Kazuhide Takata

Late‐evening snack with branched‐chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma

Aim:  This prospective study was designed to examine whether consumption of a branched‐chain amino acid (BCAA)‐enriched nutrient mixture as a late‐evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC).

Sustained upregulation of sodium taurocholate cotransporting polypeptide and bile salt export pump and downregulation of cholesterol 7α-hydroxylase in the liver of patients with end-stage primary biliary cirrhosis

To examine the mRNA expression of hepatobiliary transporters in primary biliary cirrhosis (PBC) patients and to compare bile acid absorption, synthesis, and efflux in patients with non-end-stage and end-stage PBC, we obtained liver samples from PBC patients by percutaneous needle biopsy. End-stage PBC was defined as follows: histological stage IV; cirrhosis; serum total bilirubin, ≥4.0 mg/dl; and Child-Pugh Class C. The mRNA expression levels of sodium taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and hepatic cholesterol 7α-hydroxylase (CYP7A1) were significantly higher in the PBC patients than in the controls (P < 0.01). The mRNA levels of NTCP and BSEP were significantly higher in the end-stage PBC patients than in the controls (P < 0.01). However, hepatic CYP7A1 mRNA expression decreased significantly (by 70%) in the patients with end-stage PBC as compared to the controls and the patients with non-end-stage PBC (P < 0.01). The hepatic expression of transporters mediating bile acid influx and efflux showed sustained elevation, whereas that of the rate-limiting enzyme for bile acid biosynthesis was attenuated in the end-stage PBC patients. Thus, mechanisms may be present preventing the accumulation of toxic bile acids in the hepatocytes of end-stage PBC patients.

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.

Clinical features of Wilson disease: Analysis of 10 cases

Aim:  The diagnosis of Wilson disease is based on the results of several clinical and biochemical tests. This study aimed to clarify the clinical features and spectrum of Wilson disease, including severe Wilson disease.

Adjusting the starting dose of telaprevir according to renal function decreases adverse effects and affects the sustained virological response rate.

Background Telaprevir (TVR) plays a major role in renal damage and anemia associated with TVR/pegylated interferon/ribavirin therapy for chronic hepatitis C. Adjusting the TVR starting dose may reduce these adverse effects. We aimed to determine whether adjusting the starting dose according to renal function reduces TVR-associated renal damage and anemia and affects the sustained virological response (SVR). Patients and methods Our study included 112 patients infected with hepatitis C genotype 1 treated with pegylated interferon/ribavirin/TVR triple therapy. The TVR starting dose adjusted according to renal function was calculated as TVR/unadjusted estimated glomerular filtration rate (eGFR) ratio=TVR/(eGFR×body surface area/1.73). Results A TVR/unadjusted eGFR ratio of 32 or greater was a predictor of renal impairment and anemia in multivariate analysis (odds ratio 12.09, P<0.001, and OR 4.14, P<0.001, respectively). Patients with a TVR/unadjusted eGFR ratio of 32 or greater developed significant renal impairment and anemia (P<0.001 and P=0.002, respectively). SVR was significantly reduced in patients with a TVR/unadjusted eGFR ratio less than 23 versus 23 or greater (66.7 and 87.2%, respectively, P=0.045). SVR tended to increase stepwise [<23.0 (66.7%), ≥23 to <32 (84.8%), and ≥32 (89.6%), respectively]. The TVR/unadjusted eGFR ratio was correlated significantly with the serum TVR concentration (r=0.541, P<0.001). Conclusion Adjusting the TVR starting dose according to the TVR/unadjusted eGFR ratio decreased adverse effects and affected the SVR rate. The TVR starting dose should be adjusted by a TVR/unadjusted eGFR ratio of 23 or greater to less than 32 to safely achieve SVR.

Fitz–Hugh–Curtis syndrome in a man positive for Chlamydia trachomatis

Fitz–Hugh–Curtis syndrome (FHCS) is characterized by perihepatic and pelvic inflammation and occurs mostly in women of childbearing age. Here, we report a case of FHCS caused by Chlamydia trachomatis in a 50-year-old man. The patient presented to our hospital with right upper quadrant abdominal pain, and enhanced computed tomography revealed perihepatic and pelvic free fluid and early-phase hepatic capsular enhancement. A urine specimen was positive for Chlamydia trachomatis. The patient was diagnosed with FHCS due to Chlamydia trachomatis infection. In conclusion, FHCS cannot be excluded when men present with right upper quadrant abdominal pain without significant signs of biliary tract disease.

The Rate of Referral of Hepatitis Virus Carriers to Hepatologists and the Factors Contributing to Referral

Objective The aims of the present study were to determine the proportions of hepatitis B surface antigen (HBsAg)-positive and anti-hepatitis C virus (HCV)-positive patients, and identify the characteristics that influenced referral to a hepatologist. Methods The present study included patients who were positive for HBsAg (n=153) or anti-HCV (n=574); their viral status was tested by non-hepatologists between January 2008 to December 2012. We performed a multivariate analysis to investigate the factors associated with the referral of patients to hepatologists. Results The rates of hepatitis B virus (HBV) and the percentage of suspected HCV carriers at the hospital were 1.4% and 3.5%, respectively. Among the 727 patients who were seropositive for HBV or HCV, 107 (14.7%) were referred to a hepatologist. A multivariate analysis to investigate the factors contributing to referral revealed that (i) an alanine aminotransferase (ALT) level of ＞30 IU/L [odds ratio (OR), 3.24; 95% confidence interval (CI), 2.10-5.03; p＜0.001]; (ii) undergoing testing at an internal medicine department (OR, 2.79; 95% CI, 1.80-4.38; p＜0.001); and (iii) HBsAg-positivity (OR, 2.22; 95% CI, 1.35-3.61; p=0.002) were factors that significantly influenced referral. Conclusion Hepatologists must educate non-hepatologists, especially non-internists, to promote the referral of hepatitis-virus carriers, especially HCV carriers, even in patients with ALT levels of ＜30 IU/L.

Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C

Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.

The Incidence of Hepatocellular Carcinoma after Balloon-Occluded Retrograde Transvenous Obliteration

Balloon-occluded retrograde transvenous obliteration (BRTO) is a highly effective therapy for gastric varices with liver cirrhosis. We have investigated the incidence of hepatocellular carcinoma (HCC) after BRTO. We enrolled 71 patients with viral hepatitis in which HCC had not appeared with liver imaging findings at the time of BRTO. The overall survival rate after BRTO was 86.8%, 76.1%, and 50.5% at 1, 3, and 5 years. The occurrence rate of HCC after BRTO was 20.9%, 41.1%, and 60.7% at 1, 3, and 5 years, especially showing a higher occurrence of HCC at one year. Meanwhile, the occurrence rate of HCC after treatment which excluded BRTO for esophagogastric varices in patients was 6.3%, 19.2%, and 42.5% at 1, 3, and 5 years. The log-rank test revealed that the occurrence rate of HCC after treatment was significantly higher in the BRTO group compared with that in the non-BRTO group (). The recurrence rate of HCC after BRTO was 35.8% and 80.0% at 1 and 3 years. The present study demonstrated a high incidence of HCC after BRTO in liver cirrhosis patients with viral hepatitis infection. We have suggested the potential for BRTO to accelerate hepatocarcinogenesis.