Photodynamic therapy with talaporfin sodium for endoscopically unresectable gastric cancer using a novel simultaneous light-emitting method.

We describe a case of gastric cancer treated by photodynamic therapy (PDT) with talaporfin sodium using a novel simultaneous light-emitting method. An 82-year-old man was diagnosed with gastric cancer near the cardia with suspected deep submucosal invasion. Surgical resection was deemed high-risk owing to an underlying pulmonary disease. After ruling out endoscopic procedures due to intense fibrosis resulting from the scarring, PDT with talaporfin sodium was chosen. PDT was successfully conducted using an endoscope with simultaneous light emission. The patient experienced a complete response to the treatment and showed no signs of recurrence during follow-up. This case highlights the potential of PDT with talaporfin sodium as a viable alternative for challenging cases, particularly in patients unsuitable for surgery and endoscopic resection. Furthermore, the novel simultaneous light-emitting method may improve the efficiency of the procedure. This case demonstrates the potential of PDT in gastric cancer treatment, especially for high-risk patients.

Successful second-line treatment with cabozantinib for hepatocellular carcinoma harboring cytoplasmic mesenchymal-epithelial transition factor amplification.

A 72-year-old man with metastatic hepatocellular carcinoma previously received first-line systemic therapy with atezolizumab plus bevacizumab. His disease was judged to be progressing 5 months after treatment initiation. Comprehensive genomic profiling revealed cytoplasmic mesenchymal-epithelial transition factor amplification. On the basis of an expert panel's recommendation, he received cabozantinib as second-line therapy. The tumors shrank markedly and continued to shrink 6 months after treatment. Comprehensive genomic profiling could provide useful information for selecting effective second-line treatments for patients with hepatocellular carcinoma after first-line immunotherapy.

Post-allogeneic Hematopoietic Stem Cell Transplantation Portal Hypertension Not Associated with Liver Cirrhosis, Veno-occlusive Disease, or Graft-versus-host Disease: A Case Report.

We herein report a rare case of idiopathic portal hypertension (IPH)-like disease that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A 53-year-old woman who underwent allo-HSCT for acute myeloid leukemia showed portal hypertension with radiological and histopathological findings consistent with IPH, distinct from veno-occlusive disease (VOD) and graft-versus-host disease (GVHD) of the liver. This case highlights the importance of considering IPH-like disease as a potential cause of portal hypertension after allo-HSCT. Awareness of this complication can aid in the early diagnosis and appropriate management of patients post allo-HSCT.

EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma.

Cleavage of erythropoietin-producing hepatocellular ephrin receptor A2 (EphA2) triggers malignant progression and yields an N-terminal fragment (EphA2-NF) detectable in sera from patients with pancreatic ductal carcinoma. We established a quantitative automated chemiluminescence immunoassay for EphA2-NF and evaluated serum EphA2-NF levels as a biomarker to diagnose pancreatic ductal carcinoma in the test and validation cohorts. The EphA2-NF value was elevated (above the cutoff: mean ± SD) in more than half of the patients with stage I/II pancreatic ductal carcinoma. Among patients receiving standard chemotherapy for pancreatic ductal carcinoma [gemcitabine plus nab-paclitaxel (GnP)], the median survival time of patients with elevated serum EphA2-NF was half that of patients with values below the cutoff. Patients with intraductal papillary mucinous neoplasm (IPMN), a precancerous pancreatic ductal carcinoma lesion, also show high serum EphA2 levels, which are associated with an increase in pancreatic duct size and the development of pancreatic ductal carcinoma in some cases. IHC showed loss of EphA2-NF staining in IPMN with pancreatic ductal carcinoma, but not in the normal epithelium or IPMN without pancreatic ductal carcinoma, regardless of the histologic grade. These results suggest that EphA2 cleavage is an essential event that occurs very early in pancreatic ductal carcinoma development, and that the consequent release of EphA2-NF can be detected in the serum. Thus, serum EphA2-NF could be a diagnostic biomarker for very early-stage pancreatic ductal carcinoma and pancreatic ductal carcinoma development from high-risk IPMN and as a prognostic biomarker after chemotherapy with GnP. SIGNIFICANCE: EphA2 N-terminus deletion is involved in pancreatic ductal carcinoma development from high-risk IPMN and EphA2-NF produced by cleavage can be used as a serum biomarker to diagnose pancreatic ductal carcinoma and predict pancreatic ductal carcinoma development from high-risk IPMN.

