Virus-associated Liver Cirrhosis Research Articles

Etiological changes of liver cirrhosis and hepatocellular carcinoma-complicated liver cirrhosis in Japan: Updated nationwide survey from 2018 to 2021.

A nationwide survey in 2018 showed decreasing involvement of viral hepatitis and increasing involvement of nonviral liver diseases in the etiology of livercirrhosis (LC) in Japan. An updated nationwide survey was undertaken in 2023. Cases of LC diagnosed between 2018 and 2021 were collected from 75 institutions, and the etiologies of LC were investigated. In addition, the data obtained were compared with the results of previous studies. Among the 15517 cases, alcohol-related liver disease (ALD)-associated LC was the most frequent cause (n=5,487, 35.4%). Hepatitis C virus-associated LC, nonalcoholic steatohepatitis (NASH)-associated LC, and hepatitis B virus-associated LC were ranked as second, third, and fourth, respectively. In comparison to the previous survey, the ratios of viral hepatitis-associated LC decreased (HBV: from 11.5% to 8.1%; HCV: from 48.2% to 23.4%), while the ratios of ALD-associated LC and NASH-associated LC increased (from 19.9% to 35.4% and from 6.3% to 14.6%, respectively). Regarding cases of LC with hepatocellular carcinoma (n=5906), HCV-associated LC (1986 cases, 33.6%) was the most frequent cause. Alcohol-related liver disease-associated LC, NASH-associated LC, and HBV-associated LC were the second-, third-, and fourth-ranked causes, respectively. In comparison to the previous survey, as the cause of hepatocellular carcinoma-complicated LC, HCV-associated LC decreased from 60.3% to 33.6%, while the ratios of ALD-associated LC and NASH-associated LC increased from 14.2% to 28.6% and from 4.2% to 14.0%, respectively. The major causes of LC in Japan are suggested to have been shifting from viral hepatitis to nonviral chronic liver diseases.

Changes in intestinal microbiota of HBV-associated liver cirrhosis with/without hepatic encephalopathy.

The compositional balance of intestinal microbiota plays an important role in maintaining homeostasis. This study aimed to investigate the intestinal flora of hepatitis B virus-associated liver cirrhosis (HBV-LC) with or without hepatic encephalopathy (HE) and how it relates to the disease. A total of 20 patients with HBV-LC were enrolled in this study, along with 10 healthy adults. The participants were divided into HE group, non-HE group, and control group. Fecal samples were collected under the condition of patients’ daily diet, and the 16S rRNA test was performed for each fecal sample. The relative abundance of Bacteroidia, Streptococcaceae, Streptococcus, Veillonella, Bacteroidales, Lactobacillales, Pasteurellales, and Veillonella parvula increased in the HBV-LC group. Meanwhile, the relative weights of Pasteurellales, Pasteurellaceae, Haemophilus, and Selenomonas significantly increased in the HE group. Furthermore, in the non-HE group, the relative abundance of Veillonella increased. Intestinal microbiota was significantly different from controls with respect to a lack of potentially beneficial autochthonous bacteria and overgrowth of potentially pathogenic genera in patients with HBV-LC. Moreover, there was a greater change in the relative abundance of intestinal flora when complicated with HE.

