Search

Background and Aim Acute kidney injury (AKI) is a life‐threatening complication of liver cirrhosis. Here, we evaluated the risk factors and characteristics of AKI in cirrhosis. Patients/Methods This was a single‐center retrospective study. A total of 199 Japanese patients with decompensated liver cirrhosis (104 men, median age 61 years) were enrolled and received tolvaptan orally. Survival rates and new onset of AKI were monitored, and risk factors were evaluated. Results Forty‐six patients (23.1%) suffered an AKI complication and exhibited significantly poorer survival (P, In cirrhosis, AKI incidence was increased in patients with encephalopathy and poor liver function. While proton pump inhibitor/H2 blocker or kanamycin/rifaximin treatment may reduce the risk of AKI.

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

Background and Aim Wilson's disease (WD) is a rare inherited disease that causes systemic copper accumulation. This study examined the long‐term course of WD patients with liver disease. Methods The 12 patients (9 female patients) enrolled in the study had a median age of 28 years (range: 19–57 years) at their first visit to our hospital. Clinical course and fibrosis markers were assessed in all patients. Results The median age at diagnosis was 24 years (range: 5–42 years). One patient had acute liver failure (ALF) and 11 patients had chronic liver disease (CLD, 5 with cirrhosis). The patients were followed‐up for >20 years. The patient with ALF underwent liver transplantation; the postoperative course during the subsequent 20 years was good. Of the six patients with CLD, liver cirrhosis developed in four patients with interrupted chelating therapy. Two of the patients with cirrhosis died; one of these two patients died at 21 years after liver transplantation. However, the remaining patients with continued treatment exhibited a favorable clinical course for 30 years and none developed hepatocellular carcinoma (HCC). The duration of chelation therapy was significantly negatively correlated (P, The duration of chelation therapy for Wilson's disease complicated by liver disease was significantly negatively correlated with the fibrosis‐4 index and aspartate aminotransferase to platelet ratio index (APRI) score at the last visit.

BACKGROUND AND AIM The incidence of mortality and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has been reported, but the long-term outcomes of Japanese patients with NAFLD are not fully evaluated. METHODS We enrolled 365 Japanese patients with biopsy-confirmed NAFLD (1990-2008) followed for ≥ 6 months: 185 males (50.7%); median age (54 years); advanced fibrosis 108 (29.8%); HCC, n = 26 (7.1%); diabetes, n = 191 (52.3%); dyslipidemia, n = 234 (64.1%); and hypertension, n = 193 (52.9%). We analyzed the survival and new-onset HCC rates for hepatic fibrosis as well as complications and the treatment of lifestyle-related diseases. RESULTS During the median 7.1-year follow-up, 44 patients (12.1%) died: n = 28 liver-related (10 years liver-related death, 9.4%) and n = 16 non-liver-related deaths (10 years non-liver-related death, 4.9%). Both incidence rates were significantly higher in the advanced fibrosis group. The incidence of HCC at 10 years was 20.1% in the advanced fibrosis group, and the mortality was increased in patients with higher age, history of HCC, lower seru\m level of albumin, higher level of γ-glutamyltransferase, and insulin treatment for diabetes. Risk factors for HCC onset were higher levels of aspartate aminotransferase and triglyceride and hypertension treatment. Platelet count

BACKGROUND AND AIM The incidence of acute hepatitis A [AH (A)] is decreasing because of improvements in hygiene; however, cases of sporadic severe hepatitis are still being reported. We assessed the epidemiology of AH (A) in Japan. METHODS This was a hospital-based retrospective study, in which 126 AH (A) patients (96 men [76%], median age 39 [range, 19-66] years) were enrolled. Patients diagnosed with AH (A) before 2001 (n = 79) and after 2001 (n = 47) were compared. RESULTS The incidence of AH (A) showed peaks in 1990, 1999, and 2018. After 2001, one patient had hepatitis B virus, four had human immunodeficiency virus, and three had syphilis coinfections. Before and after 2001, HAV was transmitted, respectively, by raw oysters (28% and 26%), overseas travel (19% and 28%), and sexual contact (0% and 19%) (P

BACKGROUND AND AIM To elucidate features of nonobese non-alcoholic fatty liver disease (NAFLD), we assessed Japanese patients with NAFLD stratified by body mass index (BMI) and by sex. METHODS Biopsy-proven 762 NAFLD patients (404 men) were classified into three groups by the Japanese criteria: nonobese group (BMI

