A combination of hepatic encephalopathy and body mass index was associated with the point of no return for improving liver functional reserve after sofosbuvir/velpatasvir treatment in patients with hepatitis C virus-related decompensated cirrhosis.

AIMS: The real-world efficacy of sofosbuvir/velpatasvir treatment for patients with hepatitis C virus-related decompensated cirrhosis is unclear. We aimed to identify factors that improve liver functional reserve after treatment. METHODS: This was a multicenter retrospective study of 12-week sofosbuvir/velpatasvir treatment. A total of 48 patients with Child-Pugh (CP) class B or C were enrolled at 11 institutions. We evaluated changes in liver functional reserve at 24 weeks post-treatment. RESULTS: At baseline, 40 and eight patients were CP class B and C, respectively. The overall rate of sustained virologic response 12 weeks post-treatment was 95.8% (46/48). Serum albumin, alanine aminotransferase and α-fetoprotein levels, and the FIB-4 index were significantly improved post-treatment (P < 0.05). Among patients who achieved sustained virologic response 12 weeks post-treatment, those with CP class A increased from 0 to 24 patients (56%) at 24 weeks post-treatment. In multivariate analysis, body mass index (BMI) ≥25 was an independent factor that inhibited CP class improvement (P < 0.05). In decision tree analysis, after treatment, the initial divergent variable for CP class improvement was hepatic encephalopathy, followed by serum sodium level and BMI. CONCLUSION: Sofosbuvir/velpatasvir treatment improved the liver functional reserve in patients with hepatitis C virus-related decompensated cirrhosis at 24 weeks post-treatment. However, BMI ≥25 inhibited improvement in CP class. Additionally, decision tree analysis revealed that a combination of hepatic encephalopathy, serum sodium levels, and BMI were diversity profiles associated with no improvement in liver functional reserve after the treatment.

Suppression of Local Tumor Progression in Perivascular Hepatocellular Carcinoma by Combination Therapy with Radiofrequency Ablation and Percutaneous Ethanol Injection: A Propensity Score Matching Analysis.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) has replaced percutaneous ethanol injection (PEI) as the treatment of choice for hepatocellular carcinoma (HCC); however, control of local tumor progression (LTP) remains a challenge in perivascular HCC. The aim of this study was to determine whether PEI added to RFA can reduce the LTP rate in perivascular HCC patients. METHODS: We retrospectively analyzed 167 patients, with 197 newly diagnosed HCC nodules with peritumoral vessels, who underwent either RFA plus PEI or RFA monotherapy as the first-line treatment between June 2001 and April 2015. Ethanol was injected inside the tumor close to the peritumoral vessels in the combination therapy group. Patients were matched 1:1 according to their propensity scores to reduce selection bias; cumulative LTP was then analyzed using log-rank tests and Cox proportional hazard regression analyses. RESULTS: The two matched groups comprised 62 tumors each. The overall median follow-up period was 34 months (range, 1-140 months). In the RFA plus PEI group, the cumulative LTP rates were 5.7%, 15.5%, and 20.4% at 1, 3, and 5 years, respectively; in the RFA monotherapy group, the rates were 13.2%, 32.0%, and 40.2%, respectively. The rates were significantly lower in the RFA plus PEI group (p = 0.032). Cox proportional hazard regression analysis showed that PEI combination treatment was significantly associated with a reduced risk of local HCC recurrence (hazard ratio, 0.44; 95% confidence interval, 0.19-0.93; p = 0.031). DISCUSSION/CONCLUSION: The risk of LTP after RFA for perivascular HCC can be significantly reduced by injecting ethanol close to the peritumoral vessels.

Multiple focal fatty changes in the liver in patients with porphyria cutanea tarda: A case series and review of the literature.