ДИСПАНСЕРИЗАЦИЯ ПАЦИЕНТОВ С ВИРУС-АССОЦИИРОВАННЫМИ ЦИРРОЗАМИ ПЕЧЕНИ В ПЕРИОД ПАНДЕМИИ COVID-19

Background. Liver cirrhosis (LC) is the end stage of a number of chronic liver diseases, at least half of the cases being due to chronic viral hepatitis B and C. Higher morbidity and mortality from COVID-19 have been proven in patients with cirrhosis. Poor access to routine follow-up monitoring in many countries during the Covid-19 pandemic period has negatively impacted LC (including virus-associated one) prognosis. Objective. To evaluate the effectiveness of routine follow-up monitoring of patients with virus-associated LC in Gomel during the COVID-19 pandemic period. Material and methods. 127 medical records of outpatients with virus-associated LC registered at the Gomel Central City Clinical Polyclinic over 2020-2021 were analyzed. Markers of hepatitis C virus infection were detected in 92.1%, those of hepatitis B virus infection - in 7.9% of the patients. Results. 38.6% of the patients underwent a complete follow-up examination, 48.8% had an incomplete one, 12.6% did not attend it. Those having skipped the examination were more likely to consult a doctor because of physical complaints (χ2=9.77, p=0.002), 32.3% of them being hospitalized. The total number of examined patients with class A cirrhosis (according to the Child-Pugh score) accounted for 26%, those with class B - to 44%, with class C – to 49%. Conclusions. It is necessary to provide LC patients with comprehensive follow-up monitoring even during the COVID-19 pandemic period.

Twenty-year longitudinal follow-up after liver transplantation: a single-center experience with 251 consecutive patients.

BackgroundThe outcomes of liver transplantation (LT) have improved, but actual 20-year survival data have rarely been presented.MethodsLongitudinal follow-up data of 20-year LT survivors were retrospectively analyzed. The LT database of our institution was searched to identify patients who underwent primary LT from January 2000 to December 2001. The study cohort of 251 patients was divided into three groups 207 adults who underwent living donor LT (LDLT), 22 adults who underwent deceased donor LT (DDLT), and 22 pediatric patients who underwent LT.ResultsHepatitis B virus–associated liver cirrhosis and biliary atresia were the most common indications for adult and pediatric LT, respectively. Seven patients required retransplantation, including six who underwent DDLT and one who underwent LDLT. Twenty-two patients died within 3 months after LT and 69 died at later intervals. The overall survival rates at 1, 3, 5, 10, and 20 years were 86.4%, 79.6%, 77.7%, 72.8%, and 62.6%, respectively, in the adult LDLT group; 86.4%, 72.7%, 72.7%, 72.7%, and 68.2%, respectively, in the adult DDLT group; and 86.4%, 86.4%, 81.8%, 81.8%, and 77.3%, respectively, in the pediatric LT group (P=0.545). Common immunosuppressive regimens at 20 years included tacrolimus monotherapy, tacrolimus–mycophenolate dual therapy, cyclosporine monotherapy, and mycophenolate monotherapy.ConclusionsThe present study is the first report of actual 20-year survival data from a Korean high-volume LT center. The graft and patient survival outcomes reflected the early experiences of LT in our institution, with long-term outcomes being similar regardless of graft type and patient age.

Portal vein wedge resection and patch venoplasty using autologous and homologous vein grafts during surgery for hepatobiliary malignancies.

Obtaining tumor-free resection margins is one of the most important factors for achieving favorable prognosis of patients undergoing resection for hepatobiliary malignancies. In this study, we present our experience of portal vein (PV) wedge resection and patch venoplasty using autologous or homologous vessel grafts for resecting perihilar cholangiocarcinoma, hepatocellular carcinoma, and distal bile duct cancer. Case 1 was 68-year-old male patient with type IV perihilar cholangiocarcinoma who underwent central bisectionectomy with caudate lobectomy and bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 14 months after surgery. Case 2 was 77-year-old male patient with type IIIA perihilar cholangiocarcinoma who underwent left medial sectionectomy with caudate lobectomy, bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 17 months after surgery. Case 3 was 54-year-old male patient with hepatitis B virus-associated liver cirrhosis and hepatocellular carcinoma with PV tumor thrombus who underwent left hepatectomy. The PV wall defect was repaired with an autologous greater saphenous vein patch. This patient survived 11 months after surgery. Case 4 was 65-year-old female patient with distal bile duct cancer who underwent pylorus-preserving pancreaticoduodenectomy, and main PV wedge resection and patch venoplasty with a cryopreserved iliac artery allograft patch. This patient survived 21 months after surgery. In conclusion, PV wedge resection and patch venoplasty can be used to facilitate complete tumor resection in patients undergoing various extents of surgical resection for hepatobiliary malignancies.

ABO-Incompatible Living Donor Liver Transplantation With a Simplified Desensitization and Immunosuppression Protocol: A Single-Center Retrospective Study.