Background and Aim Given the use of direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV), their effects on hepatocarcinogenesis should be determined. Methods This study enrolled 349 patients with HCV who underwent DAA treatment at our hospital between 2014 and 2018. Their median age was 65 years, and 184 were male; 301 cases were of HCV serotype 1, and 48 were of serotype 2. The DAA treatment was daclatasvir/asunaprevir in 107 cases, sofosbuvir (SOF)/ledipasvir in 147 cases, ritonavir-boosted ombitasvir/paritaprevir in 28 cases, elbasvir/grazoprevir in 19 cases, and SOF/ribavirin in 48 cases. The patients' histories included hepatocellular carcinoma (HCC) in 45 cases, liver transplant (LT) in 10 cases, and kidney transplant (KT) in 17 cases. Results Sustained virological responses occurred in 335 cases (96%). DAA treatment was initiated a median of 16.3 months after HCC treatment. After DAA treatment, 15 cases (33%) had recurrence of HCC after a median of 11.6 months, and 3 cases (1%) developed de novo HCC. Six LT patients and one KT patient had HCC; however, no HCC was observed after DAA. The incidence of HCC was significantly higher in patients with multiple HCC treatments in the Cox hazard model (hazard ratio 1.664, 95% confidence interval 1.134-2.441, P < 0.01). Surgical resection or LT reduced the risk of HCC. Conclusions DAA did not increase the rate of HCC, even in immunosuppressed patients. However, careful follow-up for HCC recurrence is required in previously treated cases.

Background and Aim Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have common hepatic histological features, but few studies have compared the genomic backgrounds of these two diseases. Here, we compared the genetic differences between ALD and NAFLD. Methods This study enrolled 318 Japanese patients with ALD (n = 118; male, 86%; median age, 62 years; liver cirrhosis, 58%; hepatocellular carcinoma [HCC], 31%) and NAFLD (n = 200; male, 55%; age, 61 years; cirrhosis, 19%; HCC, 12%). The genotype frequencies of 10 single nucleotide polymorphisms (SNPs) were analyzed. Results The ADH1B genotype GG and ALDH2 genotype GG were observed more frequently, and the percentage of patients with the MTP genotype GG was lower in ALD compared with NAFLD patients (ADH1B, 16 vs 4%; ALDH2 84 vs 44%; MTP 62 vs 72%, respectively; all P

AIMS Steatohepatitic hepatocellular carcinoma (SH-HCC) is a newly proposed concept, which shows histological features of steatohepatitis in HCC lesions, and it is strongly associated with metabolic syndrome (MS) and steatosis/steatohepatitis in non-cancerous lesions. Recently, a substantial number of HCC associated with MS were reported to have developed from pre-existing inflammatory hepatocellular adenoma (HCA). To elucidate the characteristic features of SH-HCC, we clinicopathologically investigated strictly diagnosed SH-HCC and non-SH-HCC (standard HCC). METHODS This was a retrospective multicenter study. A clinicopathological investigation was undertaken to compare 62 cases with SH-HCC features to 31 age- and sex-matched standard HCC cases, including an immunohistochemical study using markers for classification of HCA and diagnosis of HCC. RESULTS The characteristic features of SH-HCC compared with standard HCC include a higher rate of complications of MS, more frequent non-alcoholic fatty liver disease as an underlying liver disease, and HCC development in non-cirrhotic liver. The rate of solitary tumors showed no difference between the two groups, but the median diameter of the main tumor was greater in SH-HCCs (45 mm/20 mm, P = 0.01). The HCCs were mostly moderately differentiated, and the patterns were mainly trabecular in both groups. Positive findings for serum amyloid A and C-reactive proteins, classification markers of inflammatory HCA, were significantly higher in cancerous lesions of SH-HCC cases (50%/13%, P

