Liver Histological Findings Research Articles

Successful living donor liver transplantation using a graft from a hepatitis B surface antigen‐positive donor

Liver transplantation using a graft from a donor with a positive hepatitis B surface antigen (HBsAg) has been contraindicated owing to the extremely high risk for recurrent disease leading to graft loss. However, the severe shortage of donors often forces the transplant community to utilize suboptimal donors, especially in the setting of living donor liver transplantation (LDLT). Here, we report a case of successful LDLT for a patient with hepatitis B-related cirrhosis utilizing a graft from an HBsAg-positive 'healthy carrier' donor using a combination prophylaxis of lamivudine and adefovir dipivoxil. To date, the patient has been doing well with normal liver function tests and liver histological findings at 4 years after the transplantation and the donor has also been doing well. Although virological recurrence appears to be universal despite prophylaxis, re-evaluation of the use of a graft from a healthy HBsAg-positive donor is warranted in this era of combination prophylaxis.

Depletion of High‐density Lipoprotein and Appearance of Triglyceride‐rich Low‐density Lipoprotein in a Japanese Patient With FIC1 Deficiency Manifesting Benign Recurrent Intrahepatic Cholestasis

Lipoprotein metabolism in FIC1 deficiency due to ATP8B1 mutations has never been studied sufficiently. This study was performed to investigate the detailed lipoprotein metabolism in benign recurrent intrahepatic cholestasis (BRIC) caused by FIC1 deficiency. Lipoprotein profile and major lipoprotein regulators such as lecithin:cholesterol acyltransferase (LCAT), hepatic triglyceride lipase (HTGL), lipoprotein lipase, and cholesteryl ester transfer protein in a Japanese patient with BRIC were serially examined during a bout of cholestasis. Liver expression of farnesoid X receptor (FXR), which suppresses high-density lipoprotein (HDL) generation, was also examined. Hypercholesterolemia and lipoprotein X accumulation were never observed throughout this study. When the cholestasis was severe, triglyceride-rich low-density lipoprotein (LDL) accounted for most of the plasma lipoproteins whereas HDL was hardly detectable. Concurrently, activities of all regulators were decreased, together with decreases of the serum parameter for liver protein synthesis. In particular, suppressions of LCAT and HTGL activities were severe and greatly contributed to the appearance of triglyceride-rich LDL. As the cholestasis improved, this LDL gradually transformed into normal LDL with the recoveries of LCAT and HTGL activities. The activities of all regulators for the last 1 to 2 months were normal but HDL remained depleted. His liver showed low FXR expression compared with control livers. The present study showed an appearance of triglyceride-rich LDL due to suppressions of LCAT and HTGL activities and a depletion of HDL that is not able to be explained by lipoprotein regulators or FXR in our patient.

Current therapy for autoimmune hepatitis

The treatment of autoimmune hepatitis is evolving as the pathogenic pathways that underlie the disease are defined, new immunosuppressive agents are tested, and site-specific molecular interventions become feasible. Prednisone alone or at a reduced dose combined with azathioprine is the conventional treatment. Patients with HLA genotype DRB1*0301 have a poorer treatment response and a more frequent need for liver transplantation than those with HLA genotype DRB1*0401. Therapy to the point when liver test results and histological findings are normal reduces, but does not eliminate, the occurrence of relapse. Treatment failure warrants reassessment with regard to the accuracy of the original diagnosis and the exclusion of variant forms of hepatitis or concomitant alternative diseases. Ciclosporin might be effective as short-term, front-line therapy in infants and adults, and calcineurin inhibitors might salvage patients who are refractory to corticosteroid regimens. Mycophenolate mofetil can induce an improvement in laboratory test results and reduce the requirement for corticosteroids. Sirolimus is effective for treatment of de novo autoimmune hepatitis that develops after liver transplantation. Synthetic peptides that block autoantigen presentation, cytokine manipulations, oral tolerance regimens, T-cell vaccination, and gene therapy are all interventions that will be able to emerge after a reliable animal model of the human disease has been developed.

