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The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase&nbsp

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Background: We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. Methods: A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. Results: The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. The objective response rate and disease control rate in all patients were 18.4% and 63.2%, respectively. Sixteen patients experienced no adverse events (AEs), whereas 4 patients discontinued therapy due to AEs. The median time to progression (TTP) was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P = 0.02). Patients with an AFP response (reduction ≥20% from baseline) at 6 weeks had a significantly longer TTP than those without an AFP response (P = 0.02). Conclusion: Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6 weeks could be a predictor of disease progression.

Although Makuuchi's criteria are widely used to determine the cut-off for safe liver resection, there have been few reports of concrete data supporting their validity. Here, we verified the utility of Makuuchi's criteria by comparing the operative mortality rates associated with liver resection between hepatocellular carcinoma (HCC) patients meeting or exceeding the criteria.A database was built using data from 15 597 patients treated between 2000 and 2007 for whom values for all three variables included in Makuuchi's criteria for liver resection (clinical ascites, serum bilirubin, and indocyanine green clearance) were available. The patients were divided into those fulfilling (n = 12 175) or exceeding (n = 3422) the criteria. The postoperative mortality (death for any reason within 30 days) and long-term survival were compared between the two groups.The operative mortality rate was significantly lower in patients meeting the criteria than in those exceeding the criteria (1.07% vs. 2.01%, respectively; p 0.001). On multivariate analysis, exceeded the criteria was significantly associated with the risk for operative mortality (relative risk 2.08; 95% confidence interval (CI), 1.23-3.52; p = 0.007). Surgical indication meeting or exceeding the criteria was an independent factor for overall survival (hazard ratio 1.27; 95% CI, 1.18-1.36; p 0.001).Makuuchi's criteria are suitable for determining the indication for resection of HCC due to the reduction in risk of operative mortality.

Alanine aminotransferase (ALT) is a criterion for the introduction of nucleotide/nucleoside analog (NA), and ALT levels are decreased by NA treatment. However, the association between post-treatment ALT levels and hepatocellular carcinoma (HCC) risk remains unclear. To fill this gap, we aimed to establish a target value of ALT level during NA treatment.In total, 413 patients with chronic hepatitis B who received entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate were enrolled. The subsequent development of HCC was examined and a target value of ALT level during NA treatment as a risk marker for HCC was evaluated.The median follow-up duration was 5.1 years, during which time 27 patients (8.6%) developed HCC. ALT level at the start of treatment was not associated with HCC development (p = 0.08). When stratified by ALT at 1 year after NA initiation, the cumulative 3- and 5-year rates of HCC for patients with ALT ≥21 IU/L were 11.5% and 18.1%, and those with ALT21 IU/L was 2.3% and 6.5%, respectively. Patients with ALT21 IU/L had a significantly lower risk of HCC development compared with patients with ALT ≥21 IU/L (p = 0.002). In multivariable analysis adjusting age, sex, and platelet counts, ALT ≥21 IU/L was an independent risk factor of HCC development with hazard ratio of 4.5 (95% confidence interval: 1.01-20.4).ALT21 IU/L at 1 year after NA initiation has a lower risk of HCC and could be used as a target value for NA treatment.

Objective Rifaximin is used to treat hepatic encephalopathy. However, whether or not rifaximin and lactulose combination therapy can enhance the treatment outcomes and reduce the hospitalization rate of patients with hepatic encephalopathy that are resistant to lactulose has yet to be determined. The present study investigated the hospitalization rate before and after rifaximin add-on therapy in patients resistant to lactulose. Methods A total of 36 patients who were resistant to lactulose with add-on rifaximin therapy were enrolled. Patients who were hospitalized and/or did not achieve normalization of ammonia levels under lactulose administration were defined as treatment-resistant. The primary outcome was the change in hospitalization rate due to hepatic encephalopathy at 24 weeks before and after rifaximin administration. Results Before rifaximin administration, 15 (41.6%) patients were hospitalized due to hepatic encephalopathy. After rifaximin administration, 8 (22.2%) patients were hospitalized due to hepatic encephalopathy. The hospitalization rates were significantly reduced after rifaximin administration (p=0.02). The median (interquartile range) ammonia levels upon rifaximin administration (baseline) and 8, 12, and 24 weeks after rifaximin administration were 124 (24-310) μg/dL, 78 (15-192) μg/dL, 67 (21-233) μg/dL, and 77 (28-200) μg/dL, respectively. Furthermore, the ammonia levels were significantly reduced by rifaximin add-on therapy (p=0.005, p=0.01, and p=0.01). Conclusion The addition of rifaximin to lactulose treatment in treatment-resistant patients decreases the hospitalization rate among patients with hepatic encephalopathy and may be used as an add-on treatment.

