Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort.

BACKGROUND & AIMS: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study. METHODS: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C). RESULTS: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS. CONCLUSION: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Impact of COVID-19 pandemic on surveillance of hepatocellular carcinoma: A study in patients with chronic hepatitis C after sustained virologic response.

Background: The current coronavirus disease 2019 (COVID-19) pandemic has strongly influenced many aspects of the medical care, including cancer surveillance. Aims: We investigated how the COVID-19 pandemic influenced surveillance for hepatocellular carcinoma (HCC), focusing on patients with hepatitis C virus infection who were receiving surveillance for HCC after sustained virologic response (SVR) in Japan. Methods: Patients who achieved SVR between 1995 and 2017 and continued receiving surveillance were compared by month in terms of the rate at which they kept their scheduled visits for HCC surveillance from July 2019 to May 2020. Results: The percentage of kept scheduled visits was above 97% before February 2020. By contrast, it declined sharply after March 2020 when COVID-19 became pandemic; the percentages were 75.5% in March, 63.0% in April and 49.1% in May 2020 (July 2019-February 2020 vs March-May 2020, P < 0.0001). Similar declines were observed in patients with cirrhosis or advanced fibrosis and in those with a history of HCC. Whereas most patients who cancelled a scheduled visit before February 2020 did not reschedule it, the majority of patients with cancellations after March 2020 did want to reschedule. Conclusions: The percentages of scheduled visits that were kept declined rapidly after COVID-19 became pandemic in Japan, although the spread of COVID-19 is relatively mild and the legal restriction of people's behaviour and movement is absent. Instituting measures to follow-up with cancelled patients and resume surveillance will be necessary in the future.

Viral eradication reduces all-cause mortality, including non-liver-related disease, in patients with progressive hepatitis C virus-related fibrosis.

BACKGROUND AND AIM: Eradication of hepatitis C virus (HCV) with interferon (IFN)-based therapy has been reported to reduce all-cause mortality in patients with chronic HCV infection. However, the impact of HCV eradication on non-liver-related mortality and causes of death has not been sufficiently investigated in patients with progressive HCV-related fibrosis. METHODS: We enrolled 784 chronic HCV patients with progressive liver fibrosis (aspartate aminotransferase to platelet ratio index >1). Cause of death, incidence of hepatocellular carcinoma, and all-cause mortality including non-liver-related mortality were analyzed. RESULTS: Of these 784 patients, 170 achieved sustained virological response (SVR) (eradication of HCV) with IFN-based therapy (IFN-SVR), and 614 did not receive IFN-based therapy (non-IFN patients, chronic HCV infection). The median follow-up duration was 10.3 years. Two hundred seventy-three patients died during follow-up (liver-related death, n = 171; non-liver-related death, n = 102). The mortality rate from non-liver-related disease was 63.6% (7/11) in IFN-SVR patients and 36.3% (95/262) in non-IFN patients, respectively. In multivariate analysis, the eradication of HCV associated with not only hepatocellular carcinoma incidence (hazard ratio (HR), 0.162; 95% confidence interval (CI), 0.092-0.284), and all-cause mortality (HR, 0.094; 95% CI, 0.047-0.187), but non-liver-related mortality (HR, 0.286; 95% CI, 0.127-0.644) as well. CONCLUSIONS: Eradication of HCV reduced both liver-related and non-liver-related mortality in patients with progressive HCV-related fibrosis.

Post-treatment levels of α-fetoprotein predict long-term hepatocellular carcinoma development after sustained virological response in patients with hepatitis C.

AIM: The rate of hepatocellular carcinoma (HCC) development is reportedly lower in patients with chronic hepatitis C virus (HCV) who have achieved a sustained virological response (SVR) than in patients who were unresponsive to therapy. However, the development of HCC is sometimes observed in patients with SVR. Therefore, we clarified the predictive power of clinical factors for HCC incidence in patients with SVR using receiver operating characteristic (ROC) curve analysis that takes time dependence into account. METHODS: A total of 571 patients with HCV who achieved SVR with interferon-based therapy were enrolled. Univariate and multivariate Cox proportional hazards models and time-dependent ROC curves were used to analyze clinical factors associated with the development of HCC. RESULTS: Twenty-four patients developed HCC during the follow-up period (median duration, 9.0 years). The 5-, 10-, 15-, and 20-year cumulative incidence rates for HCC were 1.7%, 4.8%, 5.8%, and 6.6%, respectively. Multivariate Cox proportional hazards models showed that older age (hazard ratio [HR], 3.648), male sex (HR, 7.560), lower platelet count at 24 weeks after the end of treatment (SVR24) (HR, 3.939), and higher α-fetoprotein (AFP) at SVR24 (HR, 3.630) were independently associated with HCC development. In addition, time-dependent ROC analysis showed that, compared to platelet count at SVR24, AFP at SVR24 had higher predictive power for HCC incidence approximately 7 years after SVR. CONCLUSIONS: Elevated AFP at SVR24 is a risk factor for HCC in patients with HCV, even those who achieve SVR. α-Fetoprotein is a good predictor of HCC development.

HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics.

BACKGROUND & AIMS: Several hepatitis B virus (HBV) markers have been identified as factors associated with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We clarified the predictive power of HBV markers for the development of HCC using receiver operating characteristic (ROC) analysis with a consideration of time dependence. METHODS: A total of 1031 CHB patients who were not treated with nucleos(t)ide analogue therapy were enrolled. Univariate, multivariate, and time-dependent ROC curves for HBV markers associated with the development of HCC were analyzed. RESULTS: Seventy-eight patients developed HCC during the follow-up period (median duration 10.7years). Different levels or statuses of several HBV markers (HBV genotype, HBV DNA, HBV core-related antigen (HBcrAg), hepatitis B e antigen (HBeAg), and basal core promoter (BCP)), but not hepatitis B surface antigen, were significantly associated with the incidence of HCC by univariate analysis using the log-rank test. Cox proportional hazards models using the covariates of HBV genotype status, HBV DNA levels, HBcrAg levels, HBeAg status, and BCP status indicated that HBcrAg >2.9logU/ml (hazard ratio (HR), 5.05; 95% confidence interval (CI), 2.40-10.63) and BCP mutation (HR, 28.85; 95% CI, 4.00-208.20) were independently associated with the incidence of HCC. Additionally, time-dependent ROC analysis showed that HBcrAg was superior to HBV DNA in terms of predictive power for HCC development throughout the follow-up period. CONCLUSIONS: Elevation of HBcrAg levels in CHB patients is associated with the development of HCC. HBcrAg is an excellent predictor of HCC development. LAY SUMMARY: Hepatitis B virus (HBV) core-related antigen (HBcrAg) is an excellent predictor of hepatocellular carcinoma (HCC) development in chronic hepatitis B patients without nucleos(t)ide analogue therapy. HBcrAg was superior to HBV DNA in terms of predictive power for HCC development by time-dependent receiver operating characteristic analysis.

Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection: a propensity score analysis.

BACKGROUND & AIMS: Eradication of hepatitis C virus (HCV) by interferon (IFN)-based therapy has been reported to reduce all-cause mortality rates in patients with chronic HCV infection. However, the impact of HCV eradication on non-liver-related mortality including the causes of death has not been sufficiently investigated in patients with chronic HCV infection. METHODS: We enrolled 2743 patients with chronic HCV infection. Causes of death, incidence of hepatocellular carcinoma (HCC), and all-cause mortality including non-liver-related diseases, were analysed. RESULTS: Of these 2743 patients, 587 achieved sustained virological response (SVR) (eradication of HCV) by IFN-based therapy (IFN-SVR), 475 did not (without HCV eradication) (IFN-non-SVR), or 1681 did not receive IFN-based therapy (non-IFN patients) (Cohort 1); of these, 309 were selected from IFN-SVR and non-IFN groups using propensity score matching (Cohort 2).The median follow-up duration was 11.4 years. In Cohort 1 patients, mortality rates from non-liver-related diseases were 71.0% (22/31) in IFN-SVR patients, 34.9% (37/106) in IFN-non-SVR patients and 50.0% (248/496) in non-IFN patients respectively. In Cohort 2 patients, mortality rates from non-liver-related diseases were 72.2% (13/18) in IFN-SVR patients and 46.8% (29/62) in non-IFN patients respectively. The eradication of HCV reduced all-cause mortality (hazard ratio (HR), 0.265; 95% confidence interval (CI), 0.058-0.380) including non-liver-related mortality (HR, 0.439; 95% CI, 0.231-0.834) and the incidence of HCC (HR, 0.275; 95% CI, 0.156-0.448). CONCLUSIONS: Eradication of HCV reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.

Long- and short-term outcomes of ERCP for bile duct stones in patients over 80 years old compared to younger patients: a propensity score analysis.