Liver biopsy performance and histological findings among patients with chronic viral hepatitis: A Danish database study

We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis (> or =F2) and 13.9% had cirrhosis (F4). The frequency of cirrhosis varied from 8.3 to 18.6% among centres, and was independently associated with age, male gender, elevated alanine-aminotransferase (ALT) and non-Danish origin. Among 141 patients with hepatitis C and known duration of infection, cirrhosis had developed in 23% after 20 y of infection. Age above 40 y was a better predictor of cirrhosis than elevated ALT. National database comparison may identify factors of importance for improved management of patients with chronic viral hepatitis.

Non Alcoholic Fatty Liver Disease: Correlation With Clinical Hormonal and Biochemical Parameters

BACKGROUND: Non alcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis (NASH) and cirrhosis. The aim of this study was to describe the variance of clinical and laboratory parameters that could play a role in the development of NASH in a group of patients with NAFLD. PATIENTS AND METHODS: Clinical, biochemical and histological features of 36 patients with NAFLD were analyzed. Insulin and leptin serum levels were measured and Body Mass Index (BMI) and insulin resistance (HOMA index) were calculated. The same parameters were analyzed in 10 healthy controls. RESULTS: Signs of chronic liver disease and histological findings of advanced fibrosis were detected in 2 patients (5,5%), while hepatomegaly was a frequent finding (21 patients, 58,3%). NASH was confirmed in 21 patients (58,3%).Statistically significant difference was found between patients and controls in BMI (32 vs 25, p=0,002), insulin levels (33,3 vs 9,5, p=0,015) and HOMA index (9,4 vs 2,3 p=0,006). In comparing NASH patients with fatty liver (FL) patients, we observed similar levels (31,1 vs 32) of BMI, while insulin levels were higher in NASH patients (42 vs 22 p=0,044), as well as HOMA (11 vs 7,5) and leptin levels (22 vs 16,6) although this differences did not reach a statistical significance. CONCLUSIONS: This study confirms the important role of obesity and insulin resistance in a group of greek NAFLD patients. A positive correlation is also found between severity of liver damage and degree of insulin resistance. I N T R O D U C T I O N NAFLD is an increasingly recognized condition that refers to a wide spectrum of liver damage, ranging from simple fatty liver to steatohepatitis, which can progress to advanced fibrosis and cirrhosis. NAFLD should be differentiated from steatosis resulting from secondary causes such as genetic disorders (lipodystrophy, dysbetalipoproteinemia, etc), nutritional disorders (starvation, total parenteral nutrition, protein caloric malnutrition etc), drugs (estrogens, glucocorticoids, amiodarone, valproic acid Department of Internal Medicine, “SOTIRIA” Hospital, Athens, Greece Laboratory of Biochemistry, 401 Hospital, Athens, Greece Department of Pathology , “Sotiria” Hospital, Athens, Greece List οf AbbreviAtions: NAFLD: Non alcoholic fatty liver disease NASH: Steatohepatitis BMI: Body Mass Index FL: Fatty liver HOMA: Homeostatic Model Assessment

Therapeutic Potential of Cardiotrophin 1 in Fulminant Hepatic Failure

Administration of cardiotrophin 1 (CT-1) can treat experimental fulminant hepatic failure (FHF). Rat model with FHF induced by D-galactosamine (D-gal). Fulminant hepatic failure is a rapidly progressive disease that lacks effective nonsurgical treatment. Cardiotrophin 1 is a member of the interleukin 6 family that can protect cells from damage in some animal disease models. A rat model of FHF was induced by an intraperitoneal injection of D-gal (1.4 g/kg of body weight). Cardiotrophin 1 was administered at different time points after D-gal injection. Administration of CT-1 at 12 and 18 hours had a survival rate of 80% (12/15) and 70% (7/10), respectively, which was significantly higher than that of nontreatment (28% [5/18]). In addition, improvement of liver histologic findings, shortening of activated clotting time, and decrease in serum levels of total bilirubin and alanine aminotransferase were detected with CT-1 treatment. Administration of CT-1 decreased apoptotic cells and increased Ki-67 cells in the liver tissues. In vitro, CT-1 administration significantly decreased apoptotic cells and sequentially down-regulated the expression of proapoptotic molecules and up-regulated the expression of antiapoptotic molecules at different culture periods. D-galactosamine culture induced morphologic damage in a hepatocyte cell line, which was greatly improved by CT-1 administration. In addition, CT-1-treated cells demonstrated increased expression of glycoprotein 130 and up-regulation of cyclin D1 and heat shock protein 90. Cardiotrophin 1 may improve the outcome of D-gal-induced FHF through its effects on antiapoptosis and cell repair.

