Had Hepatitis C Virus Infection Research Articles

Advancing Diagnosis of Current Hepatitis C Virus Infection: A Key to Hepatitis C Elimination in the United States.

More than 2 million adults have hepatitis C virus (HCV) infection in the United States, and new infections continue to increase. Without treatment, HCV infection can lead to advanced liver disease and death. Treatment is recommended for nearly everyone with hepatitis C, resulting in a cure in >95% of people treated and raising the possibility of hepatitis C elimination. Testing is the first step to accessing life-saving treatment. The Centers for Disease Control and Prevention recommends hepatitis C screening for all adults, all pregnant persons, and anyone with risk; yet about one-third of people with hepatitis C remain unaware of their infection. Testing begins with a hepatitis C antibody test, followed, when reactive, by a nucleic acid test to detect HCV RNA. This antibody-first, 2-step testing strategy misses early infections and can result in incomplete diagnoses. Advancements in hepatitis C diagnostics and the US regulatory landscape have created an opportunity to include viral-first testing strategies and improve hepatitis C diagnosis. This journal supplement features 8 articles detailing challenges and opportunities for improving hepatitis C diagnostics in support of advancing hepatitis C elimination in the United States.

Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases

Background and aimsTo explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated...

Evaluation of the Cherokee Nation Hepatitis C Virus Elimination Program - Cherokee Nation, Oklahoma, 2015-2020.

Approximately 2.4 million persons in the United States have hepatitis C virus (HCV) infection, and 66,700 acute HCV infection cases were estimated for 2020 (1,2). American Indian or Alaska Native (AI/AN) persons are disproportionately affected by HCV infection and experienced the highest rates of acute HCV infection (2.1 cases per 100,000 persons) and HCV-associated mortality (10.17 per 100,000 persons) in the United States during 2020 (1). During 2015, Cherokee Nation Health Services (CNHS) in Oklahoma implemented an HCV elimination program, which includes universal HCV screening, primary HCV workforce expansion, and harm reduction services (3). To assess progress 5 years after program initiation, CNHS analyzed deidentified health record data. During November 1, 2015-October 31, 2020, a total of 1,423 persons received a diagnosis of HCV infection. Among these persons, 1,227 (86.2%) were linked to HCV care, and 871 (61.2%) initiated HCV treatment; 702 (49.3%) returned for their 12-week post treatment completion visit, at which time 698 (49.1%) had achieved laboratory-confirmed sustained virologic response (SVR), defined as undetectable HCV RNA at ≥12 weeks after completion of treatment (SVR12). Although CNHS has linked the majority of persons diagnosed with HCV infection to care, and those who returned for the SVR12 visit had high cure rates (99.4%), treatment initiation was lower than expected. Future activities should prioritize addressing gaps in treatment initiation after linkage to care and confirmation of hepatitis C cure with SVR12 testing.

Vital Signs: Hepatitis C Treatment Among Insured Adults - United States, 2019-2020.

IntroductionOver 2 million adults in the United States have hepatitis C virus (HCV) infection, and it contributes to approximately 14,000 deaths a year. Eight to 12 weeks of highly effective direct-acting antiviral (DAA) treatment, which can cure ≥95% of cases, is recommended for persons with hepatitis C.MethodsData from HealthVerity, an administrative claims and encounters database, were used to construct a cohort of adults aged 18–69 years with HCV infection diagnosed during January 30, 2019–October 31, 2020, who were continuously enrolled in insurance for ≥60 days before and ≥360 days after diagnosis (47,687). Multivariable logistic regression was used to assess the association between initiation of DAA treatment and sex, age, race, payor, and Medicaid restriction status; adjusted odds ratios (aORs) and 95% CIs were calculated.ResultsThe prevalence of DAA treatment initiation within 360 days of the first positive HCV RNA test result among Medicaid, Medicare, and private insurance recipients was 23%, 28%, and 35%, respectively; among those treated, 75%, 77%, and 84%, respectively, initiated treatment within 180 days of diagnosis. Adjusted odds of treatment initiation were lower among those with Medicaid (aOR = 0.54; 95% CI = 0.51–0.57) and Medicare (aOR = 0.62; 95% CI = 0.56–0.68) than among those with private insurance. After adjusting for insurance type, treatment initiation was lowest among adults aged 18–29 and 30–39 years with Medicaid or private insurance, compared with those aged 50–59 years. Among Medicaid recipients, lower odds of treatment initiation were found among persons in states with Medicaid treatment restrictions (aOR = 0.77; 95% CI = 0.74–0.81) than among those in states without restrictions, and among persons whose race was coded as Black or African American (Black) (aOR = 0.93; 95% CI = 0.88–0.99) or other race (aOR = 0.73; 95% CI = 0.62–0.88) than those whose race was coded as White.Conclusions and Implications for Public Health PracticeFew insured persons with diagnosed hepatitis C receive timely DAA treatment, and disparities in treatment exist. Unrestricted access to timely DAA treatment is critical to reducing viral hepatitis–related mortality, disparities, and transmission. Treatment saves lives, prevents transmission, and is cost saving.

