An acute stage of hepatitis C infection has been described, but most patients remain asymptomatic until years later. If symptoms manifest, they are consistent with a mild case of liver inflammation: malaise, nausea, jaundice and upper abdominal pain may be observed and may last for several weeks.

About 75% of patients who contract hepatitis C develop chronic hepatitis C, but disease progress is very slow. During years, fatigue and recurrent nausea may be the only signs of a persistent infection. Symptoms exacerbate over time and correspond to increasing replacement of hepatocytes by fibrous connective tissue. A patient presenting with liver cirrhosis may claim lethargy, nausea, vomiting, anorexia, weight loss and loss of libido. Jaundice and dermatological symptoms are frequently observed. Patients may feel pressure pain in the upper right abdomen. Neurological symptoms have been described and may comprise difficulties in concentration and memory impairment. Symptoms associated with hepatocellular carcinoma are similar and in fact, most patients who are diagnosed with hepatitis C-induced cancer also suffer from cirrhosis [8].

• Easy Bruising

  bruising and bleeding, a swollen abdomen, and abdominal pain or tenderness. [everydayhealth.com]

  bruising and bleeding Generalized abdominal pain These symptoms and physical changes occur because when the liver fails, it can no longer carry out its necessary functions. [emedicinehealth.com]

  Being infected with hepatitis B in addition to hepatitis C increases this risk further.Liver cirrhosis may lead to portal hypertension, ascites (accumulation of fluid in the abdomen), easy bruising or bleeding, varices (enlarged veins, especially in the [en.wikipedia.org]

• Fatigue

  In the Virahep-C study, 401 patients with HCV infection were evaluated for fatigue prior to and after treatment, using validated scales to assess the presence and severity of fatigue ( Sarkar, 2012 ). [hcvguidelines.org]

  Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. [ncbi.nlm.nih.gov]

  The most common symptom of chronic infection is fatigue; severe liver disease develops in 10%–20% of infected people. [web.archive.org]

  10.1097/01.aids.0000192071.72948.77, PMID: 16251829 Issn Print: 0269-9370 Publication Date: 2005/10/01 Checking for direct PDF access through Ovid Abstract Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue [doi.org]

  Symptoms can include: fatigue muscle aches loss of appetite Most symptoms of chronic hepatitis C don’t appear until cirrhosis develops and the liver begins to fail. [healthline.com]

• Pain

  She consulted the emergency department for diffuse abdominal pain, associated with vomiting. [ncbi.nlm.nih.gov]

  Symptoms of cryoglobulinemia include joint pain and swelling, a purple skin rash, swelling of the legs, and nerve pain. [britannica.com]

  In both acute and chronic hepatitis C infection some people may experience symptoms such as exhaustion, pain in the limbs, nausea, flatulence, feelings of fullness, abdominal pain, loss of appetite, pale-coloured stools or dark urine; however, these are [infohep.org]

• Fever

  Side effects occurring immediately after administration include headache, nausea, and influenza-like symptoms, such as fever and joint pain. However, reports of anaphylactic shock are extremely rare. [ncbi.nlm.nih.gov]

  Offers new coverage of the treatment options for ruptured or complicated appendicitis · hepato-splenic "cat scratch" fever · periodic fever with ulcer · pharyngitis · adenitis · chronic fatigue syndrome · and hemophagocytic syndrome. [books.google.com]

  Other human pathogen viruses belonging to the family of Flaviviridae are those viruses causing Dengue fever, yellow fever and West Nile fever. To date, no other viruses have been classified as Hepacivirus. [symptoma.com]

  […] book's features include clear and easy-to-read disease risk maps, information on where to find health care during travel, specific health information and itineraries for popular tourist destinations, detailed country-specific information for yellow fever [books.google.ca]

• Weight Loss

  But over time, they can experience the following: tiredness weight loss nausea abdominal pain severe itching jaundice (yellow discoloration of the skin and eyes) Eventually, people can have complications such as fluid in the abdomen and difficulty thinking [hepc.liverfoundation.org]

  Symptoms can include: weakness weight loss blood clotting problems Fluid can sometimes collect in the abdomen. Jaundice (yellowing of the skin) only appears in people with advanced cirrhosis. [healthline.com]

