Eradication of hepatitis C virus infection disclosing a previously hidden,underlying autoimmune hepatitis: Autoimmune hepatitis and HCV

Chronic hepatitis C virus (HCV) infection and autoimmune disorders show a complex interplay, with HCV often being identified as the trigger of autoimmune phenomena or diseases. While there is evidence of successful HCV treatment with direct-acting antivirals (DAA) in patients with concomitant HCV and autoimmune hepatitis (AIH), there are also sparse reports of AIH developing during, or following, DAA treatment.Here we report a case of a patient with suspected concomitant HCV and AIH who underwent liver biopsy but showed no histological hallmarks of autoimmunity. The patient later developed a hepatitic flare following DAA-induced viral clearance, and a second liver biopsy showed features compatible with AIH. Response to corticosteroid and azathioprine treatment was seen. This reports demonstrates that patients with features of auto-reactivity and HCV after DAA-induced viral clearance require careful follow-up.     

Diagnostic difficulties,therapeutic strategies,and performance of scoring systems in patients with autoimmune hepatitis and concurrent hepatitis B/C

Abstract

Background. The diagnosis of autoimmune hepatitis (AIH) is already difficult, and that of AIH with chronic viral hepatitis including hepatitis B (HBV) or hepatitis C (HCV) is even more challenging. To date, only a few case-based studies have described this association. Aim. The aim was to retrospectively assess diagnostic difficulties, therapeutic approaches, and performance of the scoring systems in AIH patients with concurrent HBV and HCV. Methods. A total of 25 patients from United States, Sweden, Italy, and Turkey were retrospectively evaluated. Both revised and simplified criteria suggested by the International Autoimmune Hepatitis Group were applied for each patient. All study data were obtained from medical records. Results. Of the 25 patients, 20 (80%) had concomitant HCV and 5 (20%) had HBV. Based on the revised scoring system and simplified criteria, 18 (72%) and 12 (48%) patients were diagnosed as “probable” AIH. None of the patients were diagnosed as “definite” AIH according to both scoring systems. Patients with HCV initially were treated with immunosuppressive agents, and antiviral therapy was commenced when biochemical remission occurred. AIH patients with HBV were first treated with antiviral and thereafter, immunosuppressive therapy was started. Conclusions. This large case series describes concurrent AIH and chronic viral hepatitis. The revised scoring system for AIH had a better performance than the simplified scoring system. However, neither scoring system is optimal for diagnosing AIH alone. In these patients, a definitive diagnosis of AIH should be based on a combination of serological profiles, histological findings, scoring systems, treatment response, and outcomes.     

Hepatocellular carcinoma in patients with autoimmune hepatitis

AIM： To evaluate and confirm the low incidence of hepatocellular carcinoma （HCC） in patients with autoimmune hepatitis （AIH）. At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare. METHODS： In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS： Eighty-nine patients （32%） were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION： We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.     

Sustained viral response of a case of acute hepatitis C virus infection via needle-stick injury

A 29-year-old nurse with a hepatitis C virus (HCV) infection caused by needle-stick injury was treated with interferon-beta starting about one year after the onset of acute hepatitis. The patient developed acute hepatitis C with symptoms of general fatigues, jaundice, and ascites 4 wk after the needle-stick injury. When these symptoms were presented, the patient was pregnant by artificial insemination. She hoped to continue her pregnancy. After delivery, biochemical liver enzyme returned to normal levels. Nevertheless, HCV RNA was positive and the pathological finding indicated a progression to chronicity. The genotype was 1b with low viral load. Daily intravenous injection of interferon-beta at the dosage of six million units was started and continued for eight weeks. HCV was eradicated without severe adverse effects. In acute hepatitis C, delaying therapy is considered to reduce the efficacy but interferon-beta therapy is one of the useful treatments for hepatitis C infection in chronic phase.     

Autoimmune hepatitis in patients with chronic HBV and HCV infections: patterns of clinical characteristics,disease progression and outcome

We retrospectively investigated the characteristics, patterns of disease progression, outcome and difficulties in the management in 11 patients with concurrent autoimmune hepatitis (AIH) and HBV or HCV infections (5 HCV and 6 HBV including 2 with HDV co-infection) since there are scarce data on this issue. HCV or HBV diagnosis preceded that of AIH in all patients by many years. At initial clinical and histological assessment almost half of patients had cirrhosis (45.5%) with the group of AIH and HCV carrying the highest frequency (4/5; 80%). In two thirds of patients, mostly with HCV and HBV/HDV, AIH was assumed to be IFNalpha-induced and experienced difficulties in achieving sustained virological response. On the contrary, the outcome of patients with HBV and AIH was better compared to those with AIH and HCV or HDV. In conclusion, chronic viral hepatitis infections concomitant with AIH are often very difficult to recognize and therefore, a significant delay in AIH diagnosis in this specific group of patients is usual. HBV patients with concomitant AIH seem to carry the most favorable outcome compared to those with HCV probably because of the use of nucleos(t)ide analogues which contrary to IFN-alpha can control HBV replication with no adjacent effect, related to exacerbation of autoimmune phenomena.     