Porphyria cutanea tarda (PCT) is commonly diagnosed in cases where multiple hyperechoic nodules are observed in the liver. Pathologically, these nodules associated with PCT are focal fatty deposits. We report here, seven cases of PCT with fatty changes over multiple foci in the liver. Furthermore, the characteristics of ultrasonography (US) findings of 32 previously reported cases are summarized. The US features of these nodules showed a homogenous hyperechoic or hyperechoic rim pattern, partial confluence, and no mass effect in the vascular structures. Because multiple hyperechoic liver nodules occasionally mimic malignancies, and because their diagnosis can be challenging, clinicians should consider checking urine porphyrin levels to rule out PCT when such nodules are observed on US.

Long-Term Effects of Rifaximin on Patients with Hepatic Encephalopathy: Its Possible Effects on the Improvement in the Blood Ammonia Concentration Levels, Hepatic Spare Ability and Refractory Ascites.

Background and Objectives: To investigate the long-term efficacy of rifaximin (RFX) for hyperammonemia and efficacy for refractory ascites in patients with cirrhosis. Materials and Methods: We enrolled 112 patients with liver cirrhosis who were orally administered RFX in this study. Changes in the clinical data of patients were evaluated up to 36 months after RFX administration. The primary endpoint was a change in blood ammonia levels. Secondary endpoints included changes in clinical symptoms, Child−Pugh (CP) score, number of hospitalizations, degree of refractory ascites, adverse events, and the relationship between RFX administration and the renin-angiotensin-aldosterone system. Results: An improved rate of overt hepatic encephalopathy (HE) of 82.7% was observed 3 months after RFX administration, which significantly induced a progressive decrease in blood ammonia concentration and an improved CP score up to 36 months. No serious RFX treatment-related adverse events were observed. 36.5% in patients after RFX administration improved refractory ascites. After RFX administration, patients with satisfactory control of hepatic ascites without addition of diuretic had lower renin concentration than those with poor control (p < 0.01). At less than 41 pg/mL renin concentration, the control of refractory ascites was significantly satisfactory (p < 0.0001). Conclusions: RFX reduced blood ammonia concentration and improved hepatic spare ability and the quality of life of patients with long-term HE to up to 36 months. Our study revealed the effects of RFX against refractory ascites, suggesting that renin concentration may be a predictive marker for assessing ascites control.

Irsogladine maleate alters expression of a tight junction protein in portal hypertensive gastropathy.

BACKGROUND AND AIM: Portal hypertensive gastropathy (PHG) is characterized by noninflammatory edema and vasodilatation of the lamina propria of the mucosal epithelium. In addition, the alterations of intercellular junction proteins and dilatation of the endothelial gaps have been reported. In this study, we examined whether irsogladine maleate (IM), a gastric mucosal protective agent, has the potential to improve PHG by restoration of tight junctions (TJs). METHODS: Twenty-four patients with PHG were registered and randomly assigned into two groups: 12 patients in the IM-administration group and 12 patients in the non-administration group. In the administration group, IM (4 mg/day) was administered orally for 12 weeks. Gastric mucosa with a red color in patients with PHG were obtained endoscopically on the registration day and 12 weeks later. The endoscopic findings were evaluated, an immunohistochemical analysis of claudin-3 (a TJ protein) expression in gastric mucosal tissues by a laser microscope was performed, and claudin-3 expression was quantified by western blot analysis. RESULTS: Irsogladine maleate improved the degree of PHG in 2/12 patients endoscopically, in contrast to none of the 12 patients in the non-administration group. Immunohistochemical analysis showed that expression of claudin-3 increased in 8/12 patients in the IM-administration group and 2/12 patients in the non-administration group (P = 0.036). Western blot analysis revealed that the increase in claudin-3 after 12 weeks was significantly higher in the IM-administration group than in the non-administration group (P = 0.010). CONCLUSIONS: The present pilot study suggested that IM might improve the gastric mucosa in PHG through restoration of TJ-protein claudin-3.

