Erythropoiesis associated with viral hepatitis in end stage renal disease

We describe an end stage renal disease (ESRD) patient on maintenance hemodialysis who developed a spontaneous increase in erythropoiesis associated with an episode of viral hepatitis. Resolution of the hepatitis was accompanied by a reduction in erythropoiesis with the hemoglobin and hematocrit falling back toward the patient's low baseline levels. Plasma erythropoietin (Ep) titers were measured during the period of active erythropoiesis and were found to be low to low normal. The unusual phenomenon of increased erythropoiesis in ESRD following liver injury has been previously described and is thought to be mediated through increased hepatitic Ep production. The low Ep titers measured in our patient, however, suggest that the liver may be capable of stimulating erythropoiesis by another mechanism.     

End-stage renal disease and hepatitis C infection: comparison of alanine aminotransferase levels and liver histology in patients with and without renal damage

Background and aim: To what extent the serum levels of alanine aminotransferase (ALT) are related to histological characteristics of liver damage caused by hepatitis C virus (HCV) infection among patients with end-stage renal disease (ESRD) remains unclear.Methods: Patients with a positive anti-HCV antibody titer confirmed by supplemental tests were evaluated by liver biopsy. We compared ALT levels in patients with and without renal damage, with similar histological grades and stages of inflammation and fibrosis. Patients were divided into two groups: patients with ESRD (n = 25) and patients without renal damage (n = 39).Results: The ALT level was 42.1 ± 24.3 IU/L for the ESRD group, compared with 109.9 ± 55.8 IU/L for the non-ESRD group (P < 0.001). Liver inflammation (modified Knodell grade) was 4.0 ± 2.1 in the ESRD group versus 5.2 ± 2.4 in the non-ESRD group; fibrosis (6-point scale) was 1.1 ± 1.2 versus 1.7 ± 1.5, respectively.Conclusions: Despite histological evidence of liver inflammation, ALT levels in the ESRD group were normal, while ALT levels were significantly higher in the non-ESRD group with similar levels of liver inflammation. In conclusion, ALT levels are not a useful indicator of HCV infection in patients with ESRD and liver biopsies should be recommended for kidney transplant candidates.     

Vaccination against hepatitis B in patients with chronic liver disease awaiting liver transplantation.

BACKGROUND: Most transplant centers in the United States immunize patients awaiting liver transplantation against hepatitis B to prevent acquisition of hepatitis B through transplantation (de novo hepatitis B). A recent study showed that only 16% of patients with cirrhosis awaiting liver transplantation responded to single-dose recombinant vaccine. METHODS: We studied the immunogenicity of double-dose recombinant vaccine in patients with cirrhosis awaiting liver transplantation. RESULTS: Over a 4-year period (January 1994 to December 1997), 140 patients with cirrhosis without past or current hepatitis B infection were given double-dose recombinant vaccine (40 microg of Engerix B; SmithKline Beecham, Philadelphia, PA) at 0, 1 to 2, and 2 to 4 months. Hepatitis B surface antibody (HBsAb) was measured 1 to 3 months after completing vaccination. The response rate was 37%. However, HBsAb titers became undetectable in 35% of the responders during the post-transplant follow-up period. One hundred and thirty-seven patients underwent 144 liver transplantation procedures during the study period, and 3 patients developed de novo hepatitis B (2.2%). Livers transplanted from hepatitis B core antibody (HBcAb)-positive donors was the source of de novo hepatitis B in all cases. Two of the 3 patients who developed de novo hepatitis B were immunized before transplantation and one of them was a responder. CONCLUSION: Although the response rate to double-dose recombinant vaccines is higher than the previously reported response to single-dose vaccine, it still is less than optimal.     

Chronic hepatitis C and liver transplantation

Chronic hepatitis C virus (HCV) is a worldwide health problem. Approximately 4 million people in the United States are chronically infected with HCV. The incidence of infection peaked between 2 and 3 decades ago, and we are now beginning to see an increase in the complications of cirrhosis from HCV. This trend is expected to continue for another 2 to 3 decades. Survival is poor once complications of cirrhosis, such as liver failure or hepatocellular carcinoma, ensue, and liver transplantation is often the only option. Complications of chronic HCV are the most common indication for liver transplantation, accounting for more than 40% of transplants performed in the United States and Europe. HCV recurs in all patients and rapid development of hepatic fibrosis is very common. Several strategies have been proposed to reduce the risk of graft loss from recurrent HCV infection after transplantation, as the progression of the resulting liver disease is rapid. Although antiviral treatment is successful in some patients, it is extremely difficult to administer and requires dose reductions in the majority of cases. Retransplantation in the current era of the Model for End-Stage Liver Disease (MELD) system for prioritizing listing for transplant is associated with very low survival rates at a high cost. Furthermore, the system raises difficult ethical issues of utilization of limited resources and fairness to other transplant candidates.     

