A case of acute liver failure caused by Budd-Chiari syndrome salvaged by brain-dead donor liver transplantation.

A 24-year-old man was admitted to our hospital with abdominal distension. He was found to have acute liver failure and diagnosed with Budd-Chiari syndrome based on angiography and liver biopsy. Liver transplantation was deemed necessary when angiography showed extensive thrombotic occlusion of the hepatic veins and liver biopsy revealed submassive hepatic necrosis. The patient was found to have the JAK2V617F mutation, indicating a myeloproliferative neoplasm as the background disease. He developed hepatic encephalopathy but remained conscious on on-line hemodiafiltration. Brain-dead donor liver transplantation was performed on hospital day 30. Since then, the patient has remained well.

Two Cases of Gastric Varices with Left-sided Portal Hypertension Due to Essential Thrombocythemia Treated with Gastric Devascularization or Partial Splenic Embolization.

Left-sided portal hypertension (LSPH) is a condition of extrahepatic portal hypertension that often results in bleeding from isolated gastric varices (GVs). LSPH is sometimes caused by myeloproliferative diseases, such as essential thrombocythemia (ET). We herein report two cases of GVs with LSPH due to ET that were successfully controlled by gastric devascularization (GDS) or partial splenic embolization (PSE). Since each patient with LSPH due to ET has a different pathology, optimal treatment should be performed depending on the patient's condition, such as platelet counts, hemodynamics, or the prognosis. We believe that these cases will serve as a reference for future cases.

Prognostic study of acute-on-chronic liver failure patients: Usefulness of the fibrosis-4 index.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of liver function in cirrhotic patients. Since treatment of this condition is difficult, its prevention is of paramount importance. The predictors of ACLF are yet to be identified. To determine the prognosis of cirrhotic and ACLF patients, we conducted a retrospective study to analyze each parameter in ACLF patients. Cirrhotic patients with serum total-bilirubin level ≥5.0 mg/dL and prothrombin time (PT) value ≤40% after acute insults were diagnosed with ACLF, whereas patients who met one of the above criteria were diagnosed with extended type of ACLF (EX-ACLF). Overall, in this study, 18 ACLF and 16 EX-ACLF patients retrospectively investigated between 2008 and 2020, and each data was analyzed during and before acute insults. In the analysis during acute insults, renal and coagulation functions showed significant differences between the ACLF and EX-ACLF groups. Furthermore, the mortality rate in the ACLF group was higher than that in the EX-ACLF group. In the analysis before acute insults, aspartate aminotransferase (AST), Fibrosis-4 (FIB-4) index score, and AST to platelet ratio index (APRI) showed significant differences between the two groups. Among these, the FIB-4 index score correlated best with ACLF severity for identifying cirrhotic patients with poor prognosis. The FIB-4 index is the most useful predictor of ACLF severity. Careful management of cirrhotic patients with a high FIB-4 index score is considered beneficial to prevent ACLF occurrence.

Cumulative risk of developing a new symptom in patients with primary biliary cholangitis and its impact on prognosis.

Background and Aim: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

Two cases of portal-systemic encephalopathy caused by multiple portosystemic shunts successfully treated with percutaneous transhepatic obliteration.

BACKGROUND: Portal-systemic encephalopathy is a hepatic encephalopathy caused by portosystemic shunts and is a poor prognostic factor for cirrhotic patients. Percutaneous transhepatic obliteration is an option for controlling portal-systemic encephalopathy. We report two cases of portal-systemic encephalopathy that were successfully controlled with percutaneous transhepatic obliteration. CASE PRESENTATION: (Case 1) A 70-year-old woman experienced repeated portal-systemic encephalopathy due to a mesocaval shunt and a paraumbilical vein. She underwent percutaneous transhepatic obliteration with coils and 5% ethanolamine oleate-iopamidol. After treatment, portal-systemic encephalopathy became controllable. (Case 2) A 60-year-old man experienced repeated portal-systemic encephalopathy due to a left gastric vein shunt, a shunt from the posterior branch of the intrahepatic portal vein to the inferior phrenic vein, and a paraumbilical vein. He underwent percutaneous transhepatic obliteration of three portosystemic shunts with coils, 5% ethanolamine oleate-iopamidol, and N-butyl-2-cyanoacrylate. After treatment, the portal-systemic encephalopathy became controllable. CONCLUSIONS: Percutaneous transhepatic obliteration is particularly effective in cases involving multiple and complex portosystemic shunt pathways; however, percutaneous transhepatic obliteration is an invasive treatment, and its indications should be carefully considered. These cases will serve as a reference for successful treatment in the future cases.

