Metabolic management after sustained virologic response in elderly patients with hepatitis C virus: A multicenter study.

AIMS: Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct-acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. METHODS: We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α-fetoprotein (AFP), Fibrosis-4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. RESULTS: A total of 86 patients (6.7%) developed HCC during the follow-up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04-1.11, P = 0.0008), Fibrosis-4 index (HR 1.17, CI 1.08-1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40-6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis-4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD. CONCLUSION: MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL.

A combination of hepatic encephalopathy and body mass index was associated with the point of no return for improving liver functional reserve after sofosbuvir/velpatasvir treatment in patients with hepatitis C virus-related decompensated cirrhosis.

AIMS: The real-world efficacy of sofosbuvir/velpatasvir treatment for patients with hepatitis C virus-related decompensated cirrhosis is unclear. We aimed to identify factors that improve liver functional reserve after treatment. METHODS: This was a multicenter retrospective study of 12-week sofosbuvir/velpatasvir treatment. A total of 48 patients with Child-Pugh (CP) class B or C were enrolled at 11 institutions. We evaluated changes in liver functional reserve at 24 weeks post-treatment. RESULTS: At baseline, 40 and eight patients were CP class B and C, respectively. The overall rate of sustained virologic response 12 weeks post-treatment was 95.8% (46/48). Serum albumin, alanine aminotransferase and α-fetoprotein levels, and the FIB-4 index were significantly improved post-treatment (P < 0.05). Among patients who achieved sustained virologic response 12 weeks post-treatment, those with CP class A increased from 0 to 24 patients (56%) at 24 weeks post-treatment. In multivariate analysis, body mass index (BMI) ≥25 was an independent factor that inhibited CP class improvement (P < 0.05). In decision tree analysis, after treatment, the initial divergent variable for CP class improvement was hepatic encephalopathy, followed by serum sodium level and BMI. CONCLUSION: Sofosbuvir/velpatasvir treatment improved the liver functional reserve in patients with hepatitis C virus-related decompensated cirrhosis at 24 weeks post-treatment. However, BMI ≥25 inhibited improvement in CP class. Additionally, decision tree analysis revealed that a combination of hepatic encephalopathy, serum sodium levels, and BMI were diversity profiles associated with no improvement in liver functional reserve after the treatment.

Risk of malignancies in autoimmune hepatitis type 1 patients with a long-term follow-up in Japan.

AIM: The risk of malignancies in autoimmune diseases is high and is regarded to be due to immunological abnormalities, the use of immunosuppressive agents, and/or chronic inflammation. The aim of this study was to investigate the incidence and risk of malignancies in patients with autoimmune hepatitis (AIH) type 1 in Japan. METHODS: Two hundred and fifty-six patients diagnosed with AIH were enrolled. A person-year calculation was carried out for AIH patients, and the numbers of expected events were clarified using data from "The Monitoring of Cancer Incidence in Japan Project" in order to examine the standard incident rate (SIR) of each type of malignancy. Biochemical data regarding carcinogenesis and its background factors were also examined. RESULTS: Twenty-seven patients (10.5%) developed malignancies; 11 (4.3%) with hepatobiliary cancer and 16 (6.3%) with extrahepatic malignancies. The overall SIR for malignancies in AIH was significantly high at 2.04 (95% confidence interval [CI], 1.34-2.96), and was high among female patients at 2.49 (95% CI, 1.60-3.71). The SIR for hepatobiliary cancer was 14.14 (95% CI, 7.05-25.30), and was markedly high for female patients at 21.83 (95% CI, 10.45-40.16). The SIR for oral/pharyngeal cancer was significantly high for female patients at 14.61 (95% CI, 1.64-52.77). The risk factors for hepatobiliary cancer at the diagnosis of AIH were low levels of alanine aminotransferase (P = 0.0226), low platelet counts (P < 0.0001), and cirrhosis (P = 0.0004). The risk factor for extrahepatic malignancy was relapse of AIH (P = 0.0485). CONCLUSION: The risk of malignancies was generally high among AIH patients. Those with the risk factors of malignancies should be carefully followed up.

Marked accumulation of fluorodeoxyglucose and inflammatory cells expressing glucose transporter-3 in immunoglobulin G4-related autoimmune hepatitis.