Aims The vasopressin V2 receptor antagonist tolvaptan has been used for the treatment of cirrhotic patients with ascites; however, no predictor of efficacy and prognosis has been developed. Here, we evaluated candidate predictors of response to tolvaptan treatment. Methods This was a single-center retrospective study. Overall, 97 Japanese cirrhotic patients (60 males, median age 63 years), who were hospitalized for ascites treatment including oral tolvaptan coupled with conventional diuretics, were enrolled. The efficacy of tolvaptan was defined as a urination increase of ≥ 500 mL or a urine volume ≥ 2,000 mL/day on the day following treatment. The prognosis of tolvaptan treatment was evaluated by the post-treatment survival time by Kaplan–Meier analysis. Results Tolvaptan therapy was effective in 67% of cirrhotic patients. Patients showed -1.5 (-17.2 to +6.2) kg change in body weight and 40% achieved ≥ 2.0 kg reduction in body weight after 1 week of treatment. Platelet counts, urine sodium (Na) level, and urine Na/potassium (Na/K) ratio were higher, and the blood urea nitrogen (BUN)/creatinine (Cr) ratio was lower, in cases showing a response to tolvaptan. The combination of a BUN/Cr ratio ≥ 17.5 and urine Na/K ratio

Poorly controlled diabetes mellitus (DM) patients sometimes show serum transaminase elevations due to steatohepatitis. However, we experienced four cases with type 1 DM with sharp elevations in serum transaminases that could not be explained by steatohepatitis alone and showed bright liver. They were diagnosed with glycogenic hepatopathy (GH) clinicopathologically. The four patients had a median age of 22.5 years (range, 19-29 years) and 12.5 (4-15)-year histories of type 1 DM and showed marked increases in serum transaminases (aspartate aminotransferase, 698 U/L [469-2763 U/L]; alanine transaminase, 255 U/L [216-956 U/L]). Diabetes mellitus control was poor and hemoglobin A1c was 12.7% (11-16.5%). Three cases had a past history of diabetic ketoacidosis. Hepatomegaly and hyperdense liver were seen on computed tomography scans. Magnetic resonance imaging showed low intensity in T2-weighted images. The pathological findings revealed pale and swollen hepatocytes and glycogenated nuclei. The architecture of the liver was preserved, and steatosis and fibrosis were mild. The cytoplasm of hepatocytes stained densely positive with periodic acid-Schiff, and the positive staining disappeared after diastase digestion, suggesting glycogen deposition. No other cause of hepatitis was evident, and the diagnosis was GH. Elevated transaminases improved within 1 month with good glycemic control. Transaminase elevations were observed several times in three cases with poor glycemic control. Glycogenic hepatopathy is rare, but extremely high serum elevations of transaminases are important to identify clinically. Despite showing a good clinical course in general, GH sometimes recurs and requires strict glycemic control. Clinicians should be aware of and recognize GH when dealing with uncontrolled DM patients.

Aim Recently, the short-term efficacy of the vasopressin V2 receptor antagonist tolvaptan for the treatment of ascites in cirrhosis was reported. However, the long-term effects remain unknown. Here, we report the clinical features of decompensated cirrhosis treated using long-term tolvaptan therapy, and evaluate its safety and efficacy. Methods Fifty-five cirrhotic patients hospitalized due to ascites, despite receiving appropriate diuretic treatment, were treated with tolvaptan. We excluded 35 patients due to liver transplant (20.0%), death (28.6%), poor general status (14.3%), improved ascites (5.7%) or other reasons (31.4%). In 20 cases treated with tolvaptan for 6 months, total body water (TBW) and extracellular fluids (ECW) were measured using bioelectric impedance analysis (BIA) with an InBody720. Results The median age of the 20 patients was 64 years (range, 48–90), and 60% were male. The etiology of cirrhosis included hepatitis C (45%), alcohol-induced (20%) and other (35%). The percentage of patients with Child–Pugh class A, B and C was 0%, 40% and 60%, respectively. Biochemical findings revealed that serum creatinine levels and estimated glomerular filtration rate were not affected during 6 months of treatment with tolvaptan, and there was no renal disturbance. The median serum sodium levels were increased from 138 to 139 mEq/L, but serious adverse events related to renal and liver function were not observed. Data also revealed that long-term treatment reduced the BIA-estimated ECW/TBW ratio. Conclusion Long-term tolvaptan treatment was a safe and effective treatment for decompensated cirrhosis.