A case of frequent hypoglycemic attacks successfully controlled with capecitabine plus temozolomide and 177Lu-DOTATATE peptide receptor radionuclide therapy in a patient with recurrent pancreatic insulinoma.

A 59-year-old woman with metastatic pancreatic insulinoma, having undergone several treatment regimens including sunitinib, everolimus, lanreotide and streptozocin plus 5-fluorouracil, was admitted to our hospital because of frequent hypoglycemic attacks. These were refractory to medical treatment using diazoxide and required frequent daily intravenous glucose infusions. She was started on capecitabine and temozolomide (CAPTEM), followed by initiation of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT). The frequency of hypoglycemic attacks decreased after treatment began and she was discharged on day 58 post-admission, without requiring daily glucose infusions. CAPTEM and PRRT were continued without any major adverse events. Computed tomography revealed shrinkage of primary and metastatic lesions, an anti-tumor effect that continued 8 months after treatment was initiated. Hypoglycemic attacks caused by insulinomas are often refractory to conventional therapy; however, combination treatment using CAPTEM and PRRT has demonstrated a positive and significant response, successfully restoring glycemic control.

Aldo-keto reductase family 1 member B10 is regulated by nucleos(t)ide analogues for chronic hepatitis B.

The number of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients persists even under nucleos(t)ide analogues (NAs) treatment. Aldo-keto reductase family 1 member B10 (AKR1B10) expression has been reported in advanced chronic liver diseases as well as cancer tissues. We observed an association between related to HCC incidence and serum AKR1B10 by analyzing patients under treatment with NAs. Serum AKR1B10 levels measured by ELISA were higher in HCC cases under NA treatment compared with non-HCC cases and were associated with lamivudine- and adefovir pivoxil-, but not entecavir- or tenofovir alafenamide-treated cases. The latter drugs did not increase AKR1B10 values even in HCC cases, suggesting that they influence the reduction of AKR1B10 in any cases. This analysis was supported by in-vitro examination, which showed reduced AKR1B10 expression by entecavir and tenofovir via immunofluorescence staining. In conclusion there was a relationship between HBV-related HCC incidence and AKR1B10 under nucleos(t)ide analogues, especially in the use of lamivudine and adefovir pivoxil, but entecavir and tenofovir had suppressive effects of AKR1B10.

Plasma Antithrombin III Levels Can Be a Prognostic Factor in Liver Cirrhosis Patients with Portal Vein Thrombosis.

Liver function influences the plasma antithrombin (AT)-III levels. AT-III is beneficial for patients with portal vein thrombosis (PVT) and low plasma AT-III levels. However, whether these levels affect prognosis in patients with cirrhosis-associated PVT remains unknown. This retrospective study involved 75 patients with cirrhosis and PVT treated with danaparoid sodium with or without AT-III. The plasma AT-III level was significantly lower in patients with liver failure-related death than in those with hepatocellular carcinoma (HCC)-related death (p = 0.005), although the Child-Pugh and albumin-bilirubin (ALBI) scores were not significantly different between these two groups. Receiver operating characteristic curve analysis of the plasma AT-III levels showed cutoff values of 54.0% at 5-year survival. Low plasma AT-III levels (<54.0%) were associated with significantly worse prognosis than high levels in both overall survival (p = 0.0013) and survival excluding HCC-related death (p < 0.0001). Low plasma AT-III (<54.0%) was also associated with a significantly worse prognosis among patients with Child-Pugh A/B or ALBI grade 1/2 (p < 0.0001). Multivariate analyses indicated that low plasma AT-III levels (<54.0%) were an independent prognostic factor for poor survival outcome. Low plasma AT-III levels may be associated with mortality, particularly liver failure-related death, independent of liver function.