Detection of hepatitis C virus antibody in patients with autoimmune hepatitis and other chronic liver diseases

To clarify the relationship between autoimmune hepatitis (AIH) and the hepatitis C virus (HCV), we investigated the prevalence of antibodies to HCV (anti-HCV) by an enzyme-linked immunosorbent assay in patients with AIH, primary biliary cirrhosis (PBC), rheumatoid arthritis and multiple myeloma. The antibody was detected in 9 out of 18 patients with AIH (50%), in 3 out of 23 with PBC (23%), in 2 out of 10 with rheumatoid arthritis (20% ), and in 5 out of 9 with multiple myeloma (56% ). However, the optical density values in these patients were lower than those observed in non-A, non-B hepatitis (NANBH). Anti-HCV became negative immediately after the initiation of glucocorticoid therapy in all four antibodypositive AIH patients tested. The extracted immunoglobulin G fraction from sera of 5 anti-HCV negative AIH patients became positive for the antibody. This phenomenon was not observed in 5 normal volunteer sera. The 9 family members of three anti-HCV positive AIH patients showed no anti-HCV positivity. These results suggest that autoantibodies in AIH patients may cross-react with the HCV -related antigen. Direct association of the HCV influencing the development of AIH is unlikely. Therefore, care should be taken in the evaluation of anti-HCV positivity in patients with autoimmune diseases and multiple myeloma. This study was supported by the Ministry of Health, Science and Welfare of Japan.     

Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients

Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)‐infection, thus indicating an autoimmune response as possible cause of HCV infection‐associated encephalopathy. Data, however, are sparse. This study aimed to prove that HCV patients feature similar to those with autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric symptoms. A total of 132 noncirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29, AIH/PBC: 8) completed questionnaires addressing the domains mentioned above. Eighty‐eight underwent a comprehensive neuropsychological assessment. Patient groups were compared among each other and to 33 healthy controls. Fatigue, anxiety and depression scores were significantly increased, and the SF‐36 mental score significantly decreased in all patient groups compared to controls. Fatigue was significantly more pronounced in HCV than in HBV patients. HCV patients scored significantly worse than HBV patients but not AIH and PBC patients in the SF‐36. HCV, AIH and PBC but not HBV patients did significantly worse than controls in word learning. Recognition of words was impaired in HCV, AIH and PBC patients and recognition of figures in HCV patients, exclusively (P ≤ 0.002). HCV patients did also worse than controls and HBV patients concerning alertness and working memory (P ≤ 0.001). The neuropsychiatric profiles of HCV patients are similar to those of AIH and PBC patients but differ from those of HBV patients, suggesting an autoimmune response as a possible cause for these differences.     

Differential efficacy of corticosteroids and interferon in a patient with chronic hepatitis C-autoimmune hepatitis overlap syndrome.

The chronic hepatitis C-autoimmune hepatitis (AIH) overlap syndrome has been described in the literature, but to date appropriate therapy remains controversial. We report on a 28-year-old woman with hepatitis C-AIH overlap syndrome. The patient was infected with HCV genotype 1b and had laboratory and immunologic findings of AIH type 2 such as increased Igs and a high titer of antibodies against liver-kidney microsomes. Initial liver biopsy specimen demonstrated end-stage liver fibrosis due to chronic hepatitis. After long-lasting corticosteroid treatment, only partial remission was achieved. In contrast, short-term antiviral therapy with interferon-alpha2b in combination with ribavirin was followed by complete biochemical and virologic remission. However, 15 months later, a relapse of AIH was observed. After restarting corticosteroid treatment, transaminase levels completely normalized. Surprisingly, in this patient with overlap syndrome, short-term interferon therapy induced complete remission of chronic HCV infection and regression of severe liver fibrosis.     

Detection of hepatitis C virus antibody in patients with autoimmune hepatitis and other chronic liver diseases.

To clarify the relationship between autoimmune hepatitis (AIH) and the hepatitis C virus (HCV), we investigated the prevalence of antibodies to HCV (anti-HCV) by an enzyme-linked immunosorbent assay in patients with AIH, primary biliary cirrhosis (PBC), rheumatoid arthritis and multiple myeloma. The antibody was detected in 9 out of 18 patients with AIH (50%), in 3 out of 23 with PBC (23%), in 2 out of 10 with rheumatoid arthritis (20%), and in 5 out of 9 with multiple myeloma (56%). However, the optical density values in these patients were lower than those observed in non-A, non-B hepatitis (NANBH). Anti-HCV became negative immediately after the initiation of glucocorticoid therapy in all four antibody-positive AIH patients tested. The extracted immunoglobulin G fraction from sera of 5 anti-HCV negative AIH patients became positive for the antibody. This phenomenon was not observed in 5 normal volunteer sera. The 9 family members of three anti-HCV positive AIH patients showed no anti-HCV positivity. These results suggest that autoantibodies in AIH patients may cross-react with the HCV-related antigen. Direct association of the HCV influencing the development of AIH is unlikely. Therefore, care should be taken in the evaluation of anti-HCV positivity in patients with autoimmune diseases and multiple myeloma.     