New desensitization strategies have made ABO-incompatible living donor liver transplant an attractive option for patients with end-stage liver disease. We aimed to report our experience with 20 consecutive patients who underwent ABO-incompatible living donor liver transplant using a simplified desensitization and immunosuppression regimen. We retrospectively analyzed 20 ABO-incompatible living donor liver transplant cases (August 2015 to July 2019). The ABO-incompatible living donor liver transplant protocol involved rituximab administration (375 mg/m2 body surface area) at 2 to 3 weeks before transplant, subsequent plasma exchanges (target isoagglutinin titer of ≤1:8), basiliximab administration (20 mg on day of surgery and on postoperative day 4), and intravenous immunoglobulin administration (2 g/day from day of surgery to postoperative day 7). No graft local infusion therapy or splenectomy was performed. The living donor liver transplant procedure involved a modified rightlobe graft(18 patients), a right posterior segment graft (1 patient), or a left lobe (1 patient). The most common reason for liver transplant was hepatitis B virus-associated liver cirrhosis (16 patients); 14 patients had hepatocellular carcinoma. The mean age was 55.4 ± 6.3 years, mean Model End-stage LiverDisease score was 14.7 ± 7.7, and mean graft-to-recipient weight ratio was 1.07 ± 0.2%. The median initial anti-ABO antibody titers were 1:16 forimmunoglobulin M (range, 1:2 to 1:256) and 1:48 for immunoglobulin G (range, 1:4 to 1:>2048). The median number of plasma exchanges was 2 (range, 0-12). No patients had biopsy-confirmed antibody-mediated rejection. No bacterial or fungal infections were observed. Biliary anastomotic stricture was observed in 9 patients. This ABO-incompatible living donor liver transplant protocol with rituximab, plasma exchange, low-dose intravenous immunoglobulin, and immunosuppression (equivalent to ABO-compatible living donor liver transplant) could be a safe and effective way to overcome antibody-mediated rejection and other complications.

Portal vein wedge resection and patch venoplasty using autologous and homologous vein grafts during surgery for hepatobiliary malignancies

Obtainment of tumor-free resection margins is one of the most important factors for favorable prognosis of patients undergoing resection for hepatobiliary malignancies. In this study, we present our experience of portal vein (PV) wedge resection and patch venoplasty using autologous or homologous vessel grafts used in resection for perihilar cholangiocarcinoma, hepatocellular carcinoma and distal bile duct cancer. Case 1: A 68-year-old male patient with type IV perihilar cholangiocarcinoma underwent central bisectionectomy with caudate lobectomy and bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 14 months after surgery. Case 2: A 77-year-old male patient with type IIIA perihilar cholangiocarcinoma underwent left medial sectionectomy with caudate lobectomy and bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 16 months after surgery. Case 3: A 54-year-old male patient with hepatitis B virus-associated liver cirrhosis and hepatocellular carcinoma with PV tumor thrombus underwent left hepatectomy. The PV wall defect was repaired with an autologous greater saphenous vein patch. This patient survived 11 months after surgery. Case 4: A 65-year-old female patient with distal bile duct cancer underwent pylorus-preserving pancreaticoduodenectomy and main PV wedge resection and patch venoplasty with a cryopreserved iliac artery allograft patch. This patient survived 21 months after surgery. In conclusion, PV wedge resection and patch venoplasty provide a useful option to facilitate complete tumor resection in patients undergoing various extents of surgical resection for hepatobiliary malignancies.

Institutional standard framework and experience of living donor liver transplantation for overseas non-Korean patients at Asan Medical Center.