Longitudinal increase in albumin-bilirubin score is associated with non-malignancy-related mortality and quality of life in patients with liver cirrhosis.

Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.

Unresectable primary hepatic adenosquamous carcinoma successfully treated with systemic and transcatheter hepatic arterial injection chemotherapies followed by conversion surgery: a case report and literature review.

BACKGROUND: Primary hepatic adenosquamous carcinoma (ASC) is a type of tumor that has the features of both adenocarcinoma and squamous cell carcinoma (SCC). The prognosis for patients with ASC is poor, as the chemotherapy has been ineffective so far. CASE PRESENTATION: Here, we report a case of a 62-year-old male patient who presented with high fever. The tumor marker levels were high, and abdominal dynamic computed tomography showed a liver tumor and distant lymph node metastases. Upon further investigation, needle biopsy of the liver tumor showed a primary hepatic SCC. Because the SCC was unresectable, the patient was treated with tegafur/gimeracil/oteracil (S-1) and transcatheter hepatic arterial injection (TAI) of cisplatin. After chemotherapy, a surgical resection performed on the remaining liver tumor, made the patient cancer-free. After the operation, the liver tumor was confirmed as primary hepatic ASC. Subsequently, the patient was administered postoperative adjuvant chemotherapy, which prevented its recurrence. CONCLUSIONS: Due to the lack of an effective treatment for primary hepatic ASC, its prognosis is poor. Here, we suggest that a chemotherapy combination of 5-fluorouracil (S-1) and cisplatin along with conversion surgery might be an effective way for treating primary hepatic ASC. Our experience from this case shall be valuable to clinicians around the world involved in the treatment of primary hepatic ASC.

Balloon-occluded retrograde transvenous obliteration for gastric varices improves hepatic functional reserve in long-term follow-up.

BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (BRTO) has been widely adopted for the management of gastric fundal varices (GVs). There are a few reports that BRTO leads to the improvement of mid-term and long-term hepatic functional reserve (HFR). We retrospectively investigated the long-term effect on HFR and prognosis among patients who had undergone BRTO for GVs. METHODS: This single-center, retrospective study included 57successful patients out of 60 patients who underwent BRTO for GVs from December 2005 to September 2018. We examined the indicators of HFR (e.g., encephalopathy and ascites statuses, serum total bilirubin and albumin levels, % prothrombin time, and Child-Pugh and albumin-bilirubin [ALBI] scores) during 3 years of follow-up after BRTO. We analyzed survival using the Kaplan-Meier method and identified the independent prognostic factors via multivariate analyses. RESULTS: GVs disappeared in all patients who were successfully treated by BRTO. At 3 years after BRTO, serum albumin levels were significantly elevated (from 3.3 to 4.0 g/dL, P = 0.008), while Child-Pugh and ALBI scores were significantly decreased (from 7.0 to 5.7, P = 0.043, and from -1.94 to -2.60, P = 0.006, respectively). The median survival time among all patients was 2207 days; the survival rates after BRTO were 87.0% at 1 year, 81.8% at 3 years, 67.3% at 5 years, and 44.1% at 10 years. Multivariate analyses revealed that ascites, hepatic encephalopathy, and malignant neoplasms were independently associated with poor prognosis. CONCLUSION: BRTO for GVs has a favorable effect on long-term HFR.