Contrast-enhanced ultrasonography to detect liver metastases

The advent of contrast-enhanced ultrasound (CEUS) has called into question the efficacy of standard ultrasonographic techniques. In this study, we evaluated B-mode and color-duplex imaging and CEUS in the detection of liver metastases, using intraoperative and histological findings as a reference. Before laparotomy, 108 patients suspected of having liver metastases were prospectively examined with B-mode and color-duplex imaging, followed by contrast-enhanced ultrasound (2.4 ml SonoVue). Patients with unresectable tumors (n=8) were excluded from the analysis. The sonographic diagnosis in the remaining 100 patients was compared to the intraoperative and histological findings. CEUS improved the sensitivity for detecting liver lesions from 56.3% (B-mode) to 83.8% (CEUS) (p=0.004). In particular, the contrast agent led to an improvement in ultrasonographic detection in the following cases: nodular metastases smaller than one centimeter; after adjuvant chemotherapy; for tumors near the surface of the liver; and for lesions situated around the ligamentum teres. CEUS provides significant improvement in the detection of liver metastases, and should therefore, be performed routinely in the surveillance of cancer patients.

Perioperative complications after hepatectomy with or without intra-arterial chemotherapy for bilobar colorectal cancer liver metastases

We investigated perioperative complications of hepatic arterial infusion chemotherapy preceding major hepatectomy for multiple bilobar colorectal cancer metastases. No consensus exists concerning operative feasibility or perioperative course in patients undergoing major liver resection with neoadjuvant chemotherapy--partly because such chemotherapy is considered hepatotoxic, increasing the risk of postoperative liver failure. Clinicopathologic data were available for 41 consecutive patients with 5 or more bilobar liver metastases from colorectal cancer who underwent major liver resection with or without prior hepatic arterial chemotherapy. Data concerning operative feasibility, postoperative liver function, complication rates, and histologic findings in the non-neoplastic liver were analyzed retrospectively. Prehepatectomy and postoperative day 1 platelet counts were lower (P < .01 and P < .05), alkaline phosphatase on postoperative day 3 was higher (P < .01), and prothrombin time on day 1 was more prolonged (P < .01) in the chemotherapy group. No significant difference was seen between groups in intraoperative data, morbidity, or duration of hospitalization. Histologic examination of adjacent non-neoplastic liver confirmed mild to severe fatty degeneration in 91% of the patients undergoing neoadjuvant chemotherapy, compared with 53% in those without neoadjuvant chemotherapy (P = .023). Although the number of neoplasms in chemotherapy patients was greater than that of the other group, overall and disease-free survival rates were comparable between groups. Despite mild postoperative liver dysfunction, pre-resection hepatic arterial chemotherapy did not increase morbidity.

Diagnostic Accuracy of Magnetic Resonance and Endoscopic Retrograde Cholangiography in Primary Sclerosing Cholangitis

To evaluate the accuracy and interobserver variability of magnetic resonance cholangiography (MRC) and endoscopic retrograde cholangiography (ERC) in the diagnosis of primary sclerosing cholangitis (PSC). MRC at 1.5 T with thin- and thick-slice breath-hold technique was performed in 66 adult patients (median age, 44 y; 26 women) with an appropriate spectrum of hepatobiliary diseases. Maximum intensity projection images were reconstructed from the thin slices. ERC was performed within 48 hours of the MR examination. The reference standard of PSC diagnosis was based on a combination of clinical features and cholestatic biochemical profile with typical ERC and/or MRC abnormalities and supported by liver histology findings. Two independent reviewers who were unaware of final diagnoses analyzed all images retrospectively. PSC was diagnosed in 39 (59%) of 66 patients. MRC provided comparable and poorer depiction than ERC of extrahepatic and intrahepatic ducts, respectively. However, the diagnostic accuracy of ERC and MRC were comparable. In the MRC detection of PSC, the average sensitivity of 2 independent readers was 80%, the specificity was 87%, and the accuracy was 83%. The corresponding values for ERC were a sensitivity of 89%, a specificity of 80%, and an accuracy of 85%. Interobserver agreement for the diagnosis of PSC was good (kappa = .61) for MRC and excellent (kappa = .81) for ERC. PSC can be diagnosed with high accuracy and good interobserver agreement. MRC and ERC performed equally well in the diagnosis of PSC when used blinded to clinical information.

