Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination: A case report and review of literature.

BACKGROUND: A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment (S) 5. CASE SUMMARY: Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) revealed the nodule in S5 with a defect at the hepatobiliary phase, hyperintensity on diffusion weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC) map. Contrast-enhanced computed tomography revealed hypervascularity at the early phase, and delayed contrast-enhancement was observed at the late phase. Contrast-enhanced ultrasound (US) revealed incomplete defect at the late vascular phase. Inflammatory liver tumor, lymphoproliferative disease, intrahepatic cholangiocarcinoma (small duct type) and bile duct adenoma were suspected through the imaging studies. US guided biopsy, however, showed a noncaseating hepatic sarcoid-like epithelioid granuloma (HSEG), and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells. One month after admission, EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase, of hyperintensity on DWI, of hypointensity on ADC map, and no stain at the early phase. CONCLUSION: That the patient had received BNT162b2 messenger RNA (mRNA) coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG, and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction (DISR) might be induced by the mRNA vaccination. Fortunately, rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

Polymorphisms of hepatitis C virus non-structural protein 5A and core protein and clinical outcome of pegylated-interferon/ribavirin combination therapy.

OBJECTIVE: Hepatitis C virus (HCV genome) polymorphisms are thought to influence the outcome of pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy. This study aimed to examine non-structural protein 5A (NS5A) polymorphisms, e.g. IFN/RBV resistance-determining region (IRRDR) and IFN sensitivity-determining region (ISDR), and core protein polymorphism as predictive therapeutic markers. METHODS: Pretreatment sequences of NS5A and core regions were analyzed in 68 HCV-1b-infected patients treated with PEG-IFN/RBV. RESULTS: Of 24 patients infected withHCV having an IRRDR with 6 or more mutations (IRRDR≥6), 18 (75%) patients achieved sustained virological response (SVR), whereas only 11 (25%) of 44 patients infected with HCV having IRRDR≤5 did. IRRDR≥6 was significantly associated with SVR (p < 0.0001). On the other hand, ISDR≥2 was significantly associated with relapse (either before [breakthrough] or after end-of-treatment response [ETR[-]relapse]) (p < 0.05) and a point mutation of the core protein from Arg to Gln at position 70 (Gln(70)) was significantly associated with null-response (p < 0.05). Multivariate analysis identified IRRDR≥6 as the only viral genetic factor that independently predicted SVR. CONCLUSION: NS5A (IRRDR and ISDR) and core protein polymorphisms are associated with the outcome of PEG-IFN/RBV therapy for chronic hepatitis C. In particular, IRRDR≥6 is a useful marker for prediction of SVR.

Double-Filtration Plasmapheresis plus Interferon-ß for HCV-1b Patients with Non-Sustained Virological Response to Previous Combination Therapy.

BACKGROUND AND AIMS: Double-filtration plasmapheresis (DFPP) together with interferon (IFN) administration produces a substantial reduction in the viral load during the early stages of treatment. METHODS: Based on their responses to previous pegylated IFN and ribavirin (PEG-IFN/RBV) therapy, 20 patients were divided into null virological response (NVR; n = 12) and relapse (n = 8) groups. DFPP was used in combination with IFN-ß/RBV with subsequent administration of PEG-IFN-α2a/RBV therapy (DFPP + IFN-ß/RBV then PEG-IFN/RBV). Early viral dynamics was assessed, focusing especially on complete early virological response (cEVR) associated with sustained virological response. Additionally, the interleukin 28B gene, the IFN/RBV resistance-determining region, the IFN sensitivity-determining region and the core regions were analyzed. RESULTS: Rapid virological response was achieved in 0% (0/12) of NVR and in 75% (6/8) of relapse patients, with a significant difference between the two groups (p = 0.001). Similarly, cEVR was achieved in 8% (1/12) of NVR and in 88% (7/8) of relapse patients, with a significant difference between the two groups (p = 0.037). By multivariate logistic regression analysis, interleukin-28B major was a significant determiner of cEVR (odds ratio = 24.19, p = 0.037). CONCLUSION: DFPP + IFN-ß/RBV then PEG-IFN/RBV therapy is indicated more for relapse than for NVR patients.

Double-filtration plasmapheresis plus IFN for HCV-1b patients with non-sustained virological response to previous combination therapy: early viral dynamics.