Outcome of Treatment in Children With Chronic Viral Hepatitis C: A Single Centre Study.

ObjectiveTo review the efficacy of the combination of pegylated interferon-α 2b and ribavirin, and sofosbuvir and ribavirin in achieving sustained viral response (SVR) in chronic hepatitis C genotypes 1 and 3 in children.MethodsA retrospective descriptive study was performed for children under 15 years of age treated for chronic hepatitis C at Pakistan Kidney and Liver Institute and Research Centre, Lahore, between 2018 and 2019. Demographic data and clinical information were collected. In addition, treatment outcome was assessed by SVR, defined as the absence of detectable viral RNA in blood after 24 weeks of initiation of treatment.ResultsA total of 30 children aged 15 years and below were included in this study. Sixteen of 30 children were males, and 14 were females. Of these 30 patients, four had hepatitis C virus (HCV) genotype 1, and 26 children had HCV genotype 3. The children with genotype 1 (a+b) were given the combination of ribavirin and pegylated interferon alfa-2b (Peg-IFN-α-2b). The remaining with HCV genotype 3 were given the combination of ribavirin and sofosbuvir for 24 weeks. Overall, 27 out of 30 (90%) children attained SVR at six months (100% children with genotype 1 and 88.4% children with genotype 3).ConclusionThe combined therapy of ribavirin and sofosbuvir or Peg-IFN-α-2b and ribavirin is highly effective in treating chronic HCV infection in children.

Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study

SummaryBackgroundMore than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV.MethodsFor this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857.FindingsOur search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18–1·39). Globally, 1·5 million (95% CI 0·9–2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs.InterpretationHCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries.FundingBritish Heart Foundation and Wellcome Trust.

Long-term Liver-related Outcomes of Patients With Chronic Liver Diseases in Australia

Chronic liver disease is a major health burden that produces significant liver-related morbidity and mortality. We aimed to evaluate liver-related outcomes of patients with different causes of chronic liver disease in Australia. We collected data from 10,933 patients with chronic liver disease assessed by Hepascore (a serum fibrosis model) in Western Australia from 2004 through 2015. We obtained records of liver-related death, transplantation, decompensation, and hepatocellular carcinoma from WA Data Linkage Unit databases. Competing risk analysis was used to calculate the cumulative risk of each clinical endpoint, and risks for clinical endpoints were compared among all causes of chronic liver disease. In our final cohort for analysis, 5566 patients had hepatitis C virus (HCV) infection, 1989 had HBV infection, 119 were infected with HBV and HCV, 955 had alcohol-associated liver disease, 1597 had non-alcoholic fatty liver disease (NAFLD), 123 had alcohol-associated liver disease and metabolic risk factors, 561 had autoimmune liver disease without overlap syndrome, and 23 autoimmune overlap syndrome. Significant differences among chronic liver diseases were observed in risk of all-cause death (P <.001), liver-related death (P < .001), liver transplantation (P < .001), and decompensation (P < .001) but not hepatocellular carcinoma (P=.095). Patients with alcohol-associated liver disease had the highest 5-year cumulative risk of liver-related death (17.1%) and the second-highest 5-year cumulative risk of decompensation (29.2%). Multivariate analysis found patients with alcohol-associated liver disease had significantly higher risks of liver-related death and decompensation than patients with HCV infection with hazard ratios (HRs) of 2.39 (95% CI, 1.88-3.03) and 3.42 (95% CI, 2.74-4.27), respectively. Patients with NAFLD had a significantly lower risk of liver related death and decompensation than patients with HCV infection, with HRs of 0.67 (95% CI, 0.48-0.95) and 0.70 (95% CI, 0.52-0.94) respectively. In an analysis of patients in Western Australia, we found patients with alcohol-associated liver disease to have significantly higher risk of decompensation and liver-related death than patients with HCV infection, whereas patients with NAFLD have significantly lower risks of either outcome.