Autoimmune hepatitis--sequel of a relapsing hepatitis A in a 75-year-old woman

Acute hepatitis A virus (HAV) infection is a global cause of acute hepatitis. However, chronic HAV infection is unlikely. Nevertheless, there is some evidence that acute infection with HAV may trigger chronic active hepatitis which fulfils the criteria of autoimmune hepatitis (AIH). Whether AIH following HAV infection is virus specific remains unclear. Despite evidence that inherited factors may play a role in the development of autoimmunity after viral infection, the pathomechanism remains unclear. We describe a 75-year-old woman with a history of pulmonary sarcoidosis who developed AIH after acute HAV infection.     

Autoimmune hepatitis in a HIV-HCV co-infected patient: diagnostic ant therapeutic difficulties

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic inflammatory hepatic disorder, characterized by hypergammaglobulinemia and autoantibodies. In some cases, AIH can be associated with another liver disease; such as the hepatitis C-AIH overlap syndrome, which diagnosis and treatment may be delicate. EXEGESE: We report a type 1 AIH case in a HIV-HCV co-infected woman. AIH remission and HCV eradication were obtained with prednisone and interferon plus ribavirine. AIH relapse appeared with corticosteroid withdrawal and a new remission was obtained with immunosuppressive treatment associating prednisone and azathioprine, without opportunistic infection. CONCLUSION: This case illustrates diagnostic and therapeutic difficulties of hepatitis C-AIH overlap syndromes in an HIV-infected patient. To our knowledge, it is the first AIH case report in a HIV-HCV co-infected patient.     

Development of autoimmune hepatitis type 1 after pulsed methylprednisolone therapy for multiple sclerosis： A case reportDevelopment of autoimmune hepatitis type I after pulsed methylprednisolone therapy for multiple sclerosis： A case report

A 43-year-old woman with multiple sclerosis （MS） was treated with pulsed methylprednisolone and interferon 13 at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis （AIH）. She was successfully treated with corticosteroids. As ataxia developed after i year, she was treated with pulsed methylprednisolone for 3 days, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS.     

Efficacy of pegylated interferon plus ribavirin in combination with corticosteroid for two cases of combined hepatitis C and autoimmune hepatitis

The treatment strategy for cases of combined autoimmune hepatitis (AIH) and chronic hepatitis C (CHC) has not yet been established. A 47-year-old woman and a 53-year-old-woman were hospitalized for treatment of CHC. Ultrasonography and histological findings revealed that their liver was not cirrhotic but did have chronic damage. The histological findings of both patients were suggestive of AIH. The patients were systematically treated with pegylated interferon-alpha 2b plus ribavirin which was preceded by and combined with corticosteroid (CS), and showed sustained virological responses and normal liver function. Although these two patients with combined AIH and CHC were successfully treated with this regimen, careful attention to exacerbation of hepatic inflammation is needed because hepatitis C viral load was increased due to immunosuppression during CS treatment.     

Fulminant hepatitis caused by hepatitis C virus during treatment for multiple sclerosis

A 55-year-old woman was treated at our hospital for multiple sclerosis. Therapy consisted of glucocorticosteroids and cyclosporin. In the 7th week after these drugs were discontinued the patient developed acute liver failure due to fulminant hepatitis (FH) and died. Post-mortem examination showed massive liver necrosis. Serologic examination was negative for hepatitis B virus-related markers. Anti-hepatitis C virus (anti-HCV) antibody and serum HCV RNA were negative on admission, but HCV RNA appeared concurrently with the onset of FH. Although HCV infection rarely causes FH, it was considered to be the cause of FH in this patient, since there were no other causes of acute liver injury. We suspect that underlying immunologic abnormalities in conjunction with HCV infection may have precipitated the FH.     

A case of autoimmune hepatitis following acute hepatitis A

The pathogenesis of autoimmune hepatitis (AIH) is unclear, but viral infections have been proposed as a potential trigger in patients with genetic predisposition. We report a case of AIH following acute hepatitis A (AHA). A 57-year-old woman presented with fatigue and pitting edema for last 3 months. She had been diagnosed as an AHA 15 months ago based on clinical features, biochemical tests and positive HAV IgM antibody at a local clinic. Her biochemical tests was normalized one month after AHA diagnosis, but the serum levels of aminotransferase started to rise four months after AHA diagnosis. Antinuclear antibody was positive at a titer of 1:40, and anti-smooth muscle antibody was also positive. Hypergammaglobulinemia and liver pathology were typical for AIH. The patients had a score of 17 according to the International Autoimmune Hepatitis Group's system. She was given prednisolone and azathioprine and showed complete response to immunosuppressive therapy. The present case is the first report on AIH triggered by AHA in Korea.     

