Manifestations Of Chronic Hepatitis Research Articles

Impact des antiviraux à action directe sur l'athérosclérose subclinique chez les patients atteints d’une hépatite C chronique

The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.

Forthcoming Developments in Models to Study the Hepatitis B Virus Replication Cycle, Pathogenesis, and Pharmacological Advancements.

Hepatitis, liver cirrhosis, and hepatocellular carcinoma are all manifestations of chronic hepatitis B. Its pathogenesis and molecular mechanism remain mysterious. As medical science progresses, different models are being used to study the disease from the physiological and molecular levels. Animal models have played an unprecedented role in achieving in-depth knowledge of the disease while posing no risk of harming humans throughout the study. The scarcity of acceptable animal models has slowed progress in hepatitis B virus (HBV) research and preclinical testing of antiviral medicines since HBV has a narrow species tropism and exclusively infects humans and higher primates. The development of human chimeric mice was supported by a better understanding of the obstacles to interspecies transmission, which has substantially opened the way for HBV research in vivo and the evaluation of possible chronic hepatitis B therapeutics. Animal models are cumbersome to handle, not accessible, and expensive. Hence, it is herculean to investigate the HBV replication cycle in animal models. Therefore, it becomes essential to build a splendid in vitro cell culture system to demonstrate the mechanisms attained by the HBV for its multiplication and sustenance. We also addressed the advantages and caveats associated with different models in examining HBV.

Kidney Manifestations in Chronic Hepatitis C

Kidney Manifestations in Chronic Hepatitis C

Study of Prevalence of Autoimmune Manifestations of Chronic Hepatitis C Infection in Beni-Suef Governorate

Study of Prevalence of Autoimmune Manifestations of Chronic Hepatitis C Infection in Beni-Suef Governorate

Direct-Acting Antiviral Therapy Effect on Extrahepatic Rheumatic Manifestations in Egyptian Chronic Hepatitis C (HCV) Patients

Background: Hepatitis C virus infection is an important cause of many rheumatic diseases, especially cryoglobulinemic vasculitis, fibromyalgia, arthralgia and Sicca Syndrome. Direct acting antivirals are found to be highly effective for the treatment of chronic Hepatitis C virus infection. Objective: The aim of this study was to evaluate the clinical and serological course of extrahepatic rheumatic manifestations in chronic hepatitis C Egyptian patients after treatment with new direct-acting antivirals. Patients and Methods: This study was carried out on 60 Egyptian patients with chronic hepatitis C with one or more of the HCV- related rheumatic manifestations treated with sofosbuvir (400 mg daily) plus daclatasvir (60 mg daily) as a direct-acting antivirals for 3 months. All patients were subjected to clinical and serological course of extrahepatic rheumatic manifestations evaluation. Results: show that among the 60 patients, 21 patients (35.0%) met the criteria of mixed cryoglobulinemia syndrome (MC), 19 patients (31.7%) were complaining of arthralgia, 17 patients (28.3%) were complaining of fibromyalgia and 3 patients (5.0%) were complaining of Purpura without other criteria of mixed cryoglobulinemia syndrome. Complete clinical response was achieved in a significant number of patients with mixed cryoglobulinemia syndrome (MCS), the results also show significant clinical improvement in patients with fibromyalgia, arthralgia and purpura. Significant reduction but not complete normalization in auto-antibodies at short term follow-up was observed. Conclusion: It could be concluded that sustained virologic response correlates with clinical and immunological improvement in most patients with extrahepatic rheumatic manifestations among the studied group of chronic hepatitis C Egyptian populations.

