D.J. Suh

Diagnosis of hepatic steatosis and fibrosis by transient elastography in asymptomatic healthy individuals: a prospective study of living related potential liver donors

BackgroundThis prospective study aimed to assess the ability of transient elastography to identify histologic parameters, including steatosis, in asymptomatic healthy individuals such as potential liver donors, and to compare these findings with results in liver disease patients.MethodsForty-seven patients with abnormal liver function and/or hepatitis symptoms and 80 living related potential liver donors were consecutively enrolled, and liver biopsy and a Fibroscan test were performed in each subject. Histologic parameters were evaluated according to METAVIR scale by a single pathologist.ResultsIn liver disease patients, stiffness was significantly correlated with fibrosis stage (Spearman correlation coefficient, 0.700; P < 0.001), and the optimal stiffness cutoff values for F ≥ 2, F ≥ 3, and F = 4 were 7.35, 8.85, and 15.1 kPa respectively. In potential liver donors, however, stiffness was not correlated with fibrosis (0.023; P = 0.851). In the latter group, the area under the receiver-operating characteristics curve was 0.70 (95% confidence interval, 0.58–0.81), and the optimal stiffness cutoff value was 4.00 for F ≥ 2, which was lower than that in liver disease patients. Steatosis was not correlated with stiffness (0.088; P = 0.463) in potential liver donors.ConclusionsTransient elastography has limited value for detecting steatosis in asymptomatic healthy individuals, and the cutoff value for fibrosis should be reevaluated in these subjects.

Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve.

OBJECTIVE:Proton magnetic resonance spectroscopy (1H-MRS) has been used to assess the metabolic changes in the brain in patients with liver cirrhosis. Decreased myo-inositol and increased glutamine levels were noted to be the most sensitive spectroscopic markers for cirrhotic patients with hepatic encephalopathy (HE). The purpose of this study was to assess how the abnormalities seen on the 1H-MRS of the brain in patients with liver cirrhosis are related to clinical and laboratory parameters.METHODS:In a prospective study, localized 1H-MRS was performed in the basal ganglia and parietal white matter regions in liver cirrhosis patients with (n = 48) and without (n = 52) HE and chronic hepatitis (CH) (n = 15), and in normal controls (n = 20).RESULTS:Among cirrhotic patients, the myo-inositol levels were significantly lower (p < 0.01) and the glutamine levels were higher (p < 0.05) for patients with HE than for those without HE. The myo-inositol and glutamine levels, respectively, were inversely (r =−0.50; p < 0.001) and linearly (r = 0.50; p < 0.001) related to the Child-Pugh score. However, by subgroup analysis of Child-Pugh class C patients, there were no significant differences in the myo-inositol and glutamine levels between cirrhotic patients with (n = 40) and without HE (n = 24). A follow-up study of eight cirrhotic patients with HE showed no significant differences in the myo-inositol and glutamine levels after clinical improvement of HE.CONCLUSIONS:The abnormalities seen on the 1H-MRS of the brain of patients with liver cirrhosis are not likely to reflect the severity of HE or acute alteration in the level of consciousness. Rather, we believe they represent the chronic metabolic derangement of the brain associated with hepatic functional reserve.

Usefulness of cholangioscopy in patients with focal stricture of the intrahepatic duct unrelated to intrahepatic stones

BACKGROUND Intrahepatic duct strictures are usually caused by intrahepatic duct stones and cholangitis. However, focal strictures of the intrahepatic duct unrelated to intrahepatic stones often pose diagnostic problems. This study was undertaken to prospectively evaluate the usefulness of percutaneous transhepatic cholangioscopy in patients with focal intrahepatic duct stricture and no evidence of a stone. METHODS Seventeen patients with focal strictures of the intrahepatic duct without any evidence of a stone were included. Percutaneous transhepatic cholangioscopic examination including procurement of biopsy specimens was performed after percutaneous transhepatic biliary drainage. RESULTS A histopathologic diagnosis was obtained in all patients (9 adenocarcinomas, 1 squamous cell carcinoma, 2 hepatocellular carcinomas, 2 adenomas, and 3 benign strictures). Of the 9 patients with bile duct adenocarcinoma, 8 underwent surgery and a curative resection was possible in 7 patients (88%). Five patients (63%) had early-stage bile duct cancer in which cancer invasion was limited to the mucosa or fibromuscular layer and there was no evidence of lymph node metastasis. CONCLUSIONS Percutaneous transhepatic cholangioscopy in patients with focal stricture of the intrahepatic duct unrelated to choledocholithiasis is useful for diagnosis including the detection of early bile duct cancer.