Beneficial effects of alpha linolenic acid rich flaxseed oil on growth performance and hepatic cholesterol metabolism in high fat diet fed rats

The purpose of the study was to investigate the effect of flaxseed oil (FO), rich in alpha-linolenic acid (ALA) (18 : 3 n-3) on growth parameters and lipid metabolism of rats fed with high fat diet. High fat diet (HFD) resulted in significant alterations in hepatic lipids, increase in body weight gain and negative effect on lipoprotein metabolism. FO supplementation significantly lowered the increase in body weight gain, liver weight, plasma cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoprotein (HDL), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein (VLDL), LDL / HDL and TC / HDL ratio in HFD fed rats. FO significantly reduced the hepatic and plasma lipid levels indicating its hypolipidemic activity. On the other hand, oral administration of FO exhibited lower plasma lipoprotein profile as compared to HFD rats. Hepatic protection by FO is further substantiated by the normal liver histological findings in HFD fed rats. These data suggest that FO participate in the normal regulation of plasma lipid concentration and cholesterol metabolism in liver. No adverse effect of FO on growth parameters and plasma lipids in rats fed with fat-free diet. The results of the present study demonstrate that FO may be developed as a useful therapy for hyperlipidemia through reducing hepatic lipids, thereby proving its hypolipidemic activity.

A Double-blind Placebo-Controlled Study of Emtricitabine in Chronic Hepatitis B

Emtricitabine is a nucleoside analogue approved for treatment of human immunodeficiency virus 1 with clinical activity against hepatitis B virus (HBV). To compare the safety and efficacy of emtricitabine with placebo in patients with HBV, we conducted a randomized (2:1), double-blind study at 34 sites in North America, Asia, and Europe that enrolled adults between November 2000 and July 2002 who had chronic HBV infection but had never been exposed to nucleoside or nucleotide treatment. Each patient received either 200 mg of emtricitabine (n=167) or placebo (n=81) once daily for 48 weeks and underwent a pretreatment and end-of-treatment liver biopsy. Histologic improvement was defined as a 2-point reduction in Knodell necroinflammatory score with no worsening in fibrosis. At the end of treatment, 103 (62%) of 167 patients receiving active treatment had improved liver histologic findings vs 20 (25%) of 81 receiving placebo (P<.001), with significance demonstrated in subgroups positive (P<.001) and negative (P=.002) for hepatitis Be (HBe) antigen. Serum HBV DNA readings showed less than 400 copies/mL in 91 (54%) of 167 patients in the emtricitabine group vs 2 (2%) of 81 in the placebo group (P<.001); alanine aminotransferase levels were normal in 65% (109/167) vs 25% (20/81), respectively (P<.001). At week 48, 20 (13%) of 159 patients in the emtricitabine group with HBV DNA measured at the end of treatment had detectable virus with resistance mutations (95% confidence interval, 8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss were not different between arms. The safety profile of emtricitabine during treatment was similar to that of placebo. Posttreatment exacerbation of HBV infection developed in 23% of emtricitabine-treated patients. In patients with chronic HBV, both positive and negative for HBe antigen, 48 weeks of emtricitabine treatment resulted in significant histologic, virologic, and biochemical improvement.

Do Type and Duration of Antiretroviral Therapy Attenuate Liver Fibrosis in HIV--Hepatitis C Virus--Coinfected Patients?

