[A case of liver Mycobacterium avium complex syndrome, diagnosed by liver biopsy].

A man in his 70s was referred to our hospital for evaluation of low-grade fever, weight loss, and liver dysfunction. Serological tests for viral hepatitis or autoimmune diseases were negative. No significant findings were observed on whole-body computed tomography (CT). Histopathologic examination of a liver biopsy sample revealed a non-caseating granuloma with acid-fast bacillus using the Ziehl-Neelsen stain. Serum Mycobacterium avium complex (MAC) antibody was positive. We started treatment for pulmonary MAC disease. His clinical condition and liver function improved within two months. He was diagnosed with liver MAC disease.

[A recurrent gastric cancer with peritoneal metastasis 15 years after distal gastrectomy successfully treated with S-1 and weekly intravenous and intraperitoneal injections of Paclitaxel].

Fifteen years after receiving a distal gastrectomy for advanced gastric cancer, a 70-year-old woman was admitted to our hospital because of abdominal fullness due to ascites. Although cytological examination showed adenocarcinoma cells in the fluid, no examination revealed the primary lesion. Peritoneal metastasis was detected via immunohistochemistry using the cell block technique. After chemotherapy failure (S-1 plus CDDP, weekly PTX, and S-1 plus DOC), the patient received S-1 and weekly intravenous and intraperitoneal injections of PTX. The ascites decreased, and she has been doing well. Our experience with this case suggests that S-1 and weekly intravenous and intraperitoneal injections of PTX is a promising means of treating gastric cancer with peritoneal metastasis.

Efficacy and safety of sorafenib in very elderly patients aged 80 years and older with advanced hepatocellular carcinoma.

AIM: Sorafenib is the standard systemic therapy for patients with advanced hepatocellular carcinoma (HCC). We aimed to assess the efficacy and safety of sorafenib therapy in very elderly patients aged 80 years and older with advanced HCC. METHODS: In a retrospective multicenter study in Japan, we reviewed 185 patients (median age, 71 years; 82% male; 95% Child-Pugh class A) with advanced HCC who received sorafenib therapy. Data were compared between 24 (13%) patients aged 80 years and older and 161 (87%) patients aged less than 80 years. We used propensity score matching to adjust for differences between the two groups. RESULTS: Median overall survival was 10.6 months in all patients: 11.7 months in patients aged 80 years and older and 10.5 months in those aged less than 80 years. There were no significant differences in overall survival, tumor response, and frequency and severity of drug-related adverse events between patients aged 80 years and older and those aged less than 80 years in both the entire study cohort and the propensity-matched cohort. CONCLUSION: Sorafenib may be effective and well tolerated, even in patients with advanced HCC who are aged 80 years and older, as well as those aged less than 80 years.

[A case of superior mesenteric artery occlusion with ischemic enteritis after transcatheter therapy].

An 84-year-old female was admitted with sudden-onset upper abdominal pain. Contrast-enhanced computed tomography (CECT) revealed complete occlusion of the superior mesenteric artery (SMA). After transcatheter infusion of urokinase, embolic occlusion resolved. However, the pain recurred when she started eating. CECT revealed a lesion with thickening of the intestinal wall; therefore, laparoscopy-assisted surgery was undertaken. Histological examination yielded a definitive diagnosis of ischemic enteritis caused by SMA occlusion. Rapid diagnosis and treatment are important in SMA occlusion, and careful observation of the clinical course is recommended after transcatheter therapy.

[Pancreatic pseudocyst with fistula to the common bile duct and the duodenum].

A 35-year-old man was hospitalized for severe acute pancreatitis. On the 24th hospital day, CT scan showed a pancreatic pseudocyst in the head of the pancreas. Conservative medical treatment for 1 month was not effective, and CT scan revealed a fistulous communication of the pseudocyst to the common bile duct and duodenum. After the formation of a fistulous communication, we detected common bile duct stones composed of fatty acid calcium and we removed them endoscopically. The pseudocyst gradually decreased in size and disappeared 4 months later. Follow-up CT scan showed no sign of recurrence.

Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) can progress to hepatocellular carcinoma (HCC). We aimed to characterize the clinical features of NASH patients with HCC. METHODS: In a cross-sectional multicenter study in Japan, we examined 87 patients (median age, 72 years; 62% male) with histologically proven NASH who developed HCC. The clinical data were collected at the time HCC was diagnosed. RESULTS: Obesity (body mass index ≥25 kg/m(2)), diabetes, dyslipidemia, and hypertension were present in 54 (62%), 51 (59%), 24 (28%), and 47 (55%) patients, respectively. In nontumor liver tissues, the degree of fibrosis was stage 1 in 10 patients (11%), stage 2 in 15 (17%), stage 3 in 18 (21%), and stage 4 (ie, liver cirrhosis) in 44 (51%). The prevalence of cirrhosis was significantly lower among male patients (21 of 54, 39%) compared with female patients (23 of 33, 70%) (P = .008). CONCLUSIONS: Most patients with NASH who develop HCC are men; the patients have high rates of obesity, diabetes, and hypertension. Male patients appear to develop HCC at a less advanced stage of liver fibrosis than female patients.

Risk estimation model for nonalcoholic fatty liver disease in the Japanese using multiple genetic markers.

The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for them. For these purposes, 936 histologically proven NAFLD patients were recruited, and genome-wide association (GWA) studies were conducted for 902, including 476 NASH and 58 NASH-HCC patients, against 7,672 general-population controls. Risk estimations for NAFLD and NASH were then performed using the SNPs identified as having significant associations in the GWA studies. We found that rs2896019 in PNPLA3 [p = 2.3x10-31, OR (95%CI) = 1.85 (1.67-2.05)], rs1260326 in GCKR [p = 9.6x10-10, OR (95%CI) = 1.38(1.25-1.53)], and rs4808199 in GATAD2A [p = 2.3x10-8, OR (95%CI) = 1.37 (1.23-1.53)] were significantly associated with NAFLD. Notably, the number of risk alleles in PNPLA3 and GATAD2A was much higher in Matteoni type 4 (NASH) patients than in type 1, type 2, and type 3 NAFLD patients. In addition, we newly identified rs17007417 in DYSF [p = 5.2x10-7, OR (95%CI) = 2.74 (1.84-4.06)] as a SNP associated with NASH-HCC. Rs641738 in TMC4, which showed association with NAFLD in patients of European descent, was not replicated in our study (p = 0.73), although the complicated LD pattern in the region suggests the necessity for further investigation. The genetic variants of PNPLA3, GCKR, and GATAD2A were then used to estimate the risk for NAFLD. The obtained Polygenic Risk Scores showed that the risk for NAFLD increased with the accumulation of risk alleles [AUC (95%CI) = 0.65 (0.63-0.67)]. CONCLUSIONS: We demonstrated that NASH is genetically and clinically different from the other NAFLD subgroups. We also established risk-estimation models for NAFLD and NASH using multiple genetic markers. These models can be used to improve the accuracy of NAFLD diagnosis and to guide treatment decisions for patients.

Real-world efficacy of daclatasvir and asunaprevir with respect to resistance-associated substitutions.