Immunoglobulin (Ig)G4-related autoimmune hepatitis (AIH) is a recently proposed subtype that responds well to steroid treatment; however, its pathogenesis remains unclear. We report here a 65-year-old Japanese woman with skin itching and lip swelling. She had liver injury with jaundice, which persisted despite stopping anti-allergic agents. Blood chemistry revealed highly elevated serum IgG and IgG4 (535 mg/dL) levels, and positive anti-nuclear antibody. The diagnosis of AIH was based on liver biopsy. Notably, the IgG4+ /IgG+ cell ratio was 85%. On fluorodeoxyglucose (FDG) positron emission tomography/computed tomography, robust signal intensity was found in the liver, and in enlarged lymph nodes and salivary glands with confirmed IgG4+ cell infiltration. Immunofluorescence analysis of the liver biopsy specimen indicated clear expression of glucose transporter-3 (Glut-3) in IgG4+ inflammatory cells infiltrating into the portal area. This is the first report of simultaneous strong accumulation of FDG and Glut-3 expression in IgG4-related AIH, which might aid in elucidating the pathogenesis of this disease.

Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans.

UNLABELLED: Epithelial cell adhesion molecule (EpCAM) is a surface marker on human hepatic stem/progenitor cells that is reported as absent on mature hepatocytes. However, it has also been noted that in cirrhotic livers of diverse causes, many hepatocytes have EpCAM surface expression; this may represent aberrant EpCAM expression in injured hepatocytes or, as we now hypothesize, persistence of EpCAM in hepatocytes that have recently derived from hepatobiliary progenitors. To evaluate this concept, we investigated patterns of EpCAM expression in hepatobiliary cell compartments of liver biopsy specimens from patients with all stages of chronic hepatitis B and C, studying proliferation, senescence and telomere lengths. We found that EpCAM(+) hepatocytes were rare in early stages of disease, became increasingly prominent in later stages in parallel with the emergence of ductular reactions, and were consistently arrayed around the periphery of cords of keratin 19(+) hepatobiliary cells of the ductular reaction, with which they shared EpCAM expression. Proliferating cell nuclear antigen (proliferation marker) and p21 (senescence marker) were both higher in hepatocytes in cirrhosis than in normal livers, but ductular reaction hepatobiliary cells had the highest proliferation rate, in keeping with being stem/progenitor cell-derived transit amplifying cells. Telomere lengths in EpCAM(+) hepatocytes in cirrhosis were higher than EpCAM(-) hepatocytes (P < 0.046), and relatively shorter than those in the corresponding ductular reaction hepatobiliary cells (P = 0.057). CONCLUSION: These morphologic, topographic, immunophenotypic, and molecular data support the concept that EpCAM(+) hepatocytes in chronic viral hepatitis are recent progeny of the hepatobiliary stem/progenitor cell compartment through intermediates of the transit amplifying, ductular reaction hepatobiliary cells.

Case Report: A Rare Case of Benign Recurrent Intrahepatic Cholestasis-Type 1 With a Novel Heterozygous Pathogenic Variant of ATP8B1.

Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is a rare autosomal recessive disorder that is characterized by intermittent episodes of jaundice and intense pruritus and caused by pathogenic variants of adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1). The presence of genetic heterogeneity in the variants of ATP8B1 is suggested. Herein, we describe a unique clinical course in a patient with BRIC1 and a novel heterozygous pathogenic variant of ATP8B1. A 20-year-old Japanese man experienced his first cholestasis attack secondary to elevated transaminase at 17 years of age. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, or inborn or acquired metabolic etiologies. Since the patient also had elevated transaminase and hypoalbuminemia, he was treated with ursodeoxycholic acid and prednisolone. However, these treatments did not relieve his symptoms. Histopathological assessment revealed marked cholestasis in the hepatocytes, Kupffer cells, and bile canaliculi, as well as a well-preserved intralobular bile duct arrangement and strongly expressed bile salt export pump at the canalicular membrane. Targeted next-generation sequencing detected a novel heterozygous pathogenic variant of ATP8B1 (c.1429 + 2T > G). Taken together, the patient was highly suspected of having BRIC1. Ultimately, treatment with 450 mg/day of rifampicin rapidly relieved his symptoms and shortened the symptomatic period.

Hepatitis C Virus Elimination Using Direct Acting Antivirals after the Radical Cure of Hepatocellular Carcinoma Suppresses the Recurrence of the Cancer.