Characteristic morphological signs of the brain damage during chronic hepatitis C virus infection identified in autopsy samples

Background: The central nervous system damage is one of the most common extra hepatic manifestations of chronic hepatitis C viral (HCV) infection, with the prevalence of up to 50% of the infected cases. Previous studies have identified the main clinical, pathogenetic and neurometabolic features of this pathology, which make it possible to suggest its definite nosological independence. However, the morphological pattern of brain lesions in chronic HCV infection remains virtually unexplored, significantly limiting the possibility of comprehensive pathological diagnosis of the disease. Aim: To study morphological patterns and to identify typical and diagnostically significant pathological signs of brain involvement in chronic HCV infection. Materials and methods: This was a retrospective descriptive cross-sectional study performed with a range of immunohistochemical (IHC) and pathomorphological techniques in the autopsy brain samples from patients who died of chronic HCV infection (40 cases) and those who died without any signs of past mental and infectious disorders (the control group, 15 cases). Results: The сharacteristic morphological signs of HCV-associated brain injury are IHC expression of the NS3 viral marker, an increase in CD68-positive microglial cell count, white brain matter microgliosis, perivascular and diffuse round cell inflammatory infiltration, degeneration and loss of neurons, neurophagy, demyelination, axonal degeneration, perivascular sclerosis, fibrous cell gliosis, small perivascular hemorrhages, focal hemosiderosis and calcification. The parameters of the identified abnormalities differ significantly depending on the brain region (p < 0.001). The identification of the HCV NS3 marker in the nervous tissue has the definitive diagnostic value. Conclusion: The body of histopathological abnormalities found in various parts of the brain from the infected patients represents the morphological equivalent of the clinical and functional manifestations of HCV-associated cerebral dysfunction. The results obtained can be used to improve the pathological diagnostics of brain lesions in chronic HCV infection; their implementation is feasible in routine pathological practice.

TREATMENT OF HEPATITIS C IN SELECTED CLINICAL SETTINGS

This article aims to review the treatment strategy of Hepatitis C in compelling indications and provide the literature update, mainly discussing the EASL (European Association for the Study of the Liver) recommendations, which described the current optimal management of patients with acute and chronic HCV infections. The review will focus on HCV infection in selected clinical settings including patients with immune complex-mediated manifestations of chronic hepatitis C, patients with chronic kidney disease (CKD) or renal end-stage renal disease (ESRD), and solid organ transplant recipients.

Systematic review with meta‐analysis: extrahepatic manifestations in chronic hepatitis C virus‐infected patients in East Asia

Although the prevalence of extrahepatic manifestations of chronic hepatitis C virus (HCV) infection has been reported from Western countries, their prevalence in East Asian countries is not well known. To perform a systematic review to quantify the prevalence of selected extrahepatic manifestations of HCV among patients from East Asia. Medline, CINAHL, EMBASE, Cochrane and country-specific databases were reviewed according to standard guidelines for meta-analyses. Only articles with patients from East Asian countries were included. After review, 34 articles were selected (Japan=9; China=5, Korea=3, Taiwan=16, multiple countries=1) with 646228 subjects, 66436 with HCV. Mean age for HCV-infected patients was 56years (range 41-72years), 50% were male (range 26%-73%). The pooled prevalence of type 2 diabetes in East Asian HCV patients was 19.0% (95% confidence interval 15.6%-22.9%) (n=19 studies) with an increased risk when compared to non-HCV: odds ratio (OR) 1.58 (1.28-1.94). The prevalence of chronic kidney disease in HCV was 9.2% (5.0%-16.2%) (n=7 studies), also with a significantly increased risk: OR=1.98 (1.41-2.77). Pooled prevalence of cardiovascular disease in HCV was 8.6% (3.5%-19.9%) (n=6 studies), also with an increased risk: OR=1.55 (1.21-1.98). The prevalence of lichen planus in HCV was 8.9% (3.6%-20.6%) (n=6 studies) while the prevalence of rheumatoid arthritis was 4.5% (0.6%-25.7%) (n=4 studies). These data show increased risk of developing extrahepatic manifestations in East Asian patients with HCV. Both hepatic and extrahepatic manifestations of the infection should be used to accurately determine the total burden of the disease in the region.