Reduction in Tumor Stain at 2 Weeks after Treatment Initiation Is a Predictor of the Efficacy of Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Lenvatinib is an oral anticancer drug for patients with unresectable advanced hepatocellular carcinoma (HCC). We evaluated whether a reduction in tumor stain at 2 weeks after lenvatinib treatment in patients with unresectable HCC is a predictor of early treatment efficacy at 12 weeks. PATIENTS AND METHODS: Of the 23 patients who initiated lenvatinib treatment between April 2018 and January 2019, treatment efficacy was measured in 15 patients for more than 12 weeks after treatment. Changes in tumor stain, tumor size on contrast-enhanced computed tomography (CT), and serum levels of tumor markers were evaluated 2 weeks after lenvatinib treatment. Therapeutic efficacy was assessed by tumor stain and tumor size by contrast-enhanced CT within the first 12 weeks, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. RESULTS: At 12 weeks, efficacy evaluation of 15 patients revealed that 11 of them experienced partial responses, for a response rate of 73.3%. In the first 2 weeks, 13 patients (86.7%) experienced a decreased tumor stain, including 10 responders (90.9%) and 3 non-responders (75.0%). All patients in the non-responder group had required a lenvatinib dose reduction due to adverse events within 12 weeks. On contrast-enhanced CT, the change rate of tumor stain to HCC at 2 weeks after treatment was <0.8 among 10 responders (90.9%) and 1 non-responder (25.0%; p = 0.033). No significant differences between responders and non-responders were observed with regard to most characteristics at baseline and at 2 weeks after treatment initiation. However, significant differences were observed between groups in the presence or absence of a dose suspension period, the presence or absence of lenvatinib dose reduction from the maximum value during the first 2 weeks, and decreased tumor stain at 2 weeks after treatment initiation. CONCLUSION: Reduction in tumor stain at 2 weeks after lenvatinib treatment may be an early biomarker of efficacy at 12 weeks in patients with unresectable HCC.

The Efficacy and Therapeutic Outcome of Bipolar Radiofrequency Ablation for the Treatment for Hepatocellular Carcinoma in the Real-World Setting, Compared with Monopolar Radiofrequency Ablation Conducted during the Same Period.

BACKGROUND: Several reports have suggested that the bipolar radiofrequency ablation (RFA) system is useful for the treatment of hepatocellular carcinoma (HCC). We evaluated the efficacy and safety of the bipolar RFA system for HCC treatment in the real-world setting. METHODS: A total of 155 patients with 224 HCC tumors were enrolled. First, we examined the characteristics and outcomes of two RFA systems, monopolar and bipolar. Second, we identified the factors associated with local tumor progression in 72 patients with 104 HCC tumors, who could be followed up for at least 3 months after treatment and had been treated with the bipolar RFA system. RESULTS: Of the baseline characteristics, tumor size and location were associated with the selection of the bipolar RFA system. A sufficient ablative zone margin (≥5 mm) was obtained by bipolar RFA in 81 of 94 (86.1%). The 1- and 2-year local tumor progression rates were 15.6 and 26.3%, respectively. An alpha-fetoprotein-L3 (AFP-L3) ratio >10% (HR: 7.64; 95% CI: 1.7-39.8, p = 0.007) and an insufficient ablative zone margin (<5 mm) (HR: 4.53; 95% CI: 1.02-20.3, p = 0.047) were related to local tumor progression in Cox regression analysis. Although severe adverse events were not observed in most cases, severe hepatic infarction occurred in 1 patient. CONCLUSIONS: The bipolar RFA system is safe and effective for HCC treatment. Tumor localization within the liver is an important factor associated with bipolar RFA. Careful follow-up or reconsideration of treatment is necessary for cases with AFP-L3 ratio >10% or insufficient ablative zone margin (<5 mm), which were associated with local tumor progression.

Safety and efficacy of cold polypectomy compared to endoscopic mucosal resection and hot biopsy polypectomy.