UNLABELLED: Backgrounds and study aims: Endoscopic sphincterotomy (ES) is widely accepted as first-line therapy for bile duct stones (BDS). The major long-term pancreaticobiliary complication is BDS recurrence. Whether cholecystectomy should be performed after ES, especially in elderly patients, remains controversial. The aim of this study is to investigate the short-term and long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for BDS and to analyze risk factors for pancreaticobiliary complications. We also compared long-term outcomes in patients older and younger than age 80. PATIENTS AND METHODS: A total of 1210 patients who underwent therapeutic ERCP for BDS were retrospectively reviewed to identify risk factors for pancreaticobiliary complications. We divided these patients into two groups: Group Y (< 80 years; 960 patients) and Group O (≥ 80 years; 250 patients). There were 192 matched pairs in the propensity score analysis. RESULTS: The incidence of pancreaticobiliary complications was 13.1 % (126/960) in Group Y and 20.4 % (51/250) in Group O (P < 0.00001). Multivariate analysis showed that a gallbladder left in situ with stones was a significant independent risk factor (hazard ratio, 2.81; 95 % confidence interval, 1.62 - 4,89; P = 0.0002). There were no significant differences in the incidence of pancreaticobiliary complications between the propensity score-matched groups. CONCLUSIONS: A gallbladder in situ with stones was the only significant risk factor for pancreaticobiliary complications after treatment for BDS. Age per se should not be the major factor when deciding on treatment that minimizes the occurrence of pancreaticobiliary disease.

Long-term prognosis of patients with chronic hepatitis C who did not receive interferon-based therapy: causes of death and analysis based on the FIB-4 index.

BACKGROUND: Interferon (IFN)-based therapy has been reported to reduce the liver-related mortality rate in patients with chronic hepatitis C virus (HCV) infection. However, predictors of survival and causes of death, including non-liver-related causes, have not been sufficiently investigated in chronic HCV patients who have not received IFN-based therapy. METHODS: A total of 1723 patients with chronic HCV infection who were not treated with IFN-based therapy were enrolled. Survival from liver-related diseases and non-liver-related diseases and causes of death were analyzed on the basis of the fibrosis-4 (FIB-4) index, an index of liver fibrosis. RESULTS: The median follow-up duration was 10.3 years. Of 465 patients who died during the follow-up period, 48.4 % died of liver-related diseases; of the remainder, 51.6 % died of non-liver-related diseases. On the basis of FIB-4 index, the liver-related mortality rate increased as the FIB-4 index increased: 16.1 % in the FIB-4 index < 1.45 group, 36.7 % in the 1.45 ≤ FIB-4 index ≤ 3.25 group, and 58.7 % in the FIB-4 index > 3.25 group (p < 0.001). Conversely, the non-liver-related mortality rate decreased as the FIB-4 index increased: 83.9, 63.3, and 41.3 %, respectively (p = 0.001). In the multivariate analysis, a FIB-4 index greater than 3.25 was identified as a risk factor independently associated with both liver-related death (hazard ratio 13.020; 95 % confidence interval 4.155-40.770) and non-liver-related death (hazard ratio 1.667; 95 % confidence interval 1.188-2.340). CONCLUSIONS: Patients with chronic HCV infection and an elevated FIB-4 index may benefit from monitoring not only for the development of liver-related diseases but also for the development of non-liver-related diseases.

Impact of the branched-chain amino acid to tyrosine ratio and branched-chain amino acid granule therapy in patients with hepatocellular carcinoma: A propensity score analysis.

BACKGROUND AND AIM: It has been reported that the branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is a useful indicator of liver function and BCAA therapy is associated with a decreased incidence of hepatocellular carcinoma (HCC). However, there has not been sufficient research on the relationship between BTR and the effects of BCAA therapy after initial treatment of HCC. We investigated the impact of BTR and BCAA therapy on survival in patients with HCC. METHODS: A total of 315 patients with HCC who were treated (n = 66) or not treated (n = 249) with BCAA were enrolled; of these, 66 were selected from each group using propensity score matching. Survival from liver-related mortality was analyzed. RESULTS: In patients who did not receive BCAA therapy (n = 249), multivariate analysis for factors associated with survival indicated that low BTR (≤ 4.4) was independently associated with poor prognosis in patients with HCC (hazard ratio, 1.880; 95% confidence interval, 1.125-3.143; P = 0.016). In addition, among patients selected by propensity score matching (n = 132), multivariate analysis indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio, 0.524; 95% confidence interval, 0.282-0.973; P = 0.041). BTR was not significantly associated with survival. CONCLUSIONS: Intervention involving BCAA therapy improved survival in patients with HCC versus untreated controls, regardless of BTR. In addition, low BTR was associated with poor prognosis in patients who did not receive BCAA therapy.