Recurrent optic neuritis as the only manifestation of chronic hepatitis B virus flare: a case report

BackgroundAutoimmune reactions have been associated with acute hepatitis B virus infection. Among these optic neuritis is a rare presentation with only a handful of cases reported in the literature thus far. The pathophysiologic mechanism governing this phenomenon includes high levels of circulating immune complexes, tissue deposit, and complement activation cascade.Case PresentationIn this report, we present the case of a 46-year-old African American man with a past medical history of untreated chronic hepatitis B virus, diagnosed 5 years ago, who presented to our facility on two occasions with the chief compliant of blurry vision. He was diagnosed with optic neuritis associated with acute on chronic hepatitis B virus infection, where the recurrent visual impairment was the main presenting symptom. Because hepatitis constituted a relative contraindication for steroid therapy, our patient was solely treated with antiviral medication. Antiviral therapy resulted in complete resolution of his symptoms and improvement in his liver function.ConclusionsFurther studies are necessary to conclusively establish whether antiviral therapy can be employed as the sole therapy in immune complex-mediated optic neuritis, in the setting of active recurrent hepatitis B infection.

Pachydermoperiostosis in a patient with chronic hepatitis B virus infection referred as acromegaly: a case report

BackgroundPrimary hypertrophic osteoarthropathy also known as pachydermoperiostosis is a rare genetic disorder that has often been confused with acromegaly because of similar clinical features. Vascular endothelial growth factors which have been implicated in the clinical features of pachydermoperiostosis, have also been shown to be present in chronic hepatitis and implicated in the malignant transformation of hepatitis B infection to hepatocellular carcinoma. To the best of our knowledge there is one reported case of pachydermoperiostosis with chronic hepatitis B infection. We do not imply a causal relationship between pachydermoperiostosis and hepatitis B infection because pachydermoperiostosis is a genetic disorder; however, the question is raised whether hypertrophic osteoarthropathy is one of the many extrahepatic manifestations of chronic hepatitis B infection.Case presentationA 21-year-old African (Ghanaian) man with chronic hepatitis B infection was referred to our Endocrine unit as having acromegaly with changing facial features, enlarging hands and feet, and large knee joint effusions which affected activities of daily living. He was finally diagnosed as having pachydermoperiostosis when acromegaly, rheumatological disorders, as well as cardiopulmonary disorders were ruled out. He improved with arthrocentesis, a tapering regime of steroids, non-steroidal anti-inflammatory drugs, and proton pump inhibitors.ConclusionsThe possible role of hepatitis B in hypertrophic osteoarthropathy, that is, secondary hypertrophic osteoarthropathy, needs to be explored; however, with digital clubbing in his father our patient is likely to have pachydermoperiostosis.

Neurological manifestations in chronic hepatitis C patients receiving care in a reference hospital in sub-Saharan Africa: A cross-sectional study.

BackgroundChronic hepatitis C infection is a major public health concern, with a high burden in Sub-Saharan Africa. There is growing evidence that chronic hepatitis C virus (HCV) infection causes neurological complications. This study aimed at assessing the prevalence and factors associated with neurological manifestations in chronic hepatitis C patients.MethodsThrough a cross-sectional design, a semi-structured questionnaire was used to collect data from consecutive chronic HCV infected patients attending the outpatient gastroenterology unit of the Douala General Hospital (DGH). Data collection was by interview, patient record review (including HCV RNA quantification, HCV genotyping and the assessment of liver fibrosis and necroinflammatory activity), clinical examination complemented by 3 tools; Neuropathic pain diagnostic questionnaire, Brief peripheral neuropathy screen and mini mental state examination score. Data were analysed using Statistical package for social sciences version 20 for windows.ResultsOf the 121 chronic hepatitis C patients (51.2% males) recruited, 54.5% (95% Confidence interval: 46.3%, 62.8%) had at least one neurological manifestation, with peripheral nervous system manifestations being more common (50.4%). Age ≥ 55 years (Adjusted Odds Ratio: 4.82, 95%CI: 1.02–18.81, p = 0.02), longer duration of illness (AOR: 1.012, 95%CI: 1.00–1.02, p = 0.01) and high viral load (AOR: 3.40, 95% CI: 1.20–9.64, p = 0.02) were significantly associated with neurological manifestations. Peripheral neuropathy was the most common neurological manifestation (49.6%), presenting mainly as sensory neuropathy (47.9%). Age ≥ 55 years (AOR: 6.25, 95%CI: 1.33–29.08, p = 0.02) and longer duration of illness (AOR: 1.01, 1.00–1.02, p = 0.01) were significantly associated with peripheral neuropathy.ConclusionOver half of the patients with chronic hepatitis C attending the DGH have a neurological manifestation, mainly presenting as sensory peripheral neuropathy. Routine screening of chronic hepatitis C patients for peripheral neuropathy is therefore necessary, with prime focus on those with older age and longer duration of illness.