Backgrounds: Recently, several studies have demonstrated the usefulness of cold polypectomy (CP), a safe and simple method for the removal of small polyps. We investigated the safety and efficacy of CP compared to that of endoscopic mucosal resection (EMR) and hot biopsy polypectomy (HB). Methods: We retrospectively examined 1713 colorectal polyps (size 1-9 mm) in 731 patients. CP, EMR, and HB were performed on 476, 997, and 240 lesions, respectively. We compared the region, size, morphology, the presence of delayed bleeding as overt bleeding 24 h after operation, number of clips, pathology, the presence of antithrombotic therapy, procedure time from detection of a polyp to resection and hemostasis, device cost including device and clips, and polyp remnants. Results: The delayed bleeding in the CP group (0/476) was significantly lower compared to that in the HB group (3/240) and EMR group (7/997). There were no cases of perforations. The procedure time was significantly shorter in the CP group than in the EMR group (91.3sec vs 290.1sec, p < .0001). The CP group had a significantly lower device cost than the HB and EMR groups (49.2USD vs 58.0 USD vs 91.3 USD, p < .0001) was not inferior in terms of polyp remnants to the EMR and HB groups. (1.4% vs 0.6% vs 6.1%, p = .1599) Conclusions: CP is a safe treatment that achieves less delayed bleeding. Moreover, CP is not inferior to other groups in terms of polyp remnants and offers a cost benefit. CP can be considered useful for colonic polypectomy.

IL28B gene polymorphism is correlated with changes in low-density lipoprotein cholesterol levels after clearance of hepatitis C virus using direct-acting antiviral treatment.

BACKGROUND: Direct-acting antivirals (DAAs) rapidly clear hepatitis C virus (HCV), but the lipid dynamics after DAA treatment remain unknown. Low-density lipoprotein (LDL) cholesterolemia is the predicting factor for the onset and death of atherosclerotic cardiovascular diseases. Thus, in this study, we examined the frequency and risk of hyper-LDL cholesterolemia in HCV patients who achieved sustained virologic response (SVR) with DAA treatment. METHODS: A total of 121 patients with HCV genotype 1b, who achieved SVR with DAA treatment, were examined for serum levels of total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein, and triglycerides from the start of treatment until 2 years after SVR (SVR-2y). ΔLDL-C was defined as the change in LDL-C levels from treatment initiation to SVR-2y. Hyper-LDL cholesterolemia was defined as ≥ 140 mg/dL LDL-C at SVR-2y. Stepwise multiple regression analysis was performed to determine whether ΔLDL-C and hyper-LDL cholesterolemia are associated with other factors, including viral kinetics. RESULTS: A total of 63, 3, and 55 patients were administered daclatasvir + asunaprevir, ombitasvir + paritaprevir + ritonavir, and ledipasvir + sofosbuvir, respectively. ΔLDL-C in patients with the IL28B (rs8099917) TG/GG genotype was significantly higher than in those with IL28B TT (27.3 ± 27.0 and 9.6 ± 27.3 mg/dL; P < 0.001). In addition, IL28B TG/GG was an independent risk factor for hyper-LDL cholesterolemia (odds ratio: 8.47; P < 0.001). CONCLUSIONS: An IL28B polymorphism is associated with ΔLDL-C and hyper-LDL cholesterolemia after achieving SVR. Thus, lipid markers should be carefully monitored in patients who achieve SVR with DAA.

Non-response to daclatasvir and asunaprevir therapy in patients co-infected with hepatitis C virus genotypes 1 and 2.

Direct-acting antiviral agents for hepatitis C virus (HCV) have been developed such as combined daclatasvir (DCV) and asunaprevir (ASV) treatment. This typically enables HCV serotype 1 patients to achieve a high sustained virological response rate, but a small number of such patients fail to respond to therapy. We investigated three HCV patients who showed no response to DCV and ASV therapy. Hepatitis C genotyping was undertaken in the three patients using nested polymerase chain reaction and polymerase chain reaction direct sequencing in the core region of the HCV genome. All three patients possessed HCV serotype 1, and no mutations were identified in either the non-structural protein 3 or 5A region. The three patients were shown to be co-infected with HCV genotypes 1 and 2 because genotypes 2a and 2b were also identified. This is the first report into failed response to DCV and ASV therapy in patients co-infected with HCV genotypes 1 and 2.

Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients.

Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (P < 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (P < 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (P < 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (P < 0.05). The level of hepatic liver X receptor (LXR)ß mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.

A Probable Case of Burn-out NASH Caused by Panhypopituitarism Secondary to Craniopharyngioma.

A 38-year-old man diagnosed with craniopharyngioma at 8 years old underwent repeated surgery and radiation therapy. Complications included panhypopituitarism including growth hormone deficiency and hypogonadism at 13 years old. At 26 years of age, a slight fatty liver was found, which finally developed into liver cirrhosis (LC) at 35 years old. Viral infection or other etiologies causing LC were negative on serum examinations. Liver biopsy suggested a possibility of burn-out non-alcoholic steatohepatitis. This case indicates that a long-standing growth hormone deficiency and hypogonadism may lead to LC as a type of burn-out non-alcoholic steatohepatitis.

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a useful detection method for advanced primary biliary cirrhosis.

AIM: In primary biliary cirrhosis (PBC), damaged hepatocytes resulting from chronic cholestasis follow a compensatory mechanism that alters hepatobiliary transporter expression to reduce the accumulation of potentially toxic compounds such as bile acid. Organic anion transporter peptide 1B3 (OATP1B3), which transports agents such as gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), has reduced expression in the late stages of PBC. Therefore, we investigated the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as a useful detection method for the advanced staging of PBC. METHODS: Stage I-III PBC (non-liver cirrhosis [LC]-PBC, n = 12), stage IV (LC-PBC, n = 6), and non-PBC patients (control group, n = 4) were included in this study. We obtained liver tissue samples by percutaneous liver biopsy. Hepatic OATP1B3 expression was determined immunohistochemically, and OATP1B3 mRNA levels were assessed using real-time reverse transcription polymerase chain reaction. The relative enhancement (RE) in the hepatobiliary phase was calculated using the signal intensity of Gd-EOB-DTPA-enhanced MRI. RESULTS: Immunohistochemistry revealed markedly reduced expression of OATP1B3 in hepatocytes around the central vein in LC-PBC patients. Hepatic OATP1B3 mRNA expression in LC-PBC patients was significantly lower than that in non-LC-PBC patients (P < 0.05). The RE on MRI was significantly decreased in the LC-PBC group (0.33 ± 0.14) compared with the non-LC-PBC (0.91 ± 0.15, P < 0.01) and control (0.92 ± 0.20, P < 0.01) groups. CONCLUSION: Gd-EOB-DTPA-enhanced MRI may provide a useful detection method for liver disease in patients with LC-PBC.

Interleukin 28B polymorphism predicts interferon plus ribavirin treatment outcome in patients with hepatitis C virus-related liver cirrhosis: A multicenter retrospective study in Japan.

AIM: This study evaluated the efficacy of interferon plus ribavirin and examined whether interleukin 28B (IL28B) polymorphism influenced treatment outcome in Japanese patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). METHODS: Fourteen collaborating centers provided details of 261 patients with HCV-related LC undergoing treatment with interferon plus ribavirin. Univariate and multivariate analyses were used to establish which factors predicted treatment outcome. RESULTS: Eighty-four patients (32.2%) achieved a sustained virological response (SVR). SVR rates were 21.6% (41/190) in patients with HCV genotype 1 with high viral load (G1H) and 60.6% (43/71) in patients with non-G1H. In patients with non-G1H, treatment outcome was effective irrespective of IL28B polymorphism. In those with G1H, SVR was achieved in 27.1% of patients with the IL28B rs8099917 TT allele compared with 8.8% of those with the TG/GG alleles (P = 0.004). In patients with G1H having TT allele, treatments longer than 48 weeks achieved significantly higher SVR rates than treatments less than 48 weeks (34.6% vs 16.4%, P = 0.042). In patients with G1H having TG/GG alleles, treatments longer than 72 weeks achieved significantly higher SVR rates than treatments less than 72 weeks (37.5% vs 4.1%, P = 0.010). CONCLUSION: Interferon plus ribavirin treatment in Japanese patients with non-G1H HCV-related LC was more effective than those with G1H and not influenced by IL28B polymorphism. In those with G1H, IL28B polymorphism may predict SVR and guide treatment duration: SVR rates were higher in those with the TT allele treated for more than 48 weeks and those with the TG/GG alleles treated for more than 72 weeks.