  Symptomatic patients may experience fatigue, nausea, anorexia, myalgia (muscle pain), arthralgia, weakness, and weight loss. [britannica.com]

  If you show signs that could come from chronic hepatitis or liver failure, such as jaundice, abdominal swelling or weight loss, you should call your doctor for an evaluation. [drugs.com]

• Malaise

  If symptoms manifest, they are consistent with a mild case of liver inflammation: malaise, nausea, jaundice and upper abdominal pain may be observed and may last for several weeks. [symptoma.com]

  When present, symptoms of acute illness may include fever, malaise, nausea, jaundice, arthralgia (joint pain), dark urine, pale stools, and abdominal pain. Acute symptoms typically subside within several weeks. [britannica.com]

  Some have a feeling of being generally ill (malaise), loss of appetite, fatigue, and vague abdominal discomfort. Often, the first specific symptoms are those of cirrhosis or complications of cirrhosis. [merckmanuals.com]

  Signs and Symptoms Acute infection See Viral Hepatitis Jaundice is uncommon in acute infection Constitutional symptoms in up to 35% Malaise Weakness Anorexia Minor Fatigue Right upper quadrant abdominal ache Nausea Arthralgia s Chronic disease Most patients [fpnotebook.com]

• Nausea

  Side effects occurring immediately after administration include headache, nausea, and influenza-like symptoms, such as fever and joint pain. However, reports of anaphylactic shock are extremely rare. [ncbi.nlm.nih.gov]

  If symptoms manifest, they are consistent with a mild case of liver inflammation: malaise, nausea, jaundice and upper abdominal pain may be observed and may last for several weeks. [symptoma.com]

• Abdominal Pain

  She consulted the emergency department for diffuse abdominal pain, associated with vomiting. [ncbi.nlm.nih.gov]

  In both acute and chronic hepatitis C infection some people may experience symptoms such as exhaustion, pain in the limbs, nausea, flatulence, feelings of fullness, abdominal pain, loss of appetite, pale-coloured stools or dark urine; however, these are [infohep.org]

  Symptoms may include: a high temperature of 38C (100.4F) or above tiredness loss of appetite tummy (abdominal) pains feeling and being sick Around 1 in 5 people who experiences symptoms will also have yellowing of the eyes and skin. [nhs.uk]

  But over time, they can experience the following: tiredness weight loss nausea abdominal pain severe itching jaundice (yellow discoloration of the skin and eyes) Eventually, people can have complications such as fluid in the abdomen and difficulty thinking [hepc.liverfoundation.org]

• Loss of Appetite

  In both acute and chronic hepatitis C infection some people may experience symptoms such as exhaustion, pain in the limbs, nausea, flatulence, feelings of fullness, abdominal pain, loss of appetite, pale-coloured stools or dark urine; however, these are [infohep.org]

  If symptoms occur, they may include loss of appetite, abdominal pain, fatigue, nausea, dark urine, and jaundice. Approximately 75%–85% of HCV-infected people develop chronic hepatitis C. [web.archive.org]

  Symptoms can include: fatigue muscle aches loss of appetite Most symptoms of chronic hepatitis C don’t appear until cirrhosis develops and the liver begins to fail. [healthline.com]

  Symptoms may include: a high temperature of 38C (100.4F) or above tiredness loss of appetite tummy (abdominal) pains feeling and being sick Around 1 in 5 people who experiences symptoms will also have yellowing of the eyes and skin. [nhs.uk]

• Dyspepsia

  There were 84 patients with duodenal ulcer, 43 with gastric ulcer, and 38 with dyspepsia. [bloodjournal.org]

  In these trials, the most common adverse reactions of moderate to severe intensity (grades 2-4) were diarrhea, dyspepsia, nausea, vomiting, fatigue, headache, dizziness, somnolence, and insomnia. [news.bms.com]

• Melena

  CASE REPORT We report a case of melena occurring in a 69-year-old Japanese man who had been diagnosed with CHC and who was treated with antiviral therapy. CONCLUSIONS Finally, he was diagnosed with multiple small intestine ulcers in a short time. [ncbi.nlm.nih.gov]

