Aims: Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non-malignant complications among Japanese NAFLD and NASH patients. Methods: An English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria. Results: Hepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%-20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality. Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH-HCC). With longer follow-up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH-HCC patients also have a higher post-operative mortality than HCV-HCC patients. Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non-NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients. Conclusion: Hepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.

Introduction Intrauterine contraceptive devices (IUCD) are a commonly used, reversible, contraceptive method. Complications from insertion rarely include migration into the bladder. We report on two cases of intravesical migrated IUCD and present an algorithm for management based on recently published data. Materials and Methods The case records of two patients who underwent surgical procedures for migrated IUCD into the bladder were reviewed. A Pubmed search was performed to identify similar studies. A total of 25 papers met the criteria for inclusion. Results Both cases were managed with laparotomy and partial cystectomy. A review of literature suggests recently reported cases of IUCD migration are rising, with most cases having been reported in the last decade. Bladder calculus developing over the migrated IUCD is the most common presentation. Most cases have been managed using endourological techniques. A small number of cases have required open vesicolithotomy or laparoscopic surgery. Rarely, laparotomy has been required. Discussion IUCD migration into the bladder remains rare, however, recently the number of reported cases has risen. A thorough physical examination and radiological evaluation are warranted. Management is surgical in all cases. Most cases can be managed with endourological techniques. A treatment algorithm has been suggested in this paper based on recent data. Conclusion With the rising use of contraception worldwide, the incidence of IUCD migration is possibly going to increase. Treating doctors need to be aware of the possible complications that may arise from a migrated IUCD, including bladder calculi.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent a growing unmet medical need and an increasingly prevalent cause of cirrhosis, hepatocellular carcinoma (HCC), and death in Japan. The aim of this review was to characterize the epidemiology of NAFLD and NASH in Japan. An English and Japanese literature search was conducted in PubMed, Embase, and ICHUSHI Web, identifying 6553 studies, 67 of which were included. Prevalence of NAFLD in the Japanese population rose from the early 1990s (12.6-12.9%) to the early 2000s (24.6-34.7% of the population). Japanese NASH prevalence is estimated to be 1.9-2.7%. NAFLD and NASH are more common among males than females; however, females experience more severe disease than males. While obese patients had higher prevalence of NAFLD/NASH, nonobese individuals (body mass index [BMI] <25 kg/m 2) consistently comprised 20% to >35% of NAFLD and NASH patients. The evidence shows that, despite obesity being linked with worse disease stages, "lean-NASH" also plays an important role in NASH epidemiology. Besides obesity, diabetes and metabolic syndrome appeared to be reliably associated with disease severity. The prevalence of advanced fibrosis or cirrhotic disease was the highest in patients with NASH-HCC (44-80% with stage F3/F4 disease), while 21-50% of patients with NASH had F3/F4 disease. NAFLD/NASH is common in the Japanese population, and the prevalence of these conditions has tripled in the last two decades. Furthermore, these NAFLD/NASH patients have a high comorbidity burden. Early and efficient identification of safe and effective treatments for NAFLD/NASH patients is urgently needed.

Despite the invasive nature of liver biopsy, it remains the current standard for diagnosing non‐alcoholic steatohepatitis (NASH) and fibrosis staging. Given the rising prevalence of non‐alcoholic fatty liver disease (NAFLD) in Japan, there is a need for reliable non‐invasive tests to accurately and efficiently identify NASH and advanced (F3/F4) fibrosis. A review of published works from English and Japanese sources was undertaken in PubMed, Embase, and Ichushi Web to identify studies reporting diagnostic characteristics of NITs in biopsy‐proven Japanese NAFLD/NASH patients including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve. The performance of non‐invasive tests for two diagnostic questions were assessed, namely: (i) identifying NASH cases among NAFLD; and (ii) distinguishing advanced fibrosis (F3–4) from milder fibrosis (F0–2). Twenty‐five studies reported outcomes for serum biomarkers, imaging, scoring systems, and novel complex techniques (based on multivariable regression models) for both diagnostic questions. Serum biomarkers were the most commonly assessed method for NASH identification, whereas scoring systems and imaging techniques were most commonly studied for fibrosis staging. In general, tests for NASH identification showed higher PPVs than NPVs, suggesting their usefulness in identifying probable NASH cases. The reverse was observed for fibrosis staging, with higher NPVs than PPVs, suggesting their use in excluding patients at low risk of F3/F4 disease rather than identifying definite F3/F4 fibrosis. In Japanese studies, simple scoring systems and imaging techniques showed particular usefulness in prediction of fibrosis staging, and combinations of serum biomarkers showed diagnostic potential for NASH screening.

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