Risk factors of hepatocellular carcinoma development in non-cirrhotic patients with sustained virologic response for chronic hepatitis C virus infection.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, that is eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV-infected patients who achieved SVR. METHODS: The incidence and risk factors for HCC were evaluated in 522 patients who achieved SVR with interferon-based antiviral therapy for HCV. Patients maintained regular follow-up every 6 months for HCC surveillance. The FIB-4 index and aspartate aminotransferase to platelet count ratio index were calculated based on laboratory data at the time that SVR was documented (SVR24). RESULTS: Patients continued follow-up visits for 1.0-22.9 years (median, 7.2 years) after SVR. HCC developed in 18 patients. The incidence of HCC was 1.2% at 5 years and 4.3% at 10 years. The use of peginterferon or ribavirin for treatment and a history of antiviral therapy prior to the course when SVR was achieved were not associated with the incidence of HCC after SVR. The presence of diabetes mellitus (risk ratio 2.08; P = 0.0451) and FIB-4 index calculated at the time of SVR24 (risk ratio 1.73; P = 0.0198) were associated with a higher likelihood of HCC after SVR by multivariate analysis. CONCLUSIONS: Patients with diabetes mellitus and patients with the elevation of FIB-4 index at SVR24 are at higher risk of HCC after SVR. Surveillance for HCC should be continued in this patient subpopulation.

Long-term prognosis of patients with hepatitis B infection: causes of death and utility of nucleos(t)ide analogue therapy.

BACKGROUND: Long-term nucleos(t)ide analogue (NA) therapy for chronic hepatitis B (CHB) patients has been reported to reduce the risk of hepatocellular carcinoma (HCC) development. However, survival rates and causes of death in CHB patients either treated or not treated with NA therapy are unclear. Therefore, we investigated the prognosis of CHB in both of these groups. METHODS: A total of 919 CHB patients who were treated (n = 189) or not treated (n = 730) with NA therapy were enrolled; of these, 135 were selected from each group by propensity score matching. Survival, mortality from both HCC and non-liver related diseases, and causes of death were analyzed. RESULTS: In all patients (n = 919), cumulative survival and mortality from both HCC and non-liver related diseases did not differ significantly according to NA therapy status. Of 66 patients who died during the follow-up period, 59.1% died due to liver-related diseases (including HCC); of the remainder, 48.1% died of non-liver related malignancies. In patients selected by propensity score matching (n = 270), cumulative survival and mortality from HCC were significantly improved in those who received NA therapy compared with those who did not (p = 0.015 and 0.018, respectively). Cox proportional hazards models indicated that NA therapy was independently associated with survival of CHB patients (hazard ratio, 0.286; 95% confidence interval, 0.122-0.668; p = 0.004). CONCLUSIONS: Approximately 40% of CHB patients died of non-liver-related diseases. Additionally, in patients who required anti-viral therapy for CHB, NA therapy improved survival and mortality from HCC.

[Case of small bowel angioectasia in which the resection site was angiographically detected using intraoperative dye infusion].

A 37-year-old Japanese man undergoing treatment for dilated cardiomyopathy was presented with weakness and melena. He had conjunctival pallor and difficulty in standing;his blood pressure was 81/62 mmHg. Abdominal computed tomography revealed contrast dye leakage into the small intestine. He was diagnosed with hemorrhagic shock secondary to intestinal bleeding;we administered large volumes of intravenous fluid along with performing a blood transfusion. We then performed angiography to determine the site of bleeding angioectasia and placed a catheter into the affected artery. We identified the resection site using an intraoperative dye infusion via the catheter, and successfully performed small bowel resection. He was subsequently discharged without complications.

Oral supplementation with branched-chain amino acid granules prevents hepatocarcinogenesis in patients with hepatitis C-related cirrhosis: A propensity score analysis.