Increased hepatitis C viral load and reactivation of liver disease in HCV RNA-positive patients with onco-haematological disease undergoing chemotherapy

Aims

To evaluate changes in Hepatitis C Virus (HCV) RNA both in plasma and Peripheral Blood Mononuclear Cells (PBMC) in onco-haematological patients.

Patients and methods

8 consecutive anti-HCV/HCV RNA-positive patients with onco-haematological diseases (5 with B-cell Non-Hodgkin Lymphoma and 3 with chronic lymphocytic leukaemia) were observed during chemotherapy and after its discontinuation. All were naïve to chemotherapy. HCV RNA was sought by Real Time Polymerase Chain Reaction in Light Cycler 1.5 in plasma and PBMC samples collected before, during and after chemotherapy.

Results

An increase in HCV RNA of at least 1.5 log IU/mL in plasma and 1.1 log IU/ml in PBMC was observed in all 7 patients undergoing Rituximab-based chemotherapy; these patients showed a hepatic flare after discontinuation, life-threatening in one with cirrhosis. Also the 8th patient had cirrhosis, but was treated with Rituximab-sparing chemotherapy and did not show any increase in HCV RNA or a hepatic flare.

Conclusion

Rituximab-based chemotherapy favours an increase in HCV RNA in onco-haematological patients; this is followed by a hepatic flare, possibly immune-mediated and life threatening in cirrhotic patients.     

Management of patients with hepatitis C infection and renal disease

Hepatitis C virus(HCV) infection in patients with end-stage renal disease(ESRD) is associated with more rapid liver disease progression and reduced renal graft and patients’ survival following kidney transplantation. Evaluations and management of HCV in patients with renal disease are challenging. The pharmacokinetics of interferons(IFN), ribavirin(RBV) and some direct acting antiviral(DAA), such as sofosbuvir, are altered in patients with ESRD. With dose adjustment and careful monitoring, treatment of HCV in patients with ESRD can be associated with sustained virological response(SVR) rates nearly comparable to that of patients with normal renal function. DAA-based regimens, especially the IFNfree and RBV-free regimens, are theoretically preferred for patients with ESRD and KT in order to increase SVR rates and to reduce treatment side effects. However, based on the data for pharmacokinetics, dosing safety and efficacy of DAA for patients with severe renal impairment are lacking. This review will be focused on the evaluations, available pharmacologic data, and management of HCV in patients with severe renal impairment, patients who underwent KT, and those who suffered from HCV-related renal disease, according to the available treatment options, including DAA.     

肝移植术后丙肝复发抗病毒治疗患者持续病毒应答影响因素分析

目的分析肝移植术后丙肝复发抗病毒治疗患者产生持续病毒应答(SVR)的影响因素。方法回顾性分析2003～2009年39例肝移植术后丙肝复发并进行抗病毒(聚二乙醇干扰素和利巴韦林)治疗的患者的临床资料。结果本组中21例因不良反应停药,18例完成全疗程规范治疗,疗程25～105周;有4例(22.22%)获得SVR,其平均治疗周期是57周。统计分析显示,非ⅠB型基因(P=0.023)、治疗前丙肝病毒载量<10~6 copies/ml(P=0.044)以及早期病毒应答(EVR)(P=0.019)与SVR的获得有关。结论非ⅠB基因型、低水平HCV RNA和EVR是肝移植后丙肝复发抗病毒治疗产生SVR的影响因素。     

Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease.

The natural history of chronic hepatitis C (HCV) infections in long-term leukemia survivors has not been well characterized. We studied the prevalence of HCV infections, measured HCV RNA levels, and evaluated the severity of liver disease in patients with leukemia who achieved long-term remissions after intensive chemotherapy or bone marrow transplantation (BMT). HCV antibody tests were performed by the enzyme-linked immunosorbent assay (ELISA) and positive tests confirmed by the recombinant immunoblot assay (RIBA). HCV RNA levels were measured by the branched DNA (bDNA) assay. Seventy-five leukemia survivors with 25 or more blood donor exposures were identified. Nine (12%) were anti-HCV positive. All were infected before 1992 when second generation HCV screening tests were implemented. Mean HCV RNA levels were 10.3 x10(6) eq/mL versus 3.2 x 10(6) eq/mL (P =.056) in a control group of 20 anti-HCV positive immunocompetent individuals of comparable age who were infected twice as long (17.8 +/- 6.5 years v 9.0 +/- 4.4 years in leukemia survivors, P =.001). Liver biopsies were performed on six of the nine anti-HCV positive leukemia survivors. All showed at least moderate portal inflammation and half had evidence of bridging fibrosis. We conclude that viral loads in anti-HCV positive leukemia survivors are markedly higher than in immunocompetent controls. Our results suggest that long-term leukemia survivors with chronic HCV may have more rapidly progressive liver disease than has been previously recognized.     

Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection

AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1.METHODS: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the frequencies.Logistic regression was used to determine significant predictors of SVR.Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis.RESULTS:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the controls.The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B.The proportion of patients with a low IVL(600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the ESRD and control groups,respectively.A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups.The ESRD patients who achieved SVR showed the lowest IVL[median 21000,interquartile range(IQR):6000-23000IU/m L],compared with ESRD individuals without SVR(1680000,IQR:481000-6880000,P=0.001),controls with SVR(387000,IQR:111000-1253000)and controls without SVR(905000,IQR:451000-3020000).In ESRD,an IVL600000 IU/m L was strongly associated with SVR:24/28(85.7%)patients who achieved SVR had viraemia below this threshold.CONCLUSION:Haemodialysis decreases the viral load,especially in IL28B CC genotype carriers.A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.     

Acute alcoholic hepatitis,end stage alcoholic liver disease and liver transplantation: An Italian position statement

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.     

非生物人工肝在重型肝炎患者过渡肝移植中的应用价值

目的　评价非生物人工肝对重型病毒性肝炎 (重型肝炎 )患者等待肝移植的过渡支持作用与价值。方法　采用血浆置换和血浆吸附两种非生物人工肝支持疗法 ,对 8例拟定肝移植的中晚期重型肝炎患者进行人工肝过渡支持。结果　 8例重型肝炎患者经人工肝支持 ,4例肝衰竭得到较好的控制 ,4～ 13d后成功等到供肝。另 4例肝衰竭控制不明显 ,病情呈进行性加重 ,在待肝过程中 (人工肝支持后 3～ 8d)死亡。结论　非生物人工肝对等待肝移植的重型肝炎患者有一定的过渡支持作用 ,能否最终成功过渡与患者肝衰竭程度、并发症及待肝时间密切相关。     

Chronic hepatitis C infection and liver disease in HIV‐coinfected patients in Asia

Data on markers of hepatitis C virus (HCV) disease in HIV‐HCV‐coinfected patients in resource‐limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan^®) in 480 HIV‐infected patients with positive HCV antibody in four HIV treatment centres in South‐East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7‐42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325‐614) cells/mm³ and 208 (94.1%) of 221 patients tested had HIV‐1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4‐6.6) log₁₀ IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan^®, 143 (37.6%) had no/mild liver fibrosis (F0‐F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan^® failure. In conclusion, a high proportion of HIV‐HCV‐coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2).     

终末期肾病患者脂质过氧化水平的变化

目的 :研究慢性终末期肾病 (ESRD)脂质过氧化状况及肾替代治疗对其的影响。　 方法 :观察对象分为正常对照组、慢性肾功能不全非透析 (CRF)组、持续性不卧床腹膜透析 (CAPD)组和血液透析 (HD)组 ;测定各组以及HD前后血浆丙二醛 (MDA)、脂氢过氧化物 (LOOH)含量和血浆抗氧化型LDL抗体 (anti oxLDLAb)水平。　 结果 :ESRD患者血浆MDA、LOOH和anti oxLDLAb水平均比正常对照组明显升高 (P均 <0 0 5 ) ;CRF组血浆MDA、LOOH和anti oxLDLAb水平与SCr浓度呈正相关 (P均 <0 0 1) ,与Ccr呈负相关 (P均 <0 0 1) ;CAPD组血浆MDA含量比CRF组显著升高 (P <0 0 5 ) ;HD组血浆MDA、LOOH和anti oxLDLAb水平均比CRF组明显增高 ,MDA和LOOH浓度比CAPD组明显升高 (P均 <0 0 5 ) ;单次HD前后上述指标无明显变化 (P均 >0 0 5 )。　 结论 :ESRD患者脂质过氧化反应增强 ,并随肾功能恶化而加重 ,HD可能进一步加剧这种病理生理改变。