A Rare Case of Recurrent Generalized Peritonitis Caused by Spontaneous Urinary Bladder Rupture after Radiotherapy: A Case Report and Literature Review.

Since generalized peritonitis is a fatal disease, accurate diagnosis and treatment are important. In this paper, we report a case of recurrent generalized peritonitis associated with spontaneous urinary bladder rupture (SBR). A 65 year old woman, who underwent radiotherapy 21 years prior, was diagnosed with generalized peritonitis. Although the cause of the generalized peritonitis could not be identified, the patient recovered with conservative treatment in short period. However, recurrent episodes of generalized peritonitis occurred four times. We diagnosed the patient with urinary ascites due to SBR, based on a history of radiotherapy and dysuria. No recurrence of generalized peritonitis had occurred after accurate diagnosis and treatment with long-term bladder catheter placement. Since SBR often occurs as a late complication after radiotherapy, it is difficult to diagnose SBR, which leads to delayed treatment. This case and literature review of similar cases suggest that the information of the following might be helpful in the diagnosis of SBR: (i) history of recurrent generalized peritonitis, (ii) pseudo-renal failure, (iii) history of radiotherapy, (iv) dysuria, and (v) increase or decrease of ascites in a short period. It is important to list SBR in the differential diagnosis by knowing the disease and understanding its clinical features. This case and literature review will serve as a reference for future practices.

The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors: A multicenter retrospective study in Japan.

ABSTRACT: Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010-2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066-4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702-1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.

Balloon-occluded retrograde transvenous obliteration for treatment of gastric varices.

Rupture of gastric varices (GVs) can be fatal. Balloon-occluded retrograde transvenous obliteration (BRTO), as known as retrograde sclerotherapy, has been widely adopted for treatment of GVs because of its effectiveness, ability to cure, and utility in emergency and prophylactic treatment. Simplifying the route of blood flow from GVs to the gastrorenal shunt is important for the successful BRTO. This review outlines BRTO indications and contraindications, describes basic BRTO procedures and modifications, compares BRTO with other GVs treatments, and discusses various combination therapies. Combined BRTO and partial splenic embolization may prevent exacerbation of esophageal varices and shows promise as a treatment option.

Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers.

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).

The first case of balloon-occluded retrograde transvenous obliteration and partial splenic embolization for gastric varices in situs inversus abdominus.

Situs inversus abdominus is a congenital abnormality characterized by the mirror image positioning of the abdominal organs, making it difficult to diagnosis and treatment of many diseases. Here, we report a rare case of gastric varices in situs inversus abdominus patient. A 55-year-old man was diagnosed with F2-shaped gastric varices associated with alcoholic cirrhosis. Abdominal dynamic computed tomography showed situs inversus abdominus, and gastric varices with a gastrorenal shunt. Due to the complex anatomy, emergency interventional radiology during bleeding was extremely difficult. Therefore, after thorough consultation, we decided to treat gastric varices prophylactically by balloon-occluded retrograde transvenous obliteration. After treatment, the patient's clinical course was generally good, with no adverse events, and the gastric varices disappeared. It is important to assess anatomical positioning using three-dimensional reconstruction computed tomography images before treatment, to adequately prepare, including selecting appropriate devices (i.e., catheters and sheath). Although preventive treatment of gastric varices is controversial, in cases with anatomical complexity, preventive treatment with sufficient preparation would be recommended. To the best of our knowledge, there are no reports of treatment for gastric varices in situs inversus abdominus patient. This case will serve as a reference for successful treatment in future cases.

Changes in disease characteristics of primary biliary cholangitis: An observational retrospective study from 1982 to 2016.

