Virus-associated Liver Cirrhosis Research Articles

Late‐onset venous outflow obstruction treated by placement of a Foley balloon catheter in living donor liver transplantation using a left lobe

A 60-yr-old man having hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma underwent living donor liver transplantation using a left liver graft. On post-operative day 20, the patient developed a large amount of ascites and hypovolemic shock because of decreased venous return. Emergency laparotomy revealed that fixation of the round ligament to the abdominal wall was loose, and free movement of the graft into the right subphrenic space had caused twisting the hepatic vein. After upward traction of the round ligament, two Foley balloon catheters were inserted into the right subphrenic space to maintain the graft in the midline portion. The catheters with the balloons were removed on day 30 after re-operation. This method is easy, simple and inexpensive for the treatment of hepatic venous outflow block after partial liver transplantation.

Resolution of Preoperative Portal Vein Thrombosis After Administration of Antithrombin III in Living Donor Liver Transplantation: Case Report

A 59-year-old man with hepatitis C virus–associated liver cirrhosis was transferred to our hospital to undergo living donor liver transplantation. Coagulation was impaired (prothrombin time [International Normalized Ratio], 3.27), and antithrombin III (AT-III) activity was 23% (normal, 87%–115%). Contrast-enhanced computed tomography scans revealed portal vein thrombosis (PVT) from the junction between the splenic and superior mesenteric vein to the porta hepatica; the portal vein was completely obstructed (PVT). To prevent further development of PVT, 1500 U of AT-III was administered for 3 days, elevating the AT-III activity to 50%. A contrast-enhanced computed tomography scan obtained 9 days after AT-III administration showed resolution of PVT. Living donor liver transplantation was safely performed without portal vein grafting. Thus, a low AT-III concentration may have an important role in the pathogenesis of PVT in patients with cirrhosis.

Occurrence of hepatocellular carcinoma after hepatoblastoma resection in an adult with hepatitis C virus

Hepatoblastoma is a rare malignancy in adults. It is often diagnosed after the appearance of symptoms, therefore, the tumor size tends to be larger. In patients with no indication for a hepatic resection, the prognosis of adult hepatoblastoma is quite poor. A 54-year-old man with hepatitis C virus-associated liver cirrhosis was initially treated with a hepatic resection for a hepatic tumor, 3 cm in diameter. The tumor consisted of osteoid-like and cartilaginous foci, myxomatous stroma, and poorly differentiated hepatocellular carcinomatous cells and was diagnosed as a mixed epithelial and mesenchymal hepatoblastoma. Two years after the first operation, multicentric hepatocellular carcinomas developed in the remnant liver and were successfully treated with a secondary hepatic resection combined with radio-frequency ablation. The patient is now alive with no recurrence at 5 years after the initial hepatectomy. To the best of our knowledge, the primary hepatoblastoma was the smallest such tumor reported and this is the first report of a metachronous hepatoblastoma and hepatocellular carcinoma in an adult hepatitis patient.

Progressive visceral leishmaniasis misdiagnosed as cirrhosis of the liver: a case report

IntroductionVisceral leishmaniasis is a potentially life-threatening infectious disease which is caused by parasites of the genus Leishmania and characterized in most cases by the presence of fever as well as signs and symptoms similar to those found in liver cirrhosis.Case presentationIn this case report we describe the history of a 50-year-old Caucasian man incorrectly diagnosed as having hepatitis C virus-associated liver cirrhosis, with a massive weight loss of around 100 kg during the previous 2 years. However, suspecting a lymphoproliferative disorder, we were able to make a correct diagnosis of visceral leishmaniasis by bone marrow examination. After a course of therapy with Liposomal Amphotericin-B the patient recovered and now, 20 months post-treatment, he is well and has regained a good part of the lost weight.ConclusionsThis case taught us that patients with massive splenomegaly, even with a diagnosis of liver cirrhosis, should be investigated for infectious or lymphoproliferative diseases.