BackgroundLiver transplantation (LT) for foreign patients is a sensitive issue because of possibility of transplant tourism and difficulty in posttransplant follow-up. This study describes the institutional standard framework and experience of living donor LT (LDLT) for overseas non-Korean patients in a Korean high-volume LDLT center.MethodsThe framework and experience of LDLT for 105 non-Korean patients from 2010 to 2019 were retrospectively investigated.ResultsOnly 3.1% of patients who underwent LDLT were overseas non-Koreans; of these, 83.8% were from the United Arab Emirates and Mongolia. Selection criteria for recipients and donors were the same as for Korean citizens. Of the 105 recipients, 95 (90.5%) were adults. The most common reasons for transplantation were hepatitis B or C virus-associated liver cirrhosis. Of the 95 adults, 78 (82.1%) received right liver grafts, and 16 (16.8%) received dual grafts. The most frequent donors for adult recipients were sons and daughters, whereas the most frequent donors for pediatric recipients were parents. Of the 10 pediatric patients, eight were from the United Arab Emirates; their common primary diseases were biliary atresia, acute liver failure, hepatoblastoma, and genetic metabolic diseases. The 1-, 3-, and 5-year posttransplant overall patient survival rates in all patients were 96.2%, 92.4%, and 92.4%, respectively. The 5-year overall patient survival rates were 91.8% in adult recipients and 100% in pediatric recipients (P=0.47).ConclusionsLDLT at Korean high-volume LT centers including our institution is safe and effective for non-Korean patients with end-stage liver disease seeking alternatives not available in their own countries.

Laparoscopic Caudate Hepatectomy for a Recurrent Tumor Behind the Vena Cava After Multiple Open Hepatectomies (With Video)

BackgroundCaudate hepatectomy is one of the most difficult procedures among liver surgeries because of its deep location and proximity to the inferior vena cava (IVC), particularly in patients with a history of open hepatectomies. 1,2,3 MethodsA 77-year-old man underwent three open hepatectomies for hepatocellular carcinoma (HCC), including a sub-segmentectomy of S6 and partial hepatectomies of S7 and S8 during follow-up for hepatitis C virus-associated liver cirrhosis. However, HCC recurred in the caudate lobe behind the IVC (Supplemental video file 1). We lysed the severe adhesion in the upper abdomen, including the liver hilum, and exposed the ventral surface of the caudate lobe. We then used a Nathanson retractor to ventrally retract the severely enlarged left lobe. To counteract the severe adhesion that prevented us from controlling the hepatoduodenal ligament, we used the laparoscopic Satinsky vascular clamp for hilar inflow control. Using the anterior approach, we performed parenchymal resection from the distal side of the caudate lobe. Then, we gradually exposed the ventral surface of the IVC and separated the caudate lobe from the IVC. The IVC ligament was divided, and the caudate lobe, including the tumor behind the IVC, was removed. ResultsThe operation time was 229 min with a total hepatic hilar clamping time of 69 min and blood loss of 10 mL. The patient was discharged on postoperative day 8 without any complications. Pathological examination revealed moderately differentiated HCC (pT1N0M0) with a negative surgical margin. ConclusionsThe laparoscopic approach using specialized laparoscopic instruments is feasible for a tumor located in the caudate lobe behind the IVC, even in patients with a history of multiple open hepatectomies.

Effectiveness of entecavir in preventing hepatocellular carcinoma development is genotype-dependent in hepatitis B virus-associated liver cirrhosis.

BACKGROUNDThe oral nucleos(t)ide analogue, entecavir (ETV) was demonstrated to reduce the rate of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis. However, the reduction of HCC differs in various regions of the world. AIMTo investigate the reduction of HCC development due to ETV therapy by meta-analysis.METHODSWe surveyed the differences in HCC development following ETV treatment based on published articles using PubMed (2004-2019).RESULTSThe regions with the most marked reduction in HCC development due to ETV therapy were Spain (1.0%/year) and Canada (Southern part, 1.3%/year), and the most ineffective areas were South Korea (3.6%-3.8%/year), China (3.3%/year), Taiwan (2.4%-3.1%/year), and Hong Kong (2.8%/year). Following ETV administration, the incidence of HCC in genotype D regions (1.89% ± 0.28%/year, mean ± SE) was significantly lower than that in genotype C regions (2.91% ± 0.24%/year, P < 0.01). With regard to the initial HBV-DNA level, in genotype C patients (average: 5.61 Log10IU/mL) this was almost the same as that in genotype D patients (average: 5.46 Log10IU/mL). Moreover, there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment.CONCLUSIONThe effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.