A randomised phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel for locally advanced pancreatic cancer (JCOG1407).

AIM: We compared the efficacy of modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) with that of gemcitabine plus nab-paclitaxel (GnP) for locally advanced pancreatic cancer (LAPC). METHODS: Patients with untreated LAPC were randomly assigned (1:1) to receive mFOLFIRINOX or GnP. One-year overall survival (OS) was the primary endpoint. The major secondary end-points included progression-free survival (PFS), response rate (RR), carbohydrate antigen 19-9 (CA19-9) response, and adverse events. The sample size was 124 patients to select a more effective regimen with a minimum probability of 0.85 and to examine the null hypothesis of the 1-year OS <53%. RESULTS: Of the 126 patients enrolled from 29 institutions, 125 were deemed eligible. The 1-year OS was 77.4% (95% CI, 64.9-86.0) and 82.5% (95% CI, 70.7-89.9) in the mFOLFIRINOX and GnP arms, respectively. The median PFS was 11.2 (95% CI, 9.9-15.9) and 9.4 months (95% CI, 7.4-12.8) in the mFOLFIRINOX and GnP arms, respectively. The RR and CA19-9 response rate were 30.9% (95% CI, 19.1-44.8) and 57.1% (95% CI, 41.0-72.3) and 42.1% (95% CI 29.1-55.9) and 85.0% (95% CI, 70.2-94.3) in the mFOLFIRINOX and GnP arms, respectively. Grade 3-4 diarrhoea and anorexia were predominant in the mFOLFIRINOX arm. CONCLUSION: GnP was considered the candidate for a subsequent phase III trial because of its better RR, CA19-9 response, and mild gastrointestinal toxicities. Both regimens displayed higher efficacy in the 1-year survival than in the historical data of gemcitabine monotherapy.

Successful second conversion surgery after trastuzumab deruxtecan for recurrent HER2-positive gastric cancer.

A 65-year-old woman with HER2-positive gastric cancer with multiple liver metastases underwent first conversion surgery of gastrectomy with D2 lymph nodes dissection and three liver metastases after combination therapy with capecitabine, cisplatin, and trastuzumab. Two years later, she experienced multiple liver metastases that were refractory to combination therapy with paclitaxel albumin-bound nanoparticles and ramucirumab. She participated in the DESTINY-Gastric01 trial and received tri-weekly trastuzumab deruxtecan as third-line treatment for 26 cycles. The recurrent lesions markedly shrank, and this effect continued for 19 months. We then performed partial hepatectomy for the one remaining lesion. No adjuvant chemotherapy was given, and she remains alive without recurrence 18 months after the second conversion surgery. Trastuzumab deruxtecan may generate a notable tumor response and subsequent conversion surgery could be a treatment option for HER2-positive stage IV gastric cancer.

Impact of coronavirus disease 2019 on the number of newly diagnosed cancer patients and examinations and surgeries performed for cancer in Japan: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has rapidly and dramatically influenced healthcare across Japan. However, the influence of the COVID-19 pandemic on the number of newly diagnosed cancer, surgical treatment, and diagnostic examination for cancer types have not been completely investigated all over Japan. This study aimed to analyze the number of cases before and during the COVID-19 pandemic. METHODS: This retrospective study was a survey that asked to provide the number of cases diagnosed with gastric, colorectal, lung, breast, and cervical cancer between January 2019 and December 2020. The survey was sent to tertiary healthcare hospitals, including national cancer institutions, university hospitals, and general hospitals, all over Japan. Data obtained from 105 of 486 surveyed hospitals were evaluated, and the number of cases in each quarter in 2020 was compared with that in the equivalent quarter in 2019. RESULTS: In the second quarter (Q2), significant reductions were observed in the median number of newly diagnosed cases from 2019 to 2020: gastric cancer, 26.7% (43 vs. 32, p <  0.001); colorectal cancer, 17.9% (52 vs. 40, p <  0.001); lung cancer, 12.3% (53.5 vs. 47, p <  0.001); and breast cancer, 13.1% (43 vs. 35.5, p <  0.001). A significant reduction of 11.4% (9 vs. 8, p = 0.03) was observed in the third quarter (Q3) for cervical cancer. In Q2, the number of cases decreased by 30.9% (25 vs. 15, p <  0.001) for stage I gastric cancer, by 27.3% (12 vs. 9, p <  0.001) for stage I colorectal cancer, and by 17.6% (13 vs. 10, p <  0.001) for stage II breast cancer. The magnitude of reduction was significant for the localized stages of gastric, colorectal, and breast cancer according to diagnostic examinations in Q2 and surgical and endoscopic treatment in Q3 rather than that for lung or cervical cancer. CONCLUSIONS: COVID-19 has prolonged collateral effects on cancer care, including examination, diagnosis, and surgery, with significant effects on gastric cancer, followed by colorectal, lung, breast, and cervical cancer in Japan.