This study aimed to determine whether type and duration of therapy for human immunodeficiency virus (HIV) infection attenuates liver fibrosis in patients with HIV and hepatitis C virus (HCV) coinfection. Patients with HCV monoinfection (group 1) and HIV-HCV coinfection were retrospectively selected; the latter patients were classified into the following 3 groups: group 2, patients who received no therapy or only nucleoside reverse-transcriptase inhibitors (NRTIs); group 3, those who received highly active antiretroviral therapy (HAART); and group 4, those who initially received NRTIs followed by HAART. Fibrosis stage (scale, 0-6) and necroinflammatory score (scale, 0-18) were assessed according to the Ishak system. Data are presented as mean +/- standard deviation. Three hundred eighty-one patients (296 HCV-monoinfected patients and 85 HIV-HCV-coinfected patients) were recruited. The durations of HIV therapy before liver biopsy was performed for groups 2, 3, and 4 were 3.8 +/- 2.8, 3.3 +/- 1.8, and 6.6 +/- 2.2 years. The time from HIV diagnosis to HAART initiation was shorter for group 3 than for group 4 (9.1 +/- 7.3 vs. 34.1 +/- 13.1 months; P < .0001). Groups 1 and 3 had similar fibrosis stages (3.1 +/- 2 vs. 3.4 +/- 2.4), rates of fibrosis progression (0.13 +/- 0.09 vs. 0.16 +/- 0.11 per year), and necroinflammatory scores (6.1 +/- 1.8 vs. 6.1 +/- 2.0). Groups 2 and 4 had significantly more-advanced liver disease, as determined by fibrosis stage (4.6 +/- 1.8 vs. 4.3 +/- 2.0; P < .0009), rate of fibrosis progression (0.24 +/- 0.11 vs. 0.20 +/- 0.10 per year; P < .0001), and prevalence of cirrhosis (68% vs. 55%; P < .006), compared with group 1. HIC-HCV-coinfected subjects who receive HAART as their sole form of therapy have liver histology findings comparable to those for HCV-monoinfected patients. A similar degree of benefit is not observed for HIV-HCV-coinfected patients who receive no therapy, NRTIs, or HAART after NRTIs, despite having a longer duration of therapy.

Improvement of nonalcoholic steatohepatitis after laparoscopic Roux-en-Y gastric bypass surgery for obesity

Purpose: Nonalcoholic steatoheapatitis (NASH) is commonly associated with obesity. The effect of laparoscopic Roux-en-Y gastric bypass (LRNY) on liver disease, particularly NASH (zone 3 hepatocellular ballooning or perisinusoidal fibrosis), is poorly defined. This study described the changes in liver histologic findings after LRNY.

Traditional Chinese Medicine improves dysfunction of peroxisome proliferator-activated receptor α and microsomal triglyceride transfer protein on abnormalities in lipid metabolism in ethanol-fed rats

We report the effects of Traditional Chinese Medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma oriental, Salvia miltiorrhiza and Pueraria lobata. The rats were separated randomly into five groups; the CD group (n=10), which was fed a control diet for 10 weeks, the ED group (n=10), which was fed an isocaloric liquid diet containing ethanol for 10 weeks and given daily oral doses of TCM (0.222 g/kg/day; TCM222, 0.667 g/kg/day; TCM667, and 2.000 g/kg/day; TCM2000, n=10, respectively) over the last four weeks of the study. The ED group developed fatty livers, as determined by their lipid profiles and liver histological findings. Compared with the control group, liver/body weight, plasma triglyceride (TG) and total cholesterol (TC), liver TG and TC, plasma alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group. Also, free fatty acids (FFA) levels increased in both plasma and liver during the administration of ethanol. On the other hand, when rats were administrated with TCM, their liver/body weight, plasma TG, TC and FFA, liver TG, TC and FFA, plasma ALT and AST decreased significantly and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group. Proper function of the peroxisome proliferator-activated receptor alpha (PPARalpha) is essential for the regulation of hepatic fatty acid metabolism. Microsomal triglyceride transfer protein (MTP) is essential for the secretion of triglycerides from the liver. mRNAs for PPARalpha and MTP were reduced in the livers of ethanol-fed rats. TCM restored the mRNA levels of PPARalpha and MTP, and prevented development of fatty livers in ethanol-fed rats. Impairment of PPARalpha and MTP function during ethanol consumption contributes to the development of alcohol-induced fatty liver, which can be overcome by TCM.