Primary hyperoxaluria (PH) is a rare, autosomal recessive disorder characterized by overproduction of oxalate caused by a deficiency in a hepatic enzyme. The excess oxalate combines with calcium in the kidneys to form deposits of calcium oxalate, which can lead to nephrocalcinosis and renal failure. PH type 1 (PH1), the most common form of this disease, is caused by a deficiency of the liver-specific enzyme alanine/glyoxylate aminotransferase (AGT). Liver transplantation is performed as a definitive therapy for PH to correct the enzyme defect. Usually, liver depositions are limited and liver function is normal without fibrosis. Here, we report an adult case of liver cirrhosis caused by PH1. A 28-year-old woman was admitted to our hospital under suspicion of PH1 and the presence of nephrocalcinosis. The patient had suffered from kidney stone recurrences from 17 years of age, and was initiated on hemodialysis due to renal failure at the age of 27 years. The serum level of oxalic acid was high, whereas the AGT level in the liver tissue was decreased. Thus, the patient was definitively diagnosed with PH1. Although she had normal liver function, surface nodularity and splenomegaly were detected by computed tomography, suggesting liver cirrhosis. The native liver showed micronodular cirrhosis and portal fibrosis. Several arterioles were filled with rhomboid and polyhedral refractile oxalate crystals and various portal tracts showed these crystals. Our case suggests that long-term oxalosis can lead to liver cirrhosis; thus, PH should be considered one of the causes of liver cirrhosis.

Aim The aim of the present study is to evaluate the factors influencing biochemical response to treatment and the value of biochemical response for predicting long-term outcomes in Japanese patients with primary biliary cirrhosis (PBC). Methods Biochemical response to ursodeoxycholic acid (UDCA) or UDCA plus bezafibrate was defined as good (≤upper limit of normal [ULN]), fair (≤1.5 × ULN) or poor (>1.5 × ULN) at 2 years after initiation of UDCA treatment. Associations between various factors (including age, sex, autoantibody status and histological variables at baseline), biochemical response to treatment and long-term outcomes were evaluated in 164 Japanese PBC patients. Results Anti-gp210 positivity and a higher bile duct loss score were significant risk factors for worse alkaline phosphatase (ALP) response (odds ratios [OR], 2.78 and 1.85, respectively). Age, anti-gp210 positivity and anticentromere positivity were significant risk factors for worse alanine aminotransferase (ALT) response (OR, 1.05, 4.0 and 2.77, respectively). Anti-gp210 positivity and a higher hepatitis score were significant risk factors for worse immunoglobulin (Ig)M response (OR, 2.10 and 2.06, respectively). Worse ALP and IgM response were significant risk factors for progression to late-stage disease without jaundice (OR, 2.27 and 2.32, respectively). Worse ALT response was a significant risk factor for progression to late-stage disease with persistent jaundice (OR, 11.11). Conclusion Biochemical response to treatment at 2 years, which is influenced by autoantibody status and histological variables at baseline, can predict long-term outcomes in Japanese patients with PBC.

Aim To clarify the clinical features of patients with hepatocellular carcinoma (HCC) with cryptogenic liver diseases, we analyzed the data from a nationwide survey in Japan. Methods The survey was conducted in 2009. The factors examined included age and underlying liver diseases: alcoholic liver disease (ALD; n = 991), non-alcoholic fatty liver disease (n = 292), modest alcohol intake (intake between 20 and 70 g/day, n = 214) and cryptogenic liver diseases (n = 316). We compared the clinical features of cryptogenic HCC among patient-age subgroups. Results HCC with ALD etiology was most common among the non-viral HCC patients under 80 years old; for those aged 80 years or older, cryptogenic HCC was the most common etiology. Among the cryptogenic HCC patients, the body mass index values and the prevalences of liver cirrhosis (LC) and diabetes mellitus (DM) were significantly lower in the 80 years or older group versus the 50–79 years group. In the 80 years or older group, 28% of the patients developed HCC without cirrhosis, obesity and DM. Conclusion In the HCC patients aged 80 years and over, the etiology of most of the non-viral HCC cases was classified as cryptogenic. In light of our finding that the prevalences of obesity, DM and LC in the 80 years or older group of cryptogenic HCC patients were significantly lower those in the younger patients, it is apparent that analyses of HCC cases must take age differences into account.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome. NAFLD has become an important public health issue because of its high prevalence. NAFLD consists of two clinicopathological entities: simple steatosis, which generally follows a benign non-progressive clinical course, and non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma. The diagnosis of NAFLD is based on the following three criteria: non-alcoholic, detection of steatosis either by imaging or by histology, and appropriate exclusion of other liver diseases. Alcoholic liver disease can occur when daily alcohol consumption exceeds 20 g in women or 30 g in men. Thus, non-alcoholic indicates lower levels of these alcohol consumptions. However, there is still no clear consensus regarding the threshold alcohol consumption for defining non-alcoholic liver disease. Then, there is the strong recommendation for a change in the nomenclature, such as use of the term metabolic fatty liver and metabolic steatohepatitis. NASH has emerged as a clinicopathological entity, and even now, a liver biopsy remains the gold standard for making a definitive diagnosis. However, liver biopsy has several drawbacks. In general practice, NAFLD is a convenient-to-use term for the diagnosis and management of these patients, and serum biomarkers that indicate the severity of fibrosis serve as clinically useful tools for the identification of NAFLD in patients with bridging fibrosis or cirrhosis. In the future, improved understanding of the pathogenesis of NASH and new technologies may contribute to the diagnostic process and provide reliable, non-invasive alternatives to liver biopsy.