Clinical and epidemiological characteristics of hepatitis C virus-infected people who inject drugs: a Greek descriptive analysis.

BackgroundIt is estimated that 17,000 people who inject drugs (PWID) in Greece have hepatitis C virus (HCV) viremia. The aim of our study was to explore the characteristics of the HCV-infected, direct acting antiviral (DAA)-naïve PWID.MethodsThis is a retrospective analysis of PWID with HCV infection. We selected data from six liver clinics during the period from 1st May 2014 to 31st May 2017 in order to record the characteristics of infected PWID.ResultsWe included 800 PWID with HCV infection (78.5% male, mean age 42±10 years) who had not received DAAs before 1st June 2017. One third of the patients had comorbidities (diabetes mellitus, arterial hypertension and psychological disorders); 70% were smokers, 27% alcohol users, 67% unemployed, 29% married, and 34% had education >12 years; 65% were attending addiction programs; 57% were receiving methadone and 36% buprenorphine. Sporadic or systemic drug use was reported by 37% while 1.4% and 2.9% had HIV and HBV coinfection, respectively. The genotype distribution was 20.5%, 4.6%, 3.3%, 61% and 10% for genotypes 1a, 1b, 2, 3 and 4, respectively. Mean (±SD) liver stiffness was 9±7 kPa and 21% of the patients had cirrhosis. Half of the patients were in the F0-F1 stage of liver disease, defined as stiffness ≤7 kPa.ConclusionsOur real-life data suggest that HCV genotype 3 remains the predominant genotype among PWID. One third of PWID had comorbidities and one-fifth cirrhosis. Half of PWID had early-stage liver disease and remained without access to DAAs according to the Greek prioritization criteria.

Coexistent Ipsilateral Internal Carotid Artery Occlusion and Cerebral Venous Thrombosis in Hepatitis C.

A 58-year-old male, known to have hepatitis C virus (HCV), presented with intermittent headaches and left-sided sensorimotor symptoms. There were no focal neurological deficits on examination. Electrocardiogram was unremarkable. Computed tomography angiography head and neck displayed extracranial right internal carotid artery occlusion. Magnetic resonance imaging showed right cortical vein thrombosis, with hemorrhagic infarction. Echocardiography with bubble study was unremarkable. Hypercoagulable workup was significant for protein S deficiency. He was treated with warfarin for 6 months. Repeat protein S levels remained low 9 months later. The coexistence of arterial and venous thrombotic events gives rise to a limited differential. In this case, it may be related to chronic HCV infection. The underlying pathogenesis is not clear; however, it is possible the patient had chronic high-grade internal carotid artery stenosis, which occluded leading to his presenting symptoms. The cortical vein thrombosis is likely an incidental finding here. The extent by which HCV contributed to the cerebral thrombosis and carotid artery occlusion in our case is not clear; however, the hypercoagulable and atherosclerotic properties of the virus cannot be disregarded. The virus can promote carotid atherosclerosis and cerebral venous thrombosis as well as other venous and arterial thromboembolic events. Furthermore, HCV is associated with impaired venous flow and procoagulant properties, which can fuel a hypercoagulable state. Also of note cirrhosis is associated with protein S deficiency. We recommend considering an underlying hypercoagulable state including both arterial and venous thrombosis in HCV infection.

Hepatocellular Carcinoma and Viral Hepatitis in New York City.