Amelioration effects of traditional Chinese medicine on alcohol-induced fatty liver

To examine the effects of traditional Chinese medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata. The rats were separated randomly into five groups. One (the CD group) was fed a control diet for 10 wk, another (the ED group) fed an ethanol-containing isocaloric liquid diet for 10 wk, and the last three (the TCM group) were fed an ethanol-containing isocaloric liquid diet for 10 wk and dosed orally with TCM (222 mg/kg.d, TCM222; 667 mg/kg.d, TCM667; and 2 000 mg/kg.d, TCM2000, respectively) weekly during the last 4 wk. ED group developed fatty liver according to lipid profile and liver histological findings. Compared with the control group, liver/body weight, serum triglyceride (TG) and total cholesterol (TC), liver TG and TC, serum alanine aminotransferase (ALT) and aspartic aminotran-sferase (AST) significantly increased in the ED group. Whereas, in the rats administered with TCM, liver/body weight, serum TG and TC, liver TG and TC, serum ALT and AST were significantly decreased, and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group. TCM treatment causes significant reduction in alcohol-induced lipid hepatic accumulation, reversing fatty liver and liver damage, and can be used as a remedy for alcoholic fatty liver.

Racial differences in liver inflammation and fibrosis related to chronic hepatitis C

Background & Aims: Hepatitis C virus (HCV) infection is more prevalent in black compared with white Americans. However, the natural course of HCV in black patients has not been defined. Methods: We performed a retrospective comparison of initial liver tests, HCV genotype and viral load, and liver histology findings in 87 black and 136 white American chronic hepatitis C patients who were evaluated at the University of Maryland between 1995 and 1998. The liver biopsy examinations were interpreted by using the Knodell Histologic Activity Index (HAI) criteria. Results: Black HCV patients were older (46.3 vs. 43.3 yr; P = 0.004) and were more likely to be infected with HCV genotype 1 (95% vs. 75%). The modes of HCV transmission, estimated duration of HCV infection, and prevalence of alcohol abuse were similar in the 2 groups. Yet, black patients had lower mean total HAI scores (7.6 vs. 8.7; P = 0.021), periportal hepatocyte necrosis scores ( P = 0.021), and liver fibrosis scores ( P = 0.049). In keeping with less hepatic necroinflammatory activity, black patients had a lower mean serum alanine transaminase (ALT) level (85.5 vs. 122.7; P = 0.002). Black patients also had lower serum iron levels ( P = 0.009). There were no racial differences in the prevalence of increased iron studies and hepatic iron loading. Conclusions: Black chronic HCV patients have milder liver necroinflammation and fibrosis than white patients with similar HCV duration. These differences in liver histology were not explained by a variance in hepatic iron loading.

Influence of HFE gene polymorphism on the progression and treatment of chronic hepatitis C.

We analysed liver histology findings in a large cohort of patients with chronic hepatitis C and in roughly half of them their response to interferon-alpha-based on iron parameters and HFE status. Histological activity and virological response to antiviral therapy (n = 146) were analysed in 273 immunocompetent and nonalcoholic patients with chronic hepatitis C, in terms of serum iron load, intrahepatic iron load (n = 110) and HFE mutations. Patients who were heterozygous for the C282Y and H63D mutations exhibited higher iron serum parameters than subjects without these mutations. The intrahepatic iron load was higher in H63D patients only. No association was observed between HFE mutations and histological activity. Increased iron parameters were associated with liver disease severity by univariate analysis only. Genotype 1 and ferritinaemia were associated with a poor response to antiviral therapy, whereas the H63D mutation emerged as a positive predictive factor for end of treatment and sustained antiviral response. Therefore, in chronic hepatitis C patients serum and intrahepatic iron levels were weakly correlated with histological activity, while HFE mutations were not. As for the response to interferon-alpha, elevated ferritinaemia constituted a negative predictive factor whereas the H63D mutation was a positive one. The H63D mutation might form part of an immunogenetic profile influencing the response to interferon therapy.

Long‐term Survival Following Kasai Portoenterostomy: Is Chronic Liver Disease Inevitable?