Hepatic tropism of hepatitis C virus infection

Hepatitis C virus (HCV) infects over 170 million people worldwide and is a major cause of life-threatening liver diseases such as liver cirrhosis and hepatocellular carcinoma. In current research, we aimed to clarify the mechanism of hepatic tropism of HCV infection. Although non-hepatic cells could not permit replication of HCV RNA, exogenous expression of liver specific miRNA, miR-122 facilitated efficient replication of viral RNA through direct interaction with 5'UTR of viral genome, indicating that miR-122 is one of the key determinants for hepatic tropism of HCV infection. In spite of efficient replication of viral RNA, formation of infectious particles was not observed in non-hepatic cells exogenously expressing miR-122. We found that expression of apolipoprotein E (ApoE) facilitated the formation of infectious HCV particles in non-hepatic cells, indicating that not only miR-122 but also ApoE participate in tissue tropism of HCV infection. To understand the exact roles of miR-122 and apolipoproteins in hepatic tropism of HCV, we established miR-122 and ApoB/ApoE knockout (KO) Huh7 cells, respectively. Although slight increase of intracellular HCV RNA and infectious titers in the culture supernatants was observed, propagation of HCV was impaired in miR-122 KO Huh7 cells. After serial passages of HCV in miR-122 KO cells, we obtained an adaptive mutant that possessed G28A substitutions in the 5'UTR of the HCV genome and exhibited efficient translation and replication in both miR-122 KO Huh7 and non-hepatic cells without exogenous expression of miR-122. These results suggest that HCV mutants replicating in non-hepatic cells in an miR-122-independent manner participate in the induction of extrahepatic manifestations in chronic hepatitis C patients. Deficiency of both ApoB and ApoE strongly inhibited the formation of infectious HCV particles. Interestingly, expression not only of ApoE but also of ApoA or ApoC could rescue the production of infectious HCV particles in ApoB/ApoE KO cells, suggesting that exchangeable apolipoproteins redundantly participate in the formation of infectious HCV particles.

Cryoglobulinemia and its correlation with clinical extrahepatic manifestations in chronic hepatitis C

Cryoglobulinemia is a condition with a confirmed relationship with HCV infection, but many other extrahepatic symptoms are also present in hepatitis C. Aim: The aim of this study was to assess the incidence and type of extrahepatic manifestations and cryoglobulinemia as well as their correlation with clinical symptoms in Polish patients. Material and methods: 246 consecutive patients with hepatitis C were studied. Clinical symptoms were assessed by anamnesis and a clinical investigation. Cryoglobulins were estimated by a method basing on their ability to reverse precipitation in temperature +4ºC. Monoclonality of cryoglobulins was estimated by agarophoresis immunotyping – capillary electrophoresis and immunofixation. The presence of classical rheumatoid factor (RF-IgM) was tested using ELISA. Anti-nuclear antibodies (ANA) were tested using the indirect immunofluorescence method. Anti-CCP, anti-SSA, anti-α-fodrin antibodies, RF IgG, IgM and IgA were assessed using commercial enzymatic tests. Statistical methods were: Fisher exact test, generalized additive models, odds ratios with 95% confidence intervals, aid of spline curve, SAS system version 9.4. Results: Cryoglobulins were found in 93 persons (37.8%). Type II cryoglobulinemia was detected in 28 persons. Patients with cryoglobulinemia were elder (p<0.0004). 54 patients (21.95%) manifested clinical extrahepatic symptoms. Arthralgia was found in 27 cases (10.98%). Skin changes were found in 22 patients (8.94%). 12 persons had glomerulonephritis (4.88%). 11 patients (4.47%) had sicca syndrome. 6 patients developed peripheral polyneuropathy (2.4%). 4 persons developed B cell lymphoma (1.63%). There was no correlation between presence of symptoms and grading, staging, age, HCV genotype, and the presence of autoantibodies. Extrahepatic manifestations were present more frequently in women (p<0.0008).