• Hepatomegaly

  Inflammation leads to the enlargement of the liver (hepatomegaly) in over 60% of people infected with hepatitis C and can cause the fibroelastic sheath (Glisson’s capsule) surrounding the liver to stretch, which may be the cause of pain in the liver area [hepctrust.org.uk]

  Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, alone or in combination with antiretrovirals. [news.bms.com]

  The majority of infected children have intermittent or chronically elevated aminotransferase levels [14], [20], [21], with hepatomegaly being the only common physical finding [14]. [doi.org]

• Arthralgia

  Symptomatic patients may experience fatigue, nausea, anorexia, myalgia (muscle pain), arthralgia, weakness, and weight loss. [britannica.com]

  […] direct acting antiviral agents are now considered first line therapy Long term complications of chronic HCV infection include cirrhosis and hepatocellular carcinoma Infection with hepatitis C virus (HCV) presents as an acute illness (such as fatigue, arthralgia [bmj.com]

  Up to 20-30% of patients may develop clinical symptoms including jaundice, dark urine, pale stool, arthralgias, fatigue, abdominal pain, nausea, vomiting, and decreased appetite. [clinicaladvisor.com]

  Signs and Symptoms Acute infection See Viral Hepatitis Jaundice is uncommon in acute infection Constitutional symptoms in up to 35% Malaise Weakness Anorexia Minor Fatigue Right upper quadrant abdominal ache Nausea Arthralgia s Chronic disease Most patients [fpnotebook.com]

  […] at risk should use latex condoms with sexual activity. 12 Diagnosis and Complications Most patients (60 to 70 percent) with HCV infection are asymptomatic; when symptoms do occur, they are non-specific and include fatigue, nausea, anorexia, myalgias, arthralgias [aafp.org]

• Pruritus

  Lerner, Topical Therapies for Pruritus, Seminars in Cutaneous Medicine and Surgery, 30, 2, (118), (2011). Howard B. Pride and Mercedes E. [oadoi.org]

  Minor side effects noted were nausea seen in five (7.7%) patients, insomnia and headache in four (6.2%) patients each, and pruritus in one (1.5%) patient. [ncbi.nlm.nih.gov]

  Common adverse events with telaprevir when used in combination with ribavirin and pegylated interferon include anemia, nausea, fatigue, headache, diarrhea, pruritus, and anal or rectal irritation and pain. [medscape.com]

• Urticaria

  Symptoms of cryoglobulinemia include fatigue, myalgias, arthralgias, neuropathy, glomerulonephritis, and rashes (urticaria, purpura, leukocytoclastic vasculitis); asymptomatic cryoglobulinemia is more common. [merckmanuals.com]

  Urticaria – This effects the skin and presents as a red, itchy rash that can appear in numerous places on the body and can lead to swelling. [hepatitiscentral.com]

  Skin reactions include Raynaud’s phenomenon, livedo reticularis, urticaria, and edema. Arthralgias more frequently involve the hands and the knees symmetrically. [doi.org]

• Yellow Discoloration of the Skin

  But over time, they can experience the following: tiredness weight loss nausea abdominal pain severe itching jaundice (yellow discoloration of the skin and eyes) Eventually, people can have complications such as fluid in the abdomen and difficulty thinking [hepc.liverfoundation.org]

• Somnolence

  In these trials, the most common adverse reactions of moderate to severe intensity (grades 2-4) were diarrhea, dyspepsia, nausea, vomiting, fatigue, headache, dizziness, somnolence, and insomnia. [news.bms.com]

Ideally, patients who present with symptoms of acute hepatitis are submitted to a thorough workup to identify its etiologic agent. In fact, molecular biological techniques allow for the confirmation of hepatitis C as early as a few days after infection. Identification of a particular genotype is possible. Reverse transcription polymerase chain reaction has to be applied to detect viral RNA. Distinct test systems are available [9]. Enzyme-linked immunoassay provide reliable results, too, but positive results are not to be expected until about two months after exposure. Of note, the here described tests confirm an infection with hepatitis C virus but they don't reveal any information regarding the duration of infection. In order to diagnose chronic hepatitis C, tests need to be repeated months after initial diagnosis of hepatitis C.