ABSTRACTObjectivesExtrahepatic biliary atresia (EHBA) is the most common indication for liver transplantation in childhood. Most children who do not undergo transplant are reported to have chronic liver disease and its complications. The aim of this single‐center study was to identify children with normal laboratory indices and no clinical evidence of chronic liver disease 10 or more years after Kasai portoenterostomy (KP).MethodsA retrospective analysis of the medical notes of all children surgically treated at the authors' center between 1979 and 1991 was undertaken. Criteria for inclusion were absence of surgical complications, unremarkable clinical examination, and normal bilirubin, aspartate aminotransferase, albumin, international normalized prothrombin ratio, and platelet count.ResultsOf 244 children surgically treated during the observation period, the authors identified 28 (11%) adolescents (14 male) who fulfilled the entry criteria. Their median age was 13.4 years (range, 10.2–22.2 years). Twenty‐six with type 3 EHBA had conventional KP, whereas 2 underwent modified operations. The corrective surgery was performed at a median age of 58 days (range, 20–99 days). Median time of complete clearance of jaundice from the date of KP was 75 days (range, 21–339 days). Twelve (43%) patients had history of cholangitis at a median age of 3.4 years. The liver histologic findings were suggestive of mild to moderate fibrosis in 54.2% and cirrhosis in 40.7% of the patients who underwent biopsy. No child had gastrointestinal bleeding during follow‐up. Thirteen (46%) patients had an elective esophagogastroduodenoscopy, which was normal in all. Twenty‐six (93%) patients were in mainstream education, whereas the remaining two (7%) attended special school because of reasons unrelated to liver disease.ConclusionsA sizable proportion of children with EHBA avoid significant chronic liver disease and its complications 10 years or more after conventional surgical correction and have an excellent quality of life. Their good outcome is not hampered by isolated episodes of ascending cholangitis. Whether or not the residual histologic damage will become symptomatic during their lifetime remains to be established.

Long-term survival following Kasai portoenterostomy: is chronic liver disease inevitable?

Extrahepatic biliary atresia (EHBA) is the most common indication for liver transplantation in childhood. Most children who do not undergo transplant are reported to have chronic liver disease and its complications. The aim of this single-center study was to identify children with normal laboratory indices and no clinical evidence of chronic liver disease 10 or more years after Kasai portoenterostomy (KP). A retrospective analysis of the medical notes of all children surgically treated at the authors' center between 1979 and 1991 was undertaken. Criteria for inclusion were absence of surgical complications, unremarkable clinical examination, and normal bilirubin, aspartate aminotransferase, albumin, international normalized prothrombin ratio, and platelet count. Of 244 children surgically treated during the observation period, the authors identified 28 (11%) adolescents (14 male) who fulfilled the entry criteria. Their median age was 13.4 years (range, 10.2-22.2 years). Twenty-six with type 3 EHBA had conventional KP, whereas 2 underwent modified operations. The corrective surgery was performed at a median age of 58 days (range, 20-99 days). Median time of complete clearance of jaundice from the date of KP was 75 days (range, 21-339 days). Twelve (43%) patients had history of cholangitis at a median age of 3.4 years. The liver histologic findings were suggestive of mild to moderate fibrosis in 54.2% and cirrhosis in 40.7% of the patients who underwent biopsy. No child had gastrointestinal bleeding during follow-up. Thirteen (46%) patients had an elective esophagogastroduodenoscopy, which was normal in all. Twenty-six (93%) patients were in mainstream education, whereas the remaining two (7%) attended special school because of reasons unrelated to liver disease. A sizable proportion of children with EHBA avoid significant chronic liver disease and its complications 10 years or more after conventional surgical correction and have an excellent quality of life. Their good outcome is not hampered by isolated episodes of ascending cholangitis. Whether or not the residual histologic damage will become symptomatic during their lifetime remains to be established.

The Effects of Korean Red Ginseng (Ginseng Radix Rubra) on Liver Regeneration after Partial Hepatectomy in Dogs

We investigated the effects of the oral administration of Korean red ginseng (KRG) on morphologic change and function of liver in dogs. Fifteen adult mongrel dogs (n=15) were divided into three groups: a control group (40% hepatectomy, untreated), a 250 group (40% hepatectomy, 250 mg/kg of KRG, PO), and a 500 group (40% hepatectomy, 500 mg/kg of KRG, PO). The liver regeneration, histologic findings, CBC (WBC, RBC, PCV, and PLT), and liver function tests (AST, ALT, GGT, ALP, LDH, and T-bil) were examined during experiment. The liver regeneration rates were higher in treated groups than in the control group. But, there were no significant differences. All hematological values were within normal ranges except leukocyte counts for 3 days postoperatively. The levels of AST and ALT in the treated groups were significantly decreased compared to that in the control group (p<0.05). The numbers of degenerative cells and area of connective tissue were significantly decreased in the liver of the dog with KRG administration (p<0.01). On the basis of these results, we could conclude that KRG accelerate the liver regeneration and ameliorate the liver injury after hepatectomy in dogs.