Frequent epigenetic inactivation of SFRP genes in hepatocellular carcinoma

Activation of the Wnt signaling pathway is frequently observed in hepatocellular carcinoma (HCC), though mutation of three of its components, CTNNB1, AXIN1, and AXIN2, is observed substantially less often. We examined the relationship between Wnt signaling and epigenetic alteration of secreted frizzled-related protein (SFRP) genes in HCC. We frequently detected the active form of beta-catenin and accumulation of nuclear beta-catenin in liver cancer cell lines. We detected methylation of SFRP family genes in liver cancer cell lines (SFRP1, 9/12, 75%; SFRP2, 7/12, 58%; SFRP4, 3/12, 25%; SFRP5, 7/12, 58%) and primary HCCs (SFRP1, 9/19, 47%; SFRP2, 12/19, 63%; SFRP5, 8/19, 42%), though methylation of SFRP4 was not found in primary HCCs. SFRP methylation also was detected in hepatitis B or C virus-associated chronic hepatitis (SFRP1, 6/37, 16%; SFRP2, 14/37, 38%; SFRP5, 5/37, 14%) and liver cirrhosis (SFRP1, 10/28, 36%; SFRP2, 9/28, 32%; SFRP5, 3/28, 11%), suggesting that methylation of these genes is an early event in liver carcinogenesis. Ectopic expression of SFRPs downregulated T-cell factor/lymphocyte enhancer factor (TCF/LEF) transcriptional activity in liver cancer cells, while overexpression of a beta-catenin mutant and depletion of SFRP1 using siRNA synergistically upregulated TCF/LEF transcriptional activity. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in HCC, and suggest that their loss of function contributes to activation of Wnt signaling during hepatocarcinogenesis.

Comments on cirrhosis reversal

In this issue of the Journal, Bortolotti et al. [ [1] Bortolotti F. Guido M. Cadrobbi P. Crivellaro C. Bartolacci S. Rugge M. et al. Spontaneous regression of hepatitis B virus associated liver cirrhosis developed in childhood. Dig Liver Dis. 2005; 37: 964-967 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ] report on the complete reversal of cirrhosis in two young adult patients diagnosed as suffering from hepatitis B virus (HBV) induced cirrhosis in childhood.

SEN virus infection influences the pathological findings in liver but does not affect the incidence of hepatocellular carcinoma in patients with chronic hepatitis C and liver cirrhosis

This investigation compared the histological findings in the livers of chronic hepatitis C patients who were or were not co-infected with SEN virus (SEN-V) to determine the histological and clinical characteristics of SEN-V infection in Japan. Three hundred and ninety-two patients with hepatitis C virus-associated chronic hepatitis (CH) or liver cirrhosis (LC) were included in the study. Serum samples were tested for the presence of SEN-V DNA by nested polymerase chain reaction. The liver biopsy specimen of each patient was examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal, and portal areas; F stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; damage to the bile ducts; steatosis and irregular regeneration of hepatocytes (IR). Of the 473 patients, 194 (41.0%) were positive for SEN-V DNA. The rate of progression of F stage correlated with SEN-V DNA positivity. The blood biochemical parameters did not differ significantly between the SEN-V DNA-positive and -negative patients. The histological features of the livers of SEN-V DNA-positive patients included more severe parenchymal inflammatory cell infiltration and more IR. In particular, among those at the F2, F3 and F4 stages, the degree of IR of the SEN-V DNA-positive patients was significantly greater than that of the SEN-V DNA-negative patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence and survival rate did not differ between the SEN-V DNA-positive and-negative patients. SEN-V co-infection may influence the histopathological features of the livers of patients with type C CH and LC but does not affect the outcome of patients with type C chronic liver disease.

Ursodiol Use Is Possibly Associated with Lower Incidence of Hepatocellular Carcinoma in Hepatitis C Virus–Associated Liver Cirrhosis

Abstract In a previous study of patients with hepatitis C virus (HCV)–associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to <80 IU. Iftheaverage ALT level did not remain <80 IU after treatment with one agent, multiagent therapy was initiated. The patients were followed up for >5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean ± SD dosage of UDCA administered in group A was 473.7 ± 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 ± 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.

Sustained Low Alanine Aminotransferase Levels Can Predict the Survival for 10 Years without Hepatocellular Carcinoma Development in Patients with Hepatitis C Virus-Associated Liver Cirrhosis of Child Stage A

An analysis was performed of the patients with hepatitis C virus-associated liver cirrhosis (HCV-LC) who never developed hepatocellular carcinoma (HCC) for 10 years after the histological diagnosis of LC. Seventy-four consecutive HCV-LC patients of Child stage A were observed for >10 years prospectively for the development of HCC with frequent ultrasonography and magnetic resonance imaging or computed tomography. Of the 63 patients who fulfilled the study, 48 patients were treated and 15 were nontreated because of their stable state. They were subdivided into three groups according to their serum alanine aminotransferase (ALT) levels: the high ALT group comprised of 23 patients whose annual average serum ALT level was persistently high (≧80 IU); the low ALT group comprised of 28 patients whose annual average serum ALT level was persistently low (<80 IU), and the unclassified ALT group comprised of 12 patients. In the low ALT group, as high as 71.4% of patients had never developed HCC for 10 years, in contrast to only 17.4% in the high ALT group (p < 0.001). In the 30 patients who never developed HCC for 10 years, 20 patients belonged to the low ALT group, in contrast to only 4 belonging to the high ALT group. Sustained low ALT levels were important to survive for 10 years without developing HCC in the HCV-LC patients of Child stage A.