The incidence and mortality rate of hepatocellular carcinoma (HCC) are increasing in the United States. Viral hepatitis infection is a primary risk factor for HCC. This study describes the relationship between viral hepatitis and HCC in New York City (NYC). Viral hepatitis cases reported to the NYC Department of Health from 1999-2012 were matched to HCC cases diagnosed from 2001 to 2012 and reported to the New York State Cancer Registry. HCC cases were stratified by the presence or absence of viral hepatitis. Demographic characteristics, factors associated with specific causes of death, and survival time were analyzed for all HCC cases. From 2001-2012, a total of 8827 NYC residents had HCC diagnosed; 38.4% had hepatitis C virus (HCV) infection, 17.9% had hepatitis B virus (HBV) infection, and 2.2% had both. Patients with HCC were predominantly men (74.8%), with equal proportions of white non-Hispanic (28.6%) and Hispanic (28.9%) patients. Those with HBV infection were primarily Asian/Pacific Islanders (63.2%). The median survival time after HCC diagnosis for persons with HBV infection was 22.3 months, compared with 13.1 months for persons with HCV infection, and 6.9 months for noninfected persons. The 5-year survival rate was 37.5% for those with HBV infection, 20.0% for those with HCV infection, 29.5% among coinfected individuals, and 16.1% for those with neither infection reported. In NYC, most persons with HCC have viral hepatitis; the majority of viral hepatitis infections are due to HCV. Survival for persons with HCC differs widely by viral hepatitis status. This study highlights the importance of viral hepatitis prevention and treatment and HCC screening.

Characteristics and outcomes of transjugular intrahepatic portosystemic shunt recipients in the VA Healthcare System.

Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective treatment for complications of portal hypertension. We aimed to describe post-TIPS mortality and its predictors in the modern era of covered stents. We identified patients with cirrhosis who underwent TIPS insertion at Veterans Affairs Healthcare facilities nationally from 2004 to 2014 (n=703), most of which (95%) were performed as elective procedures. We followed patients until the date of death, transplantation, or the end of the observation period. TIPS recipients had a mean age of 59.3 years (SD 8) and 97% were men. The mean Model for End Stage Liver Disease (MELD) score was 13 (SD 4.8); 47% had hepatitis C virus (HCV) infection, 48% had variceal hemorrhage, and 40% had ascites. During a mean follow-up of 1.72 years (SD 1.9), 57.5% of TIPS recipients died (n=404) and only 5.3% underwent liver transplantation (n=37). The median survival after TIPS was 1.74 years (interquartile range 0.3-4.7). Thirty-day mortality after TIPS was 11.6% [95% confidence interval (CI) 9.4-14.2], 1-year mortality was 40.3% (95% CI 36.7-44.2), and 3-year mortality was 61.9% (95% CI 57.9-66.0). Independent predictors of post-TIPS mortality included medical comorbidity burden, low albumin, HCV infection, and high MELD score (or high international normalized ratio and bilirubin when the components of the MELD score were analyzed individually). TIPS revision was performed at least once in 27.3% of TIPS recipients. TIPS should not be considered simply as a bridge to transplantation. Burden of extra-hepatic comorbidities, HCV infection, and low serum albumin strongly predict post-TIPS mortality in addition to the MELD score.

Regional challenges: evaluation of a hepatitis outreach programme using transient elastography (FibroScan) in Victoria.

Evaluation of an outreach programme using a mobile transient elastography (TE) device (FibroScan) to improve liver disease assessment in different clinical settings. To evaluate a programme of liver fibrosis assessment by TE and to compare fibrosis scores between different sites and patient groups. Prospective cohort study. TE was conducted at a tertiary hospital and during outreach clinics in three different settings: community clinics, clinics for people who use drugs (PWUD) and regional clinics in rural Victoria. All patients referred for TE at the participating locations were eligible during the study period. A total of 200 of 623 patients was assessed and evaluated during outreach sessions (regional 100; PWUD 18; community 82). While the majority of patients in community centres were infected with hepatitis B (68%), most patients in regional clinics and in PWUD settings had hepatitis C virus (HCV) (81 and 100%, respectively). Significantly more patients assessed at regional clinics and PWUD settings presented with severe fibrosis (F3-F4, F4): regional clinics 39%; PWUD 31%; tertiary 11%; community 7%, (P <0.001). Multivariable logistic regression analysis revealed that older age, alcohol consumption, male sex, increased alanine transferase levels, HCV infection and importantly, evaluation at regional sites were independently associated with severe fibrosis. A TE-based outreach programme allows for assessment of liver fibrosis in varied and regional populations. The finding that patients in regional settings and PWUD presented with more advanced fibrosis should prompt improvements in healthcare to improve access for these populations.