Serological testing may also be conducted, but specific antibodies may be detected in patients with an active hepatitis C infection as well as in those individuals that have overcome the disease. Therefore, serological methods cannot be applied to evaluate response to treatment. For an initial diagnosis of hepatitis C infection, they are very valuable, though.

Laboratory analyses of blood samples should be conducted. Parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin need to be evaluated to assess liver function.

Detailed information about the condition of hepatic parenchyma may be obtained by histopathological analysis of a liver biopsy. While such a procedure is not required to confirm hepatitis C infection, it is very helpful to assess current inflammation, fibrous remodeling and possible malignant degeneration.

Because liver cirrhosis is a major risk factor for hepatocellular carcinoma, patients diagnosed with the former should be regularly screened for the latter [8]. Sonography and measurement of serum α-fetoprotein are applied to this end.

Testing for hepatitis B and human immunodeficiency virus infections is recommended.

• Hepatocellular Carcinoma

  A 75 year old lady was diagnosed with advanced hepatocellular carcinoma and concomitant chronic hepatitis C viral infection. [ncbi.nlm.nih.gov]

  Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009 27 1485-91. Epidemiology of hepatocellular carcinoma in USA. Hepatol Res 2007 37 Suppl 2 S88-94 ,. [doi.org]

  Long-term consequences of chronic hepatitis C are hepatic failure due to cirrhosis and hepatocellular carcinoma. [symptoma.com]

• Liver Biopsy

  […] patients with good diagnostic performance comparable to that of liver biopsy and TE. [ncbi.nlm.nih.gov]

  Are There Alternatives to Liver Biopsy? The perceived risk and discomfort associated with liver biopsy have led to the development of several noninvasive methods to assess liver fibrosis. [healio.com]

Direct-acting antivirals and possibly pegylated interferon are the mainstays of therapy. Treatment aims at complete elimination of hepatitis C virus, a condition that may be revised by means of molecular biological testing.

Until a few years ago, ribavirin and interferon have been administered for up to ten months in a combined approach to treat hepatitis C infections. This prolonged therapy has not only been associated with high incidences of side effects, but its efficacy was often not satisfactory. Direct-acting antivirals fill both gaps: If applied during twelve weeks, high cure rates can be achieved, and the incidence of side effects is much lower. Thus, nowadays, genotyping and administration of specific direct-acting antivirals is the treatment of choice. The following compounds are available:

• Sofosbuvir
• Ledipasvir
• Paritaprevir
• Ombitasvir
• Dasabuvir

Direct-acting antivirals may be combined or supplemented with ribavirin or pegylated interferon if this becomes necessary to treat intractable cases.

Unfortunately, direct-acting antivirals are very expensive drugs.

A liver transplant may be the only chance to treat hepatitis C-induced cirrhosis. However, recurrence in the graft is very likely. Common therapeutic approaches to hepatocellular carcinoma are surgical excision, arterial embolization and radiofrequency ablation.

About 75% of hepatitis C infections become chronic and approximately 25% of patients suffering from chronic hepatitis C will eventually develop liver cirrhosis, an irreversible end-stage hepatopathy characterized by extensive replacement of hepatocytes with connective tissue. Direct-acting antivirals show good efficacy in hepatitis C treatment, but the risk of hepatocellular carcinoma remains increased in cirrhosis patients even after complete elimination of the causative pathogen [6]. Additional risk factors for malignant degeneration are diabetes mellitus and alcohol intake [6] [7].

Hepatitis C is caused by a single-stranded, positive RNA virus pertaining to the family of Flaviviridae and the genus Hepacivirus. Other human pathogen viruses belonging to the family of Flaviviridae are those viruses causing Dengue fever, yellow fever and West Nile fever. To date, no other viruses have been classified as Hepacivirus. Of note, the etiologic agents of hepatitis A and B pertain to the families of Picornaviridae and Hepadnaviridae, respectively.