AIM: It has been reported that branched-chain amino acids (BCAA) supplementation can improve nutritional status and reduce liver-related complications in patients with decompensated cirrhosis. BCAA supplementation reportedly reduces the incidence of hepatocellular carcinoma (HCC) in obese cirrhotic patients infected with hepatitis C virus (HCV). We investigated the effects of oral supplementation with BCAA granules on hepatocarcinogenesis in patients with HCV-related cirrhosis using propensity score matching. METHODS: A total of 60 patients with HCV-related cirrhosis and without history of HCC who were selected by one-to-one matching of propensity scores: 30 patients receiving 12 g/day of BCAA granules for 3 months or more (BCAA group) and 30 being observed without BCAA supplementation (control group). The impact of BCAA supplementation was analyzed on the incidence of HCC. RESULTS: The 3- and 5-year rates of HCC development were 13.7% and 13.7% in the BCAA group and 35.1% and 44.5% in the control group, respectively. The BCAA group had a significantly lower rate of HCC than the control group (P = 0.032). Multivariate analysis for factors that were associated with hepatocarcinogenesis indicated that BCAA supplementation was independently associated with a reduced incidence of HCC (hazard ratio 0.131; 95% confidence interval, 0.032-0.530; P = 0.004) along with sex and serum α-fetoprotein. Obesity (body mass index, ≥25 kg/m(2) ) was not significantly associated with an increased incidence of HCC. CONCLUSION: Oral supplementation with BCAA granules is associated with a reduced incidence of HCC in patients with HCV-related cirrhosis regardless of the presence of obesity based on the propensity score analysis.

Transnasal Endoscope Locked in a Bent Position Causing Difficult Withdrawal.

We report a rare but severe complication of routine transnasal esophagogastroduodenoscopy (EGD). The tip of a transnasal endoscope was locked in a bent position. Since the bent tip was unable to be returned to a neutral position, the snare from another endoscope inserted transorally was used to straighten it, which allowed the transnasal endoscope to be withdrawn with only mild injury to the gastric mucosa. Endoscopists should be aware of this complication and how to manage it.

High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma.

BACKGROUND: Prognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site. METHODS: Of consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3 years prior to HCC diagnosis. RESULTS: In the present study, hs-AFP-L3 was elevated 1 year prior to diagnosis in 34.3 % of patients. The survival rate of patients with the hs-AFP-L3 ≥ 7 % at 1 year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3 < 7 %. CONCLUSIONS: Elevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.

Association between hepatic steatosis and hepatic expression of genes involved in innate immunity in patients with chronic hepatitis C.

BACKGROUNDS/AIMS: We investigated the association between hepatic steatosis and hepatic expression of genes involved in innate immunity, both of which are reportedly associated with resistance to peginterferon (PEG-IFN) and ribavirin combination therapy for hepatitis C virus (HCV) infection. METHODS: A total of 122 patients infected with HCV genotype 1b who underwent and completed PEG-IFN and ribavirin combination therapy were studied. Hepatic steatosis was evaluated on the basis of the liver specimen biopsied prior to antiviral therapy. The levels of mRNA of innate immunity genes (RIG-I, MDA5, LGP2, Cardif, RNF125, ISG15, and USP18) were measured by real-time polymerase chain reaction in RNA extracted from biopsied liver tissue and compared between patients with and without hepatic steatosis. RESULTS: The proportion of patients with hepatic steatosis, the hepatic expression levels of RIG-I gene, and RIG-I/Cardif and RIG-I/RNF125 ratios were significantly higher in patients in whom serum HCV RNA did not disappear throughout the treatment period. Hepatic expression of RIG-I and the ratios of RIG-I/Cardif and RIG-I/RNF125 were significantly higher in patients with steatosis than those without. CONCLUSIONS: Changes in hepatic expression of some genes involved in innate immunity were observed along with hepatic steatosis, possibly playing a mechanistic role in resistance to IFN-based therapy in patients with hepatic steatosis.

Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: a propensity score analysis.