Background and Aim Administration of tenofovir alafenamide (TAF) as prevention or treatment of hepatitis B virus (HBV) reactivation is not well known. The aim of this study is to reveal the efficacy and safety of TAF against HBV reactivation. Methods Entecavir (ETV) and TAF were given to 66 and 11 patients, respectively, as prophylaxis against or treatment of HBV reactivation during chemotherapy or immune suppression therapy from January 2010 to June 2020. The antiviral effects and safety were assessed. Results At week 24, the antiviral effects on patients receiving ETV and TAF were similar in terms of reduction of HBV DNA (−2.83 ± 1.45log IU/mL vs −3.05 ± 2.47log IU/mL; P = 0.857) and achieving undetectable levels of HBV DNA (78.8 vs 90.9%; P = 0.681). There was no significant difference in the decrease in the estimated glomerular filtration rate (eGFR) between the two groups (−0.62 ± 11.2 mL/min/1.73 m2 vs −3.67 ± 13.2 mL/min/1.73 m2; P = 0.291). Conclusion TAF is safe and effective against HBV reactivation., The aim of this study is to reveal the efficacy and safety of tenofovir alafenamide (TAF) as prophylaxis against or treatment of hepatitis B virus (HBV) reactivation. The antiviral effects in terms of HBV DNA reduction on patients receiving entecavir and TAF were similar, and there was no significant difference in renal dysfunction between both groups. TAF is safe and effective against HBV reactivation.

Background and Aims: A retrospective study was to analyze the association of plasma renin activity (PRA) with overall survival and liver disease-related events in decompensated liver cirrhosis with ascites treated by tolvaptan. Methods: We included 196 patients with decompensated cirrhosis treated with tolvaptan and for whom hepatic ascites had remained uncontrolled by conventional diuretics. Factors associated with prognosis and appearance of liver disease-related events were investigated, including vasopressin, sympathetic nervous system hormones (adrenaline, noradrenaline, and dopamine), and the renin-angiotensin system (PRA and aldosterone) at the beginning of tolvaptan treatment. Results: Age, history of hepatocellular carcinoma (HCC), and PRA were identified as independent factors for prognosis after tolvaptan treatment. The median survival time in patients with PRA ≥9.5 ng/mL/h at the beginning of tolvaptan treatment was significantly shorter than in patients with PRA p < 0.001). PRA and a history of HCC were independent factors for the occurrence of liver disease-related events. The median event-free period in patients with PRA ≥3.2 ng/mL/h was significantly shorter than that of patients with PRA p < 0.001). Conclusions: PRA is an independent predictor of prognosis and appearance of liver disease-related events in patients with decompensated cirrhosis who have started tolvaptan treatment.

Background and aim The association between liver fibrosis, fatty liver, and cardiovascular disease (CVD) risk is unknown. Hence, this study aimed to investigate the association of liver fibrosis and fatty liver with CVD risk independent of already known CVD risk comorbidities. Methods This is a prospective study registered with the University Hospital Medical Information Network clinical trial registry (UMIN000036175). Liver fibrosis was assessed by serum fibrosis markers including FIB-4, nonalcoholic fatty liver disease fibrosis score (NFS), and Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP), whereas fatty liver was diagnosed by ultrasonography. CVD risk was evaluated using the Framingham risk score (FRS), and a high CVD risk was defined as an FRS ≥ 20%. Results A total of 3512 subjects were enrolled, and high CVD risk (FRS ≥ 20%) was observed in 17.5%. Advanced fibrosis (FIB-4 ≥ 2.67, NFS ≥ 0.675, and WFA+ -M2BP ≥ 1.0) and the presence of fatty liver were significantly associated with high CVD risk independent of diabetes mellitus, dyslipidemia, and hypertension. When subjects were stratified by liver fibrosis and fatty liver, subjects with advanced fibrosis and fatty liver have the highest odds for high CVD risk (odds ratio [OR]: 5.90-35.6), followed by subjects with advanced fibrosis and without fatty liver (OR: 2.53-9.62) using subjects without advanced fibrosis and fatty liver as a reference. Conclusions Liver fibrosis and fatty liver were associated with CVD risk independent of already known CVD risk comorbidities. The assessment of liver fibrosis and fatty liver may be useful to identify high CVD risk subjects.