Standard framework and experience of living donor liver transplantation for overseas non-Korean patients at Asan Medical Center

Background: Liver transplantation (LT) for foreign patients is a sensitive issue because of the possibility of transplant tourism and the difficulty in follow-up. This study describes the standard framework and experience of living donor LT (LDLT) for over seas non-Korean patients in a Korean high-volume LDLT center. Methods: The framework and experience of LDLT for 105 non-Korean patients from 2010 to 2019 were retrospectively investigated. Results: Only 3.1% of patients who underwent LDLT were overseas non-Koreans; of these, 83.8% were from the United Arab Emir ates and Mongolia. Selection criteria for recipients and donors were the same as for Korean citizens. Of the 105 recipients, 95 (90.5%) were adults. The most common reasons for transplantation were hepatitis B or C virus-associated liver cirrhosis. Of the 95 adults, 78 (82.1%) received right liver grafts, and 16 (16.8%) received dual grafts. The most frequent donors for adult recipients were sons and daughters, whereas the most frequent donors for pediatric recipients were parents. Of the 10 pediatric patients, eight were from the United Arab Emirates; their common primary diseases were biliary atresia, acute liver failure, hepatoblasto ma, and genetic metabolic diseases. The 1-, 3-, and 5-year posttransplant overall patient survival rates in all patients were 96.2%, 92.4%, and 92.4%, respectively. The 5-year overall patient survival rates were 91.8% in adult recipients and 100% in pediatric re cipients (P=0.47). Conclusions: LDLT at Korean high-volume LT centers including our institution is safe and effective for non-Korean patients with end-stage liver disease seeking alternatives not available in their own countries.

A 2-year retrospective study of viral and host-associated risk factors in Pakistani hepatocellular carcinoma patients.

Persistent chronic hepatitis C (CHC) infection is associated strongly with serious complications such as hepatitis C virus-associated liver cirrhosis (HCV-LC) and hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC). The aim of this study was to assess the distribution of hepatitis C virus (HCV) genotypes among HCV-positive patients and examine the potential associations between viral and host-associated factors with the risk of developing HCV-HCC. HCV-positive patients (n = 300) were enrolled and divided into three groups: CHC (n = 171), HCV-LC (n = 51), and HCV-HCC (n = 78). HCV genotype 3a showed the highest prevalence among HCV-positive individuals (66% of patients), followed by genotype 1a (15% of patients). The proportion of individuals infected with mixed HCV genotypes was higher among HCV-HCC patients. Interestingly, there were a significantly higher proportion of women (54/78; 69.2%) among HCV-HCC patients compared with CHC patients (89/171 or 52%; χ = 6.47; P=1 × 10). Women with HCV had two-fold higher odds of developing HCV-HCC (odds ratio = 2.07, 95% confidence interval: 1.18-3.71). In comparison with CHC patients, significantly more HCV-HCC patients were 50 years of age or older (59/78 or 75.6% of HCV-HCC patients and 61/171 or 35.7% of CHC patients; χ = 34.27; P < 0.0001), suggesting that HCV-positive patients aged 50 years or older had an ~five-fold higher risk of developing HCV-HCC (odds ratio = 5.6, 95% confidence interval: 3.02-10.01). In summary, HCV genotype 3a had the highest prevalence in the studied HCV-positive population, and women and older patients were at a higher risk of developing HCV-LC and HCV-HCC following CHC infections.