Prevention of hepatitis B recurrence after living donor liver transplantation: Primary high‐dose hepatitis B immunoglobulin monotherapy and rescue antiviral therapy

The prevention of hepatitis B virus (HBV) recurrence is essential after liver transplantation in patients infected with HBV. We evaluated the efficacy of primary high‐dose hepatitis B immunoglobulin (HBIG) monotherapy and rescue antiviral therapy in 639 HBV‐infected adult patients who underwent living donor liver transplantation (LDLT) between February 1997 and December 2004. The overall 5‐year survival rate was 80.7%, and recurrence of hepatocellular carcinoma was the most common cause of late mortality. Pretransplant HBV replication was observed in 392 (61.3%) patients. The interval of 10,000‐IU HBIG administration to maintain antibody to hepatitis B surface antigen > 500 IU/L was 30 days in 11.4% patients, 40 to 50 days in 72.1%, and 60 days in 16.5%. At the last follow‐up, 3.9% of the patients without HBV recurrence were receiving combination therapy. Overall 1‐year, 3‐year, 5‐year, and 10‐year HBV recurrence rates were 1.4%, 5.5%, 7.3%, and 8.5%, respectively. HBV recurrence occurred after a mean of 25.7 ± 16.4 months after LDLT. After HBV recurrence, 5 of 9 patients died from rapidly progressive liver failure before treatment with adefovir, and only 1 of 29 patients died after treatment with adefovir. Need for frequent HBIG infusions (≤30 days), active pretransplant HBV replication, and hepatocellular carcinoma recurrence were significant risk factors for HBV recurrence and indications for combination therapy. Our posttransplant HBV prophylaxis regimen resulted in a 5‐year HBV recurrence rate of 7.3% and a mortality rate of 13.2% after HBV recurrence, showing the effectiveness of high‐dose HBIG monotherapy and rescue antiviral therapy. Liver Transpl, 2008.

Quantitative polymerase chain reaction assay for serum hepatitis B virus DNA as a predictive factor for post-treatment relapse after lamivudine induced hepatitis B e antigen loss or seroconversion

Background and aims: Lamivudine induces favourable virological and biochemical responses but post-treatment relapses are frequent, even in patients with hepatitis B e antigen (HBeAg) loss or seroconversion. The aim of this study was to determine whether extended lamivudine therapy for up to 12 months after HBeAg loss/seroconversion could decrease the risk of post-treatment virological relapse. In addition, we monitored serum hepatitis B virus (HBV) DNA levels using a quantitative polymerase chain reaction (PCR) assay during extended lamivudine therapy and analysed predictive factors for post-treatment relapse. Patients and methods: A total of 49 patients who exhibited HBeAg loss/seroconversion during lamivudine therapy received extended lamivudine therapy for six months (group 1, n = 23) or 12 months (group 2, n = 26) after HBeAg loss/seroconversion. Serum HBV DNA levels were quantified by a PCR based assay at the time of HBeAg loss/seroconversion, and at cessation of therapy. Results: Post-treatment virological relapse rates at two years were 59% in group 1 and 50% in group 2. Age, time interval to HBeAg loss/seroconversion, and serum HBV DNA levels at the time of cessation of therapy were independent predictive factors for post-treatment relapse. The post-treatment relapse rate was 37% at two years in patients with serum HBV DNA levels of <200 copies/ml but 73% in those with ⩾103 copies/ml. Conclusions: Extended lamivudine therapy for up to 12 months did not decrease the rate of post-treatment virological relapse, and monitoring of serum HBV DNA by a quantitative PCR method was helpful in predicting post-treatment relapse.

Exercise and diet modification in non-obese non-alcoholic fatty liver disease: analysis of biopsies of living liver donors.

Background and Aims:  We evaluated efficacy of exercise and diet modification for steatosis improvement of non‐obese non‐alcoholic fatty liver disease (NAFLD) patients.