Why is radiofrequency ablation therapy applied for hepatocellular carcinoma up to 3 nodules and smaller than 3 cm in tumor size?

BACKGROUND/AIMS: Radiofrequency ablation (RFA) has been applied for hepatocellular carcinoma (HCC) up to 3 nodules, within 3 cm in size. However, the scientific rationale of the treatment criteria for RFA has not been well analyzed. We compared the number and size of tumors with recurrence rates and survival rates. METHODOLOGY: The study participants retrospectively were enrolled 625 consecutive cases of naïve HCC treated with RFA. We analyzed recurrence rates and survival of 472 for the patients with HCC ≤ 3 nodules, ≤ 3 cm in size (Group A), and 153 for the patients exceeding limits (Group B). RESULTS: Median follow-up was 2.97 years. The survival rate of Group A was significantly higher than that of Group B (5 years: 55.6% vs. 44.2%, 10 years: 27.4% vs. 15.7%; P<0.05). Multivariate analysis of predictors for prognostic factors demonstrated that meeting the RFA criteria, Child-Pugh score A, and lower levels of des-gamma carboxy prothrombin (DCP) were independent factors significantly affecting prognosis. CONCLUSIONS: The present study is the firstto elucidate the scientific rationale for RFA treatment criteria for HCC regarding tumor number and size. We confirmed that the RFA treatment criteria select patients who stand to gain the most from RFA.

Pilot Study of Hepatic Arterial Infusion Chemotherapy with Interferon-beta and 5-fluorouracil: A New Chemotherapy for Patients with Advanced Hepatocellular Carcinoma.

BACKGROUND/AIMS: The present pilot study aimed to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with interferon-beta (IFN-ß) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). METHODOLOGY: We studied 10 patients with advanced HCC and who were unresponsive to previous HAIC using low-dose 5-FU and cisplatin. The median age was 67 years. Eight patients had portal vein tumor thrombosis and four patients had extrahepatic metastasis. Using a drug delivery system, patients were treated with HAIC of IFN-ß (600 MIU/body, three times/week) and 5-FU (250 mg/body, five times/week). Chemotherapy was repeated consecutively for 2 weeks every 4 weeks. RESULTS: Six (60%) patients had a decrease in tumor markers alpha-fetoprotein (APP) or des-gamma-carboxy prothrombin (DCP). The median overall survival was 108 days and the 1-year survival rate was 10.0%. Univariate analysis showed two significant prognostic factors related to long-term survival for more than 60 days: a decrease in APP or DCP 4 weeks after treatment (P = 0.035) and no extra hepatic metastasis (P = 0.035). Severe hepatic injury was not observed. CONCLUSIONS: HAIC with IFN-ß and 5-PU exerts modest antitumor effects and poses no particular safety concerns. This may be a new promising strategy for treatment of advanced HCC.

Restoration of albumin production by nucleoside analogue therapy in patients with chronic hepatitis B.

The clinical course of patients with chronic hepatitis B (CH-B) was greatly changed by the introduction of nucleoside analogues. We often encounter patients where the serum level of albumin recovers quickly following the treatment. In this study, we focused carefully on the changes in serum albumin level noted during nucleoside analogue therapy, in an effort to clarify the mechanism behind the restoration of albumin production. We observed changes in serum albumin levels during nucleoside analogue therapy in 12 patients with CH-B and studied the mechanism behind the restoration of albumin production following the therapy. The serum level of albumin was significantly increased very soon after the treatment was started. Prior to treatment with nucleoside analogues, the albumin signal for mRNA was only slightly seen in the peri-portal area, whereas 12 months after the treatment, the liver tissue presented an obvious signal of albumin mRNA. Serum levels of hepatocyte growth factor (HGF) were significantly decreased 12 months after the treatment. In this study, we demonstrated that nucleoside analogues decrease HGF through the suppression of hepatocyte damage, leading to the restoration of albumin production in patients with CH-B.