Serum alanine aminotransferase levels and survival after hepatectomy in patients with hepatocellular carcinoma and hepatitis C virus‐associated liver cirrhosis

We examined whether sustained alleviation of inflammation as monitored by serum alanine aminotransferase (ALT) levels was associated with longer survival in hepatectomized hepatocellular carcinoma (HCC) patients with hepatitis C virus-associated liver cirrhosis (HCV-LC). Thirty-four hepatectomized patients with HCV-LC and HCC as a single nodule, and for whom more than 5 years had elapsed after the hepatectomy, were studied. They had no histologic evidence of portal or hepatic vein invasion. They were subdivided into two groups according to their serum ALT levels in the 2 years after hepatectomy: the low ALT group comprised 13 patients whose serum ALT levels showed a sustained low level below 80 IU, and the high ALT group comprised 21 patients whose serum ALT levels showed several peaks or plateaus above 80 IU. The patients had been followed-up prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for recurrence for > 5 years. The survival period, non-recurrence interval and number of recurrences were observed. Recurrences were treated with transcatheter chemoembolization in all cases. The cumulative survival rate in the low ALT group was significantly better than that in the high ALT group (P < 0.05). The 5-year survival in the low ALT group was as high as 92.3% (12 of 13) compared with 33.3% (7 of 21) in the high ALT group (P < 0.05). The cumulative non-recurrence rate in the low ALT group was also significantly better than that in the high ALT group (P < 0.01). The survival period correlated well with the interval until the first recurrence (r = 0.545, P = 0.006). There was a tendency for the number of recurrences in the low ALT group (1.5 +/- 0.4, mean +/- SE) to be fewer than that in the high ALT group (2.2 +/- 0.4), although this was not significant. Sustained alleviation of inflammation, as indicated by low ALT levels, provides a survival advantage mainly due to the longer non-recurrence interval, and possibly because of fewer recurrences, in hepatectomized HCC patients with HCV-LC.

Synchronous Hepatocellular Carcinoma and Cholangiocarcinoma Arising in Two Different Dysplastic Nodules

We present the first reported case of explant cirrhotic liver that had synchronous cholangiocarcinoma and hepatocellular carcinoma arising in two different high-grade dysplastic nodules. The patient was a 55-year-old woman who had hepatitis B virus-associated liver cirrhosis for 3 years. The moderately differentiated cholangiocarcinoma occurred in high-grade dysplastic nodule with a 1.7-fold cell density compared with that of cirrhotic nodule. The hepatocellular carcinoma arose in a nodule-in-nodule pattern within a peripherally low-grade and centrally high-grade dysplastic nodule and had a 2.7-fold cell density compared with that of cirrhotic nodule. By immunohistochemistry, the tumor cells of the cholangiocarcinoma as well as bile ductular cells in dysplastic nodule were diffusely positive for cytokeratin 7, whereas hepatocellular carcinoma cells and dysplastic hepatocytes were negative for cytokeratin 7. The c-kit-positive hepatic progenitor cells were singly scattered between hepatocytes, and their number was highest in cirrhotic nodule and decreased in dysplastic nodule, whereas they were absent in cholangiocarcinoma and hepatocellular carcinoma arising in dysplastic nodules. Proliferation indices were progressively increased in cirrhotic nodule, dysplastic nodule, and cholangiocarcinoma or hepatocellular carcinoma, sequentially. These observations indicate that cholangiocarcinoma as well as hepatocellular carcinoma can develop in dysplastic nodule and that hepatic progenitor cells might play a role in the early stage of cholangiocarcinogenesis and hepatocarcinogenesis.

Treatment of virus-associated liver cirrhosis with tauroursodeoxycholic acid: Evaluation of cytolysis and cholestasis indexes and selected immunologic variables

Thirty patients with compensated virus-associated (hepatitis B and/or hepatitis C virus) liver cirrhosis were treated with tauroursodeoxy-cholic acid (TUDCA) at the dose of 250 mg twice daily. After 6 months of treatment, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase levels were decreased by 56%, 61%, and 69%, respectively ( P < 0.001). Most interesting, however, was the 13% reduction in gamma globulin levels (0.001 < P < 0.01). These results point to an immunomodulating action of TUDCA which, in conjunction with its ability to reduce the value of the cytolysis and cholestasis indexes, provides good evidence for a therapeutic role of this agent in the management of virus-associated liver cirrhosis.