Herbal medicine in the treatment of liver diseases

Herbal drugs have become increasingly popular and their use is widespread. Licensing regulations and pharmacovigilance regarding herbal products are still incomplete and clearcut proof of their efficacy in liver diseases is sparse. Nevertheless, a number of herbals show promising activity including silymarin for antifibrotic treatment, phyllantus amarus in chronic hepatitis B, glycyrrhizin to treat chronic viral hepatitis, and a number of herbal combinations from China and Japan that deserve testing in appropriate studies. Apart from therapeutic properties, reports are accumulating about liver injury after the intake of herbals, including those advertised for liver diseases. Acute and/or chronic liver damage occurred after ingestion of some Chinese herbs, herbals that contain pyrrolizidine alkaloids, germander, greater celandine, kava, atractylis gummifera, callilepsis laureola, senna alkaloids, chaparral and many others. Since the evidence supporting the use of botanicals to treat chronic liver diseases is insufficient and only few of them are well standardised and free of potential serious side effects, most of these medications are not recommended outside clinical trials. Particularly with regard to the latter, adequately powered randomised-controlled clinical trials with well-selected end points are needed to assess the role of herbal therapy for liver diseases.

Polyarteritis Nodosa, a vanishing vasculitis since its main cause has been identified

The polyarteritis nodosa is a vasculitis for which the main cause had been identified as hepatitis B, a chronic infectious disease inducing an overshooting immune reaction. Thanks to this discovery, the treatment of polyarteritis nodosa has changed from a symptomatic immunosuppressive therapy to a treatment strategy focusing on the disease inducing infectious agent. Vaccination against hepatitis B- virus has been instrumental in the reduction of the prevalence of polyarteritis nodosa. In case of the rare entity of polyarteritis nodosa without hepatitis B, only a symptomatic immunosuppressive therapy can be prescribed. The history of polyarteritis nodosa clearly illustrates that future research in the field of so called autoimmune diseases should focus on the causes rather than on the immunologic effector mechanisms and/or the symptomatic immunosuppressive therapy.

The etiology of liver damage imparts cytokines transforming growth factor beta1 or interleukin-13 as driving forces in fibrogenesis

It is unknown whether transforming growth factor beta1 (TGF-beta1) signaling uniformly participates in fibrogenic chronic liver diseases, irrespective of the underlying origin, or if other cytokines such as interleukin (IL)-13 share in fibrogenesis (e.g., due to regulatory effects on type I pro-collagen expression). TGF-beta1 signaling events were scored in 396 liver tissue samples from patients with diverse chronic liver diseases, including hepatitis B virus (HBV), hepatitis C virus (HCV), Schistosoma japonicum infection, and steatosis/steatohepatitis. Phospho-Smad2 staining correlated significantly with fibrotic stage in patients with HBV infection (n = 112, P < 0.001) and steatosis/steatohepatitis (n = 120, P < 0.01), but not in patients with HCV infection (n = 77, P > 0.05). In tissue with HBx protein expression, phospho-Smad2 was detectable, suggesting a functional link between viral protein expression and TGF-beta1 signaling. For IL-13, immunostaining correlated with fibrotic stage in patients with HCV infection and steatosis/steatohepatitis. IL-13 protein was more abundant in liver tissue lysates from three HCV patients compared with controls, as were IL-13 serum levels in 68 patients with chronic HCV infection compared with 20 healthy volunteers (72.87 +/- 26.38 versus 45.41 +/- 3.73, P < 0.001). Immunohistochemistry results suggest that IL-13-mediated liver fibrogenesis may take place in the absence of phospho-signal transducer and activator of transcription protein 6 signaling. In a subgroup of patients with advanced liver fibrosis (stage > or =3), neither TGF-beta nor IL-13 signaling was detectable. Conclusion: Depending on the cause of liver damage, a predominance of TGF-beta or IL-13 signaling is found. TGF-beta1 predominance is detected in HBV-related liver fibrogenesis and IL-13 predominance in chronic HCV infection. In some instances, the underlying fibrogenic mediator remains enigmatic.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.