Anti-Cytosolic 5'-Nucleotidase 1A (cN1A) Positivity in Muscle is Helpful in the Diagnosis of Sporadic Inclusion Body Myositis: A Study of 35 Japanese Patients

Sporadic Inclusion Body Myositis (sIBM) is a refractory myositis developing in the elderly. Recently, anti-cytosolic 5'-nucleotidase 1A (cN1A) antibodies were reported to be present specifically in sIBM. To assess the clinicopathological features and usefulness of anti-cN1A positivity in muscle specimens, we evaluated a group of Japanese patients with sIBM. Among Japanese patients with myositis who underwent a muscle biopsy from 1991 through 2014 in our hospital, we identified cases of sIBM that met the European Neuromuscular Center (ENMC) criteria. We then analyzed clinical course, pathological findings, and treatment response. Of 282 patients with myositis, 35 (12%) were given a diagnosis of sIBM (24 men and 11 women). The median age at onset was 67 ± 7 (55-81) years, and that at diagnosis was 70 ± 7 years. Remarkably, 5 (14%) patients concurrently had hepatitis C virus (HCV) infection and 4 (11%) had heart disease. Pathologically, we found rimmed vacuoles in 32 (91%) patients and anti-cN1A positivity in perinuclear regions and rimmed vacuoles in 31 (89%) patients. Remarkably, anti-cN1A antibody positivity was significantly higher in sIBM than in polymyositis (30%), dermatomyositis (10%), and morphologically normal cases (0%), suggesting its high specificity for sIBM. Twelve (34%) patients received immunosuppressants, 8 (23%) received prednisone, and 5 (14%) received intravenous immunoglobulins (IVIg). Clinical symptoms transiently improved in 5 patients given prednisone and in 4 patients given IVIg, but these treatments failed to be radical therapies. In our study of Japanese patients with sIBM, anti-cN1A antibody positivity in muscle specimens was highly sensitive and specific pathologically. Therefore, the expression of anticN1A antibody may be greatly useful for the diagnosis of sIBM. Although the concurrent presence of HCV infection and heart disease was notable, other epidemiological characteristics were consistent with the results of previous studies.

Working together to tackle HCV infection: ombitasvir/paritaprevir/ritonavir and dasabuvir combination.

An estimated 184 million people worldwide have hepatitis C virus (HCV) infection. Chronic infection can ultimately result in liver cirrhosis and hepatic failure. Eradication of the virus by antiviral treatment can hinder the development of the aforementioned complications. Historically, the combination therapy of PEGylated interferon/ribavirin was considered the standard-of-care therapy for HCV. Such therapy did not demonstrate satisfactory cure rates and had significant side effects that precluded its widespread use among HCV patients. In view of this situation, scientific advances have led to the development of new interferon-free regimens that are better tolerated, more effective and with shorter duration of therapy. One of the newest members of this family is the all-oral regimen (ombitasvir/paritaprevir/ritonavir co-packaged with dasabuvir) that has recently received FDA approval for the treatment of adult patients with genotype 1 HCV infection, including those with compensated cirrhosis. This new combination was found to be safe and well tolerated with high rates of sustained virologic response of up to 100%. An overview of the current knowledge about this regimen is reviewed herein.

Transmission clustering among newly diagnosed HIV patients in Chicago, 2008 to 2011: using phylogenetics to expand knowledge of regional HIV transmission patterns.