Expression and clinical significance of serum miR-125b-5p in patients with hepatitis B related liver diseases

Objective To investigate the expression and clinical significance of serum miR-125b-5p in patients with hepatitis B related liver diseases. Methods 159 cases of hepatitis B related liver disease (case group) and 64 cases of health examinees (control group) in our hospital were selected. The case group was further divided into three subgroups according to the disease type, namely, chronic hepatitis B (CHB) group (n=40), hepatitis B virus associated liver cirrhosis (HBV-LC) group (n=65) and HBV associated hepatocellular carcinoma (HBV-HCC) group (n=54). Then the levels of miR-125b-5p, albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), HBV-DNA, total bilirubin (TBIL), total cholesterol (TC), alpha fetoprotein (AFP), triglyceride (TG) and prothrombin time (PT) were measured in each group. Results The levels of ALT, AST, HBV-DNA, TBIL, PT, AFP, TC and TG in the case group were higher than those in the control group (P 0.05); The expression level of serum miR-125b-5p was positively correlated with the pathological grade, tumor node metastasis (TNM) stage, lymphatic vascular infiltration, lymph node metastasis and recurrence (P 0.01), which were all smaller than miR-125b-5p combined with AFP (χ2=12.657, 13.052, P<0.01). Conclusions Serum miR-125b-5p is elevated in hepatitis B related liver diseases, such as CHB, HBV-LC, HBV-HCC, and is associated with disease progression; High levels of miR-125b-5p, HBV-DNA, and AFP are risk factors for adverse prognosis outcomes in patients with hepatitis B-related liver disease; The sensitivity and specificity of combined detection of miR-125b-5p and AFP in the diagnosis of HBV-HCC are relatively high, so the combined detection of the two indicators can be widely applied in clinical practice. Key words: MicroRNAs; Hepatitis B, chronic; Liver cirrhosis; Liver neoplasms

Living donor liver transplantation using left trisection graft with caudate lobe

Summary Background: Due to small remnant volume or anatomical variation, a right liver graft may be precluded in adult living donor liver transplantation (LDLT). Right posterior section, right anterior section graft, or dual donor grafts have been proposed as alternative grafts of right and left liver grafts. Here, we report a case of LDLT using left trisection graft with caudate lobe. Methods: The recipient was a 55-years old female with hepatitis B virus associated liver cirrhosis. The donor had a type III portal vein (PV) anomaly. Donor’s right hepatic artery (HA) was extrahepatically divided into right anterior and posterior HA and left HA was originated from left gastric artery. Preoperative cholangiography showed trifurcation of bile duct. Left trisection graft with caudate lobe was measured 620 gram that was 0.88% of graft to recipient weight ratio. Results: With J shaped incision, hilar dissection of the donor was performed to isolate the left and right anterior and posterior branches of the HA and PV. Then, the liver was transected in a plane that was demarcated on the liver surface, temporarily occluding the right posterior branch of the HA and PV. We encountered 1 PV opening, 1 hepatic vein opening, 3 HAs, and 3 bile duct openings in the left trisection graft with caudate lobe that were safely anastomosed in the recipient. There was no complication in donor and recipient side after operation. Conclusions: Although it was a complex operation, left trisection graft with caudate lobe might be a feasible option for special situations involving donors unsuitable for right liver donation.

Clinical and laboratory outcomes of stem cell transplantation in patients with decompensated liver cirrhosis: single-arm pilot trial

Introduction The high prevalence of hepatitis C virus-associated liver disease has led to increasing number of Egyptian patients having end-stage liver disease and requiring liver transplantation. Because of several limitations of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells (MSCs) for liver diseases. Aim The aim of this study was to assess the efficacy of using bone marrow-derived MSC on clinical manifestations, liver function, Child–Pugh score, and Model for End-stage Liver Disease score in patients with decompensated liver cirrhosis. Patients and methods This is a pilot single-arm prospective trial that included 13 patients with hepatitis C virus-associated liver cirrhosis who received transdifferentiated MSC via ultrasound-guided percutaneous portal vein infusion plus regular conventional treatment for patients with cirrhosis. Patients were followed up weekly for the first month and monthly for 6 months. Results There was significant improvement in some clinical manifestations, including frequency of attacks of hematemesis, ascites, and lower limb edema after MSC infusion compared with baseline data. Moreover significant increase was detected in mean serum albumin level as it began with 24.62 ± 3.93 and became 27.81 ± 4.14 (P = 0.009) after 6 months of follow-up. Moreover, the results showed improvement in Child–Pugh, but no changes were detected in Model for End-stage Liver Disease score after MSC infusion compared with baseline. Conclusion Our data show that transdifferentiated MSC injection may improve some clinical manifestations and some indices of liver function in patients with decompensated liver cirrhosis with successful tolerability.