According to genomic differences, at least seven genotypes of hepatitis C virus have been described. In many countries, genotypes 1 and 3 are the most common triggers of hepatitis C. There seems to be no relation between social status and the likelihood to contract these virus strains. In contrast, genotypes 4 and 5 account for major shares of cases only in low-income countries [2]. Infections with multiple genotypes of hepatitis C virus have repeatedly been described.

It has been proposed that hepatitis C virus genotypes evolved in a process that conferred increasing resistance to the human immune system [3]. This is of major importance for treatment of hepatitis C infections, since individual genotypes may be more or less sensitive to current therapeutic options.

Additionally, genotypic differences have to be considered in vaccine development. Current research mainly focuses on genotype 1, because no other genotype causes that many cases of hepatitis C. However, more than half of all cases are non-genotype 1 hepatitis C [2].

The hepatitis C virus is distributed throughout the whole world and it has been estimated that worldwide prevalence ranges between 2 and 3% [4]. This would correspond to up to 220 million people - an alarming number that also results from the high share of chronic hepatitis C cases. Indeed, most infections with hepatitis C virus become chronic. During early stages of the disease, patients are asymptomatic, and this fact often delays diagnosis and initiation of treatment. Long-term consequences of chronic hepatitis C are hepatic failure due to cirrhosis and hepatocellular carcinoma. These sequelae cause more than 350,000 deaths every year; about one out of four patients presenting with liver cirrhosis or hepatocellular carcinoma suffers from chronic hepatitis C.

The hepatitis C virus is one of several human pathogen hepatotropic viruses. It replicates within hepatocytes and may cause direct cytopathic effects, but according to current knowledge, liver damage in hepatitis C patients does not primarily result from virus-mediated cell lysis. Instead, host immune mechanisms seem to account for hepatic inflammation and induction of remodeling processes if the virus cannot be eliminated in a timely manner. Cytotoxic T lymphocytes have been proposed as effective inhibitors of viral replication, but these same cells may cause progressive liver damage [5].

If the above described pathomechanisms persist for more than half a year, for several years or decades even, replacement of functional liver parenchyma with fibrous connective tissue leads to cirrhosis. The inability to clear the virus may result from evasion of host defense mechanisms by the pathogen, e.g., by modulation of lymphocyte function or generation of mutated quasispecies.

Liver cirrhosis is considered a major risk factor for hepatocellular carcinoma even after successful treatment of hepatitis C [6].

Any practice that involves utilization of non-sterile needles, i.e., intravenous drug abuse, piercing and tattooing under unhygienic conditions, should be strictly avoided.

Sexual transmission of hepatitis C virus continues to be a matter of debate. However, men who have sex with men seem to have a high risk for contracting the disease, possibly because anal intercourse predisposes for lesions that lead to direct contact to blood [10]. Consequently, practice of safer sex is highly recommended to prevent acute and chronic hepatitis C.

Health care givers are considered at risk for hepatitis C infections. If an accident such as a needle-stick injury is registered, the affected person should be tested for hepatitis C virus repeatedly until six months later. This way, a possible infection may be recognized early and treatment can be initialized in a timely manner.

Hepatitis C is an infectious disease that frequently follows a chronic course, thus leading to chronic hepatitis C. Its causative agent is an RNA virus designated hepatitis C virus. Transmission mainly occurs through blood of infected individuals. Thus, transfusion of untested blood and blood products, organ transplantation, intravenous drug abuse and utilization of non-sterile needles are associated with significant risks of infection. However, routine screens of blood and organ donations as well as the implementation of measures to prevent graft infection have contributed to decrease the rate of hepatitis C infections acquired in medical procedures [1]. This may not necessarily apply to developing countries.

While the infection is initially asymptomatic, the majority of patients develops chronic hepatitis C and in about 25% of these people, viral infection of the liver will eventually lead to liver cirrhosis or hepatocellular carcinoma. More than 20 years may pass between infection and irreversible fibrosis or malignant degeneration and in some patients, only very mild symptoms manifest before they reach this final stage of the disease.