It remains unclear whether hepatocellular carcinoma (HCC) recurrence in hepatitis C virus (HCV)-infected patients can be suppressed by the elimination of the virus using direct-acting antivirals (DAAs) after radical HCC treatment. We evaluated the sustained inhibitory effect of DAAs on HCC recurrence after curative treatment. This multicenter retrospective study included 190 HCV-positive patients after radical treatment for early-stage HCC. Patients were classified into the DAA treatment group (n = 70) and the non-DAA treatment group (n = 120) after HCC treatment. After propensity score matching (PSM), 112 patients were assessed for first and second recurrences using the Kaplan-Meier method and analyzed using a log-rank test. The first recurrence rates at 1 and 3 years were 3.6% and 42.1% in the DAA treatment group and 21.7% and 61.9% in the non-DAA treatment group, respectively (p = 0.0026). Among 85 patients who received radical treatment, the second recurrence rate at 3 years was 2.2% in the DAA treatment group and 33.9% in the non-DAA treatment group (p = 0.0128). In HCV-positive patients with early-stage HCC, the first and second recurrences were suppressed by DAA therapy after radical treatment, suggesting that the inhibitory effect of DAA therapy on HCC recurrence was sustained.

Growth differentiation factor 15 as a novel diagnostic and therapeutic marker for autoimmune hepatitis.

Growth differentiation factor 15 (GDF15) has been reported to be associated with fibrosis and cancer in liver disease. Diagnosis of autoimmune hepatitis (AIH) is often difficult because of the lack of specific markers. We investigated whether GDF15 is useful for diagnosing AIH and determined its therapeutic effects. We enrolled 171 Japanese patients as follows: AIH (n = 45), hepatitis B (HB) (n = 17), hepatitis C (HC) (n = 15), primary biliary cholangitis (PBC) (n = 20), and 74 healthy controls. Serum GDF15 levels were measured, and immunohistological analyses of GDF15 were performed using liver tissue of AIH patients. (1) GDF15 levels (pg/ml) were higher in AIH (1994.3 ± 1258.0) and HC (1568.0 ± 822.3) than in HB (953.2 ± 871.4), PBC (643.9 ± 247.0), and controls (475.3 ± 145.3) (p < 0.0001), as well as in cirrhosis patients (n = 31) than in non-cirrhosis patients (n = 66) (1926.6 ± 1026.0 vs. 1249.1 ± 1124.1, p < 0.0001). In non-cirrhosis patients, GDF15 levels were higher in AIH (1914.0 ± 1327.2) than in HC (955.7 ± 502.7), HB (519.3 ± 197.5), and PBC (643.9 ± 247.0) (p < 0.0001). (2) GDF15 was positively correlated with M2BPGi (r = 0.7728), total bilirubin (r = 0.6231), and PT-INR (r = 0.6332). (3) GDF15 levels could be used to distinguish AIH from other liver diseases in non-cirrhosis patients, with an area under the curve of 0.9373 (sensitivity 93.6%, specificity 79.3%, cut-off value 931.3). (4) GDF15 in AIH decreased after treatment. (5) Immunohistological analyses in AIH liver tissues revealed that GDF15 was strongly expressed in inflammatory cells, hepatic cytoplasm, and sinusoidal endothelial cells, but decreased after treatment. GDF15 is a novel diagnostic marker for AIH and is also expected to be a therapeutic marker for AIH.Clinical Trials Registration: The study protocol was approved by the institutional review board of Kurume University (Approval No.: 19049).

TAFRO Syndrome That Responded to Prednisolone-only Treatment: Evaluating Changes in IL-6.

Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is a systemic inflammatory disorder characterized by the above-mentioned symptoms. Because of the similarity in phenotypes between TAFRO syndrome and decompensated liver cirrhosis, an accurate diagnosis is often difficult. We herein report a 62-year-old Japanese patient with TAFRO syndrome who was misdiagnosed with intractable ascites associated with liver cirrhosis. Improvement of symptoms after treatment with prednisolone was associated with interleukin-6 rather than C-reactive protein. The pathogenesis of TAFRO syndrome, which has similar clinical manifestations to liver cirrhosis, remains unclear, and our findings may help elucidate the concept of this condition.

Tenofovir Alafenamide Rescues Renal Tubules in Patients with Chronic Hepatitis B.

Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal dysfunction develops in patients with the long-term treatment of NAs including adefovir dipivoxil and tenofovir disoproxil fumarate. Recently, several studies have reported that the newly approved tenofovir alafenamide (TAF) has a safe profile for the kidney due to greater plasma stability. In this mini-review, we discuss the effectiveness of switching to TAF for NAs-related renal tubular dysfunction in patients with CHB.

Enhanced liver fibrosis score as a predictive marker for hepatocellular carcinoma development after hepatitis C virus eradication.

Advanced liver fibrosis is the most important risk factor for hepatocellular carcinoma (HCC) development after achieving sustained virological response (SVR) by direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C. Wisteria floribunda agglutinin-positive Mac-2-binding protein (M2BPGi), enhanced liver fibrosis (ELF) score, type IV collagen and fibrosis-4 (FIB-4) index have been reported as non-invasive biomarkers for liver fibrosis. In the present study, the possibility of using fibrosis biomarkers and other parameters to predict the development of HCC was evaluated. A total of 743 patients infected with hepatitis C virus who achieved SVR by using DAA were retrospectively enrolled. Of these, 122 patients whose blood samples were stored were selected. The aforementioned four fibrosis biomarkers were analyzed at baseline, at the end of treatment (EOT) and at post-treatment week 24 (PTW24). Tumor markers and laboratory tests were also analyzed. The baseline/EOT/PTW24 values for each fibrosis biomarker were as follows: ELF score: 11.5±1.2/10.8±1.1/10.4±1.0; type IV collagen: 213±85/190±67/174±55 ng/ml; M2BPGi: 4.8±3.5/2.7±2.0/2.2±1.8; and FIB-4 index: 5.31±3.82/4.36± 2.79/4.24±3.09. Of the 122 patients, 23 developed HCC. A high baseline ELF score (P=0.0264), PTW24 ELF score (P=0.0003), PTW24 α-fetoprotein level (P=0.0133), baseline FIB-4 index (P=0.0451) and low baseline prothrombin time (P=0.0455) were risk factors for HCC development based on univariate analyses. Based on the multivariate analysis, a high PTW24 ELF score was the only risk factor for HCC development (P=0.0035). The ELF score after DAA therapy was strongly associated with HCC development; therefore, it may be a useful marker for predicting HCC.

Short-term efficacy after switching from adefovir dipivoxil and tenofovir disoproxil fumarate therapy to tenofovir alaferamide for chronic hepatitis B.

The aim of the present study was to evaluate the effects of switching to tenofovir alafenamide (TAF) in patients who had received a nucleos(t)ide analog (NA) for the treatment of chronic hepatitis B (CHB). The data from 33 Japanese patients with CHB who received TAF therapy after using NA [adefovir dipivoxil (ADV) and/or tenofovir disoproxil fumarate (TDF)] were retrospectively analyzed. Specifically, the biochemical and virological markers from the start of the TAF treatment to 6 months later were assessed. Comparative evaluation was performed by dividing patients into two groups: Long-term (n=19) and short-term administration groups (n=14), with a cutoff administration duration of 10 years. In all 33 patients, the levels of serum hepatitis B surface antigen (HBsAg; 1,126±1,724 to 1,001±1,591 IU/ml; P<0.0001), serum alkaline phosphatase (ALP) (320±126 to 283±124 U/l; P=0.028), serum bone specific alkaline phosphatase (19.7±9.0 to 17.7±8.0 µg/l; P=0.0006) and urine ß2-microglobulin-creatinine ratio (U-BMG/Cr; 5,224±17,471 to 3,547±14,652 µg/g·Cre; P=0.002) significantly decreased from baseline after 6 months. Serum HBsAg, serum ALP and U-BMG/Cr showed a significant reduction in both groups. In conclusion, switching from ADV or TDF to TAF resulted in a decrease in serum HBsAg and improvement in serum ALP and U-BMG/Cr after 6 months of treatment in patients regardless of history of treatment with NA.

Prednisolone-responsive primary sclerosing cholangitis with autoimmune hemolytic anemia: a case report and review of the literature.