Germline variants in cancer-predisposing genes in pancreatic cancer patients with a family history of cancer.

BACKGROUND: Our phase II trial (FABRIC study) failed to verify the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with pancreatic ductal adenocarcinoma (PDAC) with a familial or personal history of pancreatic, breast, ovarian or prostate cancer, which suggested that a family and personal history may be insufficient to determine response to platinum-based chemotherapy. METHODS: This ancillary analysis aimed to investigate the prevalence of germline variants of homologous recombination repair (HRR)-related genes and clarify the association of germline variants with the efficacy of GEMOX and patient outcome in PDAC patients. Of 45 patients enrolled in FABRIC study, 27 patients were registered in this ancillary analysis. RESULTS: Of the identified variants in HRR-related genes, one variant was considered pathogenic and eight variants in six patients (22%) were variants of unknown significance (VUS). Objective response to GEMOX was achieved by 43% of the seven patients and tended to be higher than that of patients without such variants (25%). Pathogenic/VUS variant in HRR-related genes was an independent favorable factor for progression-free survival (hazard ratio, 0.322; P = 0.047) and overall survival (hazard ratio, 0.195; P = 0.023) in multivariable analysis. CONCLUSIONS: The prevalence of germline variants in PDAC patients was very low even among patients with a familial/personal history of pancreatic, breast, ovarian or prostate cancer. Patients with one or more germline variants in HRR-related genes classified as pathogenic or VUS may have the potential to obtain better response to GEMOX and have better outcomes.

Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.

BACKGROUND/OBJECTIVES: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. METHODS: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. RESULTS: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. CONCLUSIONS: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.

Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells.

The behaviors and fates of immune cells in cancer patients, such as dysfunction and stem-like states leading to memory formation in T cells, are in intense focus of investigation. Here we show, by post hoc analysis of peripheral blood lymphocytes of hepatocellular carcinoma patients previously undergoing vaccination with tumour-associated antigen-derived peptides in our clinical trials (registration numbers UMIN000003511, UMIN000004540, UMIN000005677, UMIN000003514 and UMIN000005678), that induced peptide-specific T cell responses may persist beyond 10 years following vaccination. Tracking TCR clonotypes at the single cell level reveals in two patients that peptide-specific long-lasting CD8+ T cells acquire an effector memory phenotype that associates with cell cycle-related genes (CCNA2 and CDK1), and are characterized by high expression of IL7R, SELL, and NOSIP along with a later stage promotion of the AP-1 transcription factor network (5 years or more past vaccination). We conclude that effective anti-tumor immunity is governed by potentially proliferative memory T cells, specific to cancer antigens.