The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1- and 2-infected patients with decompensated cirrhosis. A total of 65 patients with HCV-related decompensated cirrhosis (Child-Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed. SVR was defined as undetectable serum HCV RNA at 12 weeks after the end of treatment (SVR12). The percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 81.2% (95% confidence interval [CI], 69.5-89.9) (52/64), 98.4% (95% CI, 91.2-100.0) (60/61), and 98.5% (95% CI, 91.7-100.0) (64/65), respectively. The overall SVR rate was 92.3% (95% CI, 83.0-97.5) (60/65). Albumin-bilirubin (ALBI) scores decreased during and after treatment (p

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the multicenter study. We investigated the relationship between various AFP response thresholds (relative decline ≥ 20%, ≥ 50%, and ≥ 75%) and treatment response and progression-free survival (PFS). An AFP relative decrease of ≥ 50% was associated with an overall response rate (ORR) with an odds ratio (95% confidence interval [CI]) of 5.7 (1.9-17). Disease control rate (DCR) was associated with an AFP relative decrease of ≥ 20%, with a 100% positive predictive value and a 52.0% sensitivity. AFP relative decreases of ≥ 50% and ≥ 20% were significantly associated with PFS with a hazard ratio (HR) of 5.60 (95% CI: 1.6-19, p = 0.006) and a HR of 4.44 (95% CI: 1.9-10, p 0.001), respectively. AFP response of ≥ 50% and ≥ 20% were related to ORR and DCR, respectively, and both of these responses were also associated with PFS. AFP can be used as a real-time monitor during Atez/Bev treatment and is helpful for treatment optimization.

Background: The present study aimed to clarify the efficacy and safety of ramucirumab in a real-world setting, including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: In total, 79 patients with hepatocellular carcinoma (HCC) from 14 institutes throughout Japan were retrospectively analyzed. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and AEs were recorded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: Median overall survival (OS) in the total cohort was 7.5 months (m). Median OS was 8.8 m in patients who were administered ramucirumab as a second-line treatment, while it was 7.3 m in third- or later-line treatment. Progression-free survival rates in the second- and third- or later-line therapies were 3.2 m and 3.2 m, respectively. The disease control rate (DCR) in the study was 43%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events (AEs), the development of ascites was observed significantly more frequently in modified albumin–bilirubin (mALBI) 2b/3 patients than in mALBI 1/2a patients (54.5% vs. 25.0%, p = 0.03). Conclusions: Ramucirumab is useful as a second-line therapy and feasible as a third- or later-line treatment for HCC.

Introduction: KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. Methods: Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. Results: The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6–4.1) versus 1.4 months (95% CI 1.4–2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32–0.70). The median OS was 13.8 months (95% CI 10.1–16.9) for pembrolizumab versus 8.3 months (95% CI 6.3–11.8) for placebo (HR 0.55; 95% CI 0.37–0.80). ORR was 20.6% (95% CI 13.4–29.5) for pembrolizumab versus 2.0% (95% CI 0.1–10.6) for placebo (difference: 18.5%; 95% CI 8.3–27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3–5 TRAEs, respectively. No treatment-related deaths occurred. Conclusion: Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.

NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD. We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD—8 studies) patients. The overall NAFLD prevalence was 25.5%, higher in males (p

Carcinogenesis risk scores for chronic hepatitis B have been proposed, but it remains unclear whether these scores during nucleoside/nucleotide analogue (NA) therapy are useful for risk assessment. In this study, we examined changes of these scores and the predictability during NA treatment. 432 patients with no history of hepatocellular carcinoma (HCC) treated with NA were enrolled. PAGE-B, modified PAGE-B (mPAGE-B), and REACH-B scores were calculated at NA administration, 1 and 2 years after administration. The median follow-up duration was 5.1 years, during which 37 patients (8.6%) developed HCC. Cumulative incidence HCC development in patients with high risk of PAGE at NA administration, and 1 and 2 years after NA administration was significantly higher than those with intermediate and low-risk groups (p

An accurate evaluation of liver fibrosis is clinically important in chronic liver diseases. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for liver fibrosis. In this review, we discuss the role of M2BPGi in diagnosing liver fibrosis in chronic hepatitis B and C, chronic hepatitis C after sustained virologic response (SVR), and nonalcoholic fatty liver disease (NAFLD). M2BPGi predicts not only liver fibrosis but also the hepatocellular carcinoma (HCC) development and prognosis in patients with chronic hepatitis B and C, chronic hepatitis C after SVR, NAFLD, and other chronic liver diseases. M2BPGi can also be used to evaluate liver function and prognosis in patients with cirrhosis. M2BPGi levels vary depending on the etiology and the presence or absence of treatment. Therefore, the threshold of M2BPGi for diagnosing liver fibrosis and predicting HCC development has to be adjusted according to the background and treatment status.