We report a case of primary sclerosing cholangitis (PSC) with autoimmune hemolytic anemia (AIHA). A 47-year-old woman was diagnosed with PSC. One year later, she was admitted to our hospital for jaundice and fatigue. Magnetic resonance cholangiopancreatography (MRCP) showed worsening of the biliary stricture, and rapidly progressive anemia developed simultaneously. Based on the various laboratory findings, she was diagnosed with AIHA. The administration of prednisolone improved not only the anemia but also the biliary stricture. This case is impactful, as there are few case reports of PSC with AIHA. In addition, we were able to observe the changes in imaging findings using MRCP over time.

A randomized study of extended treatment with peginterferon alpha-2b plus ribavirin based on time to HCV RNA negative-status in patients with genotype 1b chronic hepatitis C.

OBJECTIVES: The treatment of patients with hepatitis C virus (HCV) genotype 1 with peginterferon plus ribavirin treatment for more than 48 weeks demonstrated high sustained virological response (SVR) rates. Although many studies extended the duration of therapy from 48 weeks to 72 weeks, the optimal duration has not yet been determined. METHODS: A total of 113 genotype 1b patients with high viral load were randomized at baseline to the standard (n=56) or extended (n=57) treatment group. The standard group patients received 48 weeks of peginterferon plus ribavirin treatment. In the extended group, the treatment was performed for 44 weeks after patients became negative for HCV RNA (total duration 48-68 weeks). RESULTS: The SVR rate of the standard and extended group was 36% (20 of 56) and 53% (30 of 57; P=0.07). However, the extended group patients who became negative for HCV RNA between weeks 16 and 24 had a significantly higher SVR rate (78%; 7 of 9) than that of standard group (9%, 1 of 11; P=0.005). The predictive factors for the SVR were the treatment regimen (the standard vs. extended treatment) and the time to HCV RNA negative-status. CONCLUSIONS: The extended treatment significantly increased the SVR rate in patients who were HCV RNA negative at 16-24 weeks.

The hepatic stem cell niche: identification by label-retaining cell assay.

UNLABELLED: Label retention assays remain the state-of-the-art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow. We used a sublethal dose of acetaminophen administered coincident with bromodeoxyuridine to load possible hepatic stem cells in mice with label and then administered a second, sublethal chase of acetaminophen to accomplish "washout" of label from transit amplifying cell populations. CONCLUSION: Four possible hepatic stem cell niches are identified by this approach: the canal of Hering (proximal biliary tree), intralobular bile ducts, periductal "null" mononuclear cells, and peribiliary hepatocytes. These results confirm several different and often contradictory lines of investigation regarding the intrahepatic location of stem/progenitor cells and suggest that the liver has a multi-tiered, flexible system of regeneration rather than a single stem/progenitor cell location.

Histological changes in patients who developed hepatocellular carcinoma after hepatitis C virus eradication by interferon-based therapy.

Although the incidence of hepatocellular carcinoma (HCC) occurring after hepatitis C virus (HCV) eradication has decreased, there are still reports of hepatocarcinogenesis. The present study investigated the histological changes of non-cancerous liver tissue obtained prior to interferon (IFN) therapy and after HCC development. A total of 669 HCV-infected Japanese patients who achieved sustained virological response (SVR) by IFN-based therapy were retrospectively enrolled. Of these, the present study investigated 18 patients who developed HCC after IFN-based SVR. Specimens from 9 of 18 patients were available for histological comparisons prior to IFN therapy and following HCC development. Of these 9 patients, the specimens of 5 individuals were compared via immunohistochemical staining [CD3, CD4, CD8, CD20, forkhead box P3 (FOXP3), transforming growth factor-ß1 and granzyme B]. The current study included 6 control patients with HCV-associated chronic liver disease who subsequently developed HCC (non-SVR-HCC group). Mann-Whitney and Wilcoxon tests were used to compare groups. Bonferroni correction was used for multiple comparisons. P<0.05 was used as a critical P-value, and following Bonferroni's correction, P<0.017 was considered to indicate a statistically significant difference. In the 9 patients examined, continuous inflammation and fibrosis were observed after HCC development. There was also a significant decrease in the positive rate of FOXP3 in all 5 patients at the time of HCC development compared with that prior to IFN therapy (P=0.0084). Additionally, there was a significant difference in the positive rate of FOXP3 between the 5 patients after HCC development and the control individuals (P=0.0022). In patients who developed HCC after IFN-based SVR, the frequency of FOXP3 decreased, but inflammation and fibrosis remained. The extent of the reduction of FOXP3 differed in patients who developed HCC in the presence of HCV. Inflammation and fibrosis remained for a long duration after SVR, which may be associated with hepatocarcinogenesis.

