All-oral, direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of chronic hepatitis C (CHC) treatment but their effectiveness and safety among patients with chronic ...kidney disease (CKD) remains poorly understood. Our aim was to assess the efficacy and safety of DAAs for treatment of CKD patients. The National Library of Medicine through PubMed was searched for studies evaluating the efficacy of DAAs for the treatment of patients with CKD stages 4 or 5, as defined by the Kidney Disease Outcomes Quality Initiative guidelines i.e. glomerular filtration rate (GFR) 15–29 ml/min per 1.73 m2 and GFR <15 ml/min per 1.73 m2, respectively, or hemodialysis or peritoneal dialysis. Randomized clinical trials (RCTs) and relevant cohort studies were included if they were published in English and included sustained viral response after 12 weeks (SVR12) as a primary or secondary endpoint. After applying inclusion and exclusion criteria, eight studies (one RCT and seven cohort studies) following 350 patients were selected. For patients with CKD stage 4 or 5, ± hemodialysis, the overwhelming majority of DAA regimens were well-tolerated and resulted in SVR12 rates of 90–100%. Most studies were small, with the exception of one RCT evaluating elbasvir and grazoprevir. Overall, treatment of CHC in patients with CKD is highly effective with SVR12 rates similar to those seen in patients without CKD and with acceptable adverse event profiles. In patients with hepatitis C virus (HCV) genotype (GT) 1a, 1b or 4 and Stage 4 or 5 CKD, the best evidence available is for the use of elbasvir and grazoprevir. This combination as well as the combination of paritaprevir/ritonavir/ombitasvir/dasabuvir for HCV GT-1b are recommended. More studies are needed to assess efficacy and adverse effects of DAAs and their impact on CKD patients and to fully elucidate the effect of curing CHC on the natural history and sequelae of renal disease in CHC patients with CKD.
Background and aimsThis article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is ...a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.MethodsIn May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.ResultsThese recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.ConclusionsPruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.
Alcoholic Liver Disease Joshi, Kartik; Kohli, Anita; Manch, Richard ...
Clinics in liver disease,
August 2016, Volume:
20, Issue:
3
Journal Article
Peer reviewed
Open access
In this review we critically assess the literature to evaluate the level of risk posed by alcohol as both a primary etiology of hepatocellular carcinoma (HCC) and as a cofactor in its development. ...Although there have been conflicting findings, based on the body of evidence to date, it appears that the linkage between compensated alcoholic liver disease-associated cirrhosis and HCC is best characterized as medium-high risk, with the risk increasing with age and with quantity and duration of alcohol consumption and is more pronounced in females. While abstinence is the most effective way to reduce HCC risk, its effect seems largely dependent on the severity of liver damage at the point of cessation. Alcohol clearly interacts with other etiologies and conditions including viral hepatitis B and C, hereditary hemochromatosis, diabetes, and obesity to increase the risk for developing HCC, either synergistically or additively. Continued progress in genetics, especially through mechanistic-based and genome-wide association studies may ultimately identify which single nucleotide polymorphisms are risk factors for the onset of alcoholic liver disease and its progression to HCC and lead to the development of targeted therapeutics which may help providers better manage at-risk patients.
Background
Historically, chronic hepatitis C virus (HCV) treatment was response-guided. Clinical trials with sofosbuvir indicated on-treatment virologic response was not predictive of sustained ...virologic response (SVR) and hence response-guided therapy (RGT) was abandoned. The purpose of this study is to examine the association between on-treatment 4-week HCV RNA and SVR in patients treated in real-world practice.
Methods
The study is a retrospective analysis of consecutive patients started on treatment with a sofosbuvir-containing regimen, January 1, 2014 through August 20, 2014, for HCV genotype 1–6 infection. Patients were treated by HCV specialists at 6 centers in the Project ECHO (Extension for Community Healthcare Outcomes) HCV Collaborative or in the community by primary care clinicians mentored by HCV specialists through Project ECHO. Patients were included if they were over 18 years, had evidence of chronic HCV, and were started on a sofosbuvir-containing regimen. The aspartate aminotransferase:platelet ratio index (APRI) was used to estimate fibrosis. The main outcome measures were 4-week HCV RNA and SVR.
Results
Overall SVR was 82.5 %. At week 4, HCV RNA was detected in 27.4 % of patients. Stepwise multivariable logistic-regression analyses identified APRI > 1.0, male sex, genotype 3, and detectable on treatment 4-week HCV RNA as independent predictors of failure to achieve SVR.