Adefovir Dipivoxil Alone or in Combination with Ongoing Lamivudine in Patients with Decompensated Liver Disease and Lamivudine-resistant Hepatitis B Virus

The purpose of this prospective study was to evaluate the efficacy and safety of adefovir dipivoxil with or without ongoing lamivudine in decompensated lamivudine-resistant chronic hepatitis B patients. Forty-six hepatitis B e antigen (HBeAg)-positive patients with decompensated liver function and lamivudine-resistant hepatitis B virus (HBV) were assigned to adefovir dipivoxil monotherapy (n=18) or combination therapy with ongoing lamivudine (n=28) according to their own preference. After 24 weeks of treatment, 83% of monotherapy and 86% of combination therapy showed serum HBV DNA below detection limit (<0.5 pg/mL). Alanine aminotransferase (ALT) normalized in 78% and 82% respectively. Median Child-Pugh-Turcotte (CPT) score or Model for End-Stage Liver Disease (MELD) score reduced significantly by 3 or 5 point in monotherapy and 2 or 2 point in combination therapy respectively. There were no significant differences in rate of undetectable serum HBV DNA, median change of ALT and median reduction of CPT or MELD scores between the two groups. In conclusion, both adefovir dipivoxil monotherapy and combination therapy with ongoing lamivudine result in comparable virologic, biochemical, and clinical improvements in HBeAg-positive patients with decompensated liver function and lamivudine-resistant HBV. Combination with lamivudine showed no additional benefit over monotherapy during 24 weeks of treatment in these patients.

Cholestyramine resin for erythropoietic protoporphyria with severe hepatic disease: a case report

Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by mutations in the gene encoding the enzyme ferrochelatase. In EPP, deficient ferrochelatase activity leads to the excessive production and biliary excretion of protoporphyrin (PP). The major clinical features of EPP are photosensitivity and hepatobiliary disease that may progress to severe liver disease, that are caused by the toxicity of PP. EPP-related liver disease has been treated medically or surgically including liver transplantation. We described a 20-year-old male with severe liver disease who was diagnosed with EPP based on clinical and laboratory findings. He was treated with cholestyramine resin. Six months after the treatment, he was doing well without any abdominal pain or photosensitivity.

218 SUPPRESSIVE EFFECTS OF ENTECAVIR ON VIRAL REPLICATION AND TUMOR PROLIFERATION IN PATIENTS WITH HEPATITIS B VIRUS-RELATED HEPATOCELLULAR CARCINOMA

Background and Aims: Lamivudine had comparable antiviral effects both in patients with chronic hepatitis B (CHB) and hepatits B virus (HBV)-related hepatocellular carcinoma (HCC). We aimed to investigate the antiviral and antitumoural effects of entecavir (ETV) in HBV-related HCC patients. Methods: From January 2007 to December 2007, 271 chronically HBV-infected patients were primarily treated with ETV 0.5mg/day for at least 6 months in our institution. Among these, 94 had HCC at the initiation of ETV treatment (HCC group) and 177 did not (non-HCC group). We compared antiviral responses to ETV between the two groups, and also evaluated the influence of ETV on post-treatment outcomes of HCC. Results: At baseline, the HCC group was older, and had higher Child–Pugh score and liver cirrhosis rate than the non-HCC group (all P < 0.05). 33% of the HCC group and 62% of the nonHCC group were positive for Hepatitis B e antigen (HBeAg) (P < 0.05). There were no differences in serum HBV DNA and alanine aminotransferase (ALT) levels between the two groups. The cumulative rates of HBV DNA negativity (<300 copies/ml), ALT normalization, and HBeAg loss at 48 weeks were similar for both groups (86.2%, 85.1% and 43.8%, respectively for the HCC group and 81.4%, 87.6% and 36.4%, respectively for the non-HCC group). After 48 weeks, the HCC group showed significant decreases in mean Child–Pugh and MELD scores, compared with baseline (6.9 vs. 5.8 and 10.1 vs. 8.7, respectively; both P < 0.001). Of the 94 HCC patients, 33 received curative therapies for HCC, simultaneously with ETV: hepatectomy in 9 and radiofrequency ablation in 24. For these subgroup, median recurrence-free survival was 27.9 months in the 21 patients who achieved HBV DNA negativity at week 24, significantly longer than 17.6 months in those who did not (27.9 vs. 17.6 months, P = 0.01), similar to overall survival (P = 0.067): all pretreatment characteristics of patients and tumors did not differ. Conclusions: First-line ETV was comparably efficacious in either CHB patients with or without HCC. ETV treatment improved hepatic function in HCC patients, and early virological response to ETV markedly produced a delay of post-treatment recurrence of HCC.