Dynamic thiol-disulfide homeostasis is disturbed in hepatitis B virus-related chronic hepatitis and liver cirrhosis

Background/aim: Thiol-disulfide homeostasis is an important antioxidant defense mechanism. This study was conducted to investigate dynamic thiol-disulfide homeostasis in patients with hepatitis B virus-related chronic hepatitis and liver cirrhosis. Materials and methods: Seventy-one treatment-naive patients with chronic hepatitis B (CHB), 50 patients with hepatitis B virusassociated liver cirrhosis, and 45 healthy controls were included in the study. Serum total and native thiol concentrations and serum disulfide concentrations were measured using an automated method. Results: Mean serum total thiol concentrations in the control, CHB, and cirrhosis groups were 481.64 ± 37.87 µmol/L, 438.50 ± 71.35 µmol/L, and 358.07 ± 80.47 µmol/L, respectively (P < 0.001), and mean serum native thiol concentrations in the control, CHB, and cirrhosis groups were 452.92 ± 36.43 µmol/L, 400.16 ± 65.92 µmol/L, and 328.15 ± 74.91 µmol/L, respectively (P < 0.001). Mean serum disulfide concentrations in the control, CHB, and cirrhosis groups were 14.38 ± 3.38 µmol/L, 19.19 ± 6.16 µmol/L, and 14.98 ± 5.53 µmol/L, respectively (P < 0.001). There was a progressive decrease in both mean serum native and total thiol concentrations parallel to the liver fibrosis stage. Conclusion: : Thiol-disulfide homeostasis is disturbed in patients with hepatitis B virus-related chronic hepatitis and liver cirrhosis.

Hepatitis B virus X protein co-activates pregnane X receptor to induce the cytochrome P450 3A4 enzyme, a potential implication in hepatocarcinogenesis

Hepatitis B virus X protein is a key regulator of hepatocarcinogenesis. The pregnane X receptor is a xenobiotic nuclear receptor that plays a role in the regulation of drug-metabolizing enzymes including the cytochrome P450 3A4, an enzyme important for the bioactivation of the liver carcinogen aflatoxin B1. To identify novel host factor that interacts with hepatitis B virus X protein and the functional interaction between hepatitis B virus X protein and pregnane X receptor in hepatocarcinogenesis. Co-immunoprecipitation, glutathione S-transferase pull-down, and chromatin immunoprecipitation were utilized to assess the interaction between hepatitis B virus X protein and pregnane X receptor. The functional relevance of hepatitis B virus X protein-pregnane X receptor interaction was investigated in cell cultures and hepatocellular carcinoma samples. We observed that hepatitis B virus X protein and pregnane X receptor co-localize in hepatic cells. Pregnane X receptor interacted with hepatitis B virus X protein via the ligand-binding domain of pregnane X receptor. Functionally, hepatitis B virus X protein increased the transcriptional activity of pregnane X receptor. Pregnane X receptor was able to recruit hepatitis B virus X protein to the CYP3A4 gene promoter. In clinic samples, the expression of pregnane X receptor was high in hepatitis B virus-associated liver cirrhosis and stage I hepatocellular carcinoma, but low in state II and stage III hepatocellular carcinoma. We revealed a novel function of hepatitis B virus X protein in co-activating pregnane X receptor. The increased expression of pregnane X receptor and its target gene CYP3A4 are potential biomarkers for the early stage of hepatitis B virus-associated hepatocarcinogenesis.