Development of autoimmune hepatitis type I after pulsed methylprednisolone therapy for multiple sclerosis: A case report

A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon β at a hospital.Four weeks after initiating treatment,liver dysfunction occurred and she was referred and admitted to our hospital.Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis,but not for autoimmune hepatitis (AIH).She was successfully treated with corticosteroids.As ataxia developed after 1 year,she was treated with pulsed methylprednisolone for 3 days,then readmitted to our hospital when liver dysfunction occurred.Clinical and laboratory findings led to the diagnosis of A[H.To the best of our knowledge,this is the second case of AIH developed after pulsed methylprednisolone for MS.     

Polyarteritis nodosa and cryoglobulinemic glomerulonephritis related to chronic hepatitis C

CASE REPORT: A 53-year-old man with hepatitis C virus (HCV) infection underwent cholecystectomy for presumed cholecystitis. Gallstones were not present, and histological examination demonstrated medium-sized arteritis, consistent with polyarteritis nodosa (PAN). The patient later developed rapidly progressive glomerulonephritis. Kidney biopsy demonstrated cryoglobulinemic glomerulonephritis. Because of the severity of the patient's vasculitic manifestations, treatment included pulse methylprednisolone followed by oral prednisone and monthly intravenous cyclophosphamide for 6 months. During treatment, microhematuria resolved, proteinuria decreased, and serum creatinine concentration stabilized. The patient subsequently underwent treatment for HCV with interferon resulting in a marked decrease in HCV RNA. The patient has had no relapse of his vasculitis, his renal function is stable, and viral load remains low after completing 36 weeks of interferon. CONCLUSION: Life-threatening vasculitis related to HCV was successfully treated with immunosuppressive therapy. After obtaining clinical remission, antiviral therapy was instituted, resulting in a dramatic decrease in HCV RNA.     

Autoimmune Hepatitis in a Genetically Susceptible Patient (Is It Triggered by Acute Viral Hepatitis A?)

The pathogenic mechanisms for autoimmune hepatitis (AIH) are not completely known. Susceptibility to AIH is associated with the human leukocyte antigens (HLA) class II: DR3 and DR4. Nevertheless, AIH does not have a strong genetic predisposition, suggesting that other factors are involved. Perhaps the strongest evidence of a viral cause for AIH exists for hepatitis C virus. AIH has been reported to develop rarely after acute infection with hepatitis A virus. We report on a 55-year-old woman in whom AIH developed during the convalescence period of serologically proven acute viral hepatitis type A. HLA class II DRB1*0401, which was reported to be associated with AIH with a moderate coarse and late appearance in life, was found in this patient. Steroid therapy was followed by a complete clinical remission. Our case supports the possibility that acute hepatitis A may trigger the development of AIH in a genetically susceptible subject.     

Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis

BACKGROUND & AIMS: Approximately 13% of patients with chronic hepatitis D virus (HDV) infection have liver-kidney microsomal antibodies type 3 (LKM-3) directed against family 1 uridine 5'-diphosphate-glucuronosyl- transferases (UGT-1). The aim of this study was to characterize the prevalence and specificity of LKM-3 by recombinant antigen testing systems. METHODS: Enzyme-linked immunosorbent assay (ELISA) and Western blot were performed using baculovirus-generated human UGT-1.1 and -1.6 and rabbit UGT-1.6. Sera from patients with HDV (n = 50), autoimmune hepatitis (AIH) type 2 (n = 50), hepatitis B virus (n = 26), hepatitis C virus (HCV) (n = 25), and LKM-1 autoantibody-positive HCV (n = 14) and sera from normal controls (n = 50) and italian patients with HDV and known LKM-3 autoantibodies were studied. RESULTS: Six percent of patients with HDV from Germany and 8% of patients with type 2 AIH had LKM-3. Sera from italian patients with HDV and patients with AIH type 2 recognized all three recombinant UGT-1. HDV sera from Germany selectively recognized human UGT-1. LKM-3 titers were lower in HDV than in AIH. One patient with AIH had LKM-3 as the only marker of AIH. CONCLUSIONS: This study indicates a molecular target and titer difference of LKM-3 autoantibodies in German subjects with HDV and AIH. It also suggests a geographic target and titer difference of LKM-3 in HDV. LKM-3 are identified as a rare and previously undescribed independent marker of AIH. (Gastroenterology 1996 Dec;111(6):1576-86)