Aim The aim of this study was to elucidate the clinical and histological features, response to corticosteroid therapy and long-term outcome of primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH). Methods Among 280 PBC patients under ursodeoxycholic acid administration, we identified 28 patients with AIH features fulfilling the following criteria: sustained high levels of serum aminotransferases and high immunoglobulin G levels with positivity for antinuclear antibodies or anti-smooth muscle antibodies (ASMA) and/or histological features of moderate to severe interface hepatitis or moderate to severe lobular hepatitis. We analyzed PBC patients with AIH features, focusing mainly on therapeutic responses to corticosteroids. Results Patients with PBC with AIH features included 26 women (93%). Their median age was 55 years, and the median follow-up period was 7.5 years. Eight of these 28 patients were not actually treated with corticosteroids due to medical conditions. Among the 20 patients receiving corticosteroid therapy, 15 were responders and five were non-responders. A high alkaline phosphatase (ALP) level, negativity for ASMA and positivity for gp210 were identified as risk factors for lack of a response to corticosteroid therapy. Among 28 PBC patients with AIH features, the responders to corticosteroids had an excellent prognosis, while those who could not be treated with corticosteroids and non-responders to corticosteroids had a poor outcome. Conclusion Patients with PBC with AIH features benefit from corticosteroid therapy. Features of PBC such as high ALP level, negativity for ASMA and positivity for gp210 appear to predict a poor response to corticosteroids.

Aim: To elucidate gender differences and the influence of obesity and/or metabolic syndrome-related fatty liver on alcoholic liver disease (ALD), we analyzed characteristic features of ALD. Methods: We investigated 266 ALD patients (224 males and 42 females) without hepatocellular carcinoma stratified by gender and the presence of cirrhosis. Male and female patients matched for age and total ethanol intake were also analyzed. A diagnosis of ALD was based on alcohol intake (>70 g daily for more than 5 years), clinical features, and exclusion of other liver diseases. The prevalence of obesity, lifestyle-related diseases, and psychological disorders were assessed. Results: The prevalence of psychological disorders showed a significant gender difference among all ALD patients (12% in males versus 43% in females, P

Aim: Ornithine carbamoyltransferase (OCT) is reported to be a liver-specific marker for the evaluation of hapatocellular damage. In this study, we investigated its clinical significance in non-alcoholic steatohepatitis (NASH). Methods: Serum OCT levels were measured by the ELISA (enzyme-linked immunosorbent assay) method. One hundred and twenty patients with NASH (18 liver cirrhosis induced by NASH and 9 NASH combined with hepatocellular carcinoma) were measured. Results: The serum levels of OCT and the ratios of OCT : alanine amino transferase (ALT) and OCT : aspartate amino transferase (AST) were increased in parallel with the progression of NASH. Especially, OCT and both ratios were markedly increased in hepatocellular carcinoma. As for the relationship between fibrosis grade and OCT, the serum OCT levels and the ratio of OCT : ALT levels were increased in parallel with liver fibrosis. In NASH patients with ALT within normal range, about 30% showed elevation of OCT. Conclusion: Serum OCT levels and the ratios of OCT : ALT and OCT : AST increase in parallel with the progression of NASH. It was suggested that OCT is a useful marker in the progression of NASH.