Hepatitis C virus recurrence after liver transplantation in Hungary. Trends over the past 10 years

Management of hepatitis C virus recurrence is a challenge after liver transplantation. The aim of the authors was to analyse the outcome of liver transplantation performed in hepatitis C virus positive patients during the past ten years and to compare recent data with a previous report of the authors. The authors retrospectively evaluated the data (donors, recipients, perioperative characteristics, patient and graft survival, serum titer of hepatitis C virus RNA, histology) of 409 patients who underwent liver transplantation between 2003 and 2012. 156 patients were transplanted due to hepatitis C virus associated liver cirrhosis (38%). Worse outcome was observed in these patients in comparison to hepatitis C virus negative recipients. The cumulative patient survival rates at 1, 5, and 10 year were 80%, 61%, 51% in the hepatitis C virus positive group and 92%, 85%, 79% in the hepatitis C virus negative group, respectively (p<0.001). The cumulative graft survival rates at 1, 5 and 10 year were 79%, 59% and 50% in hepatitis C virus positive and 89%, 80% and 70% in hepatitis C virus negative patients (p<0.001). Hepatitis C virus recurrence was observed in the majority of the patients (132 patients, 85%), mainly within the first year (83%). The authors observed recurrence within 6 months in 71 patients (56%), and within 3 months in 26 patients (20%). The mean hepatitis C virus recurrence free survival was 243 days. Higher rate of de novo diabetes was detected in case of early recurrence. The cumulative patient survival rates at 1, 3, 5, 10 years were 98%, 89.5%, 81% and 65% when hepatitis C virus recurrence exceeded 3 months and 64%, 53%, 30.5% and 30.5% in patients with early recurrence (p<0.001). Poor outcome of liver transplantation in hepatitis C virus positive patients is still a challenge. Hepatitis C virus recurrence is observed earlier after liver transplantation in comparison with a previous report of the authors. De novo diabetes occurs more frequently in case of early recurrence. Despite an immediate start of antiviral treatment, early recurrence has a significant negative impact on the outcome of transplantation.

Gastric variceal bleeding caused by an intrahepatic arterioportal fistula that formed after liver biopsy: a case report and review of the literature

An intrahepatic arterioportal fistula is a rare cause of portal hypertension and variceal bleeding. We report on a patient with an intrahepatic arterioportal fistula following liver biopsy who was successfully treated by hepatectomy after unsuccessful arterial embolization. We also review the literature on symptomatic intrahepatic arterioportal fistulas after liver biopsy. A 48-year-old male with bleeding gastric varices and hepatitis B virus-associated liver cirrhosis was transferred to our hospital; this patient previously underwent percutaneous liver biopsies 3 and 6 years ago. Abdominal examination revealed a bruit over the liver, tenderness in the right upper quadrant, and splenomegaly. Ultrasonographic examination, computed tomography, and angiography confirmed an arterioportal fistula between the right hepatic artery and the right portal vein with portal hypertension. After admission, the patient suffered a large hematemesis and developed shock. He was treated with emergency transarterial embolization using microcoils. Since some collateral vessels bypassed the obstructive coils and still fed the fistulous area, embolization was performed again. Despite the second embolization, the collateral vessels could not be completely controlled. Radical treatment involving resection of his right hepatic lobe was performed. For nearly 6 years postoperatively, this patient has had no further episodes of variceal bleeding.

A Case of Bacteremia by Neisseria gonorrhoeae Coincident with Massive Hemorrhage of Esophageal Varices

A 42-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to the emergency room because of multiple seizures, a history of chills and myalgia over the previous 2 weeks, and 3 days of melena. He was febrile with a temperature of 38.0℃. There were no symptoms and signs related to the genitourinary system, skin, or joints. Three sets of blood cultures were obtained and oxidase-positive, gram-negative diplococci were detected after 25.9-26.9 hr of incubation in all aerobic vials. The organism was positive for catalase and oxidase, and was identified as Neisseria gonorrhoeae, using a Vitek Neisseria-Haemophilus Identification card (bioMérieux Vitek, Inc., USA). Further, 16S rRNA sequencing of this isolate revealed a 99.9% homology with the published sequence of N. gonorrhoeae strain NCTC 83785 (GenBank Accession No. NR_026079.1). Acute bleeding by variceal rupture seems to be a likely route of introduction of N. gonorrhoeae from the mucosa into the blood. To the best of our knowledge, this is the first case of gonococcal bacteremia in Korea.