Partial splenic embolization improved stomal varices in patient with decompensated liver cirrhosis: a case report.

A 63-year-old man with decompensated liver cirrhosis was admitted for treatment of stomal hemorrhage. Eighteen months earlier, he was diagnosed with rectal and sigmoid colon cancer with multiple lymph node metastases, and he underwent colostomy surgery and postoperative chemotherapy. Sixteen months after the surgery, his stoma began to bleed repeatedly, and he required frequent blood transfusions. A contrast-enhanced computed tomography revealed ectopic varices around the stoma. We considered surgical or endoscopic treatment; however, these approaches would have been technically difficult in this patient. The patient was treated with partial splenic embolization to improve thrombocytopenia and portal hypertension. After two-stage partial splenic embolization, the platelet counts increased, and the concentration of the liver fibrosis marker, Mac-2 binding protein, decreased. In addition, blood flow in the stomal varices decreased, with no recurrence of bleeding. This is a case of recurrent hemorrhage from stomal varices that was successfully treated with partial splenic embolization in a patient with liver cirrhosis. There are no guidelines for hemorrhage from ectopic varices. PSE may present potential utility as a treatment for ectopic variceal bleeding, such as stomal varices.

Two cases of severe oral mucositis caused by atezolizumab plus bevacizumab combination therapy for hepatocellular carcinoma.

Atezolizumab is an immune checkpoint inhibitor specific for the programmed death-1 (PD-1) receptor. In this case report, we describe two cases of oral mucositis that developed following the initiation of a systemic chemotherapy regimen comprising atezolizumab and bevacizumab for recurrent hepatocellular carcinoma. After 2 or 3 cycles of treatment, each patient presented with mucosal ulcers in the mouth, oral pain, difficulty in speech and oral intake, and both were admitted to our hospital for management. Following rule out of other conditions such as pharyngeal ulcers, herpetic mucositis, denture or oral trauma, or necrotizing mucositis, both patients were diagnosed with oral mucositis as a severe immune-related adverse event. Oral candidiasis was observed in both cases and should be considered a risk factor for the development of oral mucositis. Chemotherapy was discontinued and treatment with prednisolone was started, along with supportive care. The oral mucositis improved, and prednisolone was gradually reduced; however, in one patient, discontinuation of chemotherapy led to a recurrence of hepatocellular carcinoma. The other patient was lost to follow-up. In patients with risk factors, attention must be paid to the development of oral mucositis during immune checkpoint inhibitor treatment.

3-Hydroxyl-3-methylglutaryl-coenzyme A reductase is up regulated in hepatocellular carcinoma associated with paraneoplastic hypercholesterolemia.

Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic hypercholesterolemia. However, cholesterol overproduction in HCC tissue has never been demonstrated. An aim of this study is to prove cholesterol overproduction in the HCC tissue of patients with paraneoplastic hypercholesterolemia. Six patients with HCC associated with paraneoplastic hypercholesterolemia and three control patients with HCC who did not have hypercholesterolemia were investigated regarding the expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in HCC tissue by means of immunohistochemical technique. In HCC associated with paraneoplastic hypercholesterolemia, HMG-CoA reductase was clearly stained in cancer cells whereas surrounding non-tumorous hepatocytes showed only slight expression of HMG-CoA reductase. In contrast, HCC tissues derived from patients without paraneoplastic hypercholesterolemia showed only slight expression of HMG-CoA reductase whereas surrounding non-tumorous hepatocytes showed a clear expression of HMG-CoA reductase. We morphologically proved cholesterol overproduction in HCC tissue derived from patients with paraneoplastic hypercholesterolemia. Immunohistochemistry for HMG-CoA reductase thought to be useful in the diagnosis of paraneoplastic hypercholesterolemia.