Background and Aim: Ethnic differences in non-alcoholic steatohepatitis (NASH) are well-documented, but there has been no study on the prognosis of Japanese NASH patients with cirrhosis. Accordingly, we compared cirrhotic NASH with liver cirrhosis caused by chronic hepatitis C (LC-C) to clarify its clinical features and define the risk factors for death. Methods: A prospective evaluation of the outcomes of NASH patients with severe fibrosis was started in 1990. Data on age- and sex-matched patients with biopsy-proven LC-C were collected retrospectively and used as the control. Results: There were 68 patients with cirrhotic NASH and 69 with LC-C. The Child–Turcotte–Pugh (CTP) class was similar in these two groups. Although the outcome of the NASH group was better than that of the LC-C group, cirrhotic NASH followed a similar course to that of LC-C; that is, complications of cirrhosis developed, including hepatocellular carcinoma (HCC; the 5-year HCC rate was 11.3% for NASH and 30.5% for HCV) and death (the 5-year survival rates were 75.2% and 73.8%, respectively). HCC was the leading cause of death in both groups (NASH, 47%; HCV, 68%). The occurrence of HCC and the CTP class were significant risk factors for mortality in NASH patients according to a multivariate analysis (HCC: hazard ratio [HR] 7.96, 95% confidence interval [CI] 2.45–25.88, CTP class A: HR 0.17, 95% CI 0.06–0.50). Conclusion: In conclusion, the present study confirmed that cirrhotic NASH has a similar course to LC-C. The occurrence of HCC was the strongest predictor of mortality in the NASH groups. These findings may be helpful when deciding on therapeutic interventions for NASH and also for the daily management of these patients.

Spur cell anemia is an acquired hemolytic anemia, which may occur in patients with severe liver dysfunction, especially in those with alcoholic cirrhosis. Recently, non-alcoholic steatohepatitis (NASH) has been highlighted as one of the causes of chronic liver diseases, which could progress to cirrhosis. Histological features of NASH are indistinguishable from those of alcoholic hepatitis. We report on a cirrhotic NASH patient who developed progressive indirect dominant jaundice and intractable hemolytic anemia during his follow-up. This report shows the first case of a cirrhotic NASH patient who died as a result of spur cell anemia.

Background. In hepatocellular carcinoma (HCC), a high prevalence of hepatitis C virus antibody (anti-HCV) has been reported, indicating that it may be an important etiologic factor in the pathogenesis of HCC. In this study, the authors investigated the prevalence of anti-HCV in HCC patients, as well as the same prevalence in patients with cholangiocarcinoma (CC) and combined hepatocellular–cholangiocarcinoma (combined HCC-CC), to study the clinicopathologic features of anti-HCV–positive cases. Methods. The authors examined 141 patients with primary liver cancer who were pathologically diagnosed as having HCC (121 cases), CC (13 cases), or combined HCC-CC (7 cases). Hepatitis B surface antigen (HBsAg) and anti-HCV were measured in these patients. Results. Of 121 HCC cases, 85 (70.3%) were found to be anti-HCV positive, 16 (13.2%) were HBsAg positive, and 5 (4.1%) were both anti-HCV and HBsAg positive. In 13 cases with CC and in 7 with combined HCC-CC examined, 4 (30.8%) and 5 (71.4%), respectively, were anti-HCV positive. Conclusions. The anti-HCV–positive rate was high in combined HCC-CC as well as in HCC. These three types of primary liver cancer, which were anti-HCV positive, shared two common features: male dominance and high incidences of complication with liver cirrhosis.

An association between primary sclerosing cholangitis (PSC) and chronic ulcerative colitis (CUC) is well known in Western countries, but there have been no reports on this association in Japan. We reviewed 163 consecutive CUC patients (91 males and 72 females) diagnosed from 1984 to 1990 at Tokyo Women's Medical College. Abnormal liver function tests were found in 42 patients with CUC (25.8%), but chronic liver disease was only diagnosed in seven patients (4.3%). Among these seven patients, there were four with PSC, one with small-duct PSC, one with transfusion-associated chronic hepatitis and one with Type B liver cirrhosis. No relationship was found between the documented colonic manifestations of CUC and the presence of PSC. The four PSC patients did not have a longer history of CUC at the time of diagnosis of PSC than CUC patients without PSC. At the time of PSC diagnosis, two patients were asymptomatic, one presented with right upper quadrant pain, and the other had fatigue. Three patients were diagnosed as having CUC before the onset of PSC (range 2-13 years), and the other patient had both diseases simultaneously. All four had a good prognosis. Thus PSC was the most common chronic liver disease associated with CUC in our series, and it was present in all our CUC patients with alkaline phosphatase levels exceeding twice the upper limit of normal and mild transaminase elevation.