Gallbladder and Pancreas in Henoch-Schönlein Purpura: Review of the Literature

OBJECTIVE Involvement of the pancreato-biliary system has been occasionally noted in Henoch-Schönlein purpura. Furthermore, cases of this vasculitis syndrome sometimes develop in the context of a viral hepatitis or after hepatitis vaccination. METHODS We completed a review of the literature. RESULTS Fifty reports published between 1977 and 2015 were retained for the analysis. A pancreato-biliary involvement was recognized in 34 individually well-described patients (♂:♀ = 19:15) with severe abdominal pain: pancreatitis (N = 20), acalculous cholecystitis (N = 11), both pancreatitis and cholecystitis (N = 3). In all of the pancreatitis patients, full recovery occurred (within ≤3 weeks in three-fourths of the patients). Cholecystectomy was performed in 8 cholecystitis patients. Seventeen Henoch-Schönlein patients (♂:♀ = 9:8) were associated with a viral liver disease and 4 (♂:♀ = 1:3) with a hepatitis vaccination. The vasculitis syndrome rapidly remitted in the 7 patients accompanying hepatitis A or E, in 2 patients of hepatitis B, and in the 4 patients preceded by a vaccination. Henoch-Schönlein purpura seemed to be serious in 5 patients with chronic hepatitis B and in 3 with chronic hepatitis C. CONCLUSIONS This analysis indicates that pancreato-biliary involvement is unusual in Henoch-Schönlein purpura. This complication deserves consideration in patients with especially severe abdominal pain. Finally, viral hepatitides and hepatitis vaccinations seem to be rare triggers of Henoch-Schönlein purpura.

Absence of Hepatitis Delta Infection in a Large Rural HIV Cohort in Tanzania

OBJECTIVES The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in sub-Saharan Africa are ill-defined. We determined the prevalence of HDV infection in HIV/hepatitis B virus (HBV)-co-infected individuals in rural Tanzania. DESIGN AND METHODS We screened all hepatitis B virus (HBV)-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) for anti-HDV antibodies. In positive samples, we performed a second serological test and nucleic acid amplification. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and positive patients. RESULTS Among 222 HIV/HBV-coinfected patients on ART, 219 (98.6%) had a stored serum sample available and were included. Median age was 37 years, 55% were female, 46% had WHO stage III/IV HIV disease and median CD4 count was 179 cells/μL. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8%-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. CONCLUSIONS We found no confirmed case of HDV infection among over 200 HIV/HBV-co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test.

Impfungen bei Immunsupprimierten. Mit Fokus auf HIV-positive Personen, Personen mit einer hämatologischen Stammzelltransplantation oder Organtransplantation und Personen mit funktionaler oder anatomischer Splenektomie

Personen mit einer HIV-Infektion, nach einer Organ- oder einer hämatologischen Stammzelltransplantation oder mit einer funktionalen oder anatomischen Asplenie sind gegenüber Infektionen anfälliger. Sie haben eine grössere Komplikationsrate und ein höheres Risiko für einen chronifizierten Verlauf. Impfungen wären eine ideale primäre Präventionsmassnahme, sind aber – durch dieselben Mechanismen des Immundefektes der zu schwereren Krankheitsverläufen führt – in ihrer Wirksamkeit vermindert. Die Impfungen sollen daher, wenn immer möglich, vor Beginn der Immunsuppression oder später zum Zeitpunkt der minimalsten Immunsuppression, durchgeführt werden. Trotzdem bleibt der Benefit von Impfungen bei immunsupprimierten Personen unbestritten, sofern die Indikationsstellung bezüglich Zeitpunkt und Dosierung (Dosismenge und -anzahl), die zu einem maximalen Ansprechen führt, beachtet wird. Lebendimpfungen sind wegen der Gefahr der unkontrollierten Vermehrung der Impfviren bei schwerer Immunsuppression kontraindiziert. Die Serologie soll unspezifischer gemessen werden, da schwer immunsupprimierte Personen im Falle einer relevanten Exposition durch passive Immunisierung mittels spezifischer oder unspezifischer intravenöser Immunglobuline geschützt werden können.

HIV infection, viral hepatitis and liver fibrosis among prison inmates in West Africa.

BACKGROUND Prisoners represent a vulnerable population for blood-borne and sexually transmitted infections which can potentially lead to liver fibrosis and ultimately cirrhosis. However, little is known about the prevalence of liver fibrosis and associated risk factors among inmates in sub-Saharan Africa. METHODS Screening of liver fibrosis was undertaken in a randomly selected sample of male inmates incarcerated in Lome, Togo and in Dakar, Senegal using transient elastography. A liver stiffness measurement ≥9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to-face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis. RESULTS Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8-32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1-673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar. CONCLUSIONS HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates.

Phosphatidylethanol (PEth) as a Biomarker of Alcohol Consumption in HIV-Positive Patients in Sub-Saharan Africa

Background:  Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods:  Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. Results:  (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions:  The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.