AIM: To investigate daclatasvir (DCV) and asunaprevir (ASV) efficacy in hepatitis C (HCV) patients, with respect to resistance-associated substitutions (RASs). METHODS: A total of 392 HCV-infected patients from multiple centers were included in this study. We evaluated their clinical courses and sustained virologic responses (SVR) according to pretreatment factors (gender, age, history of interferon-based regimens, platelet counts, level of viremia, pretreatment NA5A:L31, and Y93 substitutions). We also analyzed the pretreatment and post-treatment major RASs of NS3:D168, NS5A:L31 and Y93 substitutions using a direct-sequencing method in 17 patients who were unable to achieve SVR at 12 wk after treatment completion (SVR12). RESULTS: The overall SVR12 rate was 88.3%. Thirty-one patients discontinued treatment before 24 wk because of adverse events, 23 of whom achieved SVR12. There were no significant differences in SVR12 rates with respect to gender, age, history of interferon-based regimens, and platelet counts. The SVR12 rate in patients with viral loads of ≥ 6.0 log IU/mL was significantly lower than those with viral loads of < 6.0 log IU/mL (P < 0.001). The SVR12 rate in patients with Y93 substitution-positive was significantly lower than those with Y93 substitution-negative (P < 0.001). The L31 substitution-positive group showed a lower SVR12 rate than the L31 substitution-negative group, but the difference was not statistically significant. Seventeen patients who did not achieve SVR12 and had available pretreatment and post-treatment sera had additional RASs in NS3:D168, NS5:L31, and Y93 substitution at treatment failure. CONCLUSION: Combination of DCV and ASV is associated with a high SVR rate. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.

Comparison of peg-interferon, ribavirin plus telaprevir vs simeprevir by propensity score matching.

AIM: To compare efficacy of telaprevir (TVR) and simeprevir (SMV) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV) while treating chronic hepatitis C (CHC). METHODS: In all, 306 CHC patients were included in this study. There were 159 patients in the TVR combination therapy group and 147 patients in the SMV combination therapy group. To evaluate pretreatment factors contributing to sustained virological response at 12 wk (SVR12), univariate and multivariate analyses were performed in TVR and SMV groups. To adjust for patient background between TVR and SMV groups, propensity score matching was performed. Virological response during treatment and SVR12 were evaluated. RESULTS: Overall rates of SVR12 [undetectable serum hepatitis C virus (HCV) RNA levels] were 79.2% and 69.4% in TVR and SMV groups, respectively. Patients in the SMV group were older, had higher serum HCV RNA levels, lower hemoglobin, higher prevalence of unfavorable interleukin-28B (IL28B) genotype (rs8099917), and poorer response to previous PEG-IFN and RBV treatment. Propensity score matching was performed to adjust for backgrounds (n = 104) and demonstrated SVR12 rates of 74.0% and 73.1% in the TVR and SMV groups, respectively. In the TVR group, discontinuation rates were higher because of adverse events; however, breakthrough and nonresponse was more frequent in the in SMV group. Multivariate analysis revealed IL28B genotype (rs8099917) as the only independent predictive factor of SVR12 in both groups. CONCLUSION: SVR12 rates were almost identical following propensity score matching.

Clinical and pathological progression of non-alcoholic steatohepatitis to hepatocellular carcinoma.

AIM: Non-alcoholic steatohepatitis (NASH) can progress to hepatocellular carcinoma (HCC). We aimed to examine the clinical and pathological course of how NASH progresses to HCC. METHODS: In this retrospective multicenter study conducted in Japan, we examined 19 patients (53% female), who had been previously diagnosed with histologically proven NASH and developed HCC during the follow-up period. The median age of the patients at the time of initial diagnosis of NASH was 65 years. RESULTS: NASH progressed to HCC after a median follow-up period of 3.8 years (range: 0.5-11.6 years). All patients had been identified as having HCC during screening, which included 12 patients assessed by ultrasound, four patients assessed with computerized tomography, two patients that underwent serum des-γ-carboxy prothrombin testing and one patient that underwent serum α-fetoprotein testing. The median diameter of HCC tumors was 1.8 cm (range: 0.8-3.0 cm). The majority of patients (n = 13; 68%) presented with only one HCC tumor. The stage of liver fibrosis was significantly more advanced at the time of diagnosis of HCC than at the time of initial diagnosis of NASH, whereas there were no significant differences in the degree of steatosis. CONCLUSION: Screening for HCC with imaging is necessary not only in NASH patients with advanced fibrosis, but also in those with less advanced forms of fibrosis, particularly if they are old men. Liver fibrosis progresses to a more advanced stage during the development of HCC in NASH patients.