AIM: Disease characteristics of primary biliary cholangitis have changed recently. However, detailed studies on the subject have been limited. Therefore, we aimed to clarify disease characteristics of patients with recent primary biliary cholangitis using the cohort from Niigata University and 21 affiliated hospitals. METHODS: Overall, 508 patients were enrolled in this study from 1982 to 2016, divided into three cohorts according to their year of diagnosis: ≤1999, 2000-2009 and ≥2010. We compared differences in clinical characteristics, response to ursodeoxycholic acid and prognosis. RESULTS: The male-to-female ratio increased incrementally from 1:16.4 (≤1999) to 1:3.8 (≥2010) (P < 0.001). In women, the median age at diagnosis increased incrementally from 54.0 years (≤1999) to 60.5 years (≥2010) (P < 0.001) and serum albumin decreased gradually (P = 0.001), which might have affected the increase in the Fibrosis-4 Index and albumin-bilirubin score. The ursodeoxycholic acid response rate according to the Barcelona criteria increased incrementally from 26.7% (≤1999) to 78.4% (≥2010) (P < 0.010), and those according to other criteria (Paris-I, Rotterdam and Toronto) were approximately ≥80% in all cohorts. Ten-year survival rate in the ≤1999 and 2000-2009 cohorts were 98.6% and 95.6%, respectively. These earlier cohorts were also characterized by a higher rate of asymptomatic state and mild histology (83.5% [≤1999] and 84.7% [2000-2009], and 93.6% [≤1999] and 91.1% [2000-2009]). CONCLUSIONS: Patients with primary biliary cholangitis were characterized by older age at diagnosis and an increase in male to female ratio as well as higher response rates of ursodeoxycholic acid and longer survival, resulting from the early recognition of primary biliary cholangitis.

Ruptured pancreaticoduodenal pseudoaneurysm causing arterioportal fistula: combined transarterial and transportal embolization.

BACKGROUND: Arterioportal fistulas are rare vascular disorders of the abdominal viscera. They are arteriovenous communications between the splanchnic arteries and the portal vein or its tributaries. We herein report a case of an extrahepatic arterioportal fistula that was caused by rupture of a pseudoaneurysm of the pancreaticoduodenal artery and successfully treated with embolization using a combination of the arterial and percutaneous transhepatic portal venous approaches. CASE PRESENTATION: A 79-year-old man was transferred to our hospital because of the sudden appearance of a hematoma containing a large pseudoaneurysm in the mesentery of the duodenum. Emergency abdominal angiography revealed that a pseudoaneurysm of the anterior inferior pancreaticoduodenal arterial branch had perforated into the portal system (arterioportal fistula). We performed coil embolization via the inflow artery and portal vein using a percutaneous transhepatic approach. The patient recovered without complications and was discharged. CONCLUSION: This rare vascular disorder was successfully treated with an unplanned combination therapy. We believe that flexible strategy changes led to the successful treatment in this case.

[A case of liver abscess caused by hypermucoviscous Klebsiella pneumoniae with septic pulmonary embolism].

A 69-year-old man consulted a local doctor because of a chief complaint of fever and anorexia. CT showed a giant liver mass of the right hepatic lobe and multiple pulmonary nodules. The patient was admitted to our hospital. We punctured the liver mass, obtaining pus, and as gram-negative bacilli were detected from both blood and pus cultures, a liver abscess with septic pulmonary embolism was diagnosed. Following a positive string test, we identified the pathogenic bacteria as hypermucoviscous Klebsiella pneumoniae, which is highly invasive to the tissues. The patient showed improvement following the administration of an antimicrobial agent (Meropenem) and multiple abscess drainage procedures.

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy. METHODS: Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded. RESULTS: The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE). CONCLUSIONS: The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve. TRIAL REGISTRATION: This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).

Increase of Soluble Programmed Cell Death Ligand 1 in Patients with Chronic Hepatitis C.