Putting the magic in magic bullets: top three global priorities for sexually transmitted infection control

Setting practical priorities for sexually transmitted infection (STI) control is a balance between idealism and pragmatism. Infections transmitted through unsafe sex (chlamydia, gonorrhoea, syphilis, HIV, hepatitis B and human papillomavirus (HPV) infections) rank in the top five causes of the global burden of disease.1 Their distribution in populations is driven by a complex mixture of individual behaviours, social and community norms and societal and historical context. Ideally, we would be able to reduce exposure to unsafe sex to its theoretical minimum level of zero and thus eliminate a significant proportion of the current global burden of disease, particularly in resource-poor settings.2 Ideally, we would have ‘magic bullets’ for diagnosing and preventing STI in addition to specific antimicrobial agents for specific infections.3 Arguably, we have ‘bullets’ that work at the individual level; highly accurate diagnostic tests and highly efficacious vaccines, antimicrobial agents and preventive interventions.4 Introducing them into populations to achieve similarly high levels of effectiveness has been more challenging.4 In practice, the ‘magic’ in the magic bullet can be seen as overcoming the barriers to sustainable implementation in partnerships, larger sexual networks and populations (figure 1).4 We have chosen three (pragmatic) priorities for interventions that we believe could be implemented and scaled up to control STI other than HIV/AIDS. We present these starting with the partnership and moving up to the population level.

[Glomerulonephritis and vasculitis as causes of arterial hypertension]

The various types of glomerulonephritis, including many forms of vasculitis, are responsible for about 15% of cases of end-stage renal disease (ESRD). Arterial hypertension represents a frequent finding in patients suffering from glomerulonephritis or vasculitis and hypertension also serves as an indicator for these severe types of diseases. In addition, there are symptoms and signs like hematuria, proteinuria and renal failure. Especially, rapidly progressive glomerulonephritis (RPGN) constitutes a medical emergency and must not be missed by treating physicians. This disease can either occur limited to the kidneys or in the context of a systemic inflammatory disorder, like a vasculitis. If left untreated, RPGN can lead to a necrotizing destruction of glomeruli causing irreversible kidney damage within several months or even weeks. With respect to the immunologically caused vasculitis, there are - depending upon the severity and type of organ involved - many clinical warning signs to be recognized, such as arterial hypertension, hemoptysis, arthalgias, muscle pain, palpable purpura, hematuria, proteinuria and renal failure. In addition, constitutional signs, such as fever and loss of body weight may occur concurrently. Investigations of glomerulonephritis or vasculitis must contain a careful and complete examination of family history and medications used by the respective patient. Thereafter, a thorough clinical examination must follow, including skin, joints and measurement of arterial blood pressure. In addition, a spectrum of laboratory analyses is required in blood, such as full blood screen, erythrocyte sedimentation rate, CRP, creatinine, urea and glucose, and in urine, including urinalysis looking for hematuria, red cell casts and proteinuria. Importantly, proteinuria needs to be quantified by the utilization of a random urine sample. Proteinuria > 3g/d is diagnostic for a glomerular damage. These basic tests are usually followed by more specialized analyses, such as a screening for infections, including search for HIV, hepatitis B or C and various bacteria, and for systemic inflammatory diseases, including tests for antibodies, such as ANA, anti-dsDNA, ANCA, anti-GBM and anti-CCP. In cases of membranous nephropathy, antibodies against phospholipase-A2-receptor need to be looked for. Depending upon the given clinical circumstances and the type of disease, a reasonable tumor screening must be performed, especially in cases of membranous and minimal-change nephropathy. Finally, radiological examinations will complete the initial work-up. In most cases, at least an ultrasound of the kidney is mandatory. Thereafter, in most cases a renal biopsy is required to establish a firm diagnosis to define all treatment options and their chance of success. The elimination of a specific cause for a given glomerulonephritis or vasculitis, such as an infection, a malignancy or a drug-related side-effect, remains the key principle in the management of these diseases. ACE-inhibitors, angiotensin receptor-blockers, aldosteron antagonists and renin-inhibitors remain the mainstay in the therapy of arterial hypertension with proteinuria. Only in cases of persistently high proteinuria, ACE-inhibitors and angiotensin receptor blockers can be prescribed in combination. Certain types of glomerulonephritis and essentially all forms of vasculitis require some form of more specific anti-inflammatory therapy. Respective immunosuppressive drug regimens contain traditionally medications, such as glucocorticoids (e. g. prednisone), cyclosporine A, mycophenolate mofetil, cyclophosphamide, and azathioprine. With respect to more severe forms of glomerulonephritis and vasculitis, the antibody rituximab represents a new and less toxic alternative to cyclophosphamide. Finally, in certain special cases, like Goodpasture's syndrome or severe ANCA-positive vasculitis, a plasma exchange will be useful and even required.

[In Process Citation]

Elevated transaminases in asymptomatic patients can be detected in more than 5 % of the investigations. If there are no obvious reasons, the finding should be confirmed within the next 3 months. Frequent causes are non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol, hepatitis B or C, hemochromatosis and drugs or toxins. Rarer causes are autoimmune hepatitis, M. Wilson and α1-antitrypsine deficiency. There are also non-hepatic causes such as celiac disease or hemolysis and myopathies in the case of an exclusive increase of ASAT. I recommend a two-step investigational procedure; the more frequent causes are examined first before the rare causes are studied. The value of the proposed investigations is discussed.

Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV Cohort Study

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons may be at increased risk for developing type 2 diabetes mellitus because of viral coinfection and adverse effects of treatment. METHODS: We studied associations of new-onset diabetes mellitus with hepatitis B virus and hepatitis C virus coinfections and antiretroviral therapy in participants in the Swiss HIV Cohort Study, using Poisson regression. RESULTS: A total of 123 of 6513 persons experienced diabetes mellitus during 27,798 person-years of follow-up (PYFU), resulting in an incidence of 4.4 cases per 1000 PYFU (95% confidence interval [CI], 3.7-5.3 cases per 1000 PYFU). An increased incidence rate ratio (IRR) was found for male subjects (IRR, 2.5; 95% CI, 1.5-4.2), older age (IRR for subjects >60 years old, 4.3; 95% CI, 2.3-8.2), black (IRR, 2.1; 95% CI, 1.1-4.0) and Asian (IRR, 4.9; 95% CI, 2.2-10.9) ethnicity, Centers for Disease Control and Prevention disease stage C (IRR, 1.6; 95% CI, 1.04-2.4), and obesity (IRR, 4.7; 95% CI, 3.1-7.0), but results for hepatitis C virus infection or active hepatitis B virus infection were inconclusive. Strong associations were found for current treatment with nucleoside reverse-transcriptase inhibitors (IRR, 2.22; 95% CI, 1.11-4.45), nucleoside reverse-transcriptase inhibitors plus protease inhibitors (IRR, 2.48; 95% CI, 1.42-4.31), and nucleoside reverse-transcriptase inhibitors plus protease inhibitors and nonnucleoside reverse-transcriptase inhibitors (IRR, 3.25; 95% CI, 1.59-6.67) but were not found for treatment with nucleoside reverse-transcriptase inhibitors plus nonnucleoside reverse-transcriptase inhibitors (IRR, 1.47; 95% CI, 0.77-2.82). CONCLUSIONS: In addition to traditional risk factors, current treatment with protease inhibitor- and nucleoside reverse-transcriptase inhibitor-containing regimens was associated with the risk of developing type 2 diabetes mellitus. Our study did not find a significant association between viral hepatitis infection and risk of incident diabetes.

Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma

OBJECTIVE: To investigate HIV-related immunodeficiency as a risk factor for hepatocellular carcinoma (HCC) among persons infected with HIV, while controlling for the effect of frequent coinfection with hepatitis C and B viruses. DESIGN: A case-control study nested in the Swiss HIV Cohort Study. METHODS: Twenty-six HCC patients were identified in the Swiss HIV Cohort Study or through linkage with Swiss Cancer Registries, and were individually matched to 251 controls according to Swiss HIV Cohort Study centre, sex, HIV-transmission category, age and year at enrollment. Odds ratios and corresponding confidence intervals were estimated by conditional logistic regression. RESULTS: All HCC patients were positive for hepatitis B surface antigen or antibodies against hepatitis C virus. HCC patients included 14 injection drug users (three positive for hepatitis B surface antigen and 13 for antibodies against hepatitis C virus) and 12 men having sex with men/heterosexual/other (11 positive for hepatitis B surface antigen, three for antibodies against hepatitis C virus), revealing a strong relationship between HIV transmission route and hepatitis viral type. Latest CD4+ cell count [Odds ratio (OR) per 100 cells/mul decrease = 1.33, 95% confidence interval (CI) 1.06-1.68] and CD4+ cell count percentage (OR per 10% decrease = 1.65, 95% CI 1.01-2.71) were significantly associated with HCC. The effects of CD4+ cell count were concentrated among men having sex with men/heterosexual/other rather than injecting drug users. Highly active antiretroviral therapy use was not significantly associated with HCC risk (OR for ever versus never = 0.59, 95% confidence interval 0.18-1.91). CONCLUSION: Lower CD4+ cell counts increased the risk for HCC among persons infected with HIV, an effect that was particularly evident for hepatitis B virus-related HCC arising in non-injecting drug users.

[Working under pressure]

From medical view the main problems of investigation and convicts are in particular in the range of the drugs and alcohol illnesses to see transferable diseases (HIV, hepatitis B - C and tuberculosis) and psychological illnesses. These complex diseases require a close meshed and intensive support of each individual patient and represent actually the main problem during an arrest. The development of the health service could address the new requirements making possible cost-conscious acting in handling with resources in the health service. In the canton Berne 957197 inhabitants live on a total area of 5959 km2. The police and military management operates the regional and district prisons as well as the transportation service for prisoners in the canton Berne for prisoners. The canton Berne has altogether 327 places. Since May 1971 persons from the regional and district prison and the penal institutions needing hospitalisation can be accepted. In the University hospital Berne on a specially equipped guard station and be cared for their medical problems. The prisoners profit in such a way from the entire range of the university facilities.