Double-filtration plasmapheresis (DFPP) was approved in Japan in April 2008 for the retreatment of chronic hepatitis C patients with genotype 1b and high viral loads, whose hepatitis C virus was not eradicated by earlier IFN therapy or by pegylated IFN plus ribavirin (PEG-IFN/RBV) combination therapy. In this study, we assessed the early viral dynamics of 9 patients with non-sustained virological response to the combination therapy. The overall viral dynamics of DFPP plus IFN treatment with or without RBV for 4 weeks showed a reduction of > or =1 log in the viral load in 22% (2 of 9 patients), 55.6% (5/9), 77.8% (7/9) and 77.8% (7/9) at 24 h, 1, 2 and 4 weeks after the start of treatment. By contrast, DFPP plus consecutive intravenous IFN-beta for 4 weeks reduced the viral load by > or = 1 log in 33% (2/6), 50% (3/6), 83.3% (5/6) and 83.3% (5/6) at 24 h, 1, 2 and 4 weeks. The viral load declined by > or = 2 log in 50% (3/6) at 4 weeks after the start of treatment. DFPP plus consecutive intravenous IFN-beta for 4 weeks is a promising treatment for non-sustained virological response patients.

Outcome and early viral dynamics with viral mutation in PEG-IFN/RBV therapy for chronic hepatitis in patients with high viral loads of serum HCV RNA genotype 1b.

We investigated whether sustained virological response (SVR) and non-SVR by chronic hepatitis C patients to pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy are distinguishable by viral factors such as the IFN/RBV resistance-determining region (IRRDR) and by on-treatment factors through new indices such as the rebound index (RI). The first RI (RI-1st; the viral load at week 1 divided by the viral load at 24 h) and the second RI (RI-2nd; the viral load at week 2 divided by the viral load at 24 h) were calculated. The subject patients were divided into 3 groups based on RI-1st and RI-2nd: an RI-A group (RI-1st < or = 1.0), an RI-B group (RI-1st >1.0 and RI-2nd <0.7) and an RI-C group (RI-1st >1.0 and RI-2nd > or = 0.7). The SVR rate was 71.4% (10/14) in the RI-A group, 46.2% (6/13) in the RI-B group and 20.0% (3/15) in the RI-C group (p = 0.005 between the RI-A group and the RI-C group). In IRRDR > or = 6 and IRRDR < or = 5 the SVR rate was 81.3% (13/16) and 23.1% (6/26) (p = 0.0002), respectively. By combining RI and IRRDR as a predicting factor, the SVR rate was 87.5% (7/8) in the RI-A group (> or = 6 mutations in the IRRDR) and 7.7% (1/13) in the RI-C group (< or = 5 IRRDR mutations) (p = 0.0003).

Well-differentiated hepatocellular carcinoma smaller than 15 mm in diameter totally eradicated with percutaneous ethanol injection instead of radiofrequency ablation.

We describe three cases of well-differentiated hepatocellular carcinoma (HCC) smaller than 15 mm in diameter completely eradicated with percutaneous ethanol injection (PEI) instead of using radiofrequency ablation (RFA). Ultrasound (US) examination revealed one nodule each in segment 2 (hypoechoic, near bile ducts, 10 mm), in segment 5 (hyperechoic, near the gall bladder, 15 mm), and in segment 7 (hypoechoic, near the diaphragm, 15 mm). Although imaging studies revealed isovascular (case 1) and hypervascular (cases 2 and 3) nodules, histological analysis of US-guided biopsy tissue revealed well-differentiated HCC. In consideration of the location of the nodules, PEI, instead of RFA, was administered and the nodules were rendered necrotic. Although RFA is superior to PEI in the treatment of small HCCs from the viewpoint of treatment response and long survival, PEI is strongly recommended for HCCs located near bile ducts, the gall bladder, and the diaphragm, especially when the nodules are smaller than 15 mm in diameter.

Pegylated interferon plus ribavirin combination therapy for chronic hepatitis C with high viral load of serum hepatitis C virus RNA, genotype 1b, discontinued on attaining sustained virological response at week 16 after onset of acute pancreatitis.

Recent clinical trials have shown that pegylated interferon-alpha (PEG-IFN-alpha) in combination with ribavirin (RBV) improves the rate of sustained virological response (SVR), with over 50% of patients demonstrating a positive response to treatment. However, no SVR has been reported when PEG-IFN/RBV combination therapy is discontinued by week 16, especially in cases of chronic hepatitis with a high viral load of serum hepatitis C virus (HCV) RNA, genotype 1b. Here, we describe SVR in a 67-year-old woman whose PEG-IFN/RBV combination therapy for chronic hepatitis C with a high viral load of serum HCV RNA, genotype 1b, was discontinued after 16 weeks because of the onset of PEG-IFN plus RBV-induced acute pancreatitis. Among viral factors, substitution of amino acid 70 (Arg) and 91 (Leu) in the core region and HCV RNA negativity were observed after 8 weeks. Host factors including low body weight, no alcohol consumption, no coinfection with hepatitis B virus, slight fibrosis, and viral factors including early viral clearance, double wild type in the core region, may have contributed to the SVR irrespective of the discontinuation of the combination therapy at week 16. Moreover, PEG-IFN plus RBV-induced acute pancreatitis might have been related to the SVR.

Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load.

Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 µg) plus a daily oral dose of RBV (600 mg). The therapy was discontinued, however, because of the onset of acute pancreatitis (after 15 weeks, 48 weeks, and 3 weeks respectively). The drug-induced pancreatitis was diagnosed on the basis of elevated levels of amylase and lipase and the absence of other identifiable causes. High tumor necrosis factor-α was found in one patient and high interleukin-6 in the other two. The immune system stimulated by PEG-IFN and RBV combination therapy might have caused the acute pancreatitis. Further study is needed to clarify the mechanism of the onset of drug-induced pancreatitis by PEG-IFN and RBV combination therapy.

Focal nodular hyperplasia-like lesion with venous washout in alcoholic liver cirrhosis.

A case of 22 mm hypervascular nodule in segment two of the liver but without hepatitis B or C virus infection in a 32-year-old Japanese woman with a history of alcohol abuse is presented. Imaging studies such as contrast-enhanced ultrasound, computed tomography and magnetic resonance imaging showed hypervascularity in the early phase and venous washout in the late phase. Histologically, stellate scar-like fibrous septa, pericellular fibrosis, fatty change, neutrophilic infiltration, slight increase of cell density, and diffuse capillarization of the sinusoids together with small unpaired arteries were observed. The nodule was diagnosed as focal nodular hyperplasia-like lesion in alcoholic liver cirrhosis.

Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy.

UNLABELLED: A substantial proportion of hepatitis C virus (HCV)-1b-infected patients still do not respond to interferon-based therapy. This study aims to explore a predictive marker for the ultimate virological response of HCV-1b-infected patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) combination therapy. Nonstructural protein 5A (NS5A) sequences of HCV in the pretreated sera of 45 patients infected with HCV-1b were analyzed. The mean number of mutations in the variable region 3 (V3) plus its upstream flanking region of NS5A (amino acid 2334-2379), referred to as IFN/RBV resistance-determining region (IRRDR), was significantly higher for HCV isolates obtained from patients who later achieved sustained virological response (SVR) by PEG-IFN/RBV than for those in patients undergoing non-SVR. The receiver operating characteristic curve analysis estimated six mutations in IRRDR as the optimal threshold for SVR prediction. Indeed, 16 (76%) of 21 SVR, but only 2 (8%) of 24 non-SVR, had HCV with six or more mutations in IRRDR (IRRDR > or = 6) (P < 0.0001). All of 18 patients infected with HCV of IRRDR of 6 or greater examined showed a significant (> or =1 log) reduction or disappearance of serum HCV core antigen titers within 24 hours after initial dose of PEG-IFN/RBV, whereas 10 (37%) of 27 patients with HCV of IRRDR of 5 or less did (P < 0.0001). The positive predictive value of IRRDR of 6 or greater for SVR was 89% (16/18; P = 0.0007), with its negative predictive value for non-SVR being 81% (22/27; P = 0.0008). CONCLUSION: A high degree (> or =6) of sequence variation in IRRDR would be a useful marker for predicting SVR, whereas a less diverse (< or =5) IRRDR sequence predicts non-SVR.

Usefulness of a new immunoradiometric assay of HCV core antigen to predict virological response during PEG-IFN/RBV combination therapy for chronic hepatitis with high viral load of serum HCV RNA genotype 1b.

We investigated the clinical usefulness of a new immunoradiometric (IRM) assay of hepatitis C virus (HCV) core antigen in predicting virological response during pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy for chronic hepatitis with high viral loads of serum HCV RNA genotype 1b. Thirty-nine patients received a regimen of PEG-IFNalpha-2b (1.5 microg/kg/week s.c.) in combination with RBV (600-1,000 mg/day). Of the 39 patients, 18 (46.2%) achieved sustained virological response (SVR), 11 (28.2%) attained partial response (PR) and 10 (25.6%) showed no response (NR). Four weeks after the start of therapy, 1- and 2-log reductions in the amount of HCV core antigen were observed in 20 (2/10) and 0% (0/10) showing NR, 91 (10/11) and 63.6% (7/11) with PRs, and 88.9 (16/18) and 55.6% (10/18) of patients with SVR, respectively. The 1- and 2-log reductions 4 weeks after the start of therapy were not a defining condition for PR and SVR. The amount of HCV core antigen was significantly different between SVR and PR patients on days 1 and 7, and between patients with NR and SVR at all points of time. In conclusion, this new IRM assay is useful in predicting virological response during PEG-IFN/RBV therapy.

Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma.

AIM: To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI). METHODS: PEI was applied to 42 lesions in 31 patients (23 male and eight female) with HCC < 15 mm in diameter, over the past 15 years. RESULTS: Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, alpha-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Child-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively (P = 0.025). CONCLUSION: Treatment with PEI is best indicated for patients with HCC < 15 mm in Child-Pugh class A.

Blood cell, liver function, and response changes by PEG-interferon-alpha2b plus ribavirin with polaprezinc therapy in patients with chronic hepatitis C.

PURPOSE: Zinc has been reported to ameliorate hematologic side effects and improve liver function. In addition to its various effects, zinc supplementation in chronic hepatitis C patients with genotype 1b of high viral load enhanced the response to interferon (IFN) monotherapy. This study was aimed at clarifying whether zinc could improve hematologic side effects, improve liver function, and enhance the response to therapy in patients with chronic hepatitis C treated with pegylated-interferon (PEG-IFN) plus ribavirin (RBV). METHODS: The 32 patients enrolled in the study were randomly divided into two groups: a PEG-IFN-alpha2b plus RBV with zinc group (PEG/RBV + zinc, n = 16) and a PEG-IFN-alpha2b plus RBV group (PEG/RBV, n = 16). HCV-RNA, serum zinc, ALT, white blood cell, red blood cell, platelet, and hemoglobin (Hb) levels were examined. RESULTS: Serum zinc levels were significantly higher in the PEG/RBV with zinc group than in the PEG/RBV without zinc group at 4, 8, and 12 weeks. No significant differences were observed in the clearance of HCV-RNA between the two groups. The outcome of the treatment was similar; results of laboratory examinations including ALT before, during, and after therapy revealed no significant differences between the two groups at any point in all items except serum zinc levels. A sustained virological response rate was observed in 50.0% in the PEG/RBV with zinc group and 43.8% in the PEG/RBV without zinc group, with no significant difference between the two groups. CONCLUSIONS: The study demonstrated no evidence that zinc ameliorates hematologic side effects, improves liver function, and enhances the response to the therapy in chronic hepatitis C receiving PEG-IFN-alpha2b plus RBV.

Prediction of efficient virological response to pegylated interferon/ribavirin combination therapy by NS5A sequences of hepatitis C virus and anti-NS5A antibodies in pre-treatment sera.

A considerable number of patients infected with Hepatitis C virus subtype 1b (HCV-1b) do not respond to pegylated interferon/ribavirin combination therapy. In this study we explored a useful factor(s) to predict treatment outcome. A total of 47 HCV-1b-infected patients were treated with pegylated interferon/ ribavirin for 48 weeks. Sera of the patients were examined for the entire NS5A sequence of the HCV genome, HCV RNA titers and anti-NS5A antibodies. According to their responses, the patients were divided into two groups, early viral responders who cleared the virus by week 16 (EVR[16w]) and those who did not (Non-EVR[16w]). The mean number of mutations in the V3 region (aa 2356 to 2379) or that in the V3 region plus its N-terminally flanking region, which we refer to as interferon/ribavirin resistancedetermining region (IRRDR; aa 2334 to 2379), of NS5A obtained from the pretreatment sera was signifi-cantly larger for EVR(16w) compared with Non-EVR(16w). Moreover, HCV-1b isolates with > or =5 mutations in V3 or those with > or =6 mutations in IRRDR were almost exclusively found in EVR(16w). Also, the presence of detectable levels of anti-NS5A antibodies in the pretreatment sera was closely associated with EVR(16w). In conclusion, a high degree of sequence variation in V3 (> or =5) or IRRDR (> or =6) and the presence of detectable levels of anti-NS5A antibodies in the pretreatment sera would be useful factors to predict EVR(16w). On the other hand, a less diverse sequence in V3 (< or =4) or IRRDR (< or =5) together with the absence of detectable anti-NS5A antibodies could be a predictive factor for Non-EVR(16w).

Case of adult genotype C HBV carrier after acute hepatitis B, losing HBsAg and acquiring HBsAb after IFN and lamivudine treatment.