BACKGROUND & AIMS: Some patients with chronic hepatitis B virus (HBV) infection progress to hepatocellular carcinoma (HCC). However, the long-term effect of nucleos(t)ide analogue (NA) therapy on progression to HCC is unclear. METHODS: Therefore, we compared chronic hepatitis B patients who received NA therapy to those who did not, using a propensity analysis. RESULTS: Of 785 consecutive HBV carriers between 1998 and 2008, 117 patients who received NA therapy and 117 patients who did not, were selected by eligibility criteria and propensity score matching. Factors associated with the development of HCC were analyzed. In the follow-up period, HCC developed in 57 of 234 patients (24.4%). Factors significantly associated with the incidence of HCC, as determined by Cox proportional hazards models, include higher age (hazard ratio, 4.36 [95% confidence interval, 1.33-14.29], p=0.015), NA treatment (0.28 [0.13-0.62], p=0.002), basal core promoter (BCP) mutations (12.74 [1.74-93.11], p=0.012), high HBV core-related antigen (HBcrAg) (2.77 [1.07-7.17], p=0.036), and high gamma glutamyl transpeptidase levels (2.76 [1.49-5.12], p=0.001). CONCLUSIONS: NA therapy reduced the risk of HCC compared with untreated controls. Higher serum levels of HBcrAg and BCP mutations are associated with progression to HCC, independent of NA therapy.

Characteristics of elderly hepatitis C virus-associated hepatocellular carcinoma patients.

BACKGROUND AND AIM: The average age of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) patients has been rising in Japan. We evaluate characteristics of HCV-positive patients who develop HCC in older age to determine an optimal surveillance strategy. METHODS: A total of 323 patients with three or more years of follow-up before HCC diagnosis and 323 propensity-matched controls without HCC were studied. HCC patients were classified into four groups according to age at the time of HCC diagnosis: group A (≤ 60 years, n = 36), group B (61-70 years, n = 115), group C (71-80 years, n = 143), and group D (> 80 years, n = 29). Clinical and laboratory data were compared. RESULTS: Platelet counts were significantly higher in the older groups at HCC diagnosis (P < 0.0001). The rate of platelet counts decline was lower in older groups (P = 0.0107). The average integration value of serum alanine aminotransferase (ALT) in groups A, B, C, and D were 80.9 IU/L, 62.3 IU/L, 59.0 IU/L, and 44.9 IU/L, respectively (P < 0.0001). In older patients (≥ 65 years old), cirrhosis and average integration value of ALT were significantly associated with hepatocarcinogenesis, but platelet count was not. CONCLUSION: Elderly HCV-positive patients (≥ 65 years old) with low ALT values developed HCC regardless of their platelet counts. These findings should be taken into account when designing the most suitable HCC surveillance protocol for this population.

Higher hepatic gene expression and serum levels of matrix metalloproteinase-2 are associated with steatohepatitis in non-alcoholic fatty liver diseases.

We investigated the gene expression of tissue inhibitor metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) and serum levels of TIMPs, MMPs, and hyaluronic acid that are associated with liver fibrosis in 64 patients with nonalcoholic fatty liver diseases (NAFLD). Whereas, no differences were found between patients with and without nonalcoholic steatohepatitis (NASH) in serum levels of hyaluronic acid when excluding NASH patients with advanced fibrosis, the quantity of MMP2 mRNA in liver tissue and serum MMP2 levels were significantly higher in patients with NASH than those without, even focusing on patients with less advanced fibrosis, indicating the initiation of liver fibrosis.

Markedly lower follow-up rate after liver biopsy in patients with non-alcoholic fatty liver diseases than those with viral hepatitis in Japan.

BACKGROUND: Patients with non-alcoholic fatty liver diseases (NAFLD) are recommended to have periodic follow-up exams because these patients are at increased risk of the presence of non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis or hepatocellular carcinoma. We investigated the follow-up status of NAFLD patients after a liver biopsy examination. METHODS: We compared the follow-up rates of NAFLD patients who had received an ultrasonography-guided liver biopsy and patients who had received a liver biopsy for chronic viral hepatitis (hepatitis B or C). RESULTS: The 1- and 3-year follow-up rates after the liver biopsy were 92.7% and 88.3% for patients with chronic HBV infection, and 93.4% and 88.2% for patients with chronic HCV infection, respectively. In contrast, the follow-up rates for NAFLD patients were 77.6% and 49.9%, respectively, which were significantly lower than those of patients with chronic viral hepatitis (p < 0.0001). Among NAFLD patients, the respective 1- and 3-year follow-up rates were 73.0% and 44.6% for patients with simple steatosis and 80.0% and 52.4% for patients with NASH based on a pathologic diagnosis, without significant difference between these two subgroups (p = 0.5202). CONCLUSIONS: The outpatient-based follow-up rate after a liver biopsy was significantly lower in NAFLD patients compared to patients with chronic viral hepatitis, regardless of the presence of NASH. It is important to determine how to maintain regular hospital visits for NAFLD patients, preventing patient attrition.