HIV transmission cluster analyses can inform HIV prevention efforts. We describe the first such assessment for transmission clustering among HIV patients in Chicago. We performed transmission cluster analyses using HIV pol sequences from newly diagnosed patients presenting to Chicago's largest HIV clinic between 2008 and 2011. We compared sequences through progressive pairwise alignment, using neighbor joining to construct an unrooted phylogenetic tree. We defined clusters as >2 sequences among which each sequence had at least 1 partner within a genetic distance of ≤1.5%. We used multivariable regression to examine factors associated with clustering and used geospatial analysis to assess geographic proximity of phylogenetically clustered patients. We compared sequences from 920 patients, median age of 35 years, 75% male, 67% black, 23% Hispanic, and 8% had a rapid plasma reagin titer ≥1:16 concurrent with their HIV diagnosis. We had HIV transmission risk data for 54%; 43% identified as men who have sex with men (MSM). Phylogenetic analysis demonstrated 123 patients (13%) grouped into 26 clusters, the largest having 20 members. In multivariable regression, age <25, black race, MSM status, male gender, higher HIV viral load, and rapid plasma reagin ≥1:16 associated with clustering. We did not observe geographic grouping of genetically clustered patients. Our results demonstrate high rates of HIV transmission clustering, without local geographic foci, among young black MSM in Chicago. Applied prospectively, phylogenetic analyses could guide prevention efforts and help break the cycle of transmission.

Effect of pre- and post-treatment α-fetoprotein levels and tumor size on survival of patients with hepatocellular carcinoma treated by resection, transarterial chemoembolization or radiofrequency ablation: a retrospective study.

BackgroundWe evaluated treatment modalities and survival in patients with hepatocellular carcinoma (HCC), by pre-treatment and 3-month post-treatment serum alpha-fetoprotein (AFP) levels and pre-treatment tumor diameters.MethodsWe retrospectively reviewed 57 patients treated for HCC in our department from January 2002 to December 2012, including their sex, type of hepatitis, Child class, pre-treatment tumor size, pre-treatment levels of albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), red blood cells, hemoglobin, and total bilirubin, pre- and 3-month post-treatment serum AFP, and treatment modality (transarterial chemoembolization, resection or radiofrequency ablation). Survival was analyzed at 1, 3, and 5 years after treatment.ResultsThe 57 patients included 44 men and 13 women, of whom 44 had hepatitis C virus (HCV) infection, 3 had hepatitis B virus (HBV) infection, 3 had both HBV and HCV infection, 1 had both HBV and hepatitis D virus infection, and 3 had alcohol-related liver cirrhosis. Both pre- and post-treatment serum AFP levels significantly correlated with recurrent tumor size (P < 0.05 for both). Pre-treatment tumor size did not correlate with recurrent tumor size. Patients who underwent hepatic resection survived significantly longer than those who underwent transarterial chemoembolization or radiofrequency ablation (P < 0.05).ConclusionsSerum AFP level is useful in diagnosing tumor recurrence and predicting prognosis in HCC patients treated by hepatic resection, transarterial chemoembolization, and radiofrequency ablation. Hepatic resection remains the treatment of choice for HCC in suitable patients.

CD81 sequence and susceptibility to hepatitis C infection

Several cell surface molecules have hepatitis C virus (HCV) binding properties and may serve as receptors facilitating viral entry into cells. The large extracellular loop (LEL) of CD81 has been shown to bind the HCV envelope protein E2 with several critical residues for the CD81-HCV-E2 interaction. It was hypothesised that variation in the CD81 LEL sequence may modify susceptibility to HCV infection. HCV RNA negative patients with spontaneous viral clearance (RNA -ve); HCV RNA positive cases, who are affected chronically (RNA +ve); and patients at high risk of HCV infection, exposed but uninfected patients (EU) were studied. Genomic DNA was extracted from whole blood samples and four exons of the CD81 LEL gene were amplified by PCR and sequenced. The cDNA derived from CD81 (≈700 bp) was sequenced following RNA extraction from peripheral blood mononuclear cells. Patients, who are RNA positive, RNA negative, and exposed uninfected were sequenced for four DNA sections (A, B, C, and D). Sixty-two (43M:19F) patients, from all the patient cohorts, were sequenced and compared for the C section alone (which encompasses the important binding region of the molecule for envelope protein) including 21 (14M:7F) HCV RNA negative, 15 (10M:5F) HCV RNA positive and 26 (20M:6F) exposed uninfected and no sequence differences were observed. The entire CD81 sequence from cDNA was obtained in 23 cases-11 RNA -ve, 5 RNA +ve and 7 EU. In 7 of the 23 cases, the nucleotides were confirmed with the genomic sequence (4 RNA -ve and 3 EU cases). No sequence variation was found in any of the patients studied by either method, including gene sections encoding the residues most important for CD81-HCV E2 binding. The LEL of CD81 is a molecule that is highly conserved. No differences in nucleotide sequence influencing susceptibility to, or outcome of HCV infection or evidence of methylation of the gene were found.