Delayed visit and treatment of lung cancer during the coronavirus disease 2019 pandemic in Japan: a retrospective study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on cancer care remains a concern. We aimed to evaluate access to diagnosis and treatment for lung cancer during the pandemic. METHODS: Times (days) from lung cancer symptom onset or referral to visit (pre-visit time), from visit to diagnosis (pre-diagnosis time), and from diagnosis to treatment (pre-treatment time) during the pandemic were compared with the times during the pre-pandemic period. RESULTS: The number of patients diagnosed with lung cancer was 82 and 75 during the pandemic and pre-pandemic periods, respectively. The percentage of patients with advanced-stage cancer was higher (65.9% vs. 46.7%), the percentage of patients treated with surgery was lower and the percentage treated with medication was higher (24.4% vs. 41.3% and 57.3% vs. 40.0%, respectively), the pre-visit time was longer (28.2 vs. 11.4 days), and the pre-treatment time for surgery was longer (67.3 vs. 45.6 days) during the pandemic compared with the times during the pre-pandemic period, respectively. CONCLUSIONS: The COVID-19 pandemic resulted in delayed diagnoses, which could have led to patients being diagnosed with advanced disease. The pandemic also resulted in delayed therapy owing to the requirement for available intensive care unit beds for emergencies, including surgery.

Risk factors for interstitial lung disease induced by gemcitabine plus albumin-bound paclitaxel therapy in pancreatic ductal adenocarcinoma patients.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) therapy is used for unresectable pancreatic ductal adenocarcinoma, but may cause interstitial lung disease (ILD) as a serious side effect. However, the risk factors for ILD in patients receiving GnP therapy are not well established. Here, we retrospectively investigated the incidence of GnP-induced ILD in pancreatic ductal adenocarcinoma patients, and the risk factors. METHODS: We investigated the patients' background, laboratory data, previous treatment history, concomitant medications, number of doses of GnP, cumulative dosage and administration period, and occurrence of side effects. RESULTS: Of the 105 patients included in this study, ILD occurred in 10 (9.5%). Patients with ILD had a significantly higher frequency of concomitant treatment with Kampo medicines, especially goshajinkigan, which is considered to help prevent chemotherapy-induced peripheral neuropathy (CIPN) (odds ratio: 11.5, 95% confidence interval: 2.67-49.38). No significant differences were observed in other clinical characteristics. Notably, the severity of CIPN in patients who used goshajinkigan for prevention was not significantly different from that in patients who did not use goshajinkigan in this study. CONCLUSIONS: These results suggest that administration of goshajinkigan to patients receiving GnP therapy for prevention of CIPN may need to be reconsidered.

Comparative analysis of medical costs after hepatectomy versus radiofrequency ablation in patients with hepatocellular carcinoma in real-world clinical practice.

AIM: To compare the total medical costs and treatment outcomes in patients with primary hepatocellular carcinoma (HCC) according to their initial treatment, that is, hepatectomy or radiofrequency ablation (RFA), in real-world clinical practice in Japan. METHODS: This retrospective observational study was conducted using a medical claims database. Patients who underwent hepatectomy or RFA for primary HCC were matched using propensity score matching methods for available baseline characteristics. The average per-patient total medical costs from the date of initial treatment to up to 3 years were estimated. The 3-year survival and recurrence rates were estimated using the Kaplan-Meier method. RESULTS: Data of 1726 patients (863 in each group) were analyzed. The average 3-year medical costs were USD 8000 lower in the RFA group than in the hepatectomy group (USD 35,000 vs. USD 43,000). Patients in the RFA group had comparable 3-year overall survival to those in the hepatectomy group (87.6% vs. 90.4%). However, the 3-year recurrence rate was significantly higher in the RFA group than in the hepatectomy group (41.5% vs. 30.8%; hazard ratio = 1.56, 95% confidence interval: 1.31-1.87). CONCLUSIONS: In this 3-year study, patients achieved similar survival rates irrespective of initial treatment, but the RFA group had a lower total medical cost burden than the hepatectomy group. If both treatments are equally feasible, RFA may be a preferable initial curative treatment for primary HCC. However, careful consideration and adequate treatment should be given due to its higher recurrence risk.

Non-small cell lung cancer with multiple brain metastases remains relapse-free for more than 13 years: A case report.

Brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC) is usually associated with a poor prognosis. A 55-year-old Japanese man visited Tokyo Dental College Ichikawa General Hospital with complaints of motor aphasia and fatigue. Enhanced magnetic resonance imaging of the brain revealed multiple tumors. The patient's medical history included lung cancer surgery performed at another hospital 3 months prior to his visit to our hospital. Total resection of the left frontal tumor revealed BM from lung adenocarcinoma. Stereotactic radiosurgery (SRS) was performed for the remaining three BMs. At 9 months after SRS, another new BM was discovered, and SRS was again performed. More than 13 years have elapsed since the last SRS was performed, and the patient has remained relapse-free. To the best of our knowledge, this is the first case report describing a patient with NSCLC with multiple BMs who has remained relapse-free for >13 years with no neurological dysfunction, including cognitive deficit.

Longitudinal Assessment of Prognostic Understanding in Patients with Advanced Lung Cancer and Its Association with Their Psychological Distress.

BACKGROUND: Accurate prognostic understanding in patients with advanced cancer is essential for shared decision making; however, patients may experience psychological burden through knowing the incurable nature of advanced cancer. It has been unclear how their prognostic understanding fluctuates and whether accurate prognostic understanding is associated with psychological distress from the time of diagnosis over time. MATERIALS AND METHODS: We longitudinally investigated prognostic understanding in 225 patients with newly diagnosed advanced lung cancer at 16 hospitals in Japan until 24 months after diagnosis. We examined associated factors with being consistently accurate in prognostic understanding, especially focusing on its association with psychological well-being. RESULTS: The proportion of patients with an inaccurate prognostic understanding remained approximately 20% over time with the presence of patients with inconsistent understanding. Patients with consistently accurate prognostic understanding showed a significantly lower Emotional Well-Being subscale score at both 3 and 6 months after diagnosis (p = .010 and p = .014, respectively). In multivariate analyses, being consistently accurate in prognostic understanding was significantly associated with female gender and higher lung cancer-specific symptom burden at 3 months (p = .008 and p = .005, respectively) and lower emotional well-being at 6 months (p = .006). CONCLUSION: Although substantial proportions of patients with advanced lung cancer had inaccurate prognostic understanding from the time of diagnosis over time, patients with consistently accurate prognostic understanding experienced greater psychological burden. Our findings highlight the importance of continuous psychological care and support for patients who understand their severe prognosis accurately. IMPLICATIONS FOR PRACTICE: This study demonstrated that approximately 20% of patients with advanced lung cancer had an inaccurate understanding about their prognosis, not only at the time of diagnosis but also at the later time points. Being consistently accurate in prognostic understanding was significantly associated with elevated levels of psychological distress. Although accurate prognostic understanding is essential for decision making for treatment and advance care planning, health care providers should be aware of psychological burdens in patients that accept their severe prognosis accurately. Appropriate care and support for such patients are warranted from diagnosis over time.

Decline in serum albumin concentration is a predictor of serious events in nonalcoholic fatty liver disease.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which includes diabetes mellitus and hyperlipidemia. A fraction of NAFLD patients develop nonalcoholic steatohepatitis, leading to cirrhosis associated with various serious complications, including hepatocellular carcinoma, gastroesophageal varices, cardiovascular events, and other organ malignancy. Although the incidence of chronic viral hepatitis with associated complications has gradually decreased as highly effective antiviral therapies have been established, the number of patients with steatohepatitis has been increasing.This retrospective study examined data of 229 patients from 22 hospitals in our region. We examined 155 cases of chronological data and assessed the development of liver fibrosis and evaluated hepatic reserve-related markers such as platelet count, FIB-4 index, prothrombin time, and serum albumin concentration. We analyzed the relationship of these chronological changes and the incidence of NAFLD related serious complications.Data related to liver fibrosis progression, albumin, and prothrombin time were significantly associated with the occurrence of serious complications associated with cirrhosis. We compared 22 event and 133 nonevent cases of chronological changes in the data per year and found that serum albumin concentration was significantly lower in the group that developed serious complications (event cases: -0.21 g/dL/year, nonevent cases: -0.04 g/dL/year (P < .001)). This albumin decline was only the associated factor with the event incidence by multivariate analysis (P < .01).Annual decline in serum albumin concentration in patients with NAFLD is associated with serious events from the outcome of multicenter retrospective study. This highlights its potential utility as a surrogate marker to assess the efficacy of prediction of NAFLD related serious events.