Antiviral therapy advancements resulted in an era in which eradication of hepatitis C has become a goal, however, there are few reports on the long-term course of liver disease progression with antiviral therapy. The aim of this study was to use the Markov model to analyze disease progression and non-invasive liver fibrosis index in hepatitis C Patients.Patients with chronic hepatitis C (n = 1432) were diagnosed between January 2012 and May 2021 in the Musashino Red Cross Hospital. Patients with other hepatitis virus co-infection, chronic liver disease, and hepatocellular carcinoma (HCC) at the beginning of the study were excluded. A total of 618 patients with a 1-year or longer observation period were studied. The liver disease state was defined as chronic hepatitis (CH), compensated liver cirrhosis (CLC), decompensated liver cirrhosis (DLC), and HCC.Cirrhosis and high FIB-4 index (≥3.61) were 42 cases (6.8%) and 208 cases (33.6%), respectively at the start of the study. The 40 years estimated transition analysis of 40-year-old CH low FIB-4 level (3.61) revealed that the proportion of CH low/high, CLC low/high, DLC low/high, and HCC were 10.83%/10.86%, 0.35%/2.64%, 0%/3.21% 72.11% in untreated unit and 47.83%/9.21%, 6.69%/1.32%, 0.70%/0.99%, 33.27% in treated unit, respectively. Antiviral therapy suppressed liver fibrosis, disease progression, and HCC development significantly.Markov model analysis of hepatitis C virus patients showed the impact of antiviral therapy on the suppression of disease progression in the order of CH, CLC, and DLC.

Liver fibrosis is the most important prognostic factor in patients with nonalcoholic fatty liver disease (NAFLD). Several noninvasive markers for fibrosis, including blood-based markers and imaging based-markers have been developed. Indirect fibrosis markers (e.g., fibrosis-4 index and NAFLD fibrosis score) consist of standard laboratory data and clinical parameters. Given its availability and high negative predictive value for advanced fibrosis, these markers are suitable for screening at primary care. Blood-based fibrogenesis markers (enhanced liver fibrosis and N-terminal propeptide of type 3 collagen), ultrasound-based modalities (vibration-controlled transient elastography, point shear wave elastography [SWE], and two-dimensional SWE), and magnetic resonance elastography have high diagnostic accuracy for liver fibrosis and are suitable for diagnosing liver fibrosis at secondary care centers. Sequential use of these markers can increase diagnostic accuracy and reduce health care costs. Furthermore, combining noninvasive makers may assist in identifying candidates for pharmacological trials and reducing screening failure. Emerging data suggest that these noninvasive markers are associated with liver-related events (hepatocellular carcinoma and decompensation) and mortality. Furthermore, delta change in noninvasive markers over time is also associated with time-course change in fibrosis, liver-related event risk, and mortality risk. However, the association between liver fibrosis and cardiovascular disease (CVD) risk is still controversial. CVD risk may decrease in patients with decompensated liver disease and noninvasive markers may be useful for assessing CVD risk in these patients. Therefore, noninvasive markers may be utilized as measures of fibrosis as well as real-time prognostic tools, in place of liver biopsy.

Improvements in the hepatocellular carcinoma (HCC) recurrence rate and survival have been frequently reported following virus eradication after hepatitis C virus (HCV)-related HCC cure. However, the efficacy of direct-acting antiviral (DAA) therapy in patients who included those with advanced HCC and decreased hepatic functional reserve is unknown. A comparative examination was retrospectively conducted of 141 patients with hepatitis C who started DAA therapy within 1 year after undergoing curative HCC treatment and showed a sustained viral response (SVR) and 327 patients who underwent curative treatment for HCV-related HCC and did not subsequently receive antiviral therapy. Whether DAA therapy was given was identified as an independent factor related to both HCC recurrence and survival. Both the recurrence and survival rates improved significantly with DAA therapy in Child-Pugh (CP)-A, whereas no difference in the recurrence rate was seen with DAA therapy in CP-B. However, the survival rate was significantly higher in the DAA group in this class. Similarly, dividing the patients by the Milan criteria showed significant improvements in the recurrence rate and survival with DAA therapy in patients within the Milan criteria. Patients with HCC beyond the Milan criteria showed no difference in recurrence rates, but the DAA group tended to have higher survival rates. Thus, DAA after curative therapy for HCC can be expected to improve survival in patients with advanced HCC or decreased hepatic functional reserve. HCV should be aggressively eradicated in all patients eligible for curative treatment of HCC.

Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan. A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT). The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child–Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child–Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl. Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.