Conclusions
In a real-world setting, a significant proportion of sofosbuvir treated patients have detectable on-treatment 4-week HCV RNA. Detectable on-treatment 4-week HCV RNA is associated with virologic failure. More data are needed to formulate guidance for RGT with newly available HCV therapies.
Chronic hepatitis C (CHC) is associated with multiple extrahepatic manifestations that may impact infected patients. The mechanisms through which these develop include those which are immunological, ...in which the chronic persistence of virus leads to the circulation of immune complexes (mixed cryoglobulinemia) and other autoimmune phenomena, and those which are virological and related to the extrahepatic tropism of the virus to other tissues. It is estimated that 40–74 % of patients with CHC may develop at least one extrahepatic manifestation during the course of the disease. Extrahepatic syndromes may represent the first signal of hepatitis C infection in some patients. CHC is associated with a four-fold increased risk of insulin resistance and type 2 diabetes mellitus; with cardiovascular disease in 17–37 % of patients; and with increased risk for cerebrovascular deaths, with a biological gradient of cerebrovascular mortality correlating with an increasing serum viral load. CHC is also associated with lymphoproliferative disorders, particularly non-Hodgkin B-cell lymphoma. The kidney is involved in 35–60 % of patients with CHC-associated mixed cryoglobulinemia. The prevalent type of glomerulonephritis associated with mixed cryoglobulinemia is membranoproliferative glomerulonephritis. In 30 % of cases, renal involvement begins with a nephritis syndrome and acute renal failure, while in 55 % there is only mild hematuria, microalbuminuria, proteinuria and renal insufficiency. CHC is also associated with cognitive impairment, especially in memory and concentration. Thus, extrahepatic CHC manifestations involve multiple organ systems outside the liver linked to a variety of comorbidities which may lead to significantly increased mortality from non-liver-related events.
Hepatitis C virus (HCV) infection is the leading reason for liver transplantation and a common cause of hepatocellular carcinoma, the most rapidly increasing cause of cancer-related deaths in the ...United States. Of the approximately 3 million persons living with HCV infection in the United States, an estimated 38% are linked to care, 11% are treated, and 6% achieve cure. Recent development of highly effective and well-tolerated medications, such as sofosbuvir and simeprevir, to treat chronic HCV infection shows promise in curbing rising HCV-related morbidity and mortality, with the potential to cure >90% of patients. To fully benefit from these new treatments, improvement in linkage to care and treatment is urgently needed.* Lack of provider expertise in HCV treatment and limited access to specialists are well-documented barriers to HCV treatment. In September 2012, CDC funded programs in Utah and Arizona to improve access to primary care providers with the capacity to manage and treat HCV infection. Both programs were modeled on the Extension for Community Healthcare Outcomes (Project ECHO), developed by the University of New Mexico's Health Sciences Center in 2003 to build primary care capacity to treat diseases among rural, underserved populations through videoconferencing and case-based learning in "teleECHO" clinics. To assess the effectiveness of these programs in improving primary care provider capacity and increasing the number of patients initiating treatment, process and patient outcome data for each state program were analyzed. In both states, Project ECHO was successfully implemented, training 66 primary care clinicians, predominantly from rural settings. Nearly all (93%) of the clinicians had no prior experience in care and treatment of HCV infection. In both states combined, 129 (46%) of HCV-infected patients seen in teleECHO clinics received antiviral treatment, more than doubling the proportion of patients expected to receive treatment. These findings demonstrate Project ECHO's ability to expand primary care capacity to treat HCV infection, notably among underserved populations.
In this review we critically assess the literature to evaluate the level of risk posed by alcohol as both a primary etiology of hepatocellular carcinoma (HCC) and as a cofactor in its development. ...Although there have been conflicting findings, based on the body of evidence to date, it appears that the linkage between compensated alcoholic liver disease-associated cirrhosis and HCC is best characterized as medium-high risk, with the risk increasing with age and with quantity and duration of alcohol consumption and is more pronounced in females. While abstinence is the most effective way to reduce HCC risk, its effect seems largely dependent on the severity of liver damage at the point of cessation. Alcohol clearly interacts with other etiologies and conditions including viral hepatitis B and C, hereditary hemochromatosis, diabetes, and obesity to increase the risk for developing HCC, either synergistically or additively. Continued progress in genetics, especially through mechanistic-based and genome-wide association studies may ultimately identify which single nucleotide polymorphisms are risk factors for the onset of alcoholic liver disease and its progression to HCC and lead to the development of targeted therapeutics which may help providers better manage at-risk patients.
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