Treatment consists in long-term administration of direct-acting antivirals like sofosbuvir and ledipasvir as well as pegylated interferon; the specific regime should be adapted to the hepatitis C virus genotype that is causing the disease in an individual patient. Current research is focusing on the development of new antiviral drugs that induce less side effects. To date, chronic hepatitis C treatment often requires application of more than one drug and many patients claim flu-like complaints during therapy. While elimination of the pathogen is achievable, hepatic remodeling processes and degeneration may not be reversible.

Hepatitis C is an infectious disease whose causative agent is the hepatitis C virus. If such an infection persists for more than six months, the patient is diagnosed with chronic hepatitis C.

Causes

Hepatitis C is mainly transmitted through blood of infected individuals. Thus, intravenous drug abuse and utilization of non-sterile needles to pierce or tattoo are associated with significant risks of infection. Before routine screens of blood and organ donations were implemented, transfusion and transplantation were common sources of infection, too.

The virus infects and replicates within hepatocytes and in about 75% of all cases, the patient's immune system is unable to clear the virus. Then, chronic hepatitis C develops.

Symptoms

Within the first weeks after infection, hepatitis C may manifest in form of malaise, nausea, jaundice and upper abdominal pain, but some patients don't experience any symptoms. After remission of these complaints, patients are usually asymptomatic for years or even decades. However, chronic hepatitis C is associated with progressive liver damage and significant shares of patients develop liver cirrhosis or liver cancer many years later. The above mentioned symptoms aggravate, patients may lose appetite, weight and libido.

Diagnosis

The presence of hepatitis C virus can be confirmed by means of molecular biological techniques. Diagnosis of chronic hepatitis C requires several positive tests over the course of more than six months.

Additionally, blood samples may be analyzed to assess liver function. In some cases, a liver biopsy needs to be obtained.

In advanced cases of chronic hepatitis C, particularly in patients suffering from cirrhosis, regular screens are recommended to detect possible malignant degeneration of hepatocytes.

Treatment

A variety of antiviral drugs are available to eliminate the pathogen. Modern therapeutic approaches require medication over the course of three months, while significantly longer treatment was necessary until a few years ago. The overall prognosis is good.

Unfortunately, cirrhosis is an irreversible condition that does predispose for liver cancer. Thus, even though the virus is eliminated, hepatic function may remain impaired in cases of advanced chronic hepatitis C.

1. Felmlee DJ, Coilly A, Chung RT, Samuel D, Baumert TF. New perspectives for preventing hepatitis C virus liver graft infection. Lancet Infect Dis. 2016; 16(6):735-745.
2. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015; 61(1):77-87.
3. Pang PS, Planet PJ, Glenn JS. The evolution of the major hepatitis C genotypes correlates with clinical response to interferon therapy. PLoS One. 2009; 4(8):e6579.
4. Averhoff FM, Glass N, Holtzman D. Global burden of hepatitis C: considerations for healthcare providers in the United States. Clin Infect Dis. 2012; 55 Suppl 1:S10-15.
5. Larrubia JR, Moreno-Cubero E, Miquel J, Sanz-de-Villalobos E. Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control. World J Gastroenterol. 2015; 21(12):3480-3491.
6. Hedenstierna M, Nangarhari A, Weiland O, Aleman S. Diabetes and cirrhosis are risk factors for hepatocellular carcinoma after successful treatment of chronic hepatitis C. Clin Infect Dis. 2016.
7. Vandenbulcke H, Moreno C, Colle I, et al. Alcohol intake increases the risk of hepatocellular carcinoma in patients with hepatitis C virus-related compensated cirrhosis: a prospective study. J Hepatol. 2016.
8. Arguedas MR, Chen VK, Eloubeidi MA, Fallon MB. Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis. Am J Gastroenterol. 2003; 98(3):679-690.
9. Sábato MF, Shiffman ML, Langley MR, Wilkinson DS, Ferreira-Gonzalez A. Comparison of performance characteristics of three real-time reverse transcription-PCR test systems for detection and quantification of hepatitis C virus. J Clin Microbiol. 2007; 45(8):2529-2536.
10. Chan DP, Sun HY, Wong HT, Lee SS, Hung CC. Sexually acquired hepatitis C virus infection: a review. Int J Infect Dis. 2016.