly abundant in those areas facing piecemeal and confluent necrosis. In 30% of autoimmune hepatitis cases, bile-duct cells were faintly stained for Fas. A few hepatocytes positive for single-stranded DNA were found in the areas facing piecemeal necrosis and confluent necrosis. In 95% cases, many bile-duct cells were positive for single-stranded DNA. No relationship between the expression of Fas and single-stranded DNA was found in hepatocytes or bile-duct cells. However, the degree of Fas expression in hepatocytes significantly correlated with serum transaminase concentrations and was increased in parallel with the grade of activity but not with the stage of fibrosis. CONCLUSIONS: We have demonstrated that Fas expression is detected in hepatocytes of the liver with autoimmune hepatitis and that the level of Fas expression reflects the severity of inflammation in autoimmune hepatitis.

A clinicopathological study of inflammatory pseudotumors of the liver with special reference to vessels.

BACKGROUND/AIMS: Inflammatory pseudotumor of the liver is rare, and patients with inflammatory pseudotumor frequently undergo unnecessary surgical resection as a result of misdiagnosis of malignancy. In this study, we therefore investigated inflammatory pseudotumor clinicopathologically to clarify its characteristics. METHODOLOGY: Twenty patients including 3 with inflammatory pseudotumor and 17 with various malignant liver tumors were studied. We further investigated tumor vessels by means of immunohistochemistry using monoclonal antibodies against CD34, factor VIII-related antigen and alpha-smooth muscle actin. RESULTS: Although serum levels of alkaline phosphatase were significantly higher in inflammatory pseudotumor patients than in other patients, the laboratory data alone could not precisely distinguish inflammatory pseudotumor from other hepatic tumors. On imaging studies such as ultrasonography and computed tomography, significant changes in tumor size, especially size reduction, during relatively short follow-up periods were often observed in inflammatory pseudotumor but not in other liver tumors. An enhancement of the peripheral regions of inflammatory pseudotumor was frequently observed in the early phase of contrast-medium dynamic computed tomography. This might be due to abnormal vessels located in the peripheral regions of inflammatory pseudotumor which might result from obliteration of some pre-existing vessels in portal tracts within inflammatory pseudotumor. Immunohistochemical analysis further revealed that abnormal vessels in the peripheral regions of inflammatory pseudotumor were positively stained with CD34, factor VIII-related antigen and alpha-smooth muscle actin as were tumor sinusoids within hepatocellular carcinoma and tumor capillaries in other malignant liver tumors. CONCLUSIONS: Although inflammatory pseudotumor seems to have some features in imaging studies, a biopsy is needed for a correct diagnosis of inflammatory pseudotumor.