Here we report the case of a 48-year-old man, carrier of genotype C HBV for longer than 6 months after contracting sexually transmitted acute hepatitis B, who eventually lost HBsAg and acquired HBsAb by IFN/lamivudine therapy. The patient had been negative for HBsAg in 2001, but, during his stay in China from January to July in 2003, he developed acute hepatitis B after having an extra-marital sexual contact there. HBsAg was still positive and a liver biopsy indicated chronic hepatitis when he was admitted to our hospital in December 2003 for detailed examination of liver dysfunction. HBV DNA in his serum, revealed to segregate to genotype C by sequencing on admission, decreased to undetectable levels at the end of a 3-month IFN therapy, and remained undetectable during and after the successive 6-month lamivudine therapy. HBeAg seroconverted to HBeAb during the therapy, and HBsAb appeared after the therapy. To our knowledge, this is the first case of genotype C chronic hepatitis B occurring after acute hepatitis.

Well-differentiated HCC manifesting hyperattenuation on CT during arterial portography.

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) with hepatitis C virus-related cirrhosis, with unusual radiologic features, is presented. A 10-mm hypoechoic nodule disclosed by ultrasound in segment six showed hypoattenuation on computed tomography hepatic arteriography and hyperattenuation on computed tomography during arterial portography, indicating that the portal vein may have been the dominant vascularity of the nodule. Contrast-enhanced ultrasound revealed hypovascularity in the early arterial phase, isovascularity in the late vascular phase, and the same perfusion as that surrounding the liver parenchyma in the post-vascular phase, with the same pattern observed on the two imaging techniques. These findings were considered not compatible with those of well-differentiated HCC. Ultrasound-guided biopsy showed histological features of well-differentiated HCC with over two-fold the cellularity of the non-tumorous area with a high nuclear/cytoplasmic ratio, increased cytoplasmic eosinophilia, slight atypia and fatty change with an irregular thin trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.

Primary sclerosing cholangitis and hepatitis C virus infection.

Two cases of primary sclerosing cholangitis with hepatic C virus infection in a 62-year-old man and a 60-year-old woman are presented. The infection in the man was eradicated with interferon therapy in 1992. Seven years thereafter, endoscopic retrograde cholangiography revealed a diffuse 2.5-cm-long stenotic lesion in the common bile duct which was consequently resected. Histological examination of the resected specimen revealed proliferation of epithelial cells, plasma cell infiltration, and fibrosis in the submucosal layer of the common bile duct. The human leukocyte antigen DR loci were 2 and 9. In the woman, a 6-month course of interferon therapy in 1992 failed to eradicate the infection. Cholangiography in 1999 revealed multiple narrowings and dilatations of intra- and extrahepatic bile ducts. Ultrasound guided biopsy of the liver in 1992 had revealed onionskin lesions around the bile duct epithelium in the portal tract. The human leukocyte antigen DR locus was 2. From these findings, the 2 cases were diagnosed as primary sclerosing cholangitis. Further studies may provide insights into the relation between the pathogenesis of the disease and the infection.

Prediction of efficacy of interferon treatment of chronic hepatitis C and occurrence of HCC after interferon treatment by a new classification.

One hundred and twenty-one chronic hepatitis C patients were administered interferon (IFN) and divided into two groups: 31 complete responders (CR) with prolonged HCV-RNA negative 1 year after treatment and 90 non-complete responders (non-CR), including partial responders (PR) with transiently negative HCV-RNA and non-responders (NR) with continuously positive HCV-RNA. Liver biopsy specimens were classified into four grades and stages according to the degree of severity and the extent of fibrosis, respectively. No correlation was observed between the rate of IFN efficacy and grading. By staging, however, a difference in the efficacy of IFN was observed between F1 or F2 and F3 (0.05 < p < 0.1 and 0.01 < p < 0.025, respectively). Of the CR, 0% (0/5) were at F0 and 27.9% (24/86) at F1, 42.9% (6/14) at F2, and 6.3% (1/16) at F3. Another group of 118 chronic hepatitis patients (31 CR, 41 PR and 46 NR) followed up for over 2 years after IFN treatment were analyzed. By staging, 7 cases were at F0, 76 at F1, 18 at F2, and 17 at F3. HCC occurred in 1 of the 31 CR cases (representing an annual incidence rate of 1.21%), in 4 of the 41 PR cases (4.08%), and in 4 of the 46 NR cases (3.55%). HCC did not occur in any of the 7 cases at F0 (representing an annual incidence rate of 0%); it occurred in 2 of the 76 cases at F1 (1.01%), in 1 of the 18 cases at F2 (2.28%), and in 6 of the 17 cases at F3 (16.57%). These results suggest that the new classification would be conducive to roughly predicting the efficacy of IFN treatment and the occurrence of HCC after IFN treatment.