A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis

To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV). Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months. Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated. RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

Unilateral hearing loss due to pegylated interferon-α2b and ribavirin therapy

Combination of pegylated interferon and ribavirin is the standard of care in patients with chronic hepatitis C virus infection. However this therapy has many side effects, including flu-like symptoms, neuropsychiatric symptoms and cytopenias. Auditory symptoms like tinnitus and hearing loss have only rarely been reported. A 40-year-old man, incidentally detected to have hepatitis C virus (HCV) infection a year ago, was referred to our hospital for further management. He was asymptomatic and physical examination was unremarkable. Investigations revealed normal complete blood counts, renal function tests, glucose and bilirubin, and elevated alanine aminotransferase (ALT 126 U/L). Anti-HCV was positive, HCV viral load was 4.2×10 IU/mL and genotype was 3. Ultrasonography abdomen revealed normal size and echotexture of liver. He was diagnosed to have chronic HCV infection and was started on pegylated interferon α2b 80 μg subcutaneously per week (body weight 62 kg) plus oral ribavirin 800 mg/ day. He used to have fever and flu-like symptoms lasting for 2–3 days after each dose of interferon. Hemoglobin declined by 3 gm/dL by week 12 and he lost 5 kg of weight. His viral load had become negative by week 4 (rapid virological response) and remained negative at week 12 (early virological response). In the 19th week of antiviral therapy, he started having pain in left ear associated with some hearing loss. He denied any history of hearing loss or exposure to any ototoxic drugs in the past. Tympanic membrane did not reveal any abnormality. MRI of the middle ear was normal. Pure tone audiometry showed a profound sensorineural hearing loss of 70/120 dB in his left ear and normal hearing of 18/18 dB in the right ear. The patient decided to discontinue further therapy. At the end of treatment his ALT values were normal and HCV RNA was undetectable. He was prescribed multivitamins and anti-inflammatory drugs. Pain in the left ear decreased but hearing loss showed no improvement over a 6-month follow up. HCV RNA was undetectable indicating sustained virological response. This case illustrates a rare adverse reaction of sudden unilateral sensorineural hearing loss in a patient receiving pegIFNα2b and ribavirin combination therapy for chronic HCV infection. MRI ruled out other causes for such acute unilateral hearing loss such as temporal bone fracture, rupture of round or oval window membranes or vestibular schwannoma. Both unilateral and bilateral acute sensorineural hearing loss with interferon therapy have been rarely reported in literature, unilateral being more common [1–6, 9, 10]. In a prospective study, 32 (44%) of 73 patients receiving interferon developed abnormalities on audiometry [1]. These resolved completely within 7–14 days after discontinuation of therapy. In another prospective study, 9 of 27 patients with chronic hepatitis B receiving interferon-alpha developed sensorineural hearing loss [2]. They further observed that this loss increased gradually with subsequent doses but recovered completely after discontinuation of treatment. Various hypothesis for ototoxicity associated with interferon therapy are autoimmune (detection of anti-endothelial cell autoantibodies and response to prednisolone) [1, 3–5], direct S. Jain :V. Midha Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab 1410 01, India

Induction of clinical remission with adalimumab–methotrexate combination therapy in a patient with rheumatoid arthritis and concomitant hepatitis C virus infection

The patient described here is a 49-year-old woman who had hepatitis C virus (HCV) infection and rheumatoid arthritis (RA). Her RA had been successfully managed with methotrexate for about 10 years. After a sustained virological response was achieved with interferon therapy, treatment with adalimumab was instituted. This resulted in a rapid and sustained remission that lasted for more than a year, without HCV reactivation. The results in this case suggest that a sequential strategy, with initial HCV clearance followed by the targeting of remission with biologics, may be a favorable option in patients with RA and concomitant HCV infection.