Physiological variations of stem cell factor and stromal-derived factor-1 in murine models of liver injury and regeneration.

BACKGROUND/AIMS: Stem cell factor (SCF) and stromal-derived factor-1 (SDF-1) regulate the regenerative response to liver injury, possibly through activation of liver progenitor 'oval' cells and recruitment of circulating, marrow-derived progenitors. METHODS: We performed a detailed analysis of SCF, SDF-1 and oval cell proliferation induced by tyrosinaemia, 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or liver irradiation in mice by ELISA and immunofluorescence. RESULTS: Liver injury in the tyrosinaemia mouse is characterized by a dramatic decline in plasma SCF and absence of oval cell proliferation. In contrast, DDC induces bile duct (BD) and oval cell proliferation, and a modest decline in plasma SCF. Focal liver irradiation increases plasma SCF, but not oval cell density. In normal mouse liver, SCF is localized primarily to Kupffer cells, cholangiocytes and arterial smooth muscle, with little or no expression in hepatocytes. However, SCF appears in hepatocyte nuclei after injury, where its function is unknown. In all three models, SDF-1 is expressed exclusively in BD epithelium, indicating that tissue SDF-1 levels are proportional to the total mass of oval cells and cholangiocytes. However, increased plasma levels of SDF-1 in fumaryl acetoacetate hydroxylase-null mice were not accompanied by oval cell proliferation. CONCLUSION: Changes in SCF and SDF-1 varied with the nature of liver injury and were not directly related to oval cell proliferation.

Rapidly growing hepatocellular carcinoma after direct-acting antiviral treatment of chronic hepatitis C.

We report on a 62-year-old man with chronic hepatitis C who developed rapidly growing hepatocellular carcinoma (HCC) after achieving sustained virological response at post-treatment week 24 (SVR 24) by direct-acting antiviral (DAA) treatment. In 2008, he failed interferon therapy at 56 years of age. He received daclatasvir plus asunaprevir for 24 weeks after confirmation of no liver tumor by abdominal ultrasonography. He had no advanced liver fibrosis. Three months after initiation of DAA treatment, a liver tumor measuring 6 mm in diameter was detected by ultrasonography and confirmed with magnetic resonance imaging. After achieving SVR 24, the tumor increased in size to 16 mm. Two months later, a tumor biopsy was performed, and histology revealed moderately to poorly differentiated HCC. The patient's alpha-fetoprotein (AFP) level was within the normal range, but the Lens culinaris agglutinin-reactive fraction of AFP level was elevated. The diameter of the tumor increased to 32 mm at 2 months after diagnosis. Lymph node metastasis in porta hepatis was found by positron emission tomography at 4 months after diagnosis. The patient received hepatic arterial infusion chemotherapy and radiation therapy, but died later. Careful monitoring is required during and after DAA treatment because HCC can grow fast even in patients with normal AFP and no advanced liver fibrosis.

Lamivudine treatment-related morphological changes of esophageal varices in patients with liver cirrhosis.

AIM: Many studies have reported the therapeutic effects of lamivudine on cirrhotic patients with hepatitis B; however, no study has investigated the morphological changes of esophageal varices after lamivudine treatment. METHOD: The morphological changes of esophageal varices in patients with cirrhosis were retrospectively compared between 12 patients treated with lamivudine and six historical untreated patients. RESULTS: In the treated group, the HBV DNA and hyaluronic acid (HA) levels in the serum were significantly lower than those in the untreated group (P = 0.013 and P = 0.009, respectively) at the end of follow-up, with a significant improvement in the Child-Pugh-Turcotte score (P = 0.022). In the treated group, the disappearance or reduction of esophageal varices was observed in six (50%) of the 12 patients. In three (25%) of the 12 patients, esophageal varices worsened. In the remaining three patients (25%), there were no changes in esophageal varices. In the untreated group, all patients showed the worsening of esophageal varices during the follow-up period, with a significant difference between this group and the treated group (P = 0.009). The serum HA level decreased in the nine treated patients without worsening of esophageal varices. However, in the three patients with worsening, the HA level significantly increased. CONCLUSION: Lamivudine treatment for patients with cirrhosis improves not only liver function but also esophageal varices.