Objectives: To determine whether the soluble programmed cell death ligand 1 (sPD-L1) levels in patients with chronic hepatitis C (CHC) are associated with the clinical features of the disease and the efficacy of treatment, including interferon (IFN)-α. Methods: We investigated the sPD-L1 levels in the sera of 80 genotype 1b Japanese patients with CHC who underwent 12 weeks of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy followed by 12 weeks of dual therapy with pegylated IFN-α plus ribavirin. Serum was also obtained from 22 patients with chronic hepatitis B (CHB) and from 10 healthy donors (HC). The sPD-L1 levels were measured using an ELISA kit. In addition, we examined the PD-L1 expression on the cell surface of immortalized hepatocytes (HPT1) after incubation with cytokines, including IFN-γ. Results: The pretreatment serum sPD-L1 levels were significantly increased in patients with CHC (median 109.3 pg/ml, range 23.1-402.3) compared with patients with CHB (69.2 pg/ml, 15.5-144.8; P <0.001) and HC (100.3 pg/ml, 40.1-166.6; P = 0.039). No significant differences in the sustained virological response (SVR) rates were found between the TVR- (85.0%, n=40) and SMV-treated (80.0%, n=40) groups, and the pretreatment levels of serum sPD-L1 were not significantly different between patients who achieved SVR (105.0 pg/ml, 23.1-402.3) and non-SVR patients (133.5 pg/ml, 39.9-187.2; P = 0.391). The pretreatment level of sPD-L1 was positively correlated with the alanine aminotransferase and alpha-fetoprotein levels (R2 = 0.082, P = 0.016, and R2 = 0.149, P = 0.002, respectively). Although immortalized hepatocytes do not express PD-L1, we confirmed that PD-L1 expression was induced after stimulation with IFN-γ. Conclusions: In this study, we first found that sPD-L1 was increased in patients with CHC. Our results indicate that the level of serum sPD-L1 might be associated with the progression of CHC and the generation of hepatocellular carcinoma.

Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C.

AIM: To evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. METHODS: The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment. RESULTS: Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P < 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups (91.6% vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B (OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) and the adherence of RBV (> 60%) (OR = 11.052; 95%CI: 1.160-105.273, P = 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger (81.1%) and older (82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes (77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR (OR = 9.677; 95%CI: 1.114-84.087, P = 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively. CONCLUSION: Both TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.

Jejunal varices after choledochojejunostomy treated with laparotomic transcatheter variceal embolization.

Portal hypertension induces collateral shunt formation between the portal and systemic circulation, decompressing the elevated portal pressure. Ectopic varices outside of the gastroesophageal region, such as jejunal varices, are rare conditions. This report describes the successful embolization of ruptured jejunal varices resulting from an extrahepatic portal obstruction. A 62-year-old man was admitted to our hospital with recurrent massive gastrointestinal bleeding. Fourteen months earlier, he had undergone a choledochojejunostomy and pancreatic cystojejunostomy for bile duct stenosis with an enlarged pancreatic pseudocyst due to severe chronic pancreatitis. Contrast-enhanced computed tomography showed jejunal intramural dilated vessels close to the choledochojejunal anastomosis, but extravasation was not observed. Due to the lack of a rapid definitive diagnosis, the patient required massive blood transfusions. Hemorrhagic scintigraphy using 99mTc-HSAD finally identified the site of the hemorrhage. Angiography and double-balloon endoscopy revealed the anastomotic jejunal varices to be the result of an extrahepatic portal obstruction. Laparotomic transcatheter variceal embolization with microcoils was successful in halting the refractory gastrointestinal bleeding. This surgery preserved hepatopetal portal venous flow by another route, and no complications were observed. At present, 4 years post-surgery, there has been no recurrence of gastrointestinal hemorrhage. The development of jejunal varices is often associated with postoperative adhesions. Some patients with a history of hepatico- or choledochojejunostomy may experience portal hypertension resulting from extrahepatic portal obstruction, leading to the formation of jejunal varices as hepatopetal portal collaterals. The choice of therapy in each patient should be based on the individual hemodynamics of the ectopic varices.