Characterization of miR-122-independent propagation of HCV.

miR-122, a liver-specific microRNA, is one of the determinants for liver tropism of hepatitis C virus (HCV) infection. Although miR-122 is required for efficient propagation of HCV, we have previously shown that HCV replicates at a low rate in miR-122-deficient cells, suggesting that HCV-RNA is capable of propagating in an miR-122-independent manner. We herein investigated the roles of miR-122 in both the replication of HCV-RNA and the production of infectious particles by using miR-122-knockout Huh7 (Huh7-122KO) cells. A slight increase of intracellular HCV-RNA levels and infectious titers in the culture supernatants was observed in Huh7-122KO cells upon infection with HCV. Moreover, after serial passages of HCV in miR-122-knockout Huh7.5.1 cells, we obtained an adaptive mutant, HCV122KO, possessing G28A substitution in the 5’UTR of the HCV genotype 2a JFH1 genome, and this mutant may help to enhance replication complex formation, a possibility supported by polysome analysis. We also found the introduction of adaptive mutation around miR-122 binding site in the genotype 1b/2a chimeric virus, which originally had an adenine at the nucleotide position 29. HCV122KO exhibited efficient RNA replication in miR-122-knockout cells and non-hepatic cells without exogenous expression of miR-122. Competition assay revealed that the G28A mutant was dominant in the absence of miR-122, but its effects were equivalent to those of the wild type in the presence of miR-122, suggesting that the G28A mutation does not confer an advantage for propagation in miR-122-rich hepatocytes. These observations may explain the clinical finding that the positive rate of G28A mutation was higher in miR-122-deficient PBMCs than in the patient serum, which mainly included the hepatocyte-derived virus from HCV-genotype-2a patients. These results suggest that the emergence of HCV mutants that can propagate in non-hepatic cells in an miR-122-independent manner may participate in the induction of extrahepatic manifestations in chronic hepatitis C patients.

Extrahepatic manifestations in chronic hepatitis C infected patients

The importance of chronic hepatitis C infection is significant. 3% of the World's population is infected. There is at least one extrahepatic manifestation in 50% of HCV patients, which makes the prognosis and mortality worse. The pathomechanisms included are cryoglobulin production, immunmechanisms, and direct viral effects. The authors summarize the main extrahepatic manifestations, as well as treatment possibilities. The aim is to draw attention to this colourful infection in order to improve the recognition in the era of the new effective direct antiviral agents. Orv. Hetil., 2017, 158(16), 603-612.

On-treatment HBV DNA dynamics predict virological breakthrough in entecavir-treated HBeAg-positive chronic hepatitis B.

Background & aimsVirological breakthrough (VBT) could be a manifestation of chronic hepatitis B (CHB) in patients treated with long-term nucleot(s)ide analogues. We aimed to determine the association of on-treatment serum hepatitis B virus (HBV) DNA with VBT in HBeAg-positive CHB patients receiving entecavir (ETV) treatment.MethodsA retrospective cohort study, including 162 consecutive patients (95 men and 67 women; mean age, 43.1±13.4 years) with HBeAg-positive CHB treated with ETV for at least 48 weeks between August 2008 and May 2015, was conducted. Univariate and multivariate cox regression analysis were used to identify associations with VBT and clinical factors, including HBV DNA and HBeAg serum status.ResultsAmong the 162 ETV-treated HBeAg-positive CHB patients, eighteen patients (11.1%) experienced VBT (VBT group), whereas the other 144 patients were without VBT (non-VBT group). The cumulative rate of HBV DNA < 100 IU/mL in the VBT group and the non-VBT group at week 48 were 44.44% and 70.14%, and at week 96 were 58.33% and 92.56%, respectively (p = 0.015). The cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group at week 48 and week 96 were statistically significant (p = 0.014). Multivariate analysis disclosed that failure to achieve HBeAg seroclearance were the factors significantly associated with VBT.ConclusionsOur results demonstrated that on-treatment HBV DNA could probably predict VBT in ETV-treated HBeAg-positive chronic hepatitis B patients. Failure to achieve HBeAg seroclearance was associated with VBT in ETV-treated HBeAg-positive CHB patients. HBV DNA >100IU/mL at 48 weeks is potentially a predictor for VBT.

Extrahepatic Manifestations of Chronic Hepatitis C Infection: a Review and Update

Hepatitis C virus (HCV) has become an increasingly concerning global disease. While it is well known to causes a chronic hepatitis that can be largely asymptomatic until the development of cirrhosis and/or hepatocellular carcinoma (HCC), chronic HCV can also lead to extrahepatic manifestations (EHMs) which can contribute to further morbidity and mortality. This chapter will discuss the pathophysiology and data supporting the causal relationship between chronic HCV infection and its EHMs as well as address the influence of HCV treatment on these disorders, particularly in the age of direct-acting antiviral agents.

Portal Hypertension Reversibility with Treatment of Underlying Liver Disease

Cirrhosis is the end-stage manifestation of chronic hepatitis with the most common causes of chronic hepatitis in developed countries being related to hepatitis B, hepatitis C, nonalcoholic fatty liver disease (NAFLD), and alcoholic liver disease. With more advanced cirrhosis, the development of portal hypertension occurs that leads to clinical decompensation. With improvement in therapies for hepatitis B and C, we have seen regression of fibrosis and even cirrhosis. However, there are limited data on reversal of portal hypertension. This review examines the direct and indirect evidence that we will be able to see regression of portal hypertension in those with cirrhosis.

Extrahepatic manifestations in chronic hepatitis C virus carriers.

Patients with chronic hepatitis C virus (HCV) infection frequently present with extrahepatic manifestations covering a large spectrum, involving different organ systems leading to the concept of systemic HCV infection. These manifestations include autoimmune phenomena and frank autoimmune and/or rheumatic diseases and may dominate the course of chronic HCV infection. Chronic HCV infection causes liver inflammation affecting the development of hepatic diseases. HCV is also a lymphotropic virus that triggers B cells and promotes favorable conditions for B lymphocyte proliferation, including mixed cryoglobulinemia (MC) and MC vasculitis, which is the most prominent extrahepatic manifestation of chronic HCV infection. HCV may also promote a low-grade chronic systemic inflammation that may affect the development of some extrahepatic manifestations, particularly cardiovascular and cerebral vascular diseases. Recognition of extrahepatic symptoms of HCV infection could facilitate early diagnosis and treatment. The development of direct-acting antiviral agents (DDAs) has revolutionized HCV treatment. DDAs, as well as new B-cell-depleting or B-cell-modulating monoclonal antibodies, will expand the panorama of treatment options for HCV-related extrahepatic manifestations including cryoglobulinemic vasculitis. In this context, a proactive, integrated approach to HCV therapy should maximize the benefits of HCV therapy, even when liver disease is mild.

A Case of Hepatitis B Virus Related Membranous Glomerulonephritis That Well Responsed to Low Dose Corticosteroid Therapy

©Copyright 2014 by Bezmialem Vakif University Available online at www.bezmialemscience.org ©Telif Hakki 2014 Bezmialem Vakif Universitesi Makale metnine www.bezmialemscience.org web sayfasindan ulasilabilir. Glomerulonephritis (GN) is a common extrahepatic manifestation of chronic hepatitis B virus (HBV) infection, affecting approximately 20% of patients from the Middle East and Far East Asia, where HBV infection is prevalent (1) Recent data show that 30% of patients with HBV-related GN eventually progress to renal failure (2). The major pathogenetic mechanism of HBV-related GN is immune complex deposits in the kidney, leading to destruction of the epithelial side of the glomerular basement membrane and eventually resulting in protein loss into the tubules. Although treatment strategies of HBV and membranous nephropathy are well established, there is still a lack of available data in patients who not respond